Clinical Protocol should be submitted for each planned clinical study or trial. An original IND application submission lacking a clinical protocol is considered incomplete. Protocols for subsequent studies not submitted with the original IND application can be submitted at a later time as Protocol Amendments.
Investigator’s Statement Form 1572 (PDF - 718KB) must be submitted for each Investigator participating in a clinical study. Forms related to Certification and Disclosure of the Financial Interests and Arrangements of Clinical Investigators may be found here.
The main components of a clinical protocol are described in Guidance for Industry, E6 Good Clinical Practice: Consolidated Guidance (PDF - 262KB)
When submitting a new clinical protocol as part of an IND application, consider the following:
For Phase 1 trials:
Early developmental protocols should specify in detail all the elements of the study that are critical to safety. Such elements may include all clinical safety assessments, toxicity monitoring, description of toxicity-based stopping rules, dose adjustment rules for individual patients and the overall trial, and adverse event recording and reporting;
Study enrollment criteria should be written with consideration of the following: (1) background risks associated with the disease or condition studied, (2) previous knowledge of toxicities of the investigational drug observed in animal studies or with human experience, (3) warnings and precautions described in the product’s label (when approved products are investigated for other than approved uses);
It is preferable that toxicity is assessed and graded according to a standardized grading scale relevant to the studied population and that adverse events are collected, recorded, and reported in a consistent manner.
For Phase 2-3 trials:
All the above described expectations for adequate safety elements also apply to Phase 2-3 trials;
Detailed protocols describing both efficacy and safety should be submitted for Phase 2-3 trials. Objectives and purposes of a trial should be clearly stated, including description of the observations and measurements to be made to fulfill the objectives of the trial;
Clinical trial protocols should include a clear description of trial design and patient selection criteria as well as description of clinical procedures, laboratory tests, and all measures to be taken to monitor the effects of the drug;
Previous experience with the proposed primary endpoints should be discussed with relevant scientific references (including any available data regarding the measurement’s validation as relevant to clinical outcomes, biomarkers, or patient reported outcomes);
All potential deviations from trial design should be built in the protocol from the outset, including when adaptive design is considered;
Rules for adverse events’ collection, recording, and reporting should be thoroughly described;
Protocols lacking the necessary elements describing the intended investigations may be placed on Clinical Hold.
For additional information, refer to FDA guidance documents explaining various aspects of product development and protocol writing listed below.
Additional Resources for Product Development
- Guidance for Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products. (PDF - 129KB)
- Guidance for Industry: E9: Statistical Principles for Clinical Trials (PDF - 110KB)
- Guidance for Industry: Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products (PDF - 997KB)
- Guidance for Industry: Non-Inferiority Clinical Trials (PDF - 474KB)
- Guidance for Industry: Adaptive Design Clinical Trials for Drugs and Biologics (PDF - 423KB)
- Guidance for Industry: Codevelopment of Two or More New Investigational Drugs for Use in Combination (PDF - 91KB)