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T-22: Writing a Platform Master Protocol Using the Common Protocol Template

Poster Presenter

Anthony Paul Davidson

Associate Consultant Scientific Writing
Eli Lilly and Company
United States

Objectives

To create a globally accepted Platform Master Protocol (MP) using the common protocol template (CPT). The main purpose of a MP is to create a seamless framework in which evaluates each investigational agent or regimen eligible for development in pre-specified targeted populations.

Method

Recent draft guidance from the FDA provides definitions, structure, and guidelines to develop a MP. The TransCelerate template initiative continues to transform the industry through the use of a CPT. However, the CPT must be adapted for