FORM A – Signature Assurance Sheet

Instructions for IRB Forms Contents General Use of Forms ...................................................................................................................... 3 (Click an item in the table of contents and as applicable, click the Back button on the web toolbar or Alt+LeftArrow to go back to the specific form instructions you just left.) ..................... 3 FORM A – Signature Assurance Sheet ............................................................................................. 4 FORM B – General Information ....................................................................................................... 5 FORM B-1 – Expedited Certification Form ...................................................................................... 8 Form B–2 – Study Personnel List ..................................................................................................... 8 Form C - Research Description ...................................................................................................... 11 Veteran Affairs Research ............................................................................................................... 22 Forms D & E – Instructions for Proposed Informed Consent Document ...................................... 23 FORM D-2 or E-2 – Non-English-Speaking Subjects or Subjects from a Foreign Culture .............. 35 FORM F – Request for Waiver of Informed Consent Process ....................................................... 35 FORM G – NIH-Sponsored Clinical Trial ......................................................................................... 36 FORM H ......................................................................................................................................... 36 FORM H-1 - Translation Certificate ............................................................................................... 36 FORM J – HIPAA Waiver/Alteration............................................................................................... 37 FORM L – Advertisement(s)........................................................................................................... 40 FORM M – Data Collection Instrument(s) ..................................................................................... 40 FORM N – Cooperative Off-Site Research ..................................................................................... 40 FORM O – Use of Investigational New Drug(s).............................................................................. 41 FORM O-1 – Use of Approved Drug(s) for Unapproved Use ......................................................... 42 FORM O-2 – Placebo...................................................................................................................... 43 FORM P – Research Involving Investigational Devices .................................................................. 43 FORM Q – Use of Radioactive Materials (Radiation Safety).......................................................... 47 FORM R – Monitoring Participant Safety and Data Integrity ........................................................ 48 FORM T – Research Involving the Decisionally-Impaired .............................................................. 52 FORM U – Research Involving Pregnant Women, Fetuses, and/or Neonates .............................. 52 Page 1 of 55 FORM V – Research Involving Prisoners ........................................................................................ 53 FORM W – Research Involving Children ........................................................................................ 53 FORM X – Protocol-Related Conflict of Interest ............................................................................ 53 FORM EE – Institutional Biosafety Committee (IBC) ..................................................................... 53 FORM FF – Radioactive Drug Research Committee (RDRC) .......................................................... 54 FORM HH – General Clinical Research Center (GCRC) .................................................................. 54 FORM JJ – Veterans Affairs Research & Development Committee (VA R&DC) ............................ 54 AMENDMENT FORM ..................................................................................................................... 54 HDE Progress Report Form ............................................................................................................ 55 Report of Noncompliance Form .................................................................................................... 55 Repository Progress Report ........................................................................................................... 55 Copy from PDF to IRB Forms ......................................................................................................... 55 Page 2 of 55 General Use of Forms (Click an item in the table of contents and as applicable, click the Back button on the web toolbar or Alt+LeftArrow to go back to the specific form instructions you just left.) 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(The Reviewing toolbar must be visible, which can be revealed by clicking View, Toolbars, Reviewing toolbar using the drop down menu.) Page 3 of 55 FORM A – Signature Assurance Sheet Click here for General instructions on the use of forms Obtain the appropriate signatures as specified on the SIGNATURE ASSURANCE SHEET. If the principal investigator is also the chairperson of the department (or an equivalent position), the vice chairperson or equivalent should review and sign the signature assurance sheet. Submit one original of the SIGNATURE ASSURANCE SHEET. If this research is being conducted to meet UTHSCSA academic requirements, the student‟s faculty advisor, in addition to the Department Chair, should sign the Signature Assurance Page. What does the Department Chairperson’s Assurance Statement on the IRB application mean? The Institution is responsible for implementing a systematic and comprehensive human research protection program. As the supervisor of the principal investigator, the Department Chair (or equivalent), is responsible for assisting with the review of research. Before a study is reviewed by the IRB, the Department Chair must determine that a study is designed in a manner that meets the highest scientific standards and human subjects protections. Each department is free to choose a mechanism to assure human research protocols meet these rigorous scientific and human protections guidelines. By reviewing the IRB application and signing the Assurance statement, a Department Chairperson has assumed certain responsibilities and signifies that the science is meritorious and deserving of conduct in humans. The following is a list of the responsibilities reflected by signing the Assurance statement a. Scientific or scholarly validity The following issues must be addressed: 1) The research procedures are consistent with sound research design. 2) The research design is sufficient to yield the expected knowledge provided in the study protocol. 3) The knowledge expected as a result of the research has importance. In making the determination of scientific or scholarly validity, the Chair may use various mechanisms. The Chair may choose to review the study, assign review to another member of the department, draw on the knowledge and expertise of others, such as review by a funding agency (e.g., NIH, NCI) , an organizational scientific review committee (e.g., SACI, department research committee), or other entities as appropriate. In some cases, the Chair may decide to rely on a combination of these mechanisms. In all cases, the conduct of the review requires reviewers with the expertise to understand the background, aims, and methods of the research. Note - The review does not require a merit review that compares the value of the research to other research studies or a peer review designed to maximize scientific quality. Therefore, the individuals providing this type review do not require the level of disciplinary expertise required for review of relative merit or peer review. Following the Chair‟s determination of scientific or scholarly validity, the IRB will also draw upon its own knowledge and disciplinary expertise to review the study. b. Qualifications The Chair has ensured that the researcher(s) has sufficient time to conduct and complete the research and that persons listed as study personnel on the research protocol have the proper expertise and training necessary to carry out the research being proposed. The Chair has also ensured that the investigator must also have an appropriate number of qualified staff that are adequately informed about the protocol and their research-related duties and functions. When an investigator assumes a sponsor function, Page 4 of 55 the Chair ensures that the investigator is knowledgeable of the additional regulatory requirements of the sponsor and can comply with them. c. Subject population The Chair has ensured that the investigator has access to a population that will allow recruitment of the required number of participants within the proposed recruitment period. The Chair also has ensured that if participants need ancillary resources as a consequence of taking part in the research (psychological counseling or emergency treatment), the researcher has a process to make these available. d. Facilities The Chair has ensured that the facilities and equipment necessary to conduct the research study are adequate and appropriate for the type of research proposed to the IRB. e. Mentoring - Direct The Chair has and will continue to provide guidance to the researcher(s) during the course of study conduct ensuring adherence to established standards of scientific integrity, as appropriate. * If the Principal Investigator is also the Chairperson of the department, the Vice Chairperson or equivalent should sign the Signature Assurance Sheet. ** If the Principal Investigator is completing this project to meet the requirements of a UTHSCSA academic program, the student's faculty advisor, in addition to the Department Chairperson, should sign the Signature Assurance Sheet. FORM B – General Information Click here for General instructions on the use of forms Most questions in the General Information Sheet (GIS) section are self-explanatory, however, for your convenience, further clarification for several of the questions has been provided below: a. Question #6 requests that you indicate which categories of subjects you intend to recruit for your study. Some of the subject categories will require that you seek other approvals, or complete a form for that subject population in order to ensure the IRB addresses the appropriate criteria for inclusion of that population in your study. a. Sometimes investigator‟s plan to stop participation in the study but continue to follow pregnancies and outcomes by reviewing medical records. i. The Board may determined that approval of the research activity involving “follow-up by medical record review only” of pregnant women in the study and the pregnant partners of enrolled males may be given under DHHS regulation 45 CFR 46.204, as the risk to the fetus is not greater than minimal and the purpose of the follow-up research is the development of important biomedical knowledge which cannot be obtained by other means. ii. Other times the Board may recommend investigators read the FDA Guidance on establishing a pregnancy exposure registry 1. FDA Guidance recognizes that randomized, controlled studies of health effects during pregnancy require the deliberate administration of products to pregnant women and are often not feasible; that during clinical development of most products, pregnant women are actively excluded from trials, and; if pregnancy does occur during the trial, the usual procedure is to discontinue treatment and drop the patient from the study, although her pregnancy is typically followed to term. Consequently, at the time of a drug's initial marketing, except for products developed to treat conditions unique to pregnancy, there are seldom meaningful human data on the effects of that drug during pregnancy. The Board recommends considering establishing a pregnancy exposure registry is to provide clinically relevant human data that can be used in a product's labeling to provide medical care providers with useful information for treating or counseling patients who are pregnant or anticipating pregnancy. A pregnancy exposure registry can be initiated by a sponsor at any time. The decision to establish a pregnancy exposure registry should include consideration of both the need for pregnancy risk information 2. Page 5 of 55 b. and the feasibility of successfully completing the registry. (e.g., When established to assess margins of safety, to monitor for potential harm, or to detect safety signals, it is appropriate to initiate the registry as soon as possible; May also wait to be established when there is a need to evaluate suspected risks raised by spontaneous adverse events reports or published case reports. 3. A pregnancy exposure registry is a separate protocol that must comply with ethical principles and regulatory requirements involving human subjects research as specified in the federal regulations for the protection of human subjects (45 CFR part 46, 50, and 56). 4. If informed consent is to be obtained from the patient, the text of the informed consent form should be included in the registry protocol. Pregnancy exposure registries are not designed to provide direct benefit and should not represent any risk to either the pregnant woman or the fetus; therefore, the decision to participate in the registry rests solely with the pregnant woman (see subpart B of 45 CFR part 46). If the registry seeks to obtain information on the child after birth either through physical examination (minimal risk) or medical record review (no risk), either parent may consent for the child (see subpart D of 45 CFR part 46). Question #7 requests an estimate of the breakdown of subjects. This information is only an estimate but is requested when submitting a study to prompt researchers to track this information as it will also be asked at continuing review. It may be helpful to know that the 2006 estimates based on the 2000 census indicate the Bexar county breakdown for all ages is approximately 32% Anglo (approx. 49% of which are male), 8% Black (approx. 49% of which are male), 3% Other (approx. 46% of which are male), and 57% Hispanic (approx. 49% of which are male). See http://txsdc.utsa.edu/tpepp/2006ASREstimates/alldata.pdf for further details for Texas and age related distributions. TOTAL __________________________ TOTAL MALE FEMALE 1,550,160 49% 51% HISPANIC _______________________ TOTAL MALE FEMALE 57% 28% 29% BLACK ______________________ TOTAL MALE FEMALE 8% 4% 4% c. ANGLO ____________________ TOTAL MALE FEMALE 32% 16% 16% OTHER ___________________ TOTAL MALE FEMALE 3% 1.4% 1.6% Question #8 requests a breakdown of FDA regulated products used in the study. It is important to note that while the first drug/device questions are under the heading “Not Investigational Use (drug or device)” meaning they are FDA approved and FDA regulated products but since they are not investigational e.g., used only as directed and no safety or efficacy data is being gathered (for a more detailed explanation see definitions of investigational drug or investigational device) they are not subject to FDAs research regulations. (FYI no additional forms are required for these products and these are not tracked by the IRB as FDA Regulated Research solely because of one of these boxes is checked.) For those drugs/devices that do meet the definition of investigational the next section should be marked and these do require additional forms and are tracked by the IRB as FDA Regulated Research. Question #9 requests that you indicate which items apply to your research. Certain items may require that you complete and attach a form in order to ensure the IRB addresses the appropriate criteria for that component of your study. In addition, identifying which item(s) apply to your research enables accurate reporting through a database in the Office of IRB (e.g., upon request, d. Page 6 of 55 OIRB may need to generate a report of all research involving deception, or placebo-controlled trials). For Repositories: Collection of Biological Specimens for Banking [See Repository Policy, may require Repository Forms] Collection of Biological Specimens (VA Banking) [See Repository Policy, may require Repository Forms] In either case will likely require separate Repository Consent Requirements when testing for reportable diseases such as hiv and hepatitis: Subjects must be told when this testing is done for purposes of the study. (Note: They should also be informed if testing for illegal drug use.) Clarify whether HIV and/or hepatitis testing will be done for purposes of the study or as part of standard care. Would HIV and/or hepatitis testing have been required for standard clinical management (done regardless of study participation)? If not, then the screening will be done for research purposes and the specific issues must be addressed. In form C address: (i) whether a positive result will be confirmed and, if so, how and when (ii) timing between test results and informing subject (iii) structure for counseling those who are seropositive (iv) provision for transmitting the information to those who may be at risk because of exposure (see Health Department link below) (v) state who will provide counseling (vi) the extent to which confidentiality will be maintained [for example, will results be recorded in the subjects medical record, or only the subject's study/research record; will the information be available to third parties who request medical record information for billing or insurance, etc.] in the consent form: (i) why the screening is necessary (ii) Explain the meaning of a positive and negative result (explain that a positive does not mean they have HIV or AIDS only that confirmatory tests are required, a negative does not mean they are negative…) (iii) how subjects will be informed of results and whether subjects will be allowed to continue in the study (iv) that counseling and/or treatment will be available (v) the extent to which the confidentiality of the results will be maintained and safeguarded (vi) a discussion of the risks of being tested for hepatitis and risk of disclosure of positive results. All subjects who sign the local consent must be told what reporting is required by this State. The following website can provide more information regarding what diseases must be reported and what PHI is included in the report. http://www.tdh.state.tx.us/ideas/report/default.asp You may also contact the IRB office if you need further guidance. Requirements when testing for illegal drug use, the subject must be informed:  Whether the testing is done as part of standard care (would be done at this time regardless of study participation) or solely for research purposes (such as to determine study eligibility)  Whether a positive test result will exclude the subject from study participation  Whether the results will be placed in the medical record (where 3rd parties, such as an insurance company or an employer might gain access) or only in the research record [You should check with the site where the study is being conducted regarding that facility’s policy.] Deception Studies The use of deception in research is sometimes permitted. See Glossary and Form D instructions for more information Page 7 of 55 e. Question #10 requests that you indicate the type of funding you have obtained or plan to acquire in order to conduct the research. Note: NIH, CDC, HRSA, and SAMHSA, are all agencies of the Department of Health and Human Services (DHHS). If you are funded by NIH, CDC, HRSA, and/or SAMHSA, please checkmark the applicable funding agency under HHS. Question #12 requests that you specify whether your research falls under the purview of one or more of the committees listed. See Section 7 of the IRB application for details and instructions about additional materials required for IRB review if your research falls under the purview of one or more of the committees listed. Question #13 requests that you indicate all the sites at which your research will be conducted. If the research is being conducted at any other institution not listed (institution not under UTHSCSA IRB authorization agreement), additional materials may be needed. See Section 4, Form N of the IRB application for details. Question #17 asks if you need additional certification. You may need additional certification if your study is federally funded. If you answer "yes" to Question #17, the Office of the IRB will prepare the certification form and obtain the authorizing official's signature. The completed certification form is sent to the investigator, who is then responsible for submitting the form to the sponsor/agency. Question #20 asks if NIH or FDA requires a Data Monitoring Plan. If the study involves an FDA regulated drug or device, a data and safety monitoring plan (not necessarily a committee or a board, but a PLAN) is required and you should answer “yes” and submit Form R. f. g. h. i. For the NIH, you can find guidance at numerous web addresses. Here are some examples: http://grants.nih.gov/grants/guide/notice-files/not98-084.html http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html http://www.cancer.gov/clinicaltrials/conducting/dsm-guidelines http://www.niaid.nih.gov/ncn/clinical/humansubjects/hs12.htm FORM B-1 – Expedited Certification Form Click here for General instructions on the use of forms In accordance with federal regulations, a human (non-exempt) research study can be reviewed through an expedited review procedure if: a. The research activities involve no more than minimal risk; and b. The only involvement of human subjects is in one or more of several specified categories. Please carefully read the "Applicability" and "Research Category" sections of the Expedited Certification Form. Select the applicable research category(ies), and include one copy of the completed Expedited Certification Form with your IRB application submission. If you are submitting a protocol for expedited review, please mark "Expedited" for the type of review in the space provided on the General Information Sheet [Form B, Q. #1]. Form B–2 – Study Personnel List Click here for General instructions on the use of forms Page 8 of 55 Item A – List all research team members who will perform activities and/or research procedures listed in the protocol. Investigators and other members of the study staff (e.g., research nurse or coordinator, research assistant, etc.) who intervenes or interacts with subjects or obtains individually identifiable information as part of the study are generally considered “engaged” in research and must be listed in this section. Due to the restrictions of the HOP under “Research Scope of Practice for Study Personnel,” “unlicensed research personnel also may not display their educational degree (e.g. MD, RN, etc. on a name badge) in any way that would convey to the research participant or staff that he/she is a licensed practicing clinician” (See HOP for most up to date quote” Examples of when individuals are “engaged” in human research In general, individuals are considered engaged in a non-exempt human research study (and therefore would need their institution‟s designated IRB approval) when their involvement in the human subjects research includes any of the following activities:   Individual receives support from HHS (e.g., PI on an NIH grant) to conduct human subjects research, even where all activities involving human subjects are carried out by individuals. Individual intervenes for research purposes with any human subjects of the research by performing invasive or noninvasive procedures (e.g., drawing blood; collecting buccal mucosa cells using a cotton swab; administering individual or group psychotherapy; administering drugs or other treatments; surgically implanting medical devices; utilizing physical sensors; and utilizing other measurement procedures). Individual intervenes for research purposes with any human subject of the research by manipulating the environment (e.g., controlling environmental light, sound, or temperature; presenting sensory stimuli; and orchestrating environmental events or social interactions). Individual obtains for research purposes identifiable private information or identifiable biological specimens from any source. Obtaining includes, but is not limited to: (a) observing and/or recording private behavior; and (b) using, studying, or analyzing for research purposes identifiable private information or identifiable specimens already in the possession of the employees or agents of the institution. Private information or specimens is considered to be individually identifiable when they can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems. Examples of when individuals are NOT “engaged” in human research    In general, individuals are considered NOT engaged in a non-exempt human research study (and therefore would NOT need IRB approval) when their involvement in the human subjects research includes one or more of the following activities. It is important to remember that if an individual is involved in any of the activities listed below BUT is also involved in any of the activities under Engaged in Research (above), then the individual is engaged in the human subjects research project.  