safety Reporting_financial disclosures_Study close out_Trail Termin ation_Record Retention

							1safety Reporting,financial disclosures,Study close out,Trail Termin ation,Record Retention


Document adverse events and serious adverse events on the appropriate forms and report to the
appropriate individuals List financial interests that require disclosure and describe the importance of
financial disclosure to the integrity of the research data List the study records that must be saved and
the length of time they should be saved. During the first part of this module we will be reviewing safety
reporting. Regulations regarding safety reporting are located in ICH E2A, Clinical Safety Data
Management: Definitions and Standards for Expedited Reporting, ICH GCP 4.11 ICH GCP 5.16, and The
FDA 21 CFR 312.32 and 21 CFR 600 Subpart D - The FDA regulations will only apply to those investigators
conducting a clinical trial under a US Investigational New Drug application (IND). EU specific safety
reporting will be covered in a separate module. We will be examining adverse events, or AEs, serious
adverse events, or SAEs, adverse drug reactions, also known as ADRs, unexpected adverse events, or
UAEs, and the recording and reporting of these events. The definition of AE is from the ICH E2A - Clinical
Safety Data Management: Definitions and Standards for Expedited Reporting. An adverse event is "any
untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical
product". By definition, the occurrence does not necessarily have to have a causal relationship with the
treatment. This definition is congruent with many other country regulations. An AE can therefore be
any unfavorable and unintended sign temporally associated with the use of a medicinal product,
whether or not it is considered to be related to the medicinal product. Examples include abnormal
laboratory findings, signs, symptoms, or disease. Examples of AEs include: Symptoms - events the
subject experiences and reports during the reporting timeframe which may or may not be related to the
investigational product, such as pain, fever, cough or hallucinations Abnormal findings, or signs - are
physical changes that the subject may not be aware of that may be discovered during the course of a
physical exam or from results of laboratory tests. Examples include: an elevated blood pressure, glucose
in urine, or palpation of a lump The grouping of signs and symptoms that point to a final diagnosis made
by a qualified physician, such as influenza, bronchitis, or seasonal allergies. Worsening of a pre-existing
condition (other than the trial indication) is also considered an AE. Signs and symptoms that were
exhibited prior to enrollment but have increased in severity or frequency, such as a rash that spreads or
a headache that worsens in severity. And last, a pre-existing condition not reported at baseline may be
considered an adverse event. This determination is sponsor specific and sponsors are very conservative
in their reporting. Many consider a missed pre-existing condition to be an AE. Therefore, it is extremely
important that the site takes a very careful medical history at the screening visit. The local site must
check to see if the pre-existing condition precludes eligibility and if not, must be sure it is documented.
This slide lists some examples of types of events that sponsors typically do not want reported as an
adverse event. This can vary depending on sponsor preference. The sponsor should provide these
instructions in writing to the investigator, preferably in the protocol. A pre-existing condition that does
NOT worsen: Examples include: a subject that has a pre-existing condition like diabetes or congestive
heart failure (CHF). If it does not worsen during the study period, it would not be recorded as an AE.
These diagnoses would be recorded in the source document and in the medical history part of the case
report form instead. However, if the subject's diabetes or CHF worsens (changes in severity or
frequency), then the change in the pre-existing condition would be recorded as an AE on the AE case
report form page. Endpoints will usually be recorded on a separate case report form page from AEs. For
example, an endpoint for a study evaluating a new drug to treat cancer might be recurrence of the
cancer. The cancer recurrence is an endpoint, not an AE. And the last example is a pre-scheduled
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elective surgery, such as cataract surgery or a bunion removal that occurs without any complications. It
is important to be precise when reporting adverse events. At times subjects and researchers will report
and record (in CRF and/or medical records) symptoms/signs that are ambiguous. The examples on the
slide are real and result in the sponsor or CRO having to contact the site to get clarification to learn what
the "true" AE is. Altered vision ->could be blurred vision, decreased vision or spots before eyes.
Increased RBCs ( or Red Blood Cells) - is not specific. The specimen type should be identified. Is it blood
or urine? Congestion - is a term that may apply to more than one site, i.e., head, nose, sinus or chest.

Hysterectomy - surgical procedures should identify the AE or condition that led to the surgery, i.e.,
hysterectomy due to uterine polyps. Death is not an AE, but the AE that caused the death should be
recorded. Examples may be respiratory failure or cardiac failure. A motor vehicle accident (MVA) is not
an AE, but perhaps the MVA resulted in a broken femur, or scalp lacerations. A fall is not an AE, but
dizziness or vertigo, which may have caused the fall, is. Clarification is to be made by the appropriate
site personnel not the monitor or sponsor. Documentation of clarification in source documents is
required. It may be necessary for site personnel to contact the subject to get clarification. So, what is a
SERIOUS adverse event? ICH E2A defines a serious adverse event as, "An untoward medical occurrence
that results in: death or an event that is fatal, an immediately life threatening adverse experience, for
example, an anaphylactic reaction an event which results in an inpatient hospitalization or prolongation
of an existing hospitalization disability, meaning a substantial disruption of a person's ability to conduct
normal life functions. For example, a stroke with residual paralysis a congenital anomaly/birth defect, or
important medical events that may not result in death, be life-threatening, or require hospitalization
may still be considered serious adverse drug experiences when, based upon appropriate medical
judgment, they may jeopardize the patient or subject and may require medical or surgical intervention
to prevent one of the outcomes listed in the definition of serious." Examples include: allergic
bronchospasm requiring intensive treatment in the emergency room or at home blood dyscrasias which
do not require hospitalization, convulsions which do not require hospitalization, and drug dependency
or drug abuse. Severity and seriousness do not mean the same thing in a clinical trial. Severity means
intensity. Typical definitions found in the protocol include a severity rating of: Mild - no interference
with functioning Moderate - no significant or only minor interference with functioning, orSevere -
significant interference with functioning Seriousness is a regulatory definition. A serious AE is defined by
regulations as stated in the previous slide. It is a global evaluation of an event in terms of major
consequences for life. "Serious" is a regulatory definition, for events requiring expedited reporting.
"Severe" is an intensity classification. An event can be serious and not severe. For example, an
overnight hospitalization for observation following a concussion injury. This is 'serious' because it
requires hospitalization which is one of the defining characteristics of an SAE. An event can be severe
and not serious. For example, severe constipation. 'Severe' is the intensity rating of the AE. It might or
might not be serious. Severe constipation that responds to over the counter medications would not be
serious. Constipation that required a hospital admission or even surgery would be 'serious'. So, as an
example, if a subject experiences a debilitating myocardial infarction, is this an adverse event? Yes.
Therefore, the event must be documented. Is it a serious adverse event? Yes. For a serious adverse
event, the sponsor or CRO must be notified and an SAE report form completed, and submitted according
to the protocol instructions. It is the site personnel's responsibility to report a serious adverse event
3safety Reporting,financial disclosures,Study close out,Trail Termin ation,Record Retention


typically within 24 hours of becoming aware of the SAE. The sponsor will provide the phone number to
call or fax number for the SAE reporting form. Most protocols will have a section that outlines the
procedures to follow for an AE or SAE. The sponsor/monitor will also provide instructions for how to
complete the form, as these vary from sponsor to sponsor. Report the SAE to the sponsor even if it is
not thought to be caused by (or related to) the investigational product. Report the SAE to the sponsor
even if it is expected (that is, it has been observed before). Both of these concepts are explained further
in upcoming slides. Let's talk for a few minutes about adverse drug reactions. The definition of an
adverse drug reaction is stated in ICH GCP 1.1. For a new medicinal product, an adverse drug reaction is
considered an adverse event when a causal relationship between the medicinal product and the adverse
event is at least a reasonable possibility, meaning that the relationship cannot be ruled out. This may
occur at ANY DOSE of drug! Or, for a marketed medicinal product, an adverse drug reaction is an
adverse event when a response to a drug is noxious, unintended and occurs at doses normally used in
humans for prophylaxis, diagnosis or therapy of diseases, or for modification of physiological function. A
causality assessment might determine if events are "probably related" because of a timely relation to
the study product and a potential alternative etiology is not apparent. An adverse drug event may be
"possibly related" because of a timely relation to the study product, but a potential alternative etiology
exists which may explain the event. An event is considered to be "unrelated" if it is definitely related to
an etiology other than the study product. It is becoming more common to categorize causality (or
relatedness) as Yes/No, rather than list the choices on the slide and to provide the investigator with a
checklist of additional possible causes. For example, using the investigator's medical judgment as to
whether there is a reasonable possibility that the primary event was caused by study product; check
either Yes or No. Other choices, in addition to Yes/No designation might include: concomitant illness,
concomitant medication, procedure or intervention, etc. This additional information may be on the SAE
report form but might not be included on the AE CRF. An "unexpected" adverse drug reaction is defined
by ICH as any adverse reaction, the nature or severity of which is not consistent with the applicable
product information (such as the Investigator's Brochure for an unapproved investigational medicinal
product). (Some country regulations may have a more specific definition. For example, FDA states
"specificity" or severity. As mentioned earlier, the Investigator's Brochure is a summary of all available
information about the drug or biologic agent at the time of the IND submission which must be updated
regularly. Sites will receive copies of SAEs from other clinical sites to be added to the Investigator's
Brochure. Periodically, the sponsor will provide a new Investigator's Brochure with all updates. The
Package Insert is like the Investigator's Brochure but it is used for a product that has already been
approved for marketing. It is a drug or biologic product information sheet which summarizes the
information obtained during the entire development process. The Package Insert can change over time
as new data on side effects (also known as adverse drug reactions) and toxicities are accumulated. To
give you an example of an "unexpected" AE, consider an investigational product where elevated liver
enzymes are listed in the Investigator's Brochure as a potential adverse event. Therefore, if a subject
had an elevated SGPT level, that would be an expected AE. On the other hand, if the subject developed
hepatic necrosis, which is a more severe event than an elevated SGPT and not observed in previous
trials, it would be considered an "unexpected" AE. Now that we have discussed the regulatory
definitions and provided examples, let's discuss what needs to be reported, by whom and to whom and
within what timeframes. It is the investigator's responsibility to observe the reportable timeframes
4safety Reporting,financial disclosures,Study close out,Trail Termin ation,Record Retention


