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This packet contains the forms that need to be filled out in order to receive approval for a human-use research protocol involving radiation-producing machines. The approval process may involve the following steps: ! !  Review by the UCLA Radiation Safety Division (RSD) to ensure that the information provided is accurate and representative of the actual protocol Possible consultation with any one of several medical or health physicists, who are experts in measuring and calculating radiation doses to patients from various x-ray studies Review and approval by the Medical Radiation Safety Committee (MRSC)

The primary concern is for human subject protection, but operator exposure may be a concern in some studies. Research studies that involve patient or operator exposure that is different than that which would be received by a patient or operator not participating in the study are the main focus of the MRSC, although some highdose clinical studies are also of concern. This packet includes four items: ! A set of instructions ! The application form ! A protocol digest form ! Some suggestions on how to communicate risk from radiation exposures, as well as background information on how radiation doses are measured and reported in diagnostic examinations ! Two examples of completed application and digest form If questions arise during completion of these forms, please contact the RSD at (310) 825-6995 The Informed Consent form must include information on potential risks to the research subject from exposure to radiation. Since the degree of risk depends on the magnitude of the dose, it may be necessary to obtain information on the expected radiation doses before the Informed Consent form is finalized. The RSD can assist in this. When completed, the forms, plus a copy of the entire protocol, and the proposed Informed Consent form (if available), should be turned in to the RSD, who will review all the documents, ensure that any dose estimates are reasonably accurate, and compare the Informed Consent form to the actual protocol to ensure that all risks due to radiation have been addressed. This process should take between one to two weeks, depending on the complexity of the protocol. When the RSD has approved the protocol, it will be forwarded to the MRSC, which oversees the protection of human research subjects and ensures overall radiation safety. It will typically take two to four weeks to review the complete package.

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UCLA Flow Chartfor Approval of Protocol Involving Radiation-Producing M achines & Human Subjects
Principal Investigator with Research Protocol involving radiation-producing machines

UCLA Radiation Safety Division (310) 825-7147

Packet sent to Researcher
o Cover Sheet o Instructions o Application Form o Digest Form o Background Information/ o Informed Consent Guidelines

Researcher fills out Application and Digest forms, attaches Protocol, and Informed Consent form (if available)

Packet submitted to UCLA Radiation Safety Division

NO, formal calculation of dose not necessary

o Review Application o Compare Digest form to actual Protocol o Determine if Protocol is same as standard of care o Determine if formal, detailed dose calculation is necessary

YES, formal calculation of dose is necessary

Case 1
Same as Standard Treatment / Diagnosis Low Dose (<100 mrem/yr EDE) 0 - 1 CT scan <5 min fluoro

Case 2
Different than Standard Treatment / Diagnosis Low Dose (<100 mrem/yr EDE) 0 - 1 CT scan <5 min fluoro

Case 3
Same as Standard Treatment / Diagnosis High Dose (>100 mrem/yr EDE) >1 CT scan >5 min fluoro

Case 4
Different than Standard Treatment / Diagnosis High Dose (>100 mrem/yr EDE) >1 CT scan >5 min fluoro

Return packet to Researcher

Radiation Safety Officer
(with the help of medical and health physicist, if needed) -- Determine approximate EDE -- Help researcher with wording of Informed Consent form Researcher provides additional data to physicist, including specific technical factors

Physicist calculates ESE, organ doses, and EDE on basis of Digest form, and supplies technical factors -- Suggests wording for Informed Consent form

Physicist provides signed dose calculation to researcher. Researcher submits calculation and all other materials to UCLA Radiation Safety Division.

