On May 2, 2017, the U.S. Food and Drug Administration (“FDA”) and The National Institutes of Health (“NIH”), through the NIH-FDA Joint Leadership Council, released the final version of a clinical trial protocol template in an effort to assist investigators conducting clinical trials and to create cost and time efficiencies in the medical product development process.
Clinical trial protocols describe the objective(s), design, methodology, statistical considerations, and organization of a clinical trial. While FDA has released guidance in the past on the content that should be included in a protocol, the template presents this information in a standardized format. A draft version of the template was released for public comment a little more than a year ago, and the final version reflects public input from close to 200 comments submitted by 60 individuals.
According to FDA, the template should be used by clinical investigators who are writing protocols for phase 2 and 3 NIH-funded studies that require Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications, but it could also prove useful for other investigators conducting studies of medical products that are not regulated by the FDA. The FDA also expressed its hope that having a standardized template will lead to more expedient reviews of protocols by regulators, Institutional Review Boards (“IRBs”), and other entities.
The template provides both sample text to include in the actual protocol and instructions to assist with filling out the protocol. The template explains the information that should be included in key sections of the protocol, such as the Risk/Benefit Assessment section. For example, the template details that the Risk/Benefit Assessment section should include information about the risk profile from the following primary sources: the package insert or device label, if it is available for a licensed or approved product; the Investigator’s Brochure, if the product is investigational; or published literature, if the package insert, device label, and Investigator’s Brochure are not available.
Additionally, some key information that the template recommends including in the protocol is:
- Foreseeable physical, psychological, legal, social, economic, or other risks to participants in the Risks/Benefit Assessment section;
- Reasoning behind the need to expose study participants to risks along with a summary of the efforts made in the study design to minimize these risks in the Risks/Benefit Assessment section’
- Description of the objectives and endpoints of the study should be displayed in a table format in the Objectives and Endpoints section. The description should detail the selected primary and secondary endpoint(s) and how the endpoints are linked to achieving primary and secondary objectives. Further, data points collected in the study should either support an objective or have a regulatory purpose;
- The procedures for selecting each participant’s dose of study intervention and control product in the Dosing and Administration subsection under the Study Intervention section. This includes the time that each dose is administered (e.g., time of day or interval), the duration, the route of administration (e.g., nasal, oral, intramuscular), and the relation of the doses to meals; and
- Provide the criteria for discontinuing the study intervention, such as any monitoring test(s) and associated clinical decision point(s) in the Discontinuation of Study Intervention section. This Section should include the reasons for any temporary discontinuation of the study intervention such as a certain type and quantity of adverse events. Further, the Section should include the length of time and data to be collected at the time of discontinuation of the study intervention and approaches for restarting the study intervention.
Industry should make all efforts to use the template when conducting clinical trials to reduce time and cost in the medical product development process and to increase the chances of gaining approval for protocols by regulators and IRBs.