The arrival of FDA inspectors to evaluate your clinical trial program (or your CRO’s program) doesn’t have to be a jarring experience. But too often, it is. FDA clinical investigators most often find discrepancies such as:
• Not following the investigational plan.
• Deviating from the established and approved protocol.
• Inadequate record keeping.
• Poor accountability of the product (drug or device) under evaluation.
• Inadequate participant/subject protection, including no informed consent on file.
These problems are all preventable. They can be avoided by diligently keeping track of records and reporting any changes in protocols, even those due to the “reality” of finally getting your product out of preclinical laboratory testing and into a clinical scenario. A solid audit program, such as that provided by Synergy Bioscience, is very important for making sure your records and trials stand up to scrutiny.
FDA inspectors will audit your study data by comparing what you filed with the regulatory agency with records at your clinical sites. These records will include case report forms, signed and dated consent forms, physician’s progress notes, a subject’s hospital chart, and nurses notes. They visit a range of sites, including clinical investigators, sponsors, monitors, CROs, IRBs, pre-clinical labs and bioequivalence analytical labs.
Whether you are conducting your own clinical trial, have contracted a CRO, or are a CRO, you need to know how to perform a proper audit, to ensure that you and your staff can demonstrate that you’re doing what you’re supposed to be doing. Here are some essentials of performing an audit; issues that are missing or problematic should be followed up with a written corrective and preventive action (CAPA) plan. These are just a few of the records you should look for in a clinical trial audit:
• Signed versions of FDA form 1572 or an Investigator Agreement (for devices), with all appropriate investigators listed, and with CVs and licenses (during the research time) for all the investigators.
• All protocols, informed consent, and investigators brochures.
• All IRB-approved study advertisements.
• Enrollment logs.
• All IRB approval letters (initial approval, amendments, continuing review and reportable events).
• Proof the study is registered on www.clinicaltrials.gov
• Complete and accurate delegation of authority log.
• Documentation of study-specific training for study staff.
• Documented validation/calibration test methods.
• Proof that adverse events were appropriately recorded and reported to the sponsor and IRB.
Usually, a good way to audit these and other records is to choose 10 percent of the total number of subjects, and randomly pull that number of subject charts to review. Then use that sample to begin looking for source documentation.
The clinical trial audit and monitoring should be an integral part of your overall Quality Control program, ensuring that your trial is performed, and data collected, recorded, analyzed, reported and protected, according to GCP and other regulatory requirements. It is very important that these audit functions, however, be conducted by personnel who are independent from the actual operation of your trials. This is where a third-party auditor can come in, especially in pharma, biotech and device companies that are strapped for staff.
At Synergy Bioscience, we have decades of experience in quality control and laboratory audits, including clinical trial monitoring and auditing. We can help you start with a solid data reporting and recording plan, conduct interim “mock” inspections similar to a regulatory visit, and prepare you as much as possible for smoother interactions with FDA and other regulators. What issues have you had to confront in your clinical trial program? Have protocol deviations or documenting subject records been an issue with your trials? Contact us for a deeper conversation; we’d love to hear from you.