UCLA Radiation Safety Division forwards Protocol to Medical Radiation Safety Committee for review

Medical Radiation Safety Committee reviews and approves Protocol

(In Visio) c:\machin99\machf lo3.v sd

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UCLA RADIATION SAFETY DIVISION 501 Westwood Plaza, 4th Floor, 160508, (310) 825-6995

Application for Approval of a Protocol Involving Radiation-Producing Machine(s) (Human Use)
Instructions for completing the Application. Please type or print all information legibly.
You have been asked to provide an estimate of patient (and possibly operator) radiation exposure from a research protocol that uses radiationproducing machines. The Principal Investigator (PI) in any research study is responsible for knowing the radiation exposure from the exams that make up a study, the concomitant risks to the staff and the patient associated with that exposure, and to communicate this information to the patient so that Informed Consent can be given. Since doses from diagnostic exams can vary over several orders of magnitude, it is necessary that enough information about the research protocol be provided so that a reasonable estimate can be generated. The information provided by the PI, and the actual protocol will be reviewed by the UCLA Radiation Safety Division, and upon approval, forward to the Medical Radiation Safety Committee that oversees the protection of human research subjects. The object of this review is to ensure that radiation exposure to both staff and patient is reasonable, commensurate with the goals of the study, and to ensure that the researcher has an understanding of the doses and risks involved. PROCEDURE Step 1. Application Form (This must be typed). The Principal Investigator (PI) is the physician who will head this particular protocol at UCLA. The Protocol Coordinator is the individual that the Radiation Safety Division (RSD) will need to contact to answer any questions that may arise during review of the protocol. For those protocols that have a Human Subject Protection Committee (HSPC) number, please include the number with the expiration date (if already approved). By their signatures, the PI and Department/Division Chair (Chair) certify that any research will be performed within the limits of the approved protocol, that all applicable regulatory standards will be adhered to, and that the radiation exposure to subjects or staff has been accurately considered and documented. Step 2. Digest of Radiation Exposure Form In general, the Radiation Safety Division (RSD) and the Medical Radiation Safety Committee (MRSC) are only concerned with protocols where the exposure to ionizing radiation is different from that which would be received by a patient not enrolled in the protocol in question, or is substantially higher than that received from commonly performed diagnostic exams. In those cases where it is determined that the exposure is not significantly different than would otherwise be received, it may not be necessary to provide detailed dose information. To help determine if, and how, the proposed protocol significantly differs from standardized clinical procedures, please fill out the Digest of Radiation Exposure (Digest) form. This Digest is a summary of all the procedures involving ionizing radiation in the protocol. It is the responsibility of the PI to ensure that the Digest clearly and completely reflects all permutations of exams and procedures that a patient could receive during this protocol. While it is commonly difficult to know in advance the exact number of exams, views, etc., that a patient may undergo, the PI should indicate reasonable ranges of the maximum and minimum number that may be experienced over the course of a study. Step 3. Application Submittal The Application form, the Digest form, a copy of the entire Protocol submitted to the HSPC, and the proposed Informed Consent form (if available) should be submitted to the RSD, which will review the information for completeness and accuracy, compare the Digest to the actual protocol, and determine whether a formal calculation of radiation dose is necessary. The Informed Consent form MUST address radiation exposure, preferably in terms of Effective Dose (He). It is recommended to compare the He from the protocol to either background radiation dose levels, or the regulatory limits for occupational workers. For protocols that involve high skin doses, the possibility of radiation-induced skin injury or temporary hair loss should be mentioned. Step 4. Application Review The RSD can direct you to individuals who can perform calculations of actual organ dose, entrance skin exposure, and effective dose equivalent, should they be deemed necessary. Be aware that the medical and health physicists who calculate radiation doses may need additional specific information regarding technical aspects of the radiographic exams described in the Digest to be able to provide these calculations, and they may ask the PI to complete additional data sheets. Should you decide to utilize other resources to perform these calculations, you will need to provide a signed document by the PI and the Chair indicating the references and methodology used to determine exposure and effective dose. The detailed dose calculation then needs to be forwarded to the RSD for review. In those cases where a formal dose calculation is required, you may wish to enlist the services of the medical or health physicist for assistance in developing the Informed Consent form. Step 5. MRSC Approval When the RSD has approved the Dose Estimates, Protocol, and Informed Consent form, the packet will be forwarded to the MRSC for final approval.
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APPLICATION FOR APPROVAL OF A RADIATION MACHINE PROTOCOL (HUMAN USE)
Radiation Safety Officer, UCLA Radiation Safety Division, 501 Westwood Plaza, 4 th Floor, 160508, (310) 825-6995

Principal Investigator: Mailing Address: Campus Telephone: Protocol Coordinator: Title of Protocol:

Department: E-Mail Address:

Phone:

HSPC Number of Protocol: Radiation Modality Used in the Protocol (check all that apply):
Radiography Mammography Radiotherapy

HSPC Approval Expiration Date:

CT Dental Bone Densitometry

Fluoroscopy Fluoroscopy w/digital imaging (interventional DSA runs)

If fluoroscopy is checked, estimate the maximum Fluoroscopy beam-on time: We certify that this project will be carried out in accordance with all applicable regulatory requirements, and within the limits of this application, and that all operators of x-ray equipment will be appropriately licensed in the use of x-rays on humans: Principal Investigator: Department/Division Chair: Date: Date:

We certify that this protocol meets the standards of accepted practices and applicable regulatory requirements within the limits of this application, and accurately reflects the radiation dose and concomitant risk expected to be received by the patient over the course of this protocol: Radiation Safety Officer: Radiation Safety Committee: and/or Chair, Medical Radiation Safety Committee: Date: Date: Date:

APPLICATION FOR APPROVAL OF A RADIATION MACHINE PROTOCOL (HUMAN USE)
Radiation Safety Officer, UCLA Radiation Safety Division, 501 Westwood Plaza, 4 th Floor, 160508, (310) 825-6995

A. Radiological Department List List the UCLA campus departments that are providing radiological services for this protocol (i.e., UCLA Radiology, UCLA Radiation Oncology, etc.). UCLA Campus Department

Also, note any off-campus institutions providing radiological services. Institution Department Address Contact Person Contact Phone Number

B. Personnel List: NOTE: Only list those persons that are outside of the departments noted above. If all procedures are performed by the radiological departments noted above, no names are needed below. Please notify the Radiation Safety Division whenever there is a change in personnel on this protocol.
Name Last First Social Security Number Contact Phone Number

C. Attach a copy of the entire protocol and the informed consent. Submit to UCLA Radiation Safety Division.

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APPLICATION FOR APPROVAL OF A RADIATION MACHINE PROTOCOL (HUMAN USE) DIGEST FORM
Radiation Safety Officer, UCLA Radiation Safety Division, 501 Westwood Plaza, 4 th Floor, 160508, (310) 825-6995

Protocol Title: Principal Investigator’s Name: Protocol Coordinator: UCLA Radiology Contact (if applicable): Signature of Person Completing this form: _______________________________________________ and Phone #:

he purpose of this digest form is to summarize the radiation exposure that a patient might receive during the entire research protocol. It is frequently difficult to determine the various numbers and permutations of exams a patient might receive, particularly if the protocol is escalating, or involves clinical progress decisions. Please carefully consider all possible combinations of exams throughout the lifetime of the protocol. If the protocol only involves standard diagnostic exams or standard radiotherapy, fill out sections 1, 3, and 4. If nonstandard exams are involved, fill out sections 2, 3, and 4. As a guideline, standard exams are those that may be specified on a radiology requisition, and given directly to a technologist to perform. Examples include a 2-view chest x-ray, a myeloma bone survey, a head or chest CT, a barium swallow or enema, or a pyelogram. Nonstandard exams are those that involve prolonged fluoroscopy, multiple CT slices in the same location or timing studies, nonstandard x-ray views, and any interventional procedure performed under fluoroscopic guidance (catheter placement, etc.). Section 1 - Modality Radiation Modality Used in the Protocol (check all that apply):
Radiography Mammography Radiotherapy CT Dental Bone Densitometry Fluoroscopy Fluoroscopy w/digital imaging (interventional DSA runs)

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Section 2 - Standard/Non-standard Procedures For non-standard/research exams, please describe the study. For fluoroscopy, include the anatomical region, the range of patient sizes (both mass and thickness at the fluoroscoped region), the minimum and maximum fluoro "beam on" time, the percentage of time in regular, mag1, and mag2 modes, and the number and length of any digital or cine imaging runs. For non-standard CT exams, identify the scanner that will be used, include the anatomical region, the starting and stopping anatomical landmarks, the number of slices, the overlap or pitch, and the number of phases (repeated passes through the same anatomy). Please attach a memo if more space is needed.
For standard exams please describe the body area and number of scans.

