Obviously, it’s crucial that you stay in compliance during your clinical trials. That’s because failure to do so has enormous and expensive consequences. And yet, on a regular basis, firms find themselves with an FDA 483 for non-compliant behaviors. Without a doubt, an independent clinical audit for Good Clinical Practice (GCP) is a vital part of product development. The purpose of such an audit is to determine that a clinical trial is being performed in compliance with the approved protocol and other FDA regulations.
What should be on your clinical trial Investigator site audit checklist? Each checklist section described below is a very brief summary of the compliance area. However, it is important to keep in mind that this checklist is not meant to be inclusive of all items that should be examined during an audit.
Protocol Compliance – This ensures that documentation is available to substantiate that the clinical Investigator and the site staff have followed the study protocol approved by the Institutional Review Board (IRB).
Institutional Review Board – Documentation of IRB approval of the protocol and any amendments, informed consent documents, advertisements, and other information provided to prospective study subjects must be kept onsite.
Human Subject Records – This is one of the most significant areas of the site audit. Here, the auditor is looking through the study documents and records to make sure that all of the required information is captured and follows the protocol without deviations. Documents reviewed include informed consent forms, medical records, and other source documents.
Other Study Records – Other records pertinent to the study may include administrative study files, correspondence files, master subject list, appointment books, sign-in logs, screening lists, and MedWatch forms.
Informed Consent of Trial Subjects – Ensuring that each subject, or the subject’s legally acceptable representative, has given uncoerced informed consent is essential in every trial. Written IRB-approved informed consent forms, along with any other oral or written information, must be as non-technical as possible and must be understandable to the subject. The written consent form must be revised when new information becomes available that may be relevant to the subject’s willingness to continue participation in the research, and the communication of this information should be documented.
Financial Disclosure – All Investigators and relevant study staff must sign a document disclosing information about their financial interests to the sponsor. This document must be updated if circumstances change.
Electronic Records and Electronic Signatures – If electronic records are being used as detailed in the study protocol, the system used to generate, collect, or analyze the data must be documented and meet the requirements applicable to paper records. Training must also be provided to the appropriate personnel.
Test Article Control – Drug accountability at the Investigator site must be verified. The drug must be received by authorized personnel, properly labeled, inventoried, secured, and stored under the appropriate conditions. The return of any quantities of the drug to the sponsor, or otherwise disposed of, must also be documented.
Record Custody and Retention –Study records must be stored and retained according to the protocol and regulations.
Reports to Sponsor – Investigators always need to keep the Sponsor apprised if there are any safety issues or protocol deviations, as such, this section is used to determine whether required reports have been submitted to the Sponsor in accordance with the study protocol and regulations.
Investigator qualifications and Agreements – Auditors determine whether the Investigator has adequate experience in conducting trials; to ensure that they and their staff have been adequately trained, and that they are knowledgeable of GCP and the applicable regulatory requirements.
Adequate Resources –The Investigator must have sufficient time to conduct and complete the trial safely and adequately. The Investigator shall have an adequate number of qualified staff, and adequate facilities for the foreseen duration of the trial.
Medical Care of Trial Subjects – The Investigator is responsible for the wellbeing of the subjects including oversight of all trial-related decisions and ensuring that adequate medical care is provided to subjects including medical care for any adverse events related to the trial.
Communication with the IRB – Audits shall include verification that the Investigator has written and dated approval from the IRB regarding the research application, written informed consent form, consent form updates, subject recruitment, and any other written information to be provided to subjects.
Randomization Procedures and Unblinding – The Investigator is expected to follow the trial’s randomization procedures. Additionally, if the research is blinded, the Investigator must comply with the protocol requirements to maintain the blind and to promptly document and explain to the sponsor any premature unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the investigational product.
Records and Reports – The Investigator must ensure that all data reported to the sponsor is accurate, complete, legible, and timely. If there is a change or correction, it must be dated, initialed, and explained without obscuring the initial entry. This applies to both written and electronic changes or corrections.
Progress Reports – The Investigator will submit written summaries of the research status to the IRB annually, or more frequently if requested by the IRB. The Investigator must also immediately report all serious adverse events to the sponsor.
Regulatory Essentials – Auditors shall ensure that the regulatory binder contains all of the required documentation which should include, at minimum, Form FDA 1572, protocol, informed consent, Investigator’s brochure, advertisements, enrollment log, and all IRB-approved letters.
Study Staff – Auditors shall review all staff CVs and licenses to ensure that they are appropriately qualified for their delegated roles and have all been properly trained.
Data and Safety Monitoring – High-risk trials may have a data safety monitoring board (DSMB). Safety monitoring reports are reviewed to ensure there are no significant noncompliance issues or any patterns of ongoing or unresolved compliance.
Record Archiving –Reports, essential documents, and data has been neatly organized and kept in an appropriate and secure place.
Premature Termination or Suspension of a Trial – If the trial is prematurely terminated or suspended for any reason, the Investigator must promptly inform the trial subjects, assure appropriate therapy and follow-up for the subjects, and, where required by the applicable regulatory requirement(s), inform the regulatory authority(ies).
Final Report by Investigator – Upon completion of the research, the Investigator must inform the IRB and provide a summary of the research results as well as any reports required by the regulatory authority(ies).