While drugs and medical devices are both essential in modern medical care, there are times when standard clinical development processes seem to treat medical devices as an afterthought. For example, medical writers for a CRO conducting studies of both drugs and devices must learn to interpret a drug-centric guidance document to author an appropriate Clinical Study Report (CSR) for each different type of medical device, whether diagnostic, therapeutic or surgical.
The ICH E3 guidance on the structure and content of CSRs was created in its current form in 1995 and endorsed by the FDA as a guideline for industry in 1996. According to the FDA Web site, the guidance “makes recommendations on information that should be included in a core clinical study report of an individual study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects.” Thus, the guidance is meant to apply to medical device trials as well as drug studies, at least in cases when a full-dress CSR is desired for a device trial. (The FDA requires inclusion of the “results of clinical investigations involving human subjects” in Premarket Approval [PMA] applications for Class III medical devices, but the need for a complete CSR for a particular device study is an issue that must be addressed when defining the regulatory strategy for a clinical development program.)
Adapting a Drug-Centric Guidance for Clinical Study Reports
Despite the official position that the same guidelines apply to CSRs for drugs and medical devices, a medical writer who is preparing a CSR for a device trial quickly encounters several questions. The word “device” appears nowhere in the main E3 guidance, and the report structure that it outlines is clearly focused on studies of the efficacy and safety of drugs. The text makes general mentions of the “investigational product,” but nonetheless includes sections for such topics as drug concentration measurements, drug interactions, and so forth. Medical writers preparing CSRs for products like in vitro diagnostics (IVDs), which fall under the FDA’s device regulations, quickly encounter challenges in using the ICH E3 guideline as the template for an IVD CSR.
This issue has been recognized by the ICH and is addressed in their supplemental Questions & Answers document for E3. Asked, “what are the options for submission of data for topics such as… devices,” the short answer from the ICH is: adapt. They reply, “It is appropriate to create new headings in the CSR and new Appendices for these topics. The Guideline provides for and focuses on Efficacy and Safety variables known at the time. Other topics should be well referenced in the CSR body and clearly identified in the Table of Contents.”
Building a Template Library for Device CSRs
The result of this situation is that the details of the structure of device CSRs aren’t as standardized as those for drug studies, and there is divergence in their format, content, and numbering. The differences among device trials also make it difficult to create a single, one-size-fits-all CSR template for devices in cases when a full CSR is desired. An IVD study that uses non-intrusive swab samples, for instance, may collect only minimal safety information and have no expected adverse events, while a surgically implanted device may require presentation of a detailed safety analysis. After the medical writer or CRO has developed experience with a variety of different types of device trials, it’s possible to build up a library of templates derived from the E3 guidance, but adaptable to diverse circumstances. Even with a rich library of templates to choose from, it remains essential for the medical writer and sponsor to agree on the optimal structure and content to support a PMA application for each specific device.
Samuel Bell, MPH, is a medical writer with more than 20 years of experience in drug and medical device development. He has written CSRs, protocols, Investigator’s Brochures, and other regulatory documents in support of clinical development programs. His areas of experience include women’s health, endocrinology, urology, infectious diseases, musculoskeletal disorders, and a variety of other therapeutic areas.