I once worked with a site that was selected by the Japanese Ministry of Health, Labour and Welfare for a study conducted 15 years earlier. Even though the site was not participating in a trial that was conducted in Japan, the sponsor had submitted a registration and the data package included a compilation of safety and efficacy data from studies conducted almost 20 years in advance.
As expected, many changes had occurred at the site in 15 years: investigators and coordinators had come and gone; records had been sent to an off-site storage facility; and the memory of the study was well-regarded as part of the site’s history. Getting the site prepared for an audit was an epic feat. At the time, the site did not have standard operating procedures (SOPs), which made it difficult to follow the thought and activity of the study conduct so many years ago.
The moral of the story is that sites must ensure that data collection practices are so clear and understandable that someone years later can review the data and understand exactly what was done, and how. The way to ensure this is by following global regulations and site SOPs. Documentation is the key.
The mere mention of the word “audit” can strike fear in even the most meticulous among us. Yet audits are a necessary component of the drug development process and assist health authorities in validating data and ensuring that clinical sites are in compliance with the protocol, regulations and Good Clinical Practice (GCP). Consequences of negative audit findings can include, but are not limited to, a written warning for deviations from applicable statutes and regulations, withdrawal of IRB/EC approval, and even site closure.
An audit may be conducted by a clinical trial sponsor, institutional review boards or ethics committees, and health authorities such as the Food and Drug Administration. These entities may conduct both announced and unannounced site inspections under any of the following circumstances:
- to verify the accuracy and reliability of data that has been submitted to the agency;
- as a result of a complaint to the agency about the conduct of the study at a particular investigational site;
- in response to sponsor concerns;
- upon termination of the clinical site;
- during ongoing clinical trials to provide real-time assessment of the investigator’s conduct of the trial and protection of human subjects;
- at the request of an FDA review division; and
- related to certain classes of investigational products that FDA has identified as products of special interest in its current work plan (i.e., targeted inspections based on current public health concerns).
Though there is no fail-proof method for avoiding an audit, there are steps your site can take to mitigate audit findings.
- Know and observe applicable federal regulations, state law and institutional SOPs and/or policies, as well as Good Clinical Practice.
- Minimally, have a basic understanding of the therapeutic area and indication for studies conducted in your department.
- Know and observe your department’s policies and procedures for research study-related activities.
- Know and follow the IRB-approved protocol.
- Know the study-related roles and responsibilities of the principal investigator and other research team members.
- Differentiate between the study-related and healthcare provider roles and responsibilities.
- Review the protocol with the research team members; identify and discuss any concerns or questions regarding conduct of the study.
- Maintain open communication with other research team members and investigators, the principal investigator, sponsor and IRB.
- Ensure that each research team member has access to the most current documents, including, but not limited to, the informed consent document, protocol, and case report forms.
- Assist in the establishment and tracking of the budget.
- Create and use tools to assist in the compliant conduct of the study (worksheets, data collection forms, logs, checklists, etc.).
- Develop and maintain an effective system for data collection and storage.
- Implement quality assurance measures to ensure your study is conducted in accordance with the IRB approved protocol, institutional policy, and required regulations.
- Create and utilize a study participant file which is a central location of documents.
- Resolve any research study-related issues, problems, concerns and queries in a timely fashion.
- Be prepared for all monitoring visits.
The principal investigator is ultimately responsible for the proper conduct of clinical research at the site. Study procedures must be performed in accordance with health regulations and the protocol, even if it conflicts with a PI’s standard practice.
Meanwhile learn from others’ mistakes. Check out post-audit FDA warning letters at https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm.