Quality Improvement is essential to ensure that the rights and wellbeing of patients participating in clinical research are protected. The goal of an audit is to review whether clinical research is being conducted in compliance with applicable federal regulations and to help ensure the quality of data submitted with a new drug application (NDA). Of the site investigations completed by the FDA over the last 5 years, nearly 20% identified a failure to follow the investigational plan. Another 10% identified inadequate and inaccurate records. Proactively conducting self-audits helps prepare your research department for an external review and helps to improve the research processes for optimum quality.
FDA requires clinical investigators to provide access for reviewers to inspect case histories of research subjects and other records such as informed consent forms, documentation of the consent process, reported data, and regulatory records source documents. FDA may conduct both announced and unannounced audits. Additionally, for-cause audits may be conducted in cases of possible noncompliance, data discrepancies, or concerns over the ethical conduct of the study by the investigator. For-cause audits could be initiated if the study sponsor reports concerns on study conduct to the FDA and could also be conducted by the IRB and sponsor.
Below, we’ve compiled some of the most common questions from an FDA audit. It is imperative that study teams assess and review study documentation/processes on an ongoing basis. For example, colleagues within the department can be assigned random subjects to audit. It is important to pre-determine the necessary criteria used for selecting and prioritizing research protocols. Some examples may include studies with abnormally low/high accruals, studies with multiple CRCs assigned to work on them, or trials which have filed for an expedited review.
Consent Forms Procedure
- Was the correct version of the consent form used?
- Was the signed version of the consent form IRB approved?
- Were corrections to the ICF made by drawing a single line through the incorrect entry, and initiated and dated? Was the signature original, complete, and legible?
- Do the signature dates match?
- Was the consent obtained prior to any study related activities?
- Was a signed copy provided to the subject?
- Was the process for obtaining consent clearly documented?
- Were alternative treatments discussed by the treating investigator?
- Was the patient given the opportunity to read the Informed Consent Form (ICF and given adequate time to receive answers to their questions?
Eligibility Criteria Procedures
- Was patient eligibility confirmed by the investigator?
- Was the patient’s diagnosis supported by source documents (e.g. pathology or radiology)?
- Is performance status evaluated and recorded?
- Were lab parameters within acceptable ranges?
- Was life expectancy documented as required?
- Was reproductive status/counseling documented as required?
- Were study data obtained by trained personnel?
- Inadequate or missing documentation of consent or performing study procedures prior to obtaining consent.
- Missing essential documentation (documentation of consent process, oversight patient meets eligibility criteria and may be randomized, etc.)
- Lack of training and/or improper delegation of tasks assigned to research personnel
- Protocol non-compliance and failure to report deviations
- Were study activities completed at required timepoints and within the allowed protocol timeframes (e.g. physical exam, ECOG, labs, tumor assessments, miscellaneous procedures)
- Establish a buddy system between coordinators to double check work such as reviewing eligibility prior to consent and/or randomization and provide quality control checks and balances.
Conduct of the trial
- Were patients not meeting the eligibility criteria included in the trial?
- Were patient visits outside the window defined in the protocol?
- Have protocol amendments been implemented too early or too late?
- Are all personnel involved in study activities listed in the Delegation Log?
- Are the tasks assigned in accordance with the actual conduct of the trial?
- Is there documentation of GCP training available?
- Are study specific training records available?
- Was all the inventory accounted for?
- Was the storage area secure?
- Were all the temperature logs accurate and available for review?
Adverse Event Reporting
- Have the timelines for reporting adverse events been met?
- Were the reports completed will all the necessary information?
- Have all follow-up reports been submitted?
In summary, internal audits provide the opportunity for research personnel to review and improve internal research related processes While monitoring activities are responsible for providing the site with data and safety monitoring, they do not replace the need for internal measures to ensure the safety and well-being of research patients. With the nature of the complexities in clinical trials today, it is a great time to start incorporating internal audits into your process. You can find several examples of self-audit checklists on the internet to help with the process. Happy Auditing!