Individuals who are not part of the research team and release to investigators identifiable private information or identifiable biological specimens pertaining to the subjects of the research. [Note that in some cases the institution releasing identifiable private information or identifiable biological specimens may have institutional requirements that would need to be satisfied before the information or specimens may be released, and/or may need to comply with other applicable regulations or laws. For example, if the identifiable private information or identifiable biological specimens to be released were collected for another research study covered by 45 CFR part 46, then the institution releasing such information or specimens should: (a) ensure that the release would not violate the informed consent provided by the subjects to whom the information or biological specimens pertain (under 45 CFR 46.116), or (b) if informed consent was waived by the IRB, ensure that the release would be consistent with the IRB‟s determinations that permitted a waiver of informed consent under 45 CFR 46.116 (c) or (d)] Examples of individuals that might release identifiable private information or identifiable biological specimens to investigators include: (a) records clerks who release identifiable medical information; (b) laboratory technicians who release identifiable human biological specimens. [Note that the individuals who will receive the identifiable private information or identifiable biological specimens will be engaged in human subjects research.] Individuals who consult or collaborate on the human subjects research by obtaining coded private information or human biological specimens from an investigator engaged in the research who retains a link to individually identifying information (such as name or social security number), if one of the following conditions is met:  Page 9 of 55     the key to decipher the code is destroyed before the consultants or collaborators obtain the coded private information or specimens; the consultants or collaborators and the holder of the key enter into an agreement prohibiting the release of the key to the consultants or collaborators under any circumstances; the releasing investigator has IRB-approved written policies and operating procedures applicable to the research project that prohibit the release of the key to the consultants or collaborators under any circumstances; or there are other legal requirements prohibiting the release of the key to the consultants or collaborators. [Coded means that: (a) identifying information that would enable the consultant/collaborator to readily ascertain the identity of the individual has been replaced with a number, letter, symbol, and/or combination thereof (i.e., code); and (b) a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.]  Individuals from other institutions not engaged in the research who consult or collaborate on human subjects research conducted at a UTHSCSA IRB-affiliated institution that is engaged in the research, and:    the consultants or collaborators access or utilize individually identifiable private information only while at the institution that is engaged in the research; and, the consultants‟ or collaborators‟ research activities are overseen by the IRB of the institution that is engaged in the research. Individuals who perform commercial or non-collaborative services for investigators that are typically performed by those institutions for non-research purposes. For example, an appropriately qualified laboratory performs routine serum chemistry analyses of blood samples for investigators solely on a commercial basis. Individuals who only:     inform prospective subjects about the availability of research; provide prospective subjects with information about research (which may include a copy of the relevant informed consent document and other IRB-approved materials) but do not obtain subjects' consent or act as representatives of the investigators; provide prospective subjects with information about contacting investigators for information or enrollment; and/or seek or obtain the prospective subjects' permission for investigators to contact them. An example of this would be a clinician who provides patients with literature about a research study at another institution, including a copy of the informed consent document, and obtains permission from the patient to provide the patient‟s name and telephone number to investigators.  Note: the VA does not use engaged in research to determine whether a study falls under VA research regulations. Examples of when a study is considered “VA Research” 1. 2. sponsored by the VA being conducted by or under the direction of any salaried or without compensation (WOC) employee of the STVHC during her/his official duty time or in connection with her/his STVHCS responsibilities being conducted at a STVHCS facility recruiting subjects at the STVHCS or using the STVHCS‟s records (CPRS) to identify or contact subjects for research being funded or managed by the STVHCS or the Biomedical Research Foundation of South Texas 3. 4. 5. Page 10 of 55 Form C - Research Description Two important notes before you begin: Note 1 - Completing Form C may involve copying information from other electronic documents – please use the “Paste Special” function in MS Word to paste as “unformatted text” (instructions below). This will keep the font type and size in the uniform Arial 9. Note 2 - Consider whether the information you are inserting adequately addresses the information requested in the form. Grant submissions and sponsor protocols are very similar to the IRB Form C. However, they serve different purposes and may not always present the information needed by the IRB. The IRB submission forms are designed to address the safety and welfare of research participants. Grant submissions are written to demonstrate meritorious science and sponsored protocols often include sections important for the local PI but not relevant to the IRB. Attach any pages of those other documents referenced by page numbers only in Form C (this is only allowed in Question 2 below) Your answers should be understandable to the non-scientific members of the IRB. a. b. Question 1 Purpose and Objective: Describe the purpose of the study. List the specific aims, objectives or research questions/hypotheses. Question 2 Background: Briefly describe the background leading to the present study here. (This is the only section of this form where you may reference a sponsor protocol or grant application by page number and section instead of inserting the lengthy background and literature review section). Attach any pages of other documents referenced by page numbers only. This is only allowed in Question 2) a. Overview of Background: Reference pages in the grant or sponsors protocol as appropriate. b. Local Background: If there is any information not listed in the previously documented background (Grant/Sponsor Protocol/etc.) that is known locally that might influence the Board determination as to whether the study is adequately justified by the background information provide that here. c. Current Practice: If your study involves an intervention, clarify the current local standards of practice. The IRB may find this information invaluable in interpreting how the study varies from standard practice especially when in the medical community standard practice may not yet be established but local standards are adhered to. Page 11 of 55 c. d. e. Question 3 Study Design: Describe the study design. A scheme or visual diagram of the overall study design is helpful. Examples of descriptions of study designs can be found in the Glossary (Phase 1; Phase 2; Phase 3; Phase 4; Single Masked Design; Double Masked Design; Crossover Design; Concurrent Control; Historical Control; Placebo Control; Active Control Study; Double Masked, Placebo Controlled, Cross Over Design, Randomized Clinical Trial; Open Label Study; Randomized Controlled Design; Retrospective Study) Question 4 Study Population(s): There are 10 sub-questions related to your plan to recruit and enroll subjects into the study. Depending on the study design, your study recruitment plan may target subjects from one or more populations. For example, research designed to evaluate the effect of a new drug on patients with diabetes may only wish to recruit one population of patients with type 2 diabetes. In this example, only one populations table should be completed. A similar diabetes study designed to evaluate diet and exercise may wish to recruit two populations, non-diabetics and diabetics. The answers to the population sub-questions will be different between these two populations (e.g., inclusion/exclusion criteria, recruitment plan, etc.). Complete a table for each population. If the study design includes two different populations but the answers to the population subquestions are the same for both, only one table is required. Be sure to note in this section that only one table is used. a. Take into consideration the need for the IRB to evaluate your answers in the population tables in consideration of the need for a Waiver of Authorization for the use of Identifiable Protected Health Information (PHI) before actual consent/authorization is obtained. For example if you will require research team members that are not part of the patients‟ treatment team to review clinic schedules, medical records (electronic or paper) in order to identify potential subjects, this must be clearly stated in this section. Additionally, describe any telephone script to be used. i. Provide details regarding the information collected at the time of the telephone screening. [For example: Will only contact information be obtained or will data collected also include PHI?] ii. Based on the information that will be collected during the telephone contact, the investigator may need to request a Waiver of Authorization (refer to the IRB website for guidance or contact the Office of the IRB). iii. Indicate when any information (PHI) collected during the telephone screening and the initial intake appointment, if applicable, will be destroyed (as soon as possible, after completion of enrollment, after closure of the study, etc.) should the subject decline study participation. b. Take into account the need for the IRB to consider the entire process of informed consent, the timing, privacy and setting, the consent and assent, the need to consent subjects who become adults while already enrolled in the study as minors, efforts to avoid undue influence or therapeutic misconception. c. Privacy issues related to recruitment of subjects – in clinical research, investigators often use existing clinical information such as clinic appointment schedules, or inpatient census reports to identify patients who may be eligible for enrollment. Questions 3, 4 & 5 address recruitment strategies. If your study will access private, identifiable information to identify potential subjects, include a thorough explanation of the relationship between the research team members accessing the information and the subject. Are the researchers accessing this private information part of the covered entity? Are the researchers accessing private information part of this patient‟s treatment team? Question 4.b.4: Recruitment Initial Contact a. Initial contact may occur after exposure to recruitment materials, in which case the potential subject initiates contact with the research team, or initial contact could be made by those with legitimate access to the individuals contact information (treating physician or his/her staff) or it could occur when research team members (without an existing treatment relationship) attempt to contact potential subjects before or during a research study or it could be a merging of the latter two. However initial contact occurs describe the individuals involved, their authority to access PHI based on any PHI that is accessed in order to identify individuals and who contacts whom. i. EXAMPLE: “Initial contact will be made during routine clinic visits. The research team members are the health care providers for these patients.” Page 12 of 55 b. UTHSCSA has established a policy which chooses a higher standard for the protection of patients‟ rights and welfare than allowed under some interpretations of the Privacy Rule. The UTHSCSA policy requires any unsolicited communication (unless a Waiver of Authorization has been approved) about an ongoing or upcoming research study to come from the individual's treating physician or his/her staff (though this would include investigators having a treatment or research relationship with the potential subject as well). This policy was created in the spirit of the Office for Human Research Protections (OHRP), Secretary‟s Advisory Committee On Human Research Protections (SACHRP) recommendations of February 2005 in contrast to other interpretations of the Privacy Rule, e.g., as discussed by the NIH in 2003 and Office of Civil Rights (OCR) in 2004. c. Where a Waiver of Authorization is requested and approved for research staff to identify potential subjects by review of records or schedules and approval is given to contact those potential subjects under the waiver certain additional procedures are required and recommended. i. The covered entity is primarily responsible for protecting the PHI and will require a copy of the waiver but depending on the individual actually responsible for protecting PHI in the area in which you will be accessing PHI you may be required to provide them a copy as well. ii. It is recommended that procedures include a method to avoid the potential for the subject leaping to the conclusion that the research staff are part of the treatment team. Research staff should identify themselves to the potential subject, explain how they know about the subject‟s condition, and allow the subject the opportunity to remove themselves from the contact list at that time. 1. Depending on the amount of time you expect to spend explaining to each subject how you gained access to information about their condition when you approach them, you may want to create a short handout or even a business card or slightly larger sized card explaining, for example, that you were given access to schedules (by the institution) in order to offer them the opportunity to enroll in the research only after the institution was assured you would protect their privacy and confidentiality and advising them of their inherent right to ask you to remove them from your contact list (in laymen's terms of course, large print and must be IRB approved prior to implementation of course-if the study is ongoing at the time it could be expedited). We would even recommend putting our office contact info on the back to make it more official. d. Note that the VA does not allow contact of potential study participants for recruitment into research unless an IRB has specifically (i) waived the requirement for an authorization under the HIPAA Privacy Rule relative to use or disclosure of Protected Health Information (PHI) to recruit subjects for the proposed research and (ii) waived the informed consent requirement under the Common Rule to allow use of identifiable private information for recruitment into the research. The R&D Committee must also approve the research. f. Question 4.b.5: Recruitment Setting a. Specify whether the setting in which the research team complete the consenting b. process (including signing the form) takes place for example whether it is on the phone in a private setting, in person at a particular clinic in specific rooms in a private setting or possibly in the waiting room as the potential subject is waiting for a clinical appointment or in the emergency room during treatment for an emergent condition. See Guidance Concerning Pre-Screening of Research Subjects During Recruitment Phase of IRB Approved Research Page 13 of 55 g. Question 4.b.6: Recruitment a. See Guidelines for advertising Question 4.b.7: Consent and Assent Procedures a. This can include a summary of the answers in 4, 5 and 6 prior to and leading into the discussion of the consent and assent procedures but technically it should be noted that the recruitment procedures have been covered and this question is focusing on the activities that occur once the subject is in contact with an individual qualified and authorized by the PI to consent subjects or the PI who is discussing the details of their pariticipation, the risks and benefits etc. with the intent of completing the consent process either themselves of by another member of the research team. Be sure to cover how information is provided (verbally vs simply providing a written document to take home, etc.), how the consent interview is conducted (in person, by phone, etc.), the person(s) who will conduct the consent interview (whether more than one person is generally ivolved, e.g., passing off to a research nurse to have the subject and a witness sign) and how the consent is signed (privacy, who signs the consent, etc.).)If consenting a single subject will involve more than one member of the research team, describe how this process will be coordinated from start to finish. If you will be attempting for certain h. ages to obtain assent describe this process. i. Question 4.b.8: Timing a. Describe the timing of obtaining informed consent, whether there is any waiting period between informing the prospective subject and obtaining consent. (e.g., take consent home, waiting period of X hours, after consulting with family members, etc.). j. Question 4.b.9: Describe measures taken to minimize coercion or undue influence a. The investigator should carefully self evaluate circumstances that could be construed by others as resulting in a subject who refuses being made worse off than if he or she would have been, if never asked. Coercion occurs in cases where retribution is conceivable or perceived by the subject. Examples of coercion include situations where it is even implied or perceived that continued services are dependent upon participation in the research; or where refusal may affect some future care or outcome. If such a perception might be expected due to special circumstances describe the measures taken to minimize this perception. An example might be in the circumstance were a clinic only receives referrals on patients that might be qualified or may in the future be qualified for studies conducted by the clinic that steps have been taken to minimize the potential for potential subjects perceiving that continued services in some way hinge on participation in a research study like pamphlets that are handed out to each new clinic referral and posters around the clinic state their rights, detailing the fact that participation in research is not a prerequisite for continued care in the clinic. b. Coercion is less likely to be a concern that must be addressed in the answer to this question than “undue influence.” Investigators should carefully self evaluate circumstances that could be construed by others as resulting in a subject perceiving undue pressure to participate, e.g., to please the provider - which might occur for example if the researcher is also the potential subjects care provider. Describe measures taken to minimize the possibility of undue influence during consent. For example, “When the researcher is the potential subject‟s treating physician, after the researcher explains the study and answers any questions, whenever feasible, another research team member (e.g. the Study Nurse, Sub-Investigator), other than the treating doctor, completes the Informed Consent to avoid the potential for any subject feeling a sense of undue influence which may occur if the researcher is also their treating physician.” [Note: In this way the research team member can complete the consent form outside the presence of the initial researcher who generally has already explained the study and answered questions about the study]. This allows the potential subject to more readily feel at ease with potentially declining to participate at that point if that might be their decision. This is more of a concern, generally, when there is substantive research risk associated with the study. This is because with little added risk there is less concern if a person might want to participate just to please their treating physician. Question 5: Enrollment of Non-English Speaking Subjects k. Page 14 of 55 If you plan to exclude individuals who do not speak English, check box A. Excluding individuals who do not speak English is a sensitive issue, particularly if the research study includes medical treatment that could benefit some or all of the participants (therapeutic intent). Generally, the IRB requires the inclusion of non-English speaking individuals whenever there are no standard care options available or all standard care treatments have exhausted. In situations where individuals have alternative standard care treatment options available or there is no direct benefit (no therapeutic intent), the Board will consider reasonable justification for excluding non-English speakers. However in those circumstances that lie in the gray area in between in which alternatives are available but they may be not considered entirely effective, were often refused due to toxicity, and a similar decision tree to the acceptability of placebo in research, the Board will carefully weigh the justification for their exclusion. If not enrolling non-English-speaking subjects, include a justification for excluding non-Englishspeaking subjects (e.g., the study does not include the potential for direct benefit to those who do participate, survey instruments and questionnaires are not validated in other languages. Generally, not having access to someone who speaks another language, is not considered to be sufficient justification alone; (many institutions have translators available for clinical purposes where the research is taking place). In considering whether a direct benefit exists whether participate in the study may be the only means of obtaining the particular benefit. For example, in 5(1) Describe the non-English language(s) and how consent will be obtained in that/those languages. What resources are available to speak in the language of the participant? 5(2) If you will be enrolling subjects when English is their second language, describe how the researchers will determine which language to use during consent and whether there are adequate resources available for translation. [attach Form H and H-1 after ICD/instruments are translated] l. Question 6: Research Plan and Methods a. Description of Methods – Provide a systematic description of how the study will be conducted and the analyses to be used to accomplish the specific aims of the study. This section should contain a step-by-step description of all research activities. Include the treatment plan, dosing procedures, administration of study drug procedures, and study procedures (e.g., screening, treatment and follow-up procedures). The description of research methods can be supplemented with summary tables that outline the research procedures and the study visits. Example of a Schedule of Study Procedures Component / Procedure Recording info from records Eligibility Assessments Inclusion/exclusion Medical History Pregnancy test Safety Assessments Physical exam Vital signs Assessment of signs and symptoms Toxicity assessments/AEs Laboratory Assessments H&H Chem 7 Disease Assessments Bone marrow aspiration & biopsy Screening Visit Weekly End of Study Visit X X Lab  Xray  X X X X X X Page 15 of 55 Administer Study Medication X The methods section should include how the data will be collected, analyzed, and interpreted as well as the data-sharing plans as appropriate. Include sample size determination as applicable. b. List research procedures or components. List those procedures that will be done solely for research purposes. For example, administering experimental drug, obtaining imaging or diagnostic studies, administering psychometric instruments, obtaining information from the medical record, etc. Similar procedures can be grouped into components as long as they have the same level of risk (e.g., all minimal risk). For example, obtaining vital signs, height and weight, medical history and physical exam can be listed together as “eligibility assessments” or „screening procedure” rather than listing each individually in this section. (Other examples are listed in the table above.) Quantify the procedures – for example the dose used, the number of times the procedure will be performed, the volume of blood obtained, etc. Note: the following additional clarification concerning Risk, the Methods and Components sections of Form C and how they relate to the Procedures section of Form D utilizes the following acronyms: Standard care only (SO); Standard care but research related or protocol directed (S/R) and research purposes only (RO). [Click on the links for definitions of each] RISK It is clearly prudent to consider using regulatory wording concerning minimizing risk "…minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes" and explaining those points when answering the first question under #7 in Form C. This issue resonates throughout the forms and it is an issue about which the IRB must make one of their critical determinations. FORM C It would be best if in Form C procedures were clarified as to which are standard care (SO and S/R)) from research only (RO) - this is primarily for the Board to be able to prioritize their analysis of risk:benefit, considering first and primarily those research only (RO) risks, next all others in the list of research procedures (S/R) [Note that conspicuous by their absence in that section are those solely done for standard care (SO) during the time of the study but since by definition these are not even collected for research data they are not even listed in the components section (although they may be mentioned in the methods section)]. So, to clarify, in the methods, all procedures and visits are described sequentially, which may include scattered throughout the methods, standard only (SO), standard/research related (S/R) and research only (RO) procedures but in the components there should only be a discussion of research related procedures: standard/research related (S/R) and research only (RO). FORM D In addition, in the consent form, at the beginning of the procedures section, a suggestion often made in the past is to summarize those things that would have been done even if they were not in the study (Standard only (SO) and standard/research related (S/R)) and those being done additionally, solely because they are in the study (RO) followed by a sequential discussion of everything that will happen during the course of the study (with those items which are standard noted as standard care (note these may be either SO or S/R).(The problem that arises occasionally with this concept is when something is standard care only and not research at all but just being done during the timeframe that subjects are in the study. It really needs to be clearly stated that such SO procedures are not part of the research. This is a rare situation.) So in conclusion, SO S/R and RO are in the methods, S/R and RO are in the components in Form C; SO, S/R and RO are in the summary paragraph that introduces the procedures in the consent form and SO, S/R and RO are in the sequence of visits with SO noted when that is the case for that procedure (in addition if SO, additional clarification may be required). Avoiding the term RO in the consent avoids the potential for misunderstanding by the potential subject that the rest of the time they are not in the research study since if Page 16 of 55 there are no SO procedures all the remaining procedures are research related (in most cases). Of course if all those listed as RO are really only RO and none are S/R then this might technically be acceptable or if both RO and S/R are noted it might be acceptable but again the intent is to clarify the difference and when possible avoid the impression that might arise with the use of the term RO in the consent form, that all the rest of the procedures are SO when in fact they are S/R. Form C Consent Form SO Methods Section SO Procedures Section S/R S/R Components RO RO Example of a list of procedures/components: (Note that you should specify which you are using the table to describe, procedures or components. In this example procedures are listed under each component so the heading is changed to Research Components and the risk tables should be created for each component and so labeled. They should match. You will find when you try to describe the risks of each component that you may need to specify which procedure in it you are referring to for example under safety assessments you may need to provide an additional heading in the likely but not serious box to indicate the risks listed there are only referring to the EKG or Chest x-ray, etc.) Note also the intent of the investigator performing this analysis and grouping (the components table and risk:benefit tables) is so the IRB can more readily focus on those more risky procedures or components and particularly those performed solely for research purposes so listing the riskiest procedures/components first and organizing the standard practice procedures/components last provides the IRB the opportunity to focus appropriately as the progress down the list and down the tables. # Note that: A + B = Research components Local Standard Research Only Practice required by (Indicate # performed the research plan solely for research (research only) or indicate # performed outside frequency or timing for acceptable local practice) Study Medication  Placebo  Eligibility Assessments Obtain consent  Medical History/Demographics Inclusion/Exclusion review 1 C Total Number of Research Related Procedures Risks section Risk:benefit Analysis ??? Advise what is Standard care 1 2 3 Once at Baseline screening visit Page 17 of 55 Advise to expect separate consent    Singled out – 4 5 Physical exam Neurological exam Randomization Randomization (when necessary have a table for each arm) Safety Assessments Venipuncture for safety labs 24 hour urine collection 12 lead ECG Review Concomitant Medication Review Adverse events Review Drug Accountability/ Compliance Vital Signs/Weight/Height (height at screen only) Efficacy Assessments Vital Capacity (breathing test) Questionnaires Strength testing Collecting Info from Medical Records/ Results of Study Assessments 4 (SOC is 1-4 times/yr) 1 (Once at baseline) 1 (At baseline) 5 1 4 (SOC is 1-4 times/yr) 1 8 5 6 17 12 5 7 17 (includes phone visits) 16 11 16 11 4 (SOC is 1-4 times/yr) 4 (SOC is 2-4 times/yr) 4 (SOC is 2-4 times/yr) 8 12 6 8 13 (Includes phone visits) 12  12 17 (Includes phone visits) 12  7 Click here for other examples which include examples of risk:benefit tables: Example 1, Example 2, Example 3 (specific for randomization as a risk) c. Describe Risk:Benefit Analysis – for each procedure or component listed in (b) above, provide a risk and benefit analysis. Two tables are provided – if more tables are needed copy and paste. Do not leave sections blank – insert none or N/A as appropriate. Do not cut and paste from the consent form or to the consent form. Consider the fact that the consent form is written for the subject and Form C is written for the board. However with this said consider also that the risks must be consistent between the two. Risk Analysis includes: •Identifying risks Frequency Severity (when necessary additional factors such as immediacy, permanence) •Assessing potential risk consequences (when specifically appropriate added description of consequences) •Setting priorities for action (generally discussed in Form C, item 7 (2) but also discussed when appropriate in Form R) Assessing potential risk frequency and severity –Frequency: How often a risk is likely to be realized. Do not delete frequency from the risk:benefit tables. The need to know what to report promptly, later in the course of the study, results in a requirement to make an effort to estimate a priori frequency. •Past studies animal or human (clearly past human studies provides the clearest information on frequency and severity however, when the only information is frequency and severity in animals a physician may need to subjectively adjust the information taking into account their knowledge of drug or procedure (the pharmacodynamics of the drug or the physiology of humans)) •Information from colleagues experienced with the drug/procedure Page 18 of 55 •Brainstorming (it may be necessary to make an educated guess. If an investigator can say an event is likely on a scale of “likely, less likely or rarely likely to occur” then he/she is accepting the concept that it is expected at least 33% of the time. Probably more than that and this becomes the sticking point… just how often will the investigator be willing to accept that the event might occur before they consider it to be outside the expected frequency and indicate it may be a greater risk than was previously known or recognized requiring substantive action like stopping enrollment until a new consent form can be created or stopping procedures until a new dose can be approved, etc.) When necessary usually only appropriate in the consent form but consider adding description of consequences of the risk (especially when listing in both serious and not serious or when long lasting or permanent). If critical generally again, only appropriate in the consent form, note when subject should report to the ED or call 911. The reason these concepts are discussed here in Form C instructions is that often researchers/coordinators try to make the risks identical between the consent form and Form C. Technically they are speaking to two different audiences so the consent form while it should be consistent is not required to be exactly verbatim as the Form C risks. Page 19 of 55 Procedure or component 1 Delete one of the words, if you are using a table for each procedure for example vs. deleting the word procedure if you are listing several procedures for one component. [Insert short label] This label should be the same terms or terms used to describe the component in the component list. It is allowed to add a truncated list of procedures in the component if you prefer to remind the reader when many procedures are involved especially when you find yourself needing to list specific procedures separately in the risks section below with a component. List each group exposed to this procedure For each group, list the benefits of this procedure (either the procedure or a on a separate line. monitoring procedure likely to contribute to the subject‟s well being). If there are no (e.g., experimental, control, Arm A, Arm B, etc benefits, state “none”. Or state All Groups/Subjects List benefits for each component, you can list them separately on each of these lines if you have many different components with different benefits but the intent is that you group procedures with like benefits and like levels of risk so hopefully this will not be necessary Examples of benefit might include: increased monitoring if several safety labs are performed as research only in the components list indicating they would not have been performed if the subject was not participating in the study. It is allowed to list a potential benefit “Particular research protocols may hold out the prospect of direct medical benefit to the subjects themselves, even though such benefit can never be assured. The potential direct medical benefits to the subjects include health improvements which may or may not be related to the disorder responsible for the subject's incapacity” Payments or Free medical care should not be portrayed as a benefit of research participation or considered in the assessment of the risk:benefit ratio. Receipt of procedures and study items may be listed as benefits to the subject if they would not have otherwise received them as part of standard care, but not in conjunction with their being "free" or at reduced cost. Group: 1 Direct Benefit: [State "None" (or insert direct benefit, secondary benefit, or monitoring benefit)] All Groups Benefit to the community (or specify population especially if same population being recruited) / Knowledge gained benefit (philanthropic on behalf of the individual). For this procedure or component, list the reasonably foreseeable risks List the risks according to the probability (likely, less likely or rare) and magnitude (serious or not serious). (include: 1) expected adverse events; 2) rare and serious adverse events; 3) all other psychological, social, legal harms) Not serious Venipunture:  Pain  Bleeding  Bruising It is ok to list one of the procedures in the component separately when it is appropriate to single it out Serious  If you list a risk without a header the assumption is that the risk applies to all procedures in the component if the table is used to describe several procedures as one component. Likely These risks are expected to occur in more than 20 out of 100 subjects. The Board considers the definition of likelihood should be relatively consistent across all components in order to allow subjects to clearly understand the likelihood of those risks. If it is absolutely necessary to change the numbers, ensure the numbers in each of the three levels add up and do not overlap. Less likely These risks are expected to occur in 520 subjects or less out of 100 subjects. Rare These risks are expected to occur in less than 5 subjects out of 100 Do not delete frequency. Make an effort to estimate. See detailed instructions above on previous page Not serious  Serious Vomiting (though not  frequently when it occurs it is most often self limiting) Serious All those reasonable  Vomiting (dehydration) (rarely vomiting can be severe expected risks must be enough to lead to dehydration and hospitalization) listed but in the case of Occasionally it is necessary to list the same risk in two those serious risks even different boxes. When you do this it is necessary to offer those rare serious risks some explanation as to why you believe it is appropriate to are listed. This block is do so. not to be used. Yes No N/A (There is only one group) Are all groups exposed to the risks listed above? If No, Describe: [Describe here] Page 20 of 55 Click here for examples of risk:benefit tables: Example 1, Example 2, Example 3 Question 7: Safety Precautions – Section (1) For the study in general and for each risk identified in the risk analysis section above (most risky procedures foremost), describe procedures you will follow to prevent or reduce/minimize the potential risks. [In order to determine that risks are minimized the IRB will review this section and determine whether the safeguards listed in this section adequately address each of the research-related risks particularly the most common risks and the most serious so list those safety measures first. The IRB will need to be able to say you are using sound research design and not unnecessarily exposing subjects to risk so the more you can explain here to ensure they have the justification necessary to come to that conclusion the better. The IRB will also need to be able to say that when appropriate research data is being gathered by using the procedures or visits which would have been performed even if the subject were not in the study. ] Section (2) Specifically address medical interventions, personnel and equipment provided in the event of an adverse event. Section (3) Specify whether there are differences among different groups in the study. m. Question 8: Available Alternatives – Describe all available alternates to participation. For therapeutic research, this will often include a description of other acceptable treatment options. If the research involves the use of an already approved FDA drug or device, use of the product outside the study is often an alternative. In some cases, the only alternative is to decline participation in the study. This section should agree with the alternative section of the consent form. n. Question 9: Confidentiality – The questions in this section address measures used to protect unauthorized access to the information collected during the course of the study. “Identified” refers to information considered identifiable under either system DHHS or HIPAA. Therefore it includes information under DHHS that meets the definition of human subjects interpretation of “individually identifiable private information”, e.g., can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems or under HIPAA where the information meets the definition of PHI, e.g., is listed as an identifier under HIPAA or where there exists a reasonable basis to believe the information can be used to identify the individual. Include measures that will be used from the time confidential information is recorded to the storage of information at the conclusion of the research. This section should account for confidential information stored on various media (e.g., paper documents, electronic files, research materials labeled with confidential information. The confidentiality section should include description of the plan for coding research data, location(s) of confidential information storage and how access will be controlled or limited. The procedures outlined in this section should not conflict with institutional policies related to confidential information (check each institution‟s policies). Example when not destroying data: “There are no plans to destroy the data. Any future use of the data is limited to answering research questions for this study only.” [The IRB will review this section and determine whether the safeguards are sufficient to protect the confidential information obtained throughout the study.] o. Question 10: Payment – This section addresses two common payments to research subjects: incentives (or inducements) and compensation. Incentives are often used to attract or retain subjects. Compensation is offered to offset the expenses commonly incurred by subjects (e.g., parking, travel, child care, etc.). Payment of subjects is allowed – however because payments, particularly incentives, can create an “undue influence” in a subject‟s decision to participate, investigators and the IRB must be vigilant about minimizing this possibility. Undue influence often occurs through an offer of an excessive or inappropriate reward or other overture in order to obtain compliance. [The IRB will review this section and determine whether the payments are reasonable in relation to the costs incurred by the subject and whether the payment is excessive or inappropriate given the nature of the research.] d. Prorating: Compensation should not be in the form of a lump sum upon successful completion of the study as this is considered undue influence. i. Compensation should be prorated, with a portion received at each visit or at predetermined times during the study. e. Children: ii. Compensation should be given not only to compensate adults for inconvenience and/or travel expenses, but should also be applied to the Page 21 of 55 child. The Board recognizes the acceptability of these types of payments to parents and children, and recognizes the inappropriateness of other payments, for example, paying parents for including their child in research, and rejects the acceptability of financial encouragement for children‟s participation in research based on the level of risk involved (larger payments for assumption of greater risk should not be permitted IOM, 2004). 1. The Board requires the child receive a portion of the compensation. 2. The Board recommends that children receive their compensation in the form of age-appropriate gifts, savings bonds, movie tickets and so forth. 3. The amount of compensation to either the parent or child should not be an amount that is considered an undue influence. 4. Both the protocol and the consent form must be clear as to who will receive the compensation (both the parent and the child) and to indicate the form of compensation to be given. p. Question 11: Cost – (1) Consider all possible costs the subjects can incur as a result of participating in this study. List those expenses that will be paid for by the participant or their insurance company. Include the cost of medical care resulting from a research-related injury (as applicable). (2) If there are plans for subjects to be reimbursed for costs related to a research-related injury, describe these here. Question 12: PI/Sponsor – This question is applicable to research involving a drug or medical device regulated by the FDA where the local investigator has obtained an Investigational New Drug (IND) or Investigational Device Exemption (IDE). This could include research using an unapproved drug or device, or an approved drug or device used in an unapproved manner. INDs and IDEs for Significant Risk (SR) devices are issued by the FDA. IDEs are not required for NonSignificant Risk (NSR) device studies – however, the PI must follow the FDA abbreviated requirements at 21 CFR 812.2(b) for the conduct of NSR device research. Abstract - Provide a succinct and accurate description of the proposed research. State the purpose/aims. Describe concisely the research design and methods for achieving the stated goals. This section should be understandable to all members of the IRB, scientific and non-scientific. This summary will also be needed in future IRB Progress Reports. q. r. Veteran Affairs Research And the UTHSCSA IRB Click here for General instructions on the use of forms The UTHSCSA Institutional Review Board (IRB) serves as the IRB of record for research conducted by faculty/staff/personnel at the South Texas Veterans Health Care System (Audie L. Murphy Division, GCRC and Outpatient Clinics Division in San Antonio), research conducted within those facilities, and/or research involving VA patients. A Memorandum of Understanding (MOU) between UTHSCSA and Veterans Affairs (VA) establishes guidelines for responsibilities between the two entities. The IRB is charged with protection of the rights and welfare of individuals enrolled as subjects in research. In addition to the IRB, the VA Research and Development Committee (R&DC) reviews protocols with regard to VA-unique policies and scientific merit. Both IRB and VA R&DC approvals are required before any research procedures can be implemented at the VA. The VA‟s Research and Development Committee will not give final approval to an application without UTHSCSA IRB approval. “VA Research” is defined as research: 1. 2. sponsored by the VA being conducted by or under the direction of any salaried or without compensation (WOC) employee of the STVHC during her/his official duty time or in connection with her/his STVHCS responsibilities Page 22 of 55 3. 4. 5. being conducted at a STVHCS facility recruiting subjects at the STVHCS or using the STVHCS‟s records (CPRS) to identify or contact subjects for research being funded or managed by the STVHCS or the Biomedical Research Foundation of South Texas UTHSCSA researchers who use VA facilities, recruit VA patients for UTHSCSA studies, or who have joint appointments must complete mandatory education in any area applicable to the research being conducted. For specific information, contact Angela Casas at the VA Research Service Office, (210) 617-5300 ext.15523. VA Policy Notes VA policy prohibits paying human subjects to participate in research when the research is integrated with a patient‟s medical care and when it makes no special demands on the patient beyond those of usual medical care. Payment may be permitted, with IRB approval, in the following circumstances:     When the study to be performed is not directly intended to enhance the diagnosis or treatment of the medical condition for which the volunteer subject is being treated, and when the standard of practice in affiliated non-VA institutions is to pay subjects in this situation. In multi-institutional studies, when human subjects at a collaborating non-VA institution are to be paid for the same participation in the same study at the same rate proposed. In other comparable situations in which, in the opinion of the IRB, payment of subjects is appropriate. When transportation expenses are incurred by the subject that would not be incurred in the normal course of receiving treatment and which are not reimbursed by any other mechanism. [VHA Handbook 1200.5, 7, 12.a., pg 21-22] A veteran subject will not be required to pay for care received as a subject in a VA research project except if they are in an eligibility category that requires they pay a co-pay for medical services that are not part of the study. [VHA Handbook 1200.5 Appendix C, 2. a. (14)] Additional VA rules: If specimens will be banked, genetic testing done, or a commercial product developed, VA policy must be followed [VHA Handbook 1200.5 Appendix C 2. b. (7)]. For details see: http://www1.va.gov/vhapublications/ViewPublication.asp?pub_ID=89, VHA Directive 2000-043, "Banking of Human Research Subjects‟ Specimens,” November 6, 2000, requires that all human biological specimens and linked clinical data collected as part of research projects conducted by VA investigators in VA facilities or approved off-site locations will be maintained at either VA-sponsored tissue banks or VA (ORD)-approved tissue banks. Sites that may not be acceptable for storage of tissue specimens include non-academic, forprofit institutions, such as pharmaceutical or biotech companies. Consent and/or Authorization by a Legally Authorized Representative for VA Research The PI may obtain consent by a legally authorized representative only in situations where the prospective subject is incompetent or has impaired decision-making capacity, as determined and documented in the person‟s medical record in a signed and dated progress note. The determination that a subject is incompetent or has an impaired decision-making capacity must be made by a legal determination or a determination by the practitioner, in consultation with the chief of service after appropriate medical evaluation that the prospective subject lacks decision-making capacity and is unlikely to regain it within a reasonable period of time. In cases where the determination that a prospective subject lacks decision-making capacity is based on a diagnosis of mental illness, VA policy requires consultation with a psychiatrist or licensed psychologist. [For more information, see the UTHSCSA OIRB/IRB Informed Consent SOP, and the VHA Handbook 1200.5 Appendix C 2. b. (11)]- Research Involving Human Subjects with Surrogate Consent]. Forms D & E – Instructions for Proposed Informed Consent Document Click here for General instructions on the use of forms Additional Guidance documents available online Page 23 of 55 Informed Consent Guidance Checklist for Informed Consent Except under certain conditions where the IRB can waive the requirements for documentation of informed consent for minimal risk research, informed consent shall be documented by the use of a written consent form approved by the IRB and signed and dated by the subject or the subject's legally authorized representative. Informed consent is one of the primary ethical considerations underlying research with human subjects. It is too often forgotten that informed consent is an ongoing educational process that takes place between the investigator and subject. The consent process should allow for an exchange of information between the investigator and the subject, and afford ample opportunity for the subject to ask questions and consider whether or not to participate/continue to participate in the study. In most cases, the federal regulations require that informed consent be documented. It should be reiterated, however, that the consent document does not substitute for discussion. To develop a consent document for your study, follow the instructions and use the template provided below to ensure inclusion of required elements. UTHSCSA IRB policy dictates that only consent documents with a valid "IRB Approval" stamp can be used when enrolling subjects, unless waiver from this requirement is approved by the IRB. If you lose the ability to change the header into two separate headers, one for the consent form and one for the authorization it is because you have accidentally deleted the continuous section break on the signature page of the consent form. Go to the last word on the page, hit enter, click the Insert dropdown menu then select continuous under Section Break Types. Now scroll down to the header on the next page and double click into the header. You should see a title on the header “Header –Section 2-“ and you should see the header and footer toolbar popup. Click the “Link to Previous” button to unlink it. Then you can change the two headers each separately without changing the other. INSTRUCTIONS 1. Use the informed consent template. Note this is not a form to be completed, but a guide to be followed when developing your consent document(s). Always refer to the Informed Consent Policy and Procedure for the specific requirements of informed consent and documentation of consent but below are specific additional instructions OIRB staff feel will assist you in completing this document. 1. In the “General Information – “Who is conducting this research?” section: 1. 2. If you use the “Conflict of Interest” or “could result in a financial benefit” section then you need to submit a Form X as well. In the “Purpose of this study – “Why is this study being done?” section: 1. Don‟t over-do the justification for the study such that it seems like a sales pitch or overly complicate this explanation. Keep it simple. Consider using only so much explanation as would be required to understand why a reasonable person might think the effort is worthwhile. Page 24 of 55 2. In using the template language, such as, “This study will compare the effects, good and/or bad, this/these drug (s) has/have on people who take/use it/them [and if appropriate include] and on the disease/condition, with those of other commonly used drugs/interventions”, it is important to recognize the need to elaborate when necessary. For example, the study is not truly comparing to commonly used treatments if the active control is not commonly used or sometimes this is changed to state “compared to standard treatments” but Form C states in inclusion criteria that no standard treatment is effective or even exists. Modify template language as appropriate for the study submitted Examples of wording that the Board has approved in the past will be added here as they become available as additional guidance: 3. Purpose of this study – “Why is this study being done?” You are asked to participate in this research study of an investigational drug, XXXXXXX (XXXXXXX). Investigational means the drug has not been approved by the U. S. Food and Drug Administration (FDA). ZZZZZZZZZZ operations can stress the heart and other parts of your body. Improving the supply of YYYYYYY to the stressed tissues during and shortly after a ZZZZZZZZZZZ operation improves the possibility of maintaining normal metabolism and function. The study drug is the first in a class of drugs that can improve the supply of YYYYYYYYY during and shortly after a ZZZZZZZZ surgery. It is not known whether improving the supply of YYYYYYYYY will reduce the risk of complications. The researchers hope to learn whether using XXXXXXX (XXXXXXX) during high risk ZZZZZZZZZZ surgery for significant WWWWW disease can reduce the risk of developing complications such as death, heart failure, and stroke up to XX days after coronary bypass surgery as well as reduce the risk of death at XX months after surgery. It could also reduce other complications, length of hospital stay and associated costs. The study will also evaluate the safety of the drug. Significant WWWWW disease is defined as either: 1) 2) 3) or; or; ZZZZZZZ surgery is the preferred method of treatment of WWWWWW disease and is our current standard care. This study will compare the effects, good and/or bad, the investigational drug (XXXXXXX (XXXXXXXX)) has on people who use it and on the condition, with not using the drug. The safety of this drug in humans has been tested in prior research studies; however, some side effects may not yet be known. Information about Study Participants – “Who is participating in this research?” You are being asked to be a participant in this study because you have been diagnosed with WWWWW disease, you and your doctor have decided you will be having a non- Page 25 of 55 emergency ZZZZZZ surgical procedure performed using vvvvvvv, you are 50 years of age or older, and you are considered to be at high-risk for complications because you ______________ 3. In the “Information about Study Participants – “Who is participating in this research?”” section: 1. The example given is “You are being asked to be a participant in this study because [state general reason why the person was identified to participate. For example, because they have the disease being studied or they are already scheduled for the procedure being studied, etc. This is not intended to be a repetition of the inclusion criteria].” 1. This is an opportunity clearly disclose why a reader would consider it ethically ok for someone to offer an experimental treatment to a potential subject. For example, “You are being asked to be a participant in this study because you have the disease being studied and there are no currently accepted treatments or standard of care treatments have not been effective, etc. 2. Another example might be “You are being asked to be a participant in this study because you have [the disease being studied] and you don‟t yet require treatment [or treatment for… or treatment with…]. The later examples might be helpful when there is a need to justify the use of a placebo in the study for example. 3. Unfortunately often it is not as clear cut as either of these two examples. It is a difficult but necessary exercise for the investigator to attempt to describe why it would be ethically acceptable for someone with a disease or illness to participate in a study of an experimental treatment when an existing standard is available and their participation means they may either be exposed to the standard or the standard plus an experimental treatment or when they may get standard or an experimental treatment where standard is not being given or the experimental treatment is less frequent dosing than standard, etc. Rationales for such designs can be extrapolated from rationales for placebo controlled studies, e.g., if standard care is not considered effective, if it is then if it is often toxic or not accepted by patients, if it is effective and not often declined then is it because not receiving it or delaying it cannot cause irreversible health problems or extreme suffering. 4. In the “Information about Study Procedures section – “What will be done if you decide to be in the research?”: 1. Don‟t forget one of the primary concerns of the Board is to be sure the difference between what would be done even if the subject was not in the study is clearly differentiated from what is being done or added just because they have agreed to participate. It is often helpful if not absolutely necessary to begin this section with a summary paragraph that states something to the effect that, “You would have had your surgery even if you were not in this study. Because you are in the study your surgery will be a few minutes longer. You will also have an additional biopsy and more blood than usual will be taken. The one additional biopsy and 3 of the blood samples are just for the research and will not be [but will be] used in your care.” Also equally important it to clearly differentiate between what would have been done anyway, even if they were not participating and what is being done solely because they agree to participate. (standard care vs research only). There is an opportunity to do this in the template language where the statement reads Page 26 of 55 something to the effect that, “Any procedure described below as “standard care” would be done even if you do not take part in this research study.” A major deficiency in many submitted consent documents is the inclusion of this statement but the failure to actually make those procedures described below stand out as standard care (e.g. including a header or parenthetical notation with each standard care procedure or component). With this said, it is possible that it may be more appropriate to annotate only those that are “research only” as there are only a few of those and most of the rest of the study involves collection of data from procedures that would have been done anyway even if they were not participating in the study (which should have been summarized in a this way as noted in the first paragraph of #1 above). When this is the case leaving out the template language concerning standard care and instead adding a similar sentence describing instead that you will annotate those procedures below that are research only… 2. If you discuss optional blood or tissues samples don‟t forget to consider that you may need an additional consent/authorization form specifically for the repository and if the repository is being opened locally and you plan on it staying open after the current study is done it should be opened in it‟s own right as a separate protocol. This way it can remain open after the current study is finished. It is recommended that just before the “Could your participation end early” section if applicable you add “It is possible that results from this study, including future research, might discover or develop something that can be marketed and sold to make money. There are no plans to pay you any money if profits should arise from the research, including working with your specimens. Anything that results from the research, whether it is information or products, will be owned solely by the study sponsor.” 3. 5. In the Risks section – “What are the risks of participation in the research?” 1. This is a difficult section to complete. It will require close coordination between the principal investigator and anyone assisting the principal investigator to complete the forms. Regulations state at 45 CFR 46: In order to approve research the IRB shall determine that all of the following requirements are satisfied: 1. Risks to subjects are minimized and that risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits. 2. 3. The IRB is instructed in these regulations that: 1. The IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility. 4. This does not mean the subject need not be informed of risks of therapies subjects would receive even if not participating in the research when it is logical to do so or that possible long-range effects of applying knowledge gained in the research need not be disclosed if appropriate such as with genetic research. As a matter of fact the regulations state in the “Basic elements of informed consent” that, in seeking informed consent the following information shall be provided to each subject: Page 27 of 55 1. 5. A description of any reasonably foreseeable risks or discomforts to the subject; It should be noted that it does not as in the very next statement qualify the disclosure of risk as only those that apply to research only procedures: 1. A description of any benefits to the subject or to others which may reasonably be expected from the research; 6. Examples have been given but flexibility is allowed so long as the risks are th conveyed in a manner conducive to understanding by a reader of a 6-8 grade reading level and all reasonably expected risks are disclosed plus when serious risks though not reasonable expected (because they are rare) may occur, they must also be included. Rare but not serious risks are therefore conspicuous by their absence but it helps to consider whether a reasonable person would want to know. Though a risk of chipping a tooth on a device might be a rare risk and considered by definition not be serious a reasonable person would want to know about this risk before agreeing to participate in a research study. When considering which procedures in the methods section in Form C should be described in risk benefit tables (see Form C instructions above) and which of those risks should be disclosed in the consent form, in general the risks should be consistent between the two forms but specifically:  All research-only procedures must have reasonably expected risks (and rare but serious risks) described.  All standard care procedures directed by the protocol (click the link to read the definition of protocol-directed) the risks of these procedures must be described in the research consent form (with minimal exceptions – where exception is made, the consent form may notify the subject that they should expect that risks will be covered (possibly with a clinical consent form) outside the research consent process for research if that is the case.)  All standard care x-rays although data is collected for research purposes (i.e., directed by the protocol) should be noted in the procedures section as such and the risks of these procedures will be described outside the context of the research consent form. However including a discussion of those risks is acceptable on occasion, but only required in certain circumstances at the IRBs discretion. The consent form may notify the subject that they should expect that risks will be covered (possibly with a clinical consent form) outside the research consent process for research if that is the case.  All standard care procedures where data is not collected for research purposes (i.e., not directed by the protocol but the procedure just happens to be performed during that time that the subject is in the study) should be noted in the procedures section as such and the risks of these procedures will be described outside the context of the research consent form. The consent form may notify the subject that they should expect that risks will be covered (possibly with a clinical consent form) outside the research consent process for research if that is the case. However including a discussion of those risks is acceptable and on occasion and only required in certain circumstances those risks may be required by the Board when the Board deems it necessary for a subject to be able to compare the risks of the research procedure to the standard care procedure which is their alternative or to which they may be randomized. Page 28 of 55 Presenting information to patients in natural frequencies (e.g., one patient out of every 100) is an effective method of reducing any confusion resulting from the provision of numerical frequency information. Where the information is limited the current example might not be applicable. If you only have likely, not serious risks for example and you delete the likely/serious category the bulleted format might not be as easily understood. It is acceptable in some cases to insert None in those categories where no risk is anticipated or to change the bullets to a table or paragraph so long as the risks are explained well in terms of frequency, severity and if applicable permanence. Occasionally risks are theoretical (e.g., noted in animals but not yet seen in limited use thus far in humans), frequency and severity in humans not having been established and for which the investigator does not wish to offer any expectations in terms of frequency and severity. The IRB may on occasion allow this but recognizes that it is incumbent on the PI to recognize the limitations of this type of vague disclosure. During the study, where those risks result in adverse events the PI must analyze those AEs under UPIRSO criteria and without a priori estimates of frequency or severity must categorized them (e.g., liver or kidney damage or difficulty breathing) as unanticipated by the protocol documentation and serious. Therefore if possibly related the investigator must determine prompt reporting as an Unanticipated Problem Involving Risk to Subjects or Others (UPIRSO) is required (See “Concerning frequency and severity breakdown” below for further discussion of this topic). In the end it will be a determination of the IRB as to whether they agree with the manner in which risks are presented and on a case by case basis may require the stratifications listed below. 1) Example of alternate method of listing risks in a table, 2) Example of Standard method of listing risks: Likely (insert range approximately “X” – “Y”# of subjects out of 100), Likely and serious Likely and not serious Less Likely (insert range approximately “X” – “Y”# of subjects out of 100), Less Likely and serious Less Likely and not serious Rare but Serious Page 29 of 55 Concerning frequency and severity breakdown: To clarify our recommendations to investigators concerning how best to present information in informed consent forms and in this case not just helpful to potential subjects understanding but a necessary exercise, frequency and severity breakdowns make it possible for investigators to determine whether a particular event constitutes an “unanticipated problem” requiring prompt reporting to the IRB and substantive action to protect the rights, safety and welfare of subjects or others. Both the FDA and OHRP agree that events that occur more frequently or at greater severity than expected should be considered unanticipated (See our UPIRSO Policy and notes below). For an investigator to make this determination it is necessary for them to estimate or assume an a priori severity (and frequency) for each risk based on their best estimate given their best understanding of the science and the population*, otherwise how can they decide after the fact whether the event has occurred more frequently or at a greater severity that expected? [*The IRB understands it is an impracticable task to categorize all those risks associated solely with the population and their condition (e.g., not also listed as a risk of the study) as they can be innumerable but those risks already listed in the protocol represent a readily available opportunity to establish estimates for these reasonably expected risks (or if serious, even those rare risks) ahead of time.] OHRP states: (2) Serious adverse events that are expected in some subjects, but are determined to be occurring at a significantly higher frequency or severity than expected. When monitoring a research study, an investigator, a DSMB/DMC, a sponsor, or another entity assigned responsibility for monitoring the research data under the IRB-approved protocol on occasion may detect that a particular type of serious adverse event is occurring in subjects with significantly greater frequency or severity than expected ([as an example they mention mild vs. severe liver injury]). FDA states: FDA believes that an individual adverse event report cannot be readily concluded to represent an unanticipated problem, even if the event is not addressed in the investigator's brochure, protocol, or informed consent documents. Individual adverse event reports generally require an evaluation of their relevance and significance to the study, including an evaluation of other adverse events, Page 30 of 55 before they can be considered to be an unanticipated problem. FDA believes that reports that lack such evaluation should not be provided to the IRB, since the IRB will be unable to assess the significance of the report for the rights and welfare of human subjects in the study. Reports of unanticipated problems should provide information that is of some relevance to the IRB's responsibility to assure the protection of human subjects (i.e., new information that might affect the IRB's view of the study or that change the study protocol or consent form). Sponsors are required to notify investigators of serious and unexpected adverse experiences (§ 312.32(c)(1)(i)(A)), and must keep investigators informed of new observations discovered by or reported to the sponsor, particularly with respect to adverse effects and safe use. (§ 312.55(b)). With regard to the subset of "unanticipated problems" that are also adverse drug experiences, FDA believes that only the following adverse experiences (or events) should be reported to the IRB as "unanticipated problems." [Only one subset listed below] An adverse event that is described or addressed in the investigator's brochure, protocol, or informed consent documents, or expected to occur in study subjects at an anticipated rate (e.g., expected progression of disease, occurrence of events consistent with background rate in subject population), but that occurs at a greater frequency or at greater severity than expected. We recommend that a discussion of the divergence from expected rates accompany the report. 6. In the Benefits section – “How could you or others benefit from your taking part in this study?” Describe any possible benefits to the subject or others which may reasonably be expected from the research; indicate that benefits are not guaranteed. Start with a discussion of the direct benefit to each individual subject. (e.g., “You may not receive any personal benefits from being in this study.”) If statements regarding direct benefits of participation are included, they should be qualified as "possible" or that they "may" occur. Then go on to discuss the benefit to society. (e.g., “We hope the information learned from this study will benefit other people with similar conditions in the future.”) Do not state only theoretical benefit if for example you are only testing feasibility (e.g., if you are only testing to see if it is possible to raise a subjects heat rate by looking at a photograph then don‟t try to describe a benefit to the individual subjects‟ physical fitness (as might be expected when maintaining heart rates at a certain level for a certain amount of time)) Receipt of procedures and study items may be listed as benefits to the subject if they would not have otherwise received them as part of standard care, but not in conjunction with their being "free" or at reduced cost, as these statements imply a form of payment and thus should not be categorized as benefits. The FDA Information Sheet "Guidance for Institutional Review Boards and Clinical Investigators" (1998) states, "Payment to research subjects for participation in studies is not considered a benefit, it is a recruitment incentive." Forms of Page 31 of 55 payment may be referenced elsewhere, but not listed as a benefit of participation. 7. In the Alternatives section – “What other options are there to participation in this study?” Describe appropriate alternative treatments or procedures, if available. List several alternatives to participation if they exist; alternatives may include alternative drugs or therapy, palliative care, hospice care, etc. If these drugs or therapies are also used in the study clarify (e.g., “You can receive the drugs (or drug 1) used in this study without participating in the study…” rather than “Your alternatives include drug 1, drug 2,…” etc.) The consent form may say, "your study doctor will discuss these with you." The section on alternatives may be improved by including a brief summary of the risks and benefits of the alternatives but this may only be required on a case by case basis. Ensure the answer to why subjects are being asked to participate in section “Information about Study Participants – “Who is participating in this research?””, makes sense logically with the alternatives section. (e.g., If you told them they were being asked because there is not standard care available then don‟t say one of their alternatives is to have standard care outside the study) 8. In the Compensation section – Will there be any compensation for participation? Describe proposed payment for participation, if any, including proration. Any money or other incentive of monetary value should be listed in this section rather than the benefit section. If subjects are to be paid, state specifically for which visits subjects will receive payment and when such payment will be made; for example, "payment will be made at the end of each study visit," "payment will be made at the end of the last study visit" or "payment will be made within one month after the last study visit." Be as specific as possible to minimize confusion. Consider whether any aspects of the total amount or the proration plan may be considered coercive or unduly persuasive. The Board may require revision of the payment or payment schedule. 9. In the Costs section – Will taking part in this study cost anything? Describe any known or anticipated costs to the subject. State who is responsible for the costs of the study-related items such as medications, procedures, device, visits, hospitalization and treatment for possible side effects. Indicate which procedures and items will be provided at no charge If insurance will be billed for anything, include information about possible costs to the subject or their insurance. If anything is being billed to insurance, discuss what happens if the insurance does not pay. Information related to costs to subjects who participate in the study and information regarding who will cover costs for treatment of research-related injuries must be consistent with the UT Health Science Center at San AntonioInvestigator-Sponsor contract and HOP Policy 7.8.1. You should review this Page 32 of 55 section of the proposed or approved contact to ensure the language is consistent with the consent. If you have questions about contract language related to research related injuries you can contact Dr. Schmelz at 567-2357 or Kay Perry at 567-0452. You will be required to revise all applicable documents (i.e., IRB Form C, all consent documents, etc.) as appropriate after IRB review if necessary for your study and provide to the IRB a copy of the section of the contract that includes this information. Always refer to the Informed Consent Policy and Procedure for the specific requirements of informed consent and documentation of consent 2. The consent form should be written in language understandable to the subject. Whenever possible, simple sentences should be used instead of complex ones. Do not use medical or technical jargon. 3. If you are recruiting non-English-speaking subjects, the consent document needs to be in the subject‟s native language. 4. AVOID EXCULPATORY LANGUAGE through which the subject or the representative is made to waive or appear to waive any of his/her legal rights or release the investigator, the sponsor, the institution or their respective agents from liability for negligence. 5. In the procedures section: see Form C instructions concerning description of Standard Care vs. research procedures. 6. If the RESEARCH INVOLVES THE PARTICIPATION OF CHILDREN (under 18 years of age), please read the UTHSCSA IRB Policy on Children in Research. Also, you must complete and attach Form W to your IRB application. 7. If the RESEARCH INVOLVES PREGNANT WOMEN, both the mother and father must give consent after having been fully informed regarding the impact of the research on the fetus. (NOTE: Under certain conditions, the father's consent is not necessary. For a list of those conditions, contact OIRB.) Also, you must complete and attach Form U to your IRB application. 8. If the RESEARCH COULD POSSIBLY PUT AT RISK: (1) AN UNBORN CHILD, (2) A MAN’S ABILITY TO PROCREATE, or (3) A WOMAN'S ABILITY TO CONCEIVE OR CARRY A CHILD, the following statement(s) (revised to meet the needs of your particular study) should be included in the consent form: You should not become pregnant or father a baby while taking part in this study because the drugs in this study can affect an unborn baby. Women should not breastfeed a baby while taking part in this study. It is important you understand that you need to use birth control while on this study. Check with your study doctor about what kind of birth control methods to use and how long to use them. Some methods might not be approved for use in this study. [Include a statement about possible sterility when appropriate. For example, “Some of the drugs used in the study may make you unable to have children in the future.” If appropriate include a statement that pregnancy testing may be required.] 8. If VA PATIENTS deemed INCOMPETENT, are to be enrolled in the study, additional requirements may be necessary for the consent form [See VA Research Consent Form] and additional procedures must be implemented to ensure the subject's rights are protected. These additional requirements can be obtained through the Research and Development Office at the South Texas Veterans Health Care System , Audie L. Murphy Division,7400 Merton Minter Blvd., San Antonio, TX 78229-4404, (210) 617-5300. You must attach Form T to your IRB application. 9. If the researcher believes that any fluids, tissues or other substances obtained from a research subject could be part of or lead to the DEVELOPMENT OF A COMMERCIAL PRODUCT, (e.g., development of a cell line for commercial use), please address what rights the research subject will have pertaining to monetary gain from the sale of such materials. 10. If the research is part of a National Institutes of Health (NIH)-sponsored multicenter clinical trial (e.g., NIH-sponsored gynecology group study), copies of the NIH-approved sample informed consent document must also be included in the application packet. Page 33 of 55 11. If the research involves DRUGS, DEVICES, OR BIOLOGICS not approved by FDA, or not used in accordance with FDA approval, inform the subject in the purpose statement that the study includes evaluation of both the safety and effectiveness of the test article. Clearly state that the drug, device, or biologic is investigational (i.e., experimental / not approved by the Food and Drug Administration). You must also complete and attach Form O for Investigational Drugs and/or Form P for use of Investigational Devices. Each of these forms will advise whether you also need to submit additional forms. 12. The informed consent should describe the DOSE ESCALATION aspect of the study (i.e., as the research progresses, the dose for each new subject gets larger). 13. For research involving HIV SCREENING and/or AIDS RESEARCH, there are additional IRB requirements for designing and implementing the research and for obtaining informed consent. Visit the Office for Human Research Protections web site for statements on AIDS research, or contact the Office of the IRB at (210) 567-2351 to obtain copies. 14. If you are setting up a SPECIMEN BANKING REPOSITORY, see the UTHSCSA OIRB/IRB repository policy and the repository application (protocol and consent form). 15. For research involving DNA BANKING and GENETIC RESEARCH, additional issues must be addressed when obtaining informed consent. For additional information, contact OIRB at (210) 567-2351. You may be asked to obtain a federal Certificate of Confidentiality to exempt your research project from subpoena of data to protect it from third parties (e.g., insurance companies, employers) if you are collecting identifiers on genetic materials. 16. Certificate of Confidentiality: When a researcher obtains a Certificate of Confidentiality, the potential subjects must be told about the protections afforded by the certificate and any exceptions to that protection. That information should be included in the informed consent form. The National Institutes of Health (NIH) Office of Extramural Research provides an example of appropriate language (scroll to Informed Consent section at bottom of web page that opens). Researchers may adapt the language to the needs of the potential subjects and to the subject matter of the study. However, the language used must cover the basic points. For additional information on obtaining Certificates of Confidentiality, visit NIH's Frequently Asked Questions (FAQs) web page. 16. A copy of the consent/assent form should be given to the subject or the subject‟s legally authorized representative. 17. The consent form must provide the names of two medical doctors (study investigators) who are available to answer questions regarding side effects or medical complications; keep in mind that the document must provide the local contact information and 24-hour access. A number for business hours and a number for after hours may be one way to provide this information. The after-hours number could be a home phone, a pager number or an answering service. [The answering service, however, must contact the investigator in a timely manner and the investigator must return the subject's call as soon as possible.] A non-licensed physician may be listed in this capacity. For non-medical issues, such as questions regarding a study visit, you may also include the name of the study coordinator and a contact number for subjects to call during business hours. 18. Describe for each study visit: procedures to be expected at each visit; purpose of the visit/procedure; time required to complete visit (e.g., each questionnaire may add 10-15 minutes); indicate if blood will drawn at each visit for study purposes and specify what type of testing will be done on the blood; indicate how often visits will be scheduled. The Board often recommends the use of bullet format to list procedures being done at each study visit. 19. Deception: Federal regulations permit but establish limitations on the use of deception. The Investigator must provide scientific and ethical justification for deceptive procedures for the IRB review and approval. The missing information should not increase the risks of the study, and subjects must be fully debriefed. Subjects must have the opportunity to ask questions about the new information and be given the opportunity to withdraw from the study and have their data removed. Deception may not be utilized to obtain enrollments. 1. 2. May require a Form F - Alteration of Consent The investigator may need to disclose in the consent form Page 34 of 55 1. 2. 3. 4. 5. That deception at some point in the study is necessary to conduct the study; That subjects will be debriefed after the experiment is completed; That subjects will not be exposed to more than minimal risk because of the deception; and That subjects will be advised at some point as to the nature of the withheld information That the withheld information is not likely to change people's decisions to participate in the study. Always refer to the Informed Consent Policy and Procedure for the specific requirements of informed consent and documentation of consent FORM D-2 or E-2 – Non-English-Speaking Subjects or Subjects from a Foreign Culture Click here for General instructions on the use of forms Always refer to the Informed Consent Policy and Procedure for the specific requirements of informed consent and documentation of consent If you are recruiting non-English-speaking subjects, the consent document needs to be in the subject‟s native language. Use the model consent provided in Section 2, Form D-2 or Section 2, Form E-2 of the applicable IRB application as a guide for developing the consent document. If you are recruiting subjects from a foreign culture, or subjects for whom English is a second language, you may be required to develop a plan for evaluating the level of English comprehension, and the threshold for providing a translation, or explain why an evaluation would not be necessary. If you are recruiting non-English-speaking subjects, and/or subjects from a foreign culture uncommon to the local area, you may include contact information for someone who can act as a cultural consultant for your study if appropriate. If a cultural consultant is used the person should be familiar with the culture of the subject population and/or be able to verify that translated documents (if applicable) are the equivalent of the English version of documents submitted (when other certification methods are not used). If a consultant is used, the consultant should be able to provide comments/suggestions for the IRB regarding consent procedures and appropriateness of the research for the culture. In most cases it is recommended that a cultural consultant not have any direct involvement with the study. If a cultural consultant is used, please include the name, address, telephone number, and email of the person who will act as the cultural consultant for your study. If you are proposing research which involves non-English-speaking subjects, or subjects from a foreign culture (i.e., international research), please mark the appropriate selection(s) in the General Information Sheet [Section 1, Form B, #6 and/or Form B, #9]. Always refer to the Informed Consent Policy and Procedure for the specific requirements of informed consent and documentation of consent FORM F – Request for Waiver of Informed Consent Process Click here for General instructions on the use of forms Always refer to the Informed Consent Policy and Procedure for the specific requirements of informed consent and documentation of consent The IRB may waive the requirement to obtain the informed consent of some or all subjects or approve alteration of elements of informed consent if it finds and documents that the research meets certain conditions. For example, if you are conducting research involving deception, or conducting medical record reviews, your research may meet the conditions for this waiver. For certain research, the IRB may approve Page 35 of 55 waiver of the requirement for informed consent when consent to participate is assumed in the absence of an objection (passive consent). To request this waiver, complete Form F and submit it with your application submission. If you are proposing research involving a waiver of the requirement for the informed consent process, please mark the appropriate selection in the space provided on the General Information Sheet [Form B, #9]. Note: The IRB does not approve waiver or alteration of the consent process for research subject to FDA regulations, except for planned emergency care research as provided under FDA regulations Always refer to the Informed Consent Policy and Procedure for the specific requirements of informed consent and documentation of consent FORM G – NIH-Sponsored Clinical Trial Click here for General instructions on the use of forms If the research is part of a National Institutes of Health (NIH) multicenter trial, NIH requires that the IRB receive a copy of the NIH-approved sample informed consent document. Any deletion or substantive modification of information concerning risks or alternative procedures contained in the sample informed consent document must be justified in writing by the investigator and approved by the IRB. For trials sponsored by the National Cancer Institute, investigators must forward copies of such IRB-approved changes, with their justifications, to the appropriate Cooperative Group headquarters. The NIH-approved consent document and any justification for changes in the Risks and/or Alternatives sections should be submitted as part of the application packet. If you are proposing research that is part of an NIH multicenter clinical trial, please mark the appropriate selection(s) in the space provided on the General Information Sheet [Form B, #10 and/or Form B, #11] FORM H Click here for General instructions on the use of forms See Forms D-2 or E-2 FORM H-1 - Translation Certificate Click here for General instructions on the use of forms Responsibility: The PI is ultimately responsible for the translations. By signing this form, the PI is certifying that: -to the best of his/her knowledge, the translation of the document is accurate, complete, and ready to be used with prospective research subjects. -the PI has information about the credentials of the agency or individuals who provided the translation and verification and which enabled the PI to conclude they were qualified and the translation is trustworthy. This information must be made available to the IRB upon request. Translations must be made from the most recent, IRB approved (stamped) English version. Qualifications and Verification: Translations must be performed by a well qualified person. This may be an individual or a commercial translating service/agency (an agency may provide a “certified” translation). If an individual (versus an agency) provides the translation, then a second qualified person should verify the accuracy and completeness of the translation. This verification might be completed by back translation or by comparing the English version with the translated version, sentence by sentence. When using a translating service/agency, the PI should obtain a written statement that describes the method used by the agency to verify the accuracy and completeness of the translation prior to certifying it. Specific Circumstances: Page 36 of 55 Members of the research team (including the PI) may translate and/or verify as long as one individual does not perform both functions. When translation is by other qualified individuals, both the person verifying the translation and the PI must sign the form. When translation is by an agency, the PI must sign this form. Write “see attached” on the line for the name of the person verifying the translation and attach a copy of the agency‟s certification, including a description of the method used by the agency to verify the translation. FORM J – HIPAA Waiver/Alteration Click here for General instructions on the use of forms 1. 2. Click here for the “Protected Health Information (PHI)” Definition NOTE: Remember, all of the questions should be answered from the perspective of the information you are requesting under the waiver (e.g., PHI that is collected before authorization is obtained or when no authorization is ever obtained. Answers should not describe the use of PHI collected after authorization/consent form are obtained.) Describe the research in plain language: This may be the purpose statement in your protocol if written appropriately. Identify the dates or period of time during which PHI will be used by researchers, which means accessed, seen, heard, recorded, etc., without the subject‟s authorization. This question also asks to identify the dates or period of time during which PHI will be disclosed to anyone without subject authorization. A key point to consider when answering this question is that it should be answered from the perspective of including only the activity or period of time when the waiver or alteration of authorization will be in effect. 5. Describe the criteria for selecting particular records for the activity for which you are requesting the waiver or alteration of authorization. Only include those records which you are accessing without subject authorization or during the period of time the waiver or altered authorization will be in effect: (e.g., All paper medical records of diabetes patients in a diabetes clinic, all paper medical records and electronic medical information for diabetics with a laboratory result >## as identified by a list provided by the institution‟s electronic laboratory records.) Include a detailed list of the PHI to be used, collected or disclosed and source(s) of the PHI to be used without subject authorization (or during the period of time the waiver or altered authorization will be in effect). This question is asking for three sets of PHI. These may or may not be the same. 3. 4. 6. If the waiver is for the activity of identifying and possibly contacting (not considered disclosing as it is to the patients themselves) subjects by being given access to their PHI, there are three outcomes possible: the potential subject is not contacted and the data is then destroyed by the end of the study (but not disclosed); the potential subject is contacted and then agrees to be in the study (therefore, authorization is then obtained to continue to use and disclose their PHI); or the potential subject is contacted and then declines to be in the study and the data on them is then destroyed by the end of the study (but the PHI is never disclosed to anyone outside the covered entity). Therefore, the waiver would not include disclosure, but instead only be “to use” the PHI until either authorization is obtained (to use and disclose) or the data is destroyed (only kept as long as necessary to ensure they are not re-contacted). It is possible in this scenario not to actually collect identifiers that would need to be destroyed, for example accessing identifiable information in electronic medical records and calling potential subjects but never writing down their information or maintaining it as part of the research study. Or alternately, collecting identifiers and health information separately, such that no one who might access the research records would be able to re-identify the health information. This should be clearly described here. This is usually important for exempt studies. Page 37 of 55 PHI Used [without subject authorization (or during the period of time the waiver or altered authorization will be in effect): This means PHI that any member of the research team may come in contact with (see, hear or record even if later de-identified, etc.) is referred to as “used”.   [Click once to type PHI and source] Data related to …(stroke, MI, etc) from … the medical record at CTRC or UHS, etc. [Click once to type PHI and source] Data related to …(stroke, MI, etc) from … electronic medical record information at CTRC or UHS, etc. PHI Disclosed [without subject authorization (or during the period of time the waiver or altered authorization will be in effect)]: This means PHI that will be published or in some other way be sent out of the Health Care Facility (Covered Entity) is referred to as “disclosed”. Allowing an outside individual to come to the facility to view the PHI in order to gather data even if they don‟t record PHI is also considered disclosure. Disclosure should include the minimum necessary to perform the research.   7. [Click once to type PHI and source] Examples: “No PHI will be disclosed”; (For Waivers for collection of retrospective data another example would be: “All above identifiers will be removed by the ___(e.g., study coordinator)___ and what remains will be presented as aggregate data.”) [Click once to type PHI and source] Describe the plan to protect identifiers and indicate where PHI will be stored and who will have access [without subject authorization (or during the period of time the altered waiver or authorization will be in effect)]. Indicate all safeguards which will be used to protect identifiers to ensure minimal risk of improper use or disclosure of the subject's identifiable information [without subject authorization (or during the period of time the waiver or altered authorization will be in effect)]. (Examples are provided below, which may be applicable (you can change the red to black if you want to use it and delete remaining red instructions / examples. Add any applicable safeguards not listed. )  The information obtained [without subject authorization (or during the period of time the waiver or altered authorization will be in effect)] will be stored in a password-protected computer in a locked room in the dental building of UTHSCSA. Only _______will have access.  The information obtained [without subject authorization (or during the period of time the waiver or altered authorization will be in effect)] will not be disclosed unless it is de-identified per HIPAA rules. Or:  Data obtained without subject authorization (or during the period of time the waiver or altered authorization will be in effect) will be coded prior to disclosure and only _______ (the PI, the coordinator, etc.) will retain the master list linking the identifiable information to the coded data. Disclosure in this manner (of a “limited data set”) will only occur after a signed agreement (“Data Use Agreement”) has been entered into between the PI and the authorized third party.  All identifiers collected [without subject authorization (or during the period of time the waiver or altered authorization will be in effect)] during the study will be destroyed at the earliest opportunity consistent with the conduct of research, which is: ________ (explain e.g., upon completion of the Page 38 of 55 study, upon completion of data analysis). Describe the procedure that will be used to destroy all the identifiable data collected during the study (electronic, paper, audio/video, photography, other). Or:  Identifiers collected [without subject authorization (or during the period of time the waiver or altered authorization will be in effect)] during the study will not be destroyed because: (explain) ______ (the PI, the coordinator, etc.) will retain the identifiable data securely in ______ Or:  Data which is recorded will not include identifiers. The information will be recorded in such a way that the subjects cannot be identified either directly or indirectly. (For example, a key list which links codes to respective subjects would not be appropriate. This is most commonly appropriate for Exempt Category 4 research.) The research could not practicably be conducted without the waiver of the subject‟s authorization (or during the period of time the waiver or altered authorization will be in effect)] because: (explain below). (This question is asking why it is not “practicable” (possible with available means and resources) to get signed documented authorization from each subject. For Human Use studies, this should be similar to the reason why you obtained a waiver of consent or waiver of documentation of consent. For Exempt studies, it is similar to the reason why your research does not require a consent form. [The reason why it is not “practicable” (possible with available means and resources) to get signed documented authorization from each subject generally involves inavailability of subjects (e.g., not coming to the clinic with enough frequency to make individual contact during visits practicable) or scarcity of subjects in the population being recruited expected to meet criteria which would require screening an unreasonalbe number of subjects to obtain qualified subjects, etc.]) 8. [Click once to type why you could not do the activity (identify the subjects; recruit the subjects) after obtaining authorization, without a waiver.] 9. The research could not practicably be conducted without access to and use of the PHI [without subject authorization (or during the period of time the waiver or altered authorization will be in effect)] because: (explain below). (This is not the same answer as #4. This question is asking if you could do this study without any identifiable information on the subjects. Why is it not “practicable” (with available means and resources) to receive deidentified information from an authorized user in the facility (covered entity)?) [Click once to type why you couldn't simply do the research without even viewing PHI.] 10. The HIPAA regulation requires reasonable efforts to limit protected health information [without subject authorization (or during the period of time the waiver or altered authorization will be in effect)] to the minimum necessary to accomplish the intended purpose of the use, disclosure or request. Explain why PHI obtained for this request is/are the minimum information needed to meet the research objectives. (Explain why you need to use the particular PHI you have chosen (e.g., to track lab results, etc.), why you need to disclose the particular PHI you have chosen (e.g., to stratify the results, etc.) and that without these items of PHI, why the activities covered by this request would not be valid or useful.) [Click once to type the PHI being used or disclosed that is the minimum necessary to do the research.] (The section between item 8 and the affirmation/signature section is intentionally left blank so the affirmation/signature section may remain on a single page. Edit the red lettering in the approved paragraph to match your waiver circumstances.) The certification by the PI should be edited as applicable. By removing the red or the black alternative language and if leaving the red, those letters should be changed to black. Page 39 of 55 The information listed in the waiver/alteration application is accurate and all research staff (ALL study personnel including PI that are involved in the research) will comply with the HIPAA regulations and the waiver/alteration criteria. All research staff will complete HIPAA Research Training. I assure that the information I obtain as part of this waiver/alteration (including protected health information) will not be reused or disclosed to any other person or entity except as permitted by this waiver/alteration, by law, for authorized oversight of the research study, or for other research for which the use or disclosure of protected health information has been permitted by the IRB. If at any time, I want to reuse this information obtained under waiver/alteration of authorization for other purposes or disclose the information to other individuals or entity, I will seek approval by the IRB. _______________________ PI Signature _______________ Date The PI should type their name in here. Then click the button to remove the red instructions. Of course, one last check should be made to ensure that the user did not really want to keep something red before hitting this button. FORM L – Advertisement(s) Click here for General instructions on the use of forms If any materials will be used to recruit subjects for your research study, or used to retain a subject in the study, attach copies of the materials to be used. Advertisements must be reviewed and approved by the IRB prior to use. In addition, print and media advertisements to the public are required to be reviewed by UTHSCSA‟s Office of External Affairs for compliance. Sponsor's National Advertising Campaigns Human subjects recruitment material and related research information supplied to multi-site study locations requires IRB approval, but does not need review by UTHSCSA Office of External Affairs. This applies to recruitment material that does not identify the UTHSCSA, informational brochures about drugs/devices, and educational materials about the disease, dietary guideline booklets or other study-related information not related to sites. FORM M – Data Collection Instrument(s) Click here for General instructions on the use of forms If the research includes survey or interview procedures, the questionnaire, interview questions or assessment scales should be included in the application. (NOTE: If standardized scales and/or questionnaires are to be used, only submit two copies to the IRB.) The data collection instrument(s) can be submitted with your application in draft form with the understanding that the final copy will be submitted to the IRB for approval prior to use (submit final version to the IRB for review as a modification request if initial IRB approval was issued while the data collection instrument was in draft form). FORM N – Cooperative Off-Site Research Click here for General instructions on the use of forms Cooperative off-site research is defined as research involving a HSC investigator (or an investigator from an Affiliated Institution) and an institution or performance site not under the authority of the HSC IRB. Cooperative off-site research includes the following situations: 1) an HSC (or affiliate) investigator collaborates with investigators at other institutions that do not fall under the UTHSCSA IRB‟s authority; 2) an HSC investigator conducts research at other institutions/sites that do not fall under the UTHSCSA IRB‟s authority 3) an HSC investigator collaborates with investigators who are not affiliated with an institution Page 40 of 55 Cooperative research activities require additional information to ensure the appropriate IRB approvals, institutional and individual assurances are in place. Please complete and attach Form N to your IRB application submission. Note: this form is not needed for National Cancer Institute sponsored cancer trials or FDA regulated clinical trials. If you are proposing research which will be conducted at a non-UTHSCSA site(s), please mark the appropriate selection(s) in the space provided on the General Information Sheet [Form B, #15]. For guidance to help determine whether an off-site facility is considered engaged in the research, visit OHRP's "engagement memo" web page. International Research: Complete Under US Dept or Agency Where any of the sites are international and the research is conducted or supported by any U.S. department or agency that has adopted the Common Rule, unless the research is otherwise exempt from the requirements of the Common Rule or a U.S. federal department or agency conducting or supporting the research determines that the research shall be conducted under a separate assurance, the international sites require an International Assurance under OHRP. You can search to see if one is already in existence at http://ohrp.cit.nih.gov/search/actrypck.asp or you can advise the international site to go to http://www.hhs.gov/ohrp/humansubjects/assurance/filasurt.htm and scroll down to B to read about OHRPs International Assurance and begin the process of training, submission and approval. Under commercial support Where the only sites are international and the research is not conducted or supported by any U.S. department or agency as described above, question 2b may not be clear. It may be necessary to alter the heading above each answer in a manner similar to the following: Institutions engaged in international research not conducted or supported by any U.S. department or agency with an existing Review Committee (Ctrl + Alt + F1 adds a row) Person and Committee Name of the Assuring Institution & Responsible for the Review Status of Location of Protocols involving Review Human Subjects ING. Luis Fernando Diaz, Universidad Mariano Galvez de Attached President of Protocol Review Guatemala, Guatemala Committee Pending FORM O – Use of Investigational New Drug(s) Click here for General instructions on the use of forms If you are conducting research involving use of FDA approved drug(s) for approved use, complete Form O and include it with your application submission. FDA approved drugs when used in accordance with their approved labeling, in a manner, dose or regimen and for indications previously approved by the FDA generally require little in the way of additional protections. One such protection is that the IRB review the use and be provided documentation of how the drug(s) will be used in the study in particular the maximum allowed dose. This is not necessarily so that the IRB can confirm this against some outside source for accuracy Page 41 of 55 as the clinician using the drugs is already under FDA regulation and institutional credentialing to use the drug appropriately but it is so that IRB is reassured that the investigator is aware of how it will fit into the study and so that the protocol is available for other members of the research team to reference concerning how the drug(s) will be used in the study. The use of the FDA approved drug(s) being used in an approved manner will be reviewed by administrative reviewers in the OIRB, regulatory reviewers, scientific/ethical primary reviewers on the Board and any physicians on the Board and additional information such as package inserts may be requested at any point in the review process should they be felt