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APPLICATION FOR APPROVAL OF A RADIATION MACHINE PROTOCOL (HUMAN USE) DIGEST FORM
Radiation Safety Officer, UCLA Radiation Safety Division, 501 Westwood Plaza, 4 th Floor, 160508, (310) 825-6995

Section 3 In the table below, Modality can be CT, Fluoro, Mammography, Radiography, Radiotherapy, or similar. Name of Exam is the procedure title that is requested on a Radiology Requisition form, such as Chest CT, AP and OBL view of Knee, etc. Frequency of Exam may be Monthly, Annually, Weekly for 2 months, followed by annually thereafter, etc. Minimum and Maximum Numbers of Studies will be if the study goes to total completion. This information will be used to calculate the total radiation dose to the patient over the lifetime of the study.
Name of Exam on Radiology Requisition Frequency of Exam Minimum Possible Number of Studies Maximum Possible Number of Studies

Modality

Section 4 Explain how the ionizing radiation received by the patient during this study will be different from that received by a nonparticipant (with the same condition). It may be that there is no standard of care for the condition currently, or that the protocol is identical to current practices. The number and types of x-ray exams may be the same, greater, or less than that received by a patient not enrolled in this protocol. Please be specific (i.e., normal follow-up is 1 chest CT per year; this protocol will involve 4 Chest CT per year). Please attach a memo if additional space is needed.

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GUIDELINES ON INFORMED CONSENT FORM
atients shall be informed on all risks that a research protocol entails, including the risk from radiation exposure. Radiation is capable of causing two different types of injury, and we believe it is important for a protocol to address both. High doses may cause deterministic phenomena, such as skin burns and cataract formation, which have a threshold below which they do not occur. Once the threshold is exceeded, the effect worsens with increasing dose. Skin burns have been seen following complex interventional cases with protracted fluoroscopy time and/or numerous digital imaging runs. Stochastic effects, such as carcinogenesis and genetic effects, are thought to have no threshold. The effect does not get worse with increasing dose, but the probability of it occurring does increase. Estimating risk from radiation exposure is problematic because all currently available estimates are derived from populations exposed nearly instantaneously to fairly uniform whole body irradiation, unlike medical radiation, which exposes only part of the body in a non-uniform manner. While it is the stochastic effects that most radiation protection programs are concerned with, it is important to know if a procedure has the potential for causing deterministic effects, and if so, that this information is communicated to the patient.
Radiation doses should not be stated in terms of equivalent numbers of chest x-rays, unless the only exam is a chest x-ray. A chest x-ray and a chest CT are not comparable in terms of skin exposure alone. We recommend that risk not be stated in absolute terms (i.e., a 10-4 probability of developing a fatal cancer), as these estimates are highly uncertain and misleading at best. Rather, we recommend that radiation doses be stated in terms of effective dose or dose-equivalent and compared to either the natural background radiation of ~200-300 mrem/year, or the occupational dose limit of 5000 mrem/year. The risk from an effective dose-equivalent of ~10 mrem, which is approximately that delivered by a 2-view chest x-ray or most extremity radiographs, should be compared to the natural radiation that every human receives in approximately 1-2 weeks, from cosmic rays and naturally occurring radioactive elements in the soil. This level of radiation has not been shown to cause any measurable deleterious effects. The risk from an effective dose-equivalent of ~100-300 mrem, which is approximately that delivered by a head CT or a lumbar spine exam, should be compared to the natural radiation that every human receives in approximately 1 year, or a shorter period of time at a high elevation. Again, this level of radiation has not been shown to cause any measurable deleterious effects. The risk from an effective dose-equivalent of ~1000 mrem, which is approximately that delivered by a chest CT or a barium swallow, should be compared to the limit for a radiation worker, which is 5000 mrem/year. This amount of radiation has not been shown to cause any deleterious effects in numerous studies of nuclear workers, and was chosen so that radiation work would rank among Asafe@ industries, such as service and government. The risk from an effective dose-equivalent of ~5000 mrem, which is only reached in procedures involving numerous CT scans, or prolonged fluoroscopy, should be compared to the yearly limit for a radiation worker, which is 5000 mrem/year. Again, this level of radiation has not been shown to cause any measurable deleterious effects, and the projected risk should always be compared with the expected benefit from the exam. The risk for deterministic effects, such as skin injury, should be considered for any study that involves a skin dose, to one area, of >100 rads. This risk should be communicated to the patient.
BACKGROUND ON DIAGNOSTIC RADIATION EXPOSURE

