The road to market approval for orthopaedic devices can be long and arduous, but it is impossible without valid data. Regulations governing practices in clinical research demand the highest level of ethical and clinical standards, with patient protection as the highest priority. Historical precedents exist for each regulation, and each precedent comes with a story of violation or misuse of ethical obligation. While these regulations might seem overwhelming, it is important to understand that proper documentation of a clinical research trial is not just a means of organized filing for a multiplying mound of paperwork. It is a tangible trail that tells the story of the trial from conception to completion, reflecting adherence to applicable regulations and demonstrating trial integrity through transparency.
By perusing the Essential Documents, one can assess many elements of the administration of a clinical trial: the qualifications of the study staff, the accountability of the device under investigation and proper oversight controls, to name a few. The validity of data generated in a clinical trial is supported or defeated by these administrative elements. Consider this example: during a regulatory inspection, an auditor is unable to unearth any documentation indicating that the Investigator was ever trained on the deployment of an investigational artificial hip. What does that say about the data that the Investigator provided? Could the data be accepted as valid in the face of such an oversight?
The Code of Federal Regulations and International Conference on Harmonization’s Good Clinical Practice (ICH GCP) can be frustratingly vague in defining the organization of Essential Documents needed to support the quality of a clinical investigation. This article will discuss the documents most essential in clinical research, and the regulatory basis for their maintenance.
A Tour of the Typical Regulatory Binder
There are many ways to organize the Essential Documents necessary for documentation of a clinical research trial. The most widely accepted path is through the use of a regulatory binder. This binder (also known as the investigator file, investigator binder or trial master file) is the place where all study-related regulatory documents are stored and maintained – and is not necessarily a binder at all! The purpose of a regulatory binder is to maintain consistent organization of documents required by regulations. When a complete and organized regulatory binder is kept current, it not only provides a tangible demonstration of documented regulatory compliance, it also facilitates the completion of other regulatory obligations, such as periodic monitoring visits and regulatory inspections.
While the Essential Documents maintained might vary from study to study depending on the documentation needed to demonstrate regulatory compliance, many documents are commonly present as required by the Code of Federal Regulations and ICH GCP. These documents are generated in one of three periods of the life cycle of a clinical trial: before the trial commences, during the active research phase of the trial and upon the trial’s completion and close-out.