by any reviewer to be necessary however they are not a requirement prior to submission. If you are conducting research involving use of FDA approved drug(s) for unapproved use, indicate so on Form O and complete Form O-1 (in addition to Form O) and include it with your application submission (see below for Form O-1 instructions). If your research involves administration of an Investigational New Drug (in other words a drug that required or requires prior submission to the FDA for an IND), the IRB must determine the risk/benefit ratio, and that procedures for receiving, storing, dispensing, and accountability control are appropriate for human subject protections. In order for the IRB to consider approval for your protocol involving an IND, complete Form O and provide documentation that the IND is valid (e.g., sponsors protocol, letter from sponsor [may not use the investigators brochure]) include it with your application submission. Official FDA documents containing the number are also acceptable. If you are proposing research which involves use of an IND, please mark the appropriate selection(s) in the space provided on the General Information Sheet [Section 1, Form B, #8] as well. It is the PI's responsibility to make a preliminary determination regarding whether to submit to the FDA for an IND, and to include the information in the IRB application (Form B, #8 and Form O). For assistance in making a preliminary determination, contact FDA, or visit the Center for Drug Evaluation and Research (CDER) FAQ's web page. For an overview of the Food and Drug Administration (FDA) requirements for sponsors/PIs with INDs, see ORI's document: Summary FDA Requirements For Investigators Who Are Also Considered Sponsors of New Drug. For a summary of the FDA regulations outlining exemption from the IND requirements, download ORI‟s document: Summary of FDA Regulations on Exemption from IND Requirements. For information about use of an approved drug for unapproved use, see Form O-1 and Form O-1 instructions immediately below. FORM O-1 – Use of Approved Drug(s) for Unapproved Use Click here for General instructions on the use of forms If you are conducting research involving use of FDA approved drug(s) for unapproved use, indicate so on Form O and complete Form O-1 (in addition to Form O) and include it with your application submission. Certain uses of approved drugs for unapproved uses require an IND. Your responses to the questions on Form O-1 will determine whether your research meets the criteria for exemption from IND requirements. If your research does not meet the criteria for exemption from IND requirements, you will also need to include Form O (Use of Investigational New Drug) in your IRB application submission. If you are proposing research which involves use of an approved drug for an unapproved use, and/or an IND, please mark the appropriate selection(s) in the space provided on the General Information Sheet [Form B, #8]. PIs who are also sponsors and hold an IND have additional responsibilities. For an overview of the Food and Drug Administration (FDA) requirements for sponsors/PIs with INDs, see OIRB's document: Summary FDA Requirements For Investigators Who Are Also Considered Sponsors of New Drug. Page 42 of 55 FORM O-2 – Placebo Click here for General instructions on the use of forms Complete this subform if a placebo will be used in place of standard therapy. This form may also be used for requests for approval of the use of sham procedures. If the placebo will not be used in place of standard care only Form O is required. FORM P – Research Involving Investigational Devices Click here for General instructions on the use of forms Header. The header, which is located at the top of the Form, has a place to list the Study title. Place your cursor directly on the header and double-click. Once the header is open for editing purposes, input the information. 1. Identify the Device(s) to be used in the study. The Food and Drug Administration (FDA) defines a medical device can be reviewed in the IRB Glossary. Please provide a narrative description of the device. This should include a description of each important component, ingredient, property, and principle of operation of the device and of each anticipated change in the device during the course of the investigation. This information can be found in the package insert, Investigator Brochure or the Manufacturers Device Manual. 2. Is the device being used for an indication approved by the FDA (as marketed)? Please indicate whether the device is being used in accordance with labeling, and if not, describe how it will be used and provide the background information to support off label use. (The FDA does not regulate off-label use in the practice of medicine.) FDA approval means the FDA has been given "reasonable assurance" through the PMA process that the device is both safe and effective or through the PMN process that the device is substantially equivalent (SE) to a device that is both safe and effective therefore it should be a simple matter to answer 2 A) and 2 B) indicating that you are not testing for device safety or effectiveness as it has already been shown and that there are no risk to subjects since it has already been shown to be safe when used as directed in the FDA approved labeling. (HUD devices with an approved HDE are also considered FDA approved in that the FDA has been given "reasonable assurance" through the HDE process that the device does not pose an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment therefore it it is allowed to answer 2 A) and 2 B) indicating that you are not testing for device safety as safety as defined above has already been shown or effectiveness as it is not required and that there are no risk to subjects since it has already been shown to be safe by the definition above when used as directed in the FDA approved labeling. Use of an HDE is not research therefore these two answers are not as critical to your IRB approval as for other forms of FDA Approval. Investigations of an off-label use of marketed medical devices may require the submission of an IDE when the principal intent of the investigational use of a test article is to develop information about the product's safety or efficacy. However it may still qualify for use under exemption 3 or 4, or under the abbreviated requirements rules of the FDA if it is a nonsignificant risk device. Either way, it still requires review by the IRB for this determination, and documentation. Use of an HUD under an HDE is not research therefore off label use is allowed if approved by the IRB so long as any additional institutional requirements have also Page 43 of 55 been met such as any potential requirement to have the off-label use reviewed by a hospital‟s Chief of Profession Staff, etc. NOTE: Off label use of FDA approved device typically does not qualify for Medicare coverage. A local coverage decision should be obtained from the Medicare director. Regulatory Status - How has the FDA approved the investigational device to be shipped for research? The sponsor has access to strategic information such as decisions by other IRBs and previous FDA decisions. The sponsor should be able to state clearly the intended route to market, status in the market and the type of investigation exemption being sought. Knowing the regulatory status dictates the action an IRB must take. NOTE: This information can be found in the Sponsor letter from the FDA. Listed below are the routes a device may take to be legally marketed and shipped for a clinical investigation. A brief explanation of each is provided as background information for increased understanding of the process; however, the only requirement is that the determination letter from the FDA be submitted for documentation. i. 510(k)/Premarket Notification (PMN) – This means the FDA has issued the manufacturer (sponsor) a letter stating “substantial equivalency” to a device that was approved before May 28, 1976, or another equivalent device. An alternative to the PMN/510 (k) process is to submit data to a third party reviewer that is accredited by the FDA. The FDA has established the Accredited Persons Program to expedite the 510(k) process. http://www.fda.gov/cdrh/devadvice/314.html This process is for a product that is believed to be essentially the same as one cleared for marketing, and data is available to support claims of safety and efficacy. After receiving the PMN/510K from the FDA the device is considered cleared by the FDA, may be marketed or shipped for the purposes of a clinical investigation. It will be allowed by the IRB to be used in the clinical investigation so long as it is used in accordance with its FDA approved labeling, is not being testing for safety or effectiveness of the device and does not represent risk to subjects. [NOTE: If the device is a class I device that was determined to be exempt from 510k submission you will not be completing this table and you will likely need to skip section 2 and describe how the device is a non-significant risk device in section 3.] ii. Premarket Approval (PMA) – If the device is not equivalent (as explained above in A), the FDA will require a Premarket Approval. This application to the FDA is used for Class III devices (the highest risk category for devices) and any device not authorized (unless exempt) under the PMN/510(k). When a PMA is given by the FDA, it means that clinical trials have been conducted to support the claims for the product and the data has been reviewed and approved by the FDA. http://www.fda.gov/cdrh/devadvice/pma/ When the PMA is received from the FDA the sponsor may market the device and ship legally for the purposes of a clinical investigation so long as it is used in accordance with its FDA approved labeling, is not being testing for safety or effectiveness of the device and does not represent risk to subjects (which should not be the case if it is used within its approved labeling). iii. Investigational Device Exemption (IDE) – If the device is determined by the sponsor or the IRB to be significant risk, the sponsor is required to submit the study protocol to the FDA. Prior to conducting clinical trials the sponsor must obtain an Investigational Device Exemption (IDE) from the FDA. The IRB final approval will be contingent upon receiving proof of the IDE number issued by the FDA. If the sponsor determines the device to be nonsignificant risk, and the reviewing IRB agrees, no submission to the FDA is required and via abbreviated requirements may be considered to hold an IDE after IRB approval. An IDE authorizes the shipment of the unapproved device for clinical trials. The IDE involves Page 44 of 55 additional regulatory burdens on the sponsor and the PI (e.g., labeling as an investigational device and limits distribution to the investigative site (FDA, 21 CFR 812.5[a]). NOTE: Investigational Device Exemption or IDE identification code number from the FDA allows a manufacturer to conduct a clinical trial on the device and will consist of seven positions (one alpha and six numeric). Product Development Protocol (PDP) – The PDP is an alternative to the PMA process for Class III devices. Under this process the sponsor and the FDA have joined in the design, controls, requirements, and risk management for the development of a product that will meet FDA standards. Prior to study initiation the sponsor/PI has to submit a Notice of Initiation of Clinical Trials to the FDA, instead of an IDE application. The PDP process prevents wasting time and expense in developing a product that will not meet the FDA‟s standards for safety and efficacy. The IRB and FDA both must approve the clinical trial protocol. Some Class III devices will be ineligible for the PDA and require the PMA route for approval. Additionally, the FDA may revoke the PDP if the process did not meet the protocol or if the study data shows unreasonable risk. http://www.fda.gov/cdrh/devadvice/pma/app_methods.html iv. Humanitarian Device Exemption (HDE) In accordance with Section 520(m)(4) of the FFD&C act and section 21 CFR 814.124(a), IRB approval is required before a HUD is used in a facility, except in emergencies where the physician determines that approval cannot be obtained in time to prevent serious harm or death to the patient (See Emergency Use of a Device Policy). After the IRB approves the HUD for use at a facility the IRB is not required to review and approve individual uses of a HUD, although it may do so. The IRB may use its discretion to determine how to approve use of the HUD. The IRB may approve use of the HUD, for instance, without any further restrictions, under a protocol, or on a case-by-case basis. In reviewing the use of a HUD, while the UTHSCSA IRBs are cognizant that the Federal Food, Drug and Cosmetic Act Sec. 906 states, “Nothing in this Act shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate health care practitioner-patient relationship”, they are also cognizant of the FDA recommendation that the use of the HUD not exceed the scope of the indication approved in the HDE therefore at UTHSCSA:   Sponsors and investigators cannot promote the off label use of an HUD Any research, i.e., collection of safety or effectiveness data of the HUD for uses not described in labeling must have an IDE. Investigators are reminded and asked to remind sponsors that:  Investigators must report AEs on MDR  Sponsors required to submit reports to FDA An HUD device is designed to treat or diagnose a disease or condition that affects or is manifested in fewer than 4,000 people in the United States per year. If the device is for diagnostic purposes, the documentation must demonstrate that fewer than 4,000 patients per year would be subjected to diagnosis by the device in the United States. In addition to other findings the FDA issuing an HDE means the device does not pose an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment. Subsequent prospective or retrospective research on HUDs may be performed by a researcher or the HDE holder in order to collect safety and effectiveness data to support a PMA for the HDE-approved indication without an IDE. FDA considers the study exempt Page 45 of 55 from the requirement for an approved IDE as long as the HUD is used in accordance with the approved indication for use and labeling. IRB approval (21 CFR Part 56) and informed consent (21 CFR Part 50) are still needed, however, as required for FDAregulated clinical studies. Clinical investigation, however, of a HUD beyond its approved indication (e.g., for a broader or different indication) requires an approved IDE. In addition to the requirement of having an FDA-approved IDE, sponsors of these trials must also comply with the regulations governing IRBs (21 CFR Part 56) and informed consent (21 CFR Part 50). This is not intended to include required reporting by sponsors in accordance with 814.126(b)(1). Sponsors are required to provide FDA with updated information on a periodic basis demonstrating that the HUD designation is still valid, based on the most current and authoritative information available which may include information on the number of devices shipped or sold since initial marketing approval, the clinical experience with the device and a summary of any changes made to the device. For Emergency use or compassionate use see Emergency Use of a Device Policy. 2. Is the device exempt from prior submission to the FDA (meets one of the following exemption categories under 21 CFR 812.2? Your approved or unapproved device may be approved by the IRB as the subject of a clinical investigation if it fits into one of the categories for which the FDA has determined are exempt from prior submission to the FDA for an IDE. These exemptions may also be used when your device does not qualify for abbreviated requirements (only non-significant devices are qualified for abbreviated requirements)). Select a category and provide documentation from the sponsor for the justification to support the exemption category being claimed. Exemption Category 1 and 2 Choose Category 1 if the device was manufactured (in commercial distribution) before May 28, 1976. Device did not require FDA approval prior to May 28, 1976. Choose Category 2 if the device was determined by the FDA to be substantially equivalent to a product with FDA approval before May 28, 1976. This determination is provided in the form of a 510(k) exemption or 510(k) determination letter. Exemption Category 3 Choose Category 3 if the device is a diagnostic device that is non-invasive; does not required an invasive sampling procedure that presents significant risk; does not by design or intention introduce energy into a subject; is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure. Notify the sponsor that other FDA regulations apply (e.g., applicable requirements in 809.10(c)) Exemption Category 4 May select one or more: Choose Category 4 if the device is undergoing consumer preference testing (FDA approved devices); or Choose Category 4 if the study tests a modification of an existing device (FDA approved device); or Choose Category 4 if the study tests a combination of two or more devices in commercial distribution (FDA approved); AND In addition to selecting one of the three choices above you must also be able to select that the testing is not for the purpose of determining safety or effectiveness and does not put subjects at risk in order to use category 4. Exemption Category 5 and 6 – Not applicable as these categories are pertinent to the use of devices in animals. Page 46 of 55 Exemption Category 7 A custom device is intended for use by an individual patient named in the order of a physician or dentist, or is made in a specific form for that patient, or is intended to meet the special needs of the physician or dentist in the course of professional practice. Additionally, the testing is not for the purpose of determining safety or effectiveness and does not put subjects at risk. Examples of Custom Device:  External pacemaker needed for a fetus  Lead is only made as single lumen, 6 Fr.  Physician approached the manufacturer to design and make a double lumen, size 3 French, for use in a fetus.  The manufacturer had to construct this device.  Used for one unique situation for one specific subject Examples when a device is not a Custom Device:  Hydrocephalic shunts made of some other material than silicone because patients allergic to silicone. (IDE needed)  Cranial helmets for miss-shaped new- born heads. The helmets are shaped or sized i.e. “fitted” for each subject. (IDE needed)  Thoracic Aortic Aneurysm graft ordered individually for each patient (IDE needed) Custom Device Issues:  Must not be used to circumvent the regs  State of the art – new technology device  Used for unique medical anomaly  One subject use  No data collected. It is not research. (Again the UTHSCSA IRBs are cognizant that the IDE regulations apply to clinical investigations (research) and the exemption would then be for an exemption to prior submission for use in research (a clinical investigation) but given the current position of the FDA on this issue at UTHSCSA Custom Devices will not be considered research and no approval will be given to collect data in these circumstances.)  After Custom use, if there is interest to pursue research, then IDE necessary.  Custom device may be class 2 or 3. IRB Review of custom device use is not required by regulations, but an investigator may request clarification by the IRB. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfHDE/HDEInformation.cfm - link to listing of Center of Devices and Radiological Health (CDRH) Humanitarian Device Exemption summaries of safety and possible benefit http://www.fda.gov/cdrh/ode/guidance/1381.html - link for guidance to industry and FDA http://www1.va.gov/oro/docs/11-13-03-Attachment.pps - link for more information regarding HUD versus Custom device. You may wonder if your device might never have received any review by the FDA possibly because it is Exempt – If a device falls into a generic category of exempted Class I devices, a premarket notification application and FDA clearance is not required before marketing the device in the U.S. However, the manufacturer is still required in all instances for all medical devices to register their establishment and list their generic product with FDA. Examples of exempt devices are manual stethoscopes, mercury thermometers and bedpans. FORM Q – Use of Radioactive Materials (Radiation Safety) Click here for General instructions on the use of forms Page 47 of 55 With regard to radiation safety matters, the Radiation Safety Committee(s) (RSC) for each institution using ionizing radiation in research is/are responsible for reviewing and approving the study. The UTHSCSA‟s Radiation Safety Committee authorizes individuals to use radioactive material. If your research involves radioactive materials, your study may need review by the RSC, or Radiation Safety Officer (RSO). It is your responsibility to obtain approval from the RSC and include a completed Radioactive Materials Form (Form Q) with your IRB application for review. For more information, you may visit the Radiation Safety web page. If you are proposing research which falls under the purview of the RSC, indicate the date of approval, if already acquired, in the space provided on the General Information Sheet [Form B, #12]. Also, if available at the time of your application submission, include the approval letter from the RSC. FORM R – Monitoring Participant Safety and Data Integrity Click here for General instructions on the use of forms This form is not intended to take the place of more comprehensive sponsored monitoring plans. There are additional administrative considerations expected in clinical trials requiring compliance with FDA regulations. Such monitoring should conform to Good Clinical Practice (GCP) and International Committee on Harmonization (ICH) guidelines. Study phase (I-III) and plans for IND submission also influence the frequency and intensity of monitoring studies. Pivotal studies that will influence the outcome of an IND are generally subjected to rigorous monitoring. 