outlined in the protocol and to report serious adverse events immediately. The protocol should specify
when the AE collection period starts. For example: there may be a washout period before starting the
study drug. It is important to collect AEs during the washout period even though they will not be related
to the study drug. In other studies, the patient may be randomized in the emergency room and receive
drug almost immediately after signing consent. So AE collection would begin with the administration of
the study drug in this example. The protocol will give specific directions on what to report. An SAE is
typically reported within 24 hours of awareness. A severe AE may also be required to be reported within
24 hours. Other AEs might need to be reported only when regular data collection occurs. If in doubt, call
your monitor, call the sponsor, or simply report the AE. For some events, there may be incomplete
information on initial reporting. The investigator is accountable for collecting and forwarding follow-up
information to the sponsor in a timely fashion. For example, a study subject is admitted for a severe
allergic reaction at 2200. You find out about the incident the next morning at 0800. You need to send
your initial report by 0800 the following morning. The subject might still be in the ICU, or perhaps even
still in the emergency department. You will need to send the initial report and then continue to track the
subject's condition until the situation resolves. It may take hours, days or months. Once you have made
the initial report, usually the monitor or the safety department of the CRO or sponsor contacts you
regularly about follow-up data. However, if you have information about the subject's condition, you
should take the initiative to report it and not wait for a reminder. The investigator is responsible for
monitoring all subjects with known SAEs until resolution of those events, including those subjects who
have discontinued the study since some drugs have long term or cumulative adverse effects. It is very
important to collect and document as much information as possible about subjects who drop out of the
study, even if the reason is not related to an adverse event. Critical information includes: The exact date
of drop out and the last date of study drug administration, The reason for withdrawing from the study,
Any medical, physical, or laboratory data after the study drop-out, especially if the drop-out is for safety
reasons, and Any telephone contact or written correspondence in follow-up This information can help
the sponsor analyze if there are any concerns that the investigational agent may be 'intolerable' even
though it is not an SAE or despite the drug's effectiveness. Even though the subject is within his/her
rights to drop out of the study, you need to document as much information as you can. As part of the
informed consent process, if a subject wishes to withdraw or drop from a study, you should ask the
subject whether or not you can continue to use data already collected and if you can continue to collect
follow-up information. When documenting an AE or SAE, record the diagnosis, if known, rather than the
signs and symptoms. For example, if the subject has chest pain, elevated cardiac enzymes and ECG
findings consistent with an MI, then the AE would be listed as myocardial infarction. Another example
might be for a subject who is admitted to the Emergency Department with hypotension, light-
headedness, abnormal electrolytes, and elevated specific gravity, you would list 'dehydration' as the
adverse event. Expected adverse events listed in the protocol or Investigator's Brochure will be
reported using the adverse event case report form that is provided for the trial. This is one example of a
case report form for adverse events. The form is to be continually updated as events occur, change in
intensity or severity, or are resolved. If an SAE is unexpected, and associated with the investigational
product, the sponsor must report the event to the regulatory agency within timelines established by the
country regulatory agency. Thus, the investigator must immediately notify sponsor of all SAEs even if the
event is expected and even if the event is not-related to the study drug. It is the sponsor's responsibility
5safety Reporting,financial disclosures,Study close out,Trail Termin ation,Record Retention


and not the investigator's to determine if an event requires an expedited report to the regulatory
agency. A true example: A 22 year old man was receiving an investigational product for juvenile
diabetes. He was an avid outdoorsman. He was found dead on a mountain hiking trail one weekend. The
investigator reported the event as an SAE as soon as he heard about the incident on Monday morning.
Subsequently, it was the sponsor's responsibility to determine if the death was related to the
investigational product. With very little information available, the sponsor decided to send an expedited
report to the regulatory agency. The cause of death was never determined for the subject. When the
investigator reports an SAE to the sponsor, it must also be reported to the IRB/IEC. If the sponsor
notifies the investigator of SAEs at other clinical sites, in the form of a Safety Report (for example an IND
safety report), these must be reported to the IRB/IEC as well. When the IRB/IEC receives safety
notifications, they may require a change to the informed consent form based on this new information.
The investigator must keep all subjects informed of any changes that could affect their willingness to
participate in the trial. These updates often must be incorporated into an amended informed consent
form which then must be approved by the IRB/IEC and the investigator must reconsent applicable
subjects. The investigator must document the discussion with the subject regarding the new
information. In response to a volume of AEs or SAEs, the sponsor may: change the consent form to allow
for more complete disclosure of the risks involved in the research, update the Investigator's Brochure or
the package insert, temporarily suspend the study until further analysis of the risks can be done, or even
terminate the study if the sponsor believes the risks outweigh the potential benefits of the
investigational product. The investigator completes the serious adverse event form, and includes all
relevant available information, such as: a detailed description of the event including treatment,
laboratory results and test reports, concomitant medications, and hospitalization discharge summaries.
Next is an exercise to apply the information you have just reviewed on adverse events. There are a total
of four multiple choice questions which are based on a case example. Select the best response and click
on the "submit' button. At the end of the exercise you will automatically be placed back into the
PowerPoint presentation. Next we will talk about financial disclosure (FD) requirements. Local
regulatory agencies vary in their requirements. The next slides will specifically address the requirements
of the FDA. Financial disclosure regulations are found in the title 21CFR 54. These financial disclosure
regulations only apply to investigations begin conducted under a US IND. The FDA definition,
paraphrased from 21 CFR 54.2e, is "any study of a drug or device in humans that is submitted in an
application to the FDA to establish that the product is effective or any study in which a single
investigator makes a significant contribution to the demonstration of safety". Generally, this includes
Phase II and Phase III studies. In general, it does not include Phase I tolerance studies or
pharmacokinetic studies, most clinical pharmacology studies, large open safety studies conducted at
multiple sites, treatment protocols, and parallel track protocols. The sponsor may consult with the FDA
regarding which clinical studies constitute covered studies. The FDA evaluates whether clinical studies
and data are adequate by determining if appropriate steps have been taken by sponsors to minimize
bias in the design, conduct, reporting, and analysis of the research. One potential source of bias in
clinical studies is a clinical investigator's financial interest in the outcome of the study either because of
payment methods (such as a royalty), because the investigator has a proprietary interest in the product
(i.e., holding a patent), or because the investigator has an equity interest in the sponsor company of the
covered study. The sponsor informs the investigators in a trial if it is a "covered study", meaning that the
6safety Reporting,financial disclosures,Study close out,Trail Termin ation,Record Retention