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There is no standard dose for an exam involving x-rays, and no single parameter that fully describes the risk from radiation. Patient exposures can range from less than 15 mR for a PA chest x-ray, to greater than 1,000,000 mR for a therapeutic angiographic procedure. Even with a single simple procedure, patient size alone can cause exposures to vary by a factor of 10 or more. Radiation exposure, in units of mR or C/kg, only describes how much radiation was incident on the surface of the

GUIDELINES ON INFORMED CONSENT FORM
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patient. Depending on the energy and type of radiation, the same exposure can give rise to very different absorbed doses, particularly to organs that are at a greater depth within the body. The parameters that should be reported for any diagnostic exam are: first, the entrance skin exposure (ESE), which is a measure of the highest dose that the skin receives, and will be most indicative of the potential for deterministic effects like skin burns; second, the organ dose, for the organ of concern that receives the highest exposure (which will almost always be the skin); and third, the effective dose-equivalent, which is an attempt to extrapolate the nonuniform, partial-body dose from diagnostic x-rays to a wholebody equivalent. The effective dose gives a measure of the risk of radiation-induced stochastic effects such as cancer and genetic detriment. Any parameter that is calculated from a model, such as organ dose and effective dose, may have large errors if the real patient is significantly different from the Astandard patient@ used in the model. Nevertheless, these numbers may be used for relative comparisons of the total detriment due to different types of exams, and comparisons of medical exposures from both x-rays and radionuclides, and occupational and natural background exposures. The ESE and EDE are typically what the approving body would like to use to assess risk. Exams that involve fluoroscopy are much more difficult to calculate exposures and doses from. This is because different areas of the body may be irradiated, and the exposure rate during fluoroscopy constantly changes as the operator pans over different anatomy, changes technical factors, manipulates the patient, or changes magnification of the image. In addition, the same type of procedure may vary by a factor of 100 or more in Abeam on@ time, depending on the complexity of the particular case and who performs it. Similarly, exams that involve CT are difficult to calculate doses from. While the radiation exposure within a slice is more uniform than that from projectional radiography, the dose to areas just inside and just outside the slice can vary dramatically. If a procedure has been performed, and data is available on the patient size, the x-ray unit used, and the technical factors that were used during the exposure, a physicist can measure radiation exposure, calculate radiation doses to particular organs, and estimate the dose-equivalent. With accurate information, dose can be estimated to an accuracy of about 10-20%. If a dose is needed for a prospective procedure, it is necessary that some information be provided to the physicist, so that a reasonably accurate range of expected exposures may be calculated. An estimate like this may only be accurate within a factor of 5-10. Not all technical information will be readily available before the procedure is performed, but at least some reasonable ranges must be provided, in writing, for even ballpark estimates. No legitimate medical physicist will take responsibility for a dosimetry calculation without being provided reasonable background information. Dose calculations have the potential to become legal documents. The minimum information that the physicist will need to know includes patient-and-exam data, and technical factors. The patient data must include:  The range of patient sizes, including both mass and thickness  The type of exam to be performed; this usually means the name of the exam as would be written on a radiology requisition form, for instance “2view Chest X-ray”.  The anatomical views that will be used  The number of exams that will be included in the protocol  Certain technical factors, such as kVp, mA, and time. The physicist will produce a written, signed letter that will report the ESE, the organ doses, and effective dose-equivalent based on the information supplied by the researcher. In protocols that involve numerous phases or successive exams, the doses will typically be quoted for a single exam.

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