1.1 Safety Data or Event Provide a complete list of all data that are considered to be safety indicators of the study that will be collected. Typically, these data include observable physical signs (or measured lab values), reported symptoms, or occurrence of specific events (hospitalizations, injuries, car accidents). [The IRB will review this section and determine whether data/events listed in this are sufficient indicators of safety based on the nature of the study.] Example #1: See Table A. (depending on the complexity of the study and the risk involved this may be all that is needed) Example #2: Detailed information will be collected for incidents, experiences, and outcomes during and after the study procedures as necessary to identify adverse events and non-adverse event unanticipated problems including a description of the event, duration, whether an adverse event was serious, relationship to study drug, clinical outcome, action taken to eliminate immediate hazards if any, changes necessary to IRB submission documents, whether the adverse event resulted in discontinuation of study medication or withdrawal of the subject, whether completed subjects need to be notified, whether enrolled subjects need to be notified. (Also See Table A) 1.2 Responsibilities Monitoring the safety of subjects locally encompasses several major responsibilities. In this section, provide an explanation of how the responsibilities for collecting, analyzing, and reporting safety data are divided amongst the local research team. Include reporting responsibilities for internal (e.g., IRB) and external (e.g., sponsor, FDA, etc.) entities. [The IRB will review this section and determine whether the responsibilities are appropriately matched to the local team member.] 1.3 Frequency of Analysis of Safety Data. Consider the frequency of assessing safety data for an individual subject AND subjects as a whole. How often will safety data for an individual subject be assessed? How often will safety data for all the subjects enrolled be assessed? (e.g., points in time or after a specific number of subjects) [The IRB will review this section and determine whether the frequency for analyzing the safety data is sufficient. Assessing events for an individual subject is important, however to understand the nature, severity and frequency of events, the PI must analyze these data collectively. Events which alone did not raise concern when initially reviewed may be viewed differently when analyzed together. An event Page 48 of 55 that occurs more frequently than anticipated may now need to be considered as a UPIRSO. The PI should be reviewing the safety of the study as a whole periodically to assess safety issues. ] Example #1: See Table B. (depending on the complexity of the study and the risk involved this may be all that is needed) Example #2: On a monthly basis the CC PI will review updated blinded, aggregate data summarizing participant safety. These reports will include incidence, severity, and relatedness to treatment of all reported and treatment emergent Adverse Events and withdrawals from the trial due to Adverse Events. (Also See Table B) (Note this does not completely answer the question in the text but the table completes the answer and the text is used to offer more protocol specific information concerning frequency of analysis. Also note that there is some extraneous information in this answer that may even be best described in another answer – not ideal but not a problem so long as all the information is provided somewhere on the document) 1.4 Procedure for Analysis and Interpretation of Safety Data Provide a description of how the data collected (1.1 above) will be analyzed to reflect the safety of the study. In some cases, data maybe combined to create calculated indicators of safety or grouped to compare safety information. Explain the plan in sufficient detail to account for the major safety concerns for your study. Often investigators find it helpful to describe the analysis and interpretation along with the reporting requested in the next question (1.5), since the analysis often contains criteria used in the analysis that are triggers for reporting. [The IRB will review this section and determine whether the data analysis plan is thorough and addresses the varied sources of reporting criteria (e.g., defines and clarifies AE, SAE being reported to the Sponsor / FDA vs. unanticipated problems meeting criteria as UPIRSO requiring prompt reporting to the IRB]. Example #1: (This example specifies only one part of the answer as other clarifications are required for analyses for sponsor/FDA, etc. This example is limited to a description of the analysis for the IRB.): PI will analyze each incident, experience or outcome that may represent an unanticipated problem and adverse event to determine by IRB approved definitions whether unanticipated and if so whether possibly related and if so whether serious or representing a greater risk than was previously known or recognized as directed by local UPIRSO policy. Specify the process by which you make this happen (use of additional ____ form as source document; use of UPIRSO/AE tracking log initialed by PI for each event, etc.) 1.5 Reporting (a) While this may be discussed above – the specific information related to the reporting process (triggers, rules, reporting criteria, etc.) should be provided in this section. (b) Provide the procedures for the investigator to report the results of analysis by the sponsor‟s monitoring entity, for example DSMB reports, results of interim analysis, etc. To whom will these reports be forwarded, for example DSMB reports should only be forwarded to the IRB if they rise to the level of a UPIRSO. Otherwise, they should be summarized along with the rest of the year‟s safety data in the progress report. [The IRB will review this section and determine whether the plan for reporting safety assessments is adequately described.] Example #1: a. See Table C. b. See Table C. Example #2: a. Those unanticipated events that do meet UPIRSO criteria will be reported within 48 hours if local life threatening or fatal or otherwise within 7 days and those that do not meet this criteria, will be entered into a UPIRSO tracking log and reported to the IRB at the time of the progress report in a summary of incidents, experiences and outcomes for the study as a whole as stipulated by the UPIRSO policy. SAEs will be recorded on a standardized Page 49 of 55 form and will be faxed to the CC within 24 hours of the site learning of the event. (Also See table C) b. Within 72 hours, the CC will notify all sites of the occurrence of any Serious Adverse Event and the site investigator will notify her/his local IRB according to the institution‟s guidelines. (Also See table C) 1.6 Actions to be taken This question is an opportunity for the investigator to describe all the possible actions that may be initiated as a result of the results of safety analysis. The action plan should be tailored to the types of safety issues that are expected to arise from the study. Some examples of actions that can be planned include immediate medical attention, referral for other medical care, suspension of procedures, suspension of enrollment, suspension of the study, termination of the study, notification of past and present subjects, etc. [The IRB will review this section and determine whether the action plan addresses the major safety concerns of the study.] Example #1: The Local PI will provide immediate medical attention, (discuss referral for other medical care if appropriate), suspend enrollment and/or procedures as applicable, suspend the study if needed, terminate the study if necessary, notification of past and present subjects as appropriate in response to review of any incidents, experiences, and outcomes or series of events that meet criteria as a UPIRSO. Example #2: The Local PI will provide immediate medical attention, suspend enrollment and/or procedures as applicable, suspend the study if needed, terminate the study if necessary, notification of past and present subjects as appropriate in response to review of any incidents, experiences, and outcomes or series of events that meet criteria as a UPIRSO. The participant‟s treatment assignment will not be revealed unless the Clinical Site investigator feels it is absolutely necessary to direct the course of treatment. The Clinical Site investigator is responsible for following, through an appropriate health care option, adverse events that are serious or that caused the participant to discontinue before completing the study. The subject should be followed until the event resolves or is explained. Frequency of follow‐up is left to the discretion of the investigator. 1.7 Monitoring entity – (if applicable) Generally, the PI is always a safety monitor. In addition to the PI, some studies may rely on other entities to monitor the safety of the study both locally and centrally. Monitoring entities can include local medical monitors, local data and safety monitoring boards/committees (DSMB/C), external medical monitors, external safety monitors, and external DSMB/C. If the study includes a DSMB/C, provide information on the operation of the board.  Provide information on the expertise of the board members (or provide the board member list)  Provide information related to board operating procedures (provide the DSMB charter or operation plan) [The IRB will review this section and determine whether the monitoring entities are adequate.] 2. Data Integrity Data integrity addresses the accuracy, not the security, of the data. Provide details concerning how and when the investigator (or other monitors) will review the data to ensure accuracy. For example, comparing source documents to research data sheets or CRFs. Veteran Affairs Research and the UTHSCSA IRB UTHSCSA‟S Institutional Review Board (IRB) serves as the IRB of record for research conducted by faculty/staff/personnel at the VA, research conducted within those facilities, and/or research involving VA patients. A Memorandum of Understanding (MOU) between UTHSCSA and the VA establishes guidelines for responsibilities between the two entities. Page 50 of 55 The IRB is charged with protection of the rights and welfare of the individuals enrolled as subjects in research. The VA also has a Research and Development Committee (R&DC) which reviews protocols falling under VA purview for scientific merit. Both IRB and VA R&DC Committee's approvals are required before any research procedures can be implemented at the VA. If you are proposing research involving VA facilities, patients, or resources, please mark the appropriate selection(s) in the space provided on the General Information Sheet [Form B, #10, #11, and/or #13]. Additional Guidance for Investigators Related guidance: UTHSCSA UPIRSO Policy Data Monitoring Committees - FDA March 2006 “Guidance for Clinical Trial Sponsors” Data Monitoring Plans and Data Monitoring Committees – NIH and NCI policies DATA and SAFETY MONITORING PLAN A Data and Safety Monitoring Plan is required for: • All studies considered more than minimal risk. • Multi-site research where UTHSCSA is the coordinating site. • Studies where there is an NIH or FDA requirement for a plan. • Studies determined to require a DSMP by the IRB. The plan should describe how the Protocol Director (or Principal Investigator) will oversee the research participant‟s safety and welfare and how unanticipated problems involving risks to subjects or others, and adverse events will be characterized and reported. The plan should be tailored to the nature, size, and complexity of the research, the expected risks, and the type of subject population being studied. [based on OHRP guidance] MONITORING ENTITY The monitoring entity should be described in the Data Monitoring Plan submitted with the New Protocol Application. • The monitoring entity is an identified individual or group assigned to conduct interim monitoring of accumulated data from research activities to assure the continuing safety of research participants, relevance of the study question, appropriateness of the study, and integrity of the accumulating data. Membership should include expertise in the relevant field of study, statistics and research design. • The monitoring entity might be the PD, a Data Monitoring Board, or an equivalent body such as an industry-sponsored Data Monitoring Committee (DMC), a NIH sponsored cooperative group, a coordinating or statistical center, a monitoring committee formed by a sponsor other than NIH, or a Medical Monitor (an individual rather than a DMC). • FDA-regulated studies: See guidance Data Monitoring Committees - FDA March 2006 “Guidance for Clinical Trial Sponsors”. • NIH-sponsored studies: See guidance Data Monitoring Plans and Data Monitoring Committees – NIH and NCI policies WHAT A DATA MONITORING PLAN CAN INCLUDE [OHRP draft guidance 10/15/05] Investigators are required to describe their plan, if applicable, as a part of the New Protocol Application. The plan, as appropriate to the risks, size and complexity of the study, might address the following: (1) Types of data or events that are to be captured under the monitoring plan. (2) – Responsibilities and roles for gathering, evaluating and monitoring the data. Page 51 of 55 – Information about the monitoring entity (OHRP notes that the IRB has authority to observe or have a third party observe the research. OHRP 45 CFR 46.109(e)) (3) Time frames for reporting adverse events and unanticipated problems to the monitoring entity. (4) The frequency of assessments of data or events captured by the monitoring plan. (5) Definition of specific triggers or stopping rules that serve as the criteria for action. (6) As appropriate, procedures for communicating to the IRB, the study sponsor, and other appropriate entities the outcome of the reviews by the Monitoring Entity. FORM T – Research Involving the Decisionally-Impaired Click here for General instructions on the use of forms There are additional issues that need to be addressed when a research protocol involves individuals with impaired decision-making capacity. In conducting its review, the IRB will classify the research based on the degree of risk and the prospect of direct benefit to the subject. Each category includes specific conditions which must be met before the IRB can approve the research study. Complete Form T and submit it with your application submission if your research involves recruitment of decisionally-impaired individuals. In #5 “Explain the criteria you will use for determining when assent is required for subjects who are not competent” In answering this question: Investigators should consider what measurement instrument(s) will be used and what cut point in that measurement instrument will be used in determining that the capability of a subject may be so limited that they cannot reasonably be consulted, indicating assent is not required. If maturity or psychological state of the subjects involved in the research may likely make it impracticable for certain subjects in the study to reasonably be consulted indicating assent is not required explain the criteria or cut points in measurement instruments and name the measurement instrument that will be used to make this determination this should be described in the answer to this question. Or: The investigators may state that it is expected that no subjects will be so limited that they cannot reasonably be consulted therefore, all subjects will be given an explanation, at a level appropriate to their maturity and/or condition, of the procedures to be used, their meaning to the subject in terms of discomfort and inconvenience, and the general purpose of the research. If you are proposing research involving the decisionally-impaired, please mark the appropriate selection(s) in the space provided on the General Information Sheet [Form B, #6]. FORM U – Research Involving Pregnant Women, Fetuses, and/or Neonates Click here for General instructions on the use of forms When research involving pregnant women, fetal material, and/or neonates is proposed, the IRB must determine that certain criteria are met. If your research involves recruitment of pregnant women, neonates, and/or collection of fetal material, complete Form U for inclusion with your IRB application submission. If you are proposing research involving pregnant women, fetuses, and/or neonates, please mark the appropriate selection(s) in the space provided on the General Information Sheet [Form B, #6]. Page 52 of 55 If your study is Department of Health and Human Services (HHS)-funded, or funding by HHS is sought, and Section 4 on Form U is applicable, the IRB must determine that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates. The OIRB will prepare and submit a report of IRB review to the appropriate HHS institutional official. The research may not commence until IRB approval is issued. FORM V – Research Involving Prisoners Click here for General instructions on the use of forms There are special federal regulations which govern research involving prisoners enrolled as subjects. Subpart C of 45 Code of Federal Regulation (CFR) 46 applies whenever any human subject is a prisoner. A prisoner is defined as a person who is involuntarily confined/detained in a penal institution. If it is unclear if a person is deemed a “prisoner,” contact the Office of the IRB (OIRB) at (210) 567-2351 for help in making determination. In order for the IRB to approve a study where prisoners are recruited, or to issue approval for a subject to continue participation when (s)he has become a prisoner during the course of the research, there are seven conditions that must be met and the research must fit into one of four categories. In order for the IRB to consider approval for prisoner participation in your study, Complete Form V and include it in your application submission. If you are proposing research involving prisoners, please mark the appropriate selection in the space provided on the General Information Sheet [Form B, #6]. Note: If the study is HHS-funded, or funding by HHS is sought, a certification report must be submitted to OHRP. The IRB Office will prepare and submit the certification report to OHRP. An approved certification letter from OHRP must be received before a research study can commence. The IRB will forward OHRP & IRB approval materials to the Principal Investigator. Specific DHHS epidemiology research may be eligible for a waiver. Contact OIRB at (210) 567-2351 for further information. FORM W – Research Involving Children Click here for General instructions on the use of forms If you are proposing research involving individuals under the age of 18, read the UTHSCSA OIRB/IRB Policy on Children in Research, mark the appropriate selection in the space provided on the General Information Sheet [Form B, #6], and complete Form W and include it with your IRB application. For definitions of "child/children", "legally authorized representative", "guardian", "assent", "permission", and discussion of emancipated individuals, assent, and waiver of parental permission, see the ORI/IRB Informed Consent Standard Operating Procedure. FORM X – Protocol-Related Conflict of Interest Click here for General instructions on the use of forms The IRB is responsible for ensuring that financial conflicts of interest in research, derived from significant financial relationships and the financial interests they create, do not affect the rights and welfare of human subjects in research. In order to enable the IRB to make this determination, certain information must be made available for review. The two ways the IRB collects this information is determined by whether or not the research is externally-funded [Use Form X]. FORM EE – Institutional Biosafety Committee (IBC) Click here for General instructions on the use of forms Page 53 of 55 If your research involves recombinant DNA, infectious agents, and/or human gene transfer/therapy products, the Institutional BioSafety Committee (IBC) will need to review and provide provisional approval for your research prior to submission of your IRB application to the IRB (Please note, SOME vaccine trials also require IBC review and approval.). You may contact the Biological Safety Officer to help you make that determination, (210) 567-2955. In the space provided on the General Information Sheet [Form B, #12] provide the IBC # given to you, and indicate the date of IBC approval. FORM FF – Radioactive Drug Research Committee (RDRC) Click here for General instructions on the use of forms Basic research designed to study the metabolism of a radioactive drug or to gain information about human physiology, pathophysiology, or biochemistry requires review by the Radioactive Drug Research Committee (RDRC). To apply for IRB approval for a study involving Radioactive Drug(s), Principal Investigators must complete and submit a Full Board Review application to the IRB. The RDRC prefers to (but does not require) review of the research prior to IRB review in order to provide expertise and scientific comments for the IRB. Please be sure to indicate in the space provided on the General Information Sheet [Form B, #12] that your research falls under the RDRC. For more information about the RDRC, click here. FORM HH – General Clinical Research Center (GCRC) Click here for General instructions on the use of forms The UTHSCSA GCRC provides services for research investigators in the area of administration, core lab services, data safety and analysis, patient care and database management consult.. The GCRC, a facility funded by the National Institutes of Health (NIH), provides an excellent environment for investigations of the causes, progression, prevention, control and cures of human diseases and to provide an optimal setting for controlled clinical investigations. The administrative office is the first point of contact for investigators seeking GCRC support for their clinical research. Contact GCRC‟s administrative office at (210) 567-4632 if you are seeking support from GCRC. A GCRC application will need to be submitted for their review. When a Principal Investigator (PI) submits a protocol for IRB/GCRC review, those submissions may be made to the OIRB and GCRC offices simultaneously. However, the GCRC will not issue final approval until the study has been approved by the IRB. A GCRC application can be obtained by visiting the GCRC web site at: http://gcrc.uthscsa.edu/ FORM JJ – Veterans Affairs Research & Development Committee (VA R&DC) Click here for General instructions on the use of forms Once the study is approved, the IRB Office will sign the forms and forward to the VA R&D Office. AMENDMENT FORM Click here for General instructions on the use of forms Complete the appropriate tables, use the button at the bottom of the form to delete those not required or delete them manually before printing. Page 54 of 55 HDE Progress Report Form Click here for General instructions on the use of forms Click here for Specific instructions on the use of the HDE Progress Report form Report of Noncompliance Form Click here for General instructions on the use of forms Click here for Specific instructions on the use of the Report of Noncompliance form Repository Progress Report Click here for General instructions on the use of forms Click here for Specific instructions on the use of the Repository Progress Report form Copy from PDF to IRB Forms Click here for General instructions on the use of forms Click here for Specific instructions on how to Copy from PDF to IRB Forms Page 55 of 55