FDA requires the financial disclosure of all investigators participating in the study. If it is a covered study,
the sponsor will provide to the investigators the form to disclose any financial interest in the company of
the IP or to certify no such interest exists. Remember, this form is for studies being conducted under a
US IND. If an investigator is conducting this trial outside the United States, he may be required to
complete additional financial forms to comply with his country regulatory agency rules. For example, the
European Union (EU) has a required disclosure form that must be completed to allow financial
information to be passed outside of the EU. Thresholds for financial disclosure include: Proprietary
interest - any patents, trademarks or copyright, or Significant Payment - payments made by the sponsor
in excess of $25,000, significant equity interest, or stock options in excess $50,000. All investigators and
subinvestigators (listed in Section 1 and 6 of Form FDA1572) are required to complete the Financial
Disclosure form provided by the sponsor or CRO. Should the spouse and/or dependent child of those
listed on form 1572 have a financial interest, the investigator should disclose that financial interest on
their disclosure form. This requirement is noted in 21CFR54.2(d). The certification/disclosure is required
at the start of the study through 1 year following the end of study. Therefore, if the financial interest
changes from the original disclosure, the investigator or subinvestigator is required to provide the
updated information to the sponsor. Sponsors decide whether to permit the participation of a clinical
investigator with financial interest in their clinical trials. The sponsor will submit the Financial Disclosure
information to the FDA when they file for a New Drug Application (NDA). In their review of the validity
and reliability of the trial data, the FDA may consider the financial disclosures of any of the investigators.
Investigators must provide the sponsor with sufficient accurate information to allow disclosure to the
FDA of: Any compensation paid to the investigator that could influence the outcome of the study,
Significant payments, such as a grant, equipment, or a retainer for ongoing consultation or honoraria,
Any proprietary interest in the product held by the investigator, and Significant equity interest in the
sponsor held by the investigator Thresholds for disclosure include the following: For compensation for
favorable outcomes - any equity interest in sponsor tied to sales of product, e.g. royalties. For significant
payment - any payments made by the sponsor in excess of $25,000 Compensation affected by the
outcome of the trial means compensation that is explicitly greater for a favorable result or
compensation in the form of equity interest in sponsor tied to sales of the product, such as royalty
interest. Significant payments are payments made by the sponsor to the investigator or institution that
have monetary value exceeding $25,000, exclusive of the costs of conducting the clinical study.
Examples include a grant to fund ongoing research, compensation in the form of equipment, retainers
for ongoing consultation or honoraria. Proprietary interest means property or other financial interest in
the product including, but not limited to, a patent, trademark, copyright, or licensing agreement.
Significant equity interest in the sponsor means any ownership interest, stock options or other financial
interest whose value cannot be readily determined through reference to public prices or any equity
interest in a publicly traded corporation that exceeds $50,000 during the time the clinical investigator is
carrying out the study and for 1 year following completion of the study.



The final topic we will cover in this module is study closeout, trial termination, and record retention.
Regulations regarding this topic are located in: ICH GCP 4.12, 4.13, and in the essential documents
7safety Reporting,financial disclosures,Study close out,Trail Termin ation,Record Retention


section 8.4, as well as, 21 CFR 312.44, 312.62 and 312.64 (For those trials being conducted under a US
IND) Shortly after the last subject at the site completes the last protocol required visit, the monitor will
contact the investigator to schedule a "closeout" visit. The following activities will take place during the
visit: Retrieval of all remaining CRF data, Resolution of all data queries, Accountability, reconciliation,
removal/destruction of investigational product and blinding codes, Review of archiving, storage,
retention of all essential documents, Retrieval/destruction of surplus trial supplies, and Review of the
Final Study Report to IRB/IEC The goal is to retrieve all case report form data and to resolve all data
queries generated at that point. The investigator may receive data queries via fax or mail to resolve after
the closeout visit. It is important that the data queries be resolved promptly since the sponsor will not
be able to lock the database and analyze the data until all data queries are resolved. It is important for
the principal investigator (PI) to be present or available during the closeout visit. Generally the PI has to
sign paperwork, such as documentation of final investigational product reconciliation and shipment to
sponsor for destruction. Per ICH 4.13, a final report must be submitted by investigators. Typically the
final report that is submitted by the investigator to the IRB/IEC is also submitted to the sponsor.
Generally, IRB/IECs request that the content of the report include a summary of the following: The

total number of subjects screened, randomized, completed, terminated/lost to follow-up, A list of SAEs
and deaths, The date of trial commencement and closeout, and Any other issues that would be
important to know for future reference in the event of an audit or inspection. The IRB/IEC needs to be
notified in writing that their obligations for oversight have been completed. The final report also serves
this purpose. Regulatory Authorities may also require certain documentation to be submitted regarding
trial completion. In the event of a premature termination of the study, the investigator should promptly:
Notify subjects, Assure appropriate therapy and follow-up, and Inform the IRB/IEC, and where
appropriate, the regulatory authorities. In some countries, the sponsor notifies the regulatory
authorities. In other countries, the Investigator must notify the regulatory authority. The sponsor
typically will provide the investigator directions if the investigator must notify the regulatory authority.
ICH GCP 4.12.1-4.12.3 Possible reasons for premature termination or suspension of clinical trials include
termination by: The investigator or institution because of: Lack of subjects, or Subject safety issues The
sponsor or CRO may terminate a site's participation from a trial due to: Lack of or slow rate of
enrollment, Identification of significant or repeated non-compliance with protocol and/or applicable
regulatory requirements, Identification of scientific misconduct and/or fraud, Subject safety issues as a
result of the investigational product, or Suspension of trial as required by a regulatory authority The
IRB/IEC may terminate a study as the result of: Subject safety issues, or Noncompliance, scientific
misconduct, or fraud by an investigator When a trial is terminated by the investigator, the investigator
must promptly inform the institution, the sponsor and the IRB/IEC. If the sponsor terminates a study,
the investigator should notify the institution and the IRB/IEC. If the IRB/IEC is terminating a study, the
investigator must promptly inform the institution and the sponsor. In all cases of premature
termination, the investigator must provide detailed written explanations to the sponsor and the IRB/IEC,
even if they are not the party terminating the study. Before a study ends, it is important to think about
how study records and paper work will be stored or archived. The types of records to be retained
include: Original forms or faxes, Adequate reproductions via microfilm, microfiche, photocopies or other
means, and Raw data entered into a computer, either as a hard copy or stored in a computer file The PI
8safety Reporting,financial disclosures,Study close out,Trail Termin ation,Record Retention


should communicate with the medical records department where applicable If the medical records
department microfiche data, the PI needs to make arrangements to keep the actual documents for the
required regulatory period. Be aware that original forms must be kept if reproductions or copies do not
capture erasure marks, written notes, electronic deletions/additions or other changes. Who is the
custodian of the records? The investigator, the hospital or the clinic? Note that the investigator must
ensure that the records are retained for the length of time set forth in regulations regardless of who is
the custodian. The sponsor should always be notified of any transfer of responsibility for the retention
of records. Transfer of responsibility may be necessary if: a PI moves to another place of business and
will not be taking the records (records must be retained at the institution); or a PI retires or dies; the
institution/practice becomes responsible and should notify the sponsor of who is taking responsibility
for the records. Should storage of study documents become a burden, contact the sponsor. It is in their
best interest that the records be maintained. They will typically assist in working out a mutually
agreeable solution. The ICH regulations state that records should be retained: Until at least 2 years after
the approval of a marketing application in an ICH region, Until there are no pending or contemplated
marketing applications in an ICH region, or Until at least 2 years have elapsed since the formal
discontinuation of clinical development of the investigational product. Some countries may have slightly
different regulations, For example, the FDA regulations state that records should be retained: Until at
least 2 years following the date the marketing application is approved for the drug for the indication for
which it is being investigated, or If no application is to be filed, or if an application is not approved, until
2 years after the investigation is discontinued and the FDA is notified FDA and ICH regulations are similar
but somewhat different in the 2 years following marketing approval and or discontinuation of the IND.
The policy of the sponsor should be in the protocol and contract. For any questions regarding record
retention, contact the sponsor. The sponsor is the only one who knows when the record retention
period is over and they should inform the investigator when record retention is no longer required.
Therefore, do not destroy records until authorized in writing to do so by the sponsor. If in doubt, contact
the sponsor prior to destruction of any records. Maintain trial documents as specified in 'Essential
Documents for the Conduct of a Clinical Trial" - ICH (E6), Section 8. The investigator, not the sponsor or
CRO, is responsible for accuracy and completeness of study records. The investigator is also responsible
for any discrepancies found in records during an inspection. The investigator must take measures to
prevent destruction of documents by the institution or personnel handling records. Make sure that
there is restricted access to study records throughout the trial and the required record retention period.
Individuals handling or having access to the documents should understand the record retention
requirements and who to contact prior to destroying any records. For example, the medical records
department in institutions often has policies where certain records are destroyed after specified number
of years or after a patient dies. It is best if records are stored in a fireproof cabinet or room. Make sure
there is a process for efficient retrieval in the event of an audit. Record retention requirements of the
institution and the sponsor for whom the PI is conducting the research are important to know and
understand. As an example, if the institution's practice is to send all medical records to an archive every
10 years, the PI will need to know how to access those medical records that were used in the collection
of data submitted to the sponsor and make provisions for retrieval in case of an audit by the sponsor or
a regulatory authority. Again, transfer of responsibility for retention and security of records should be
communicated to the sponsor in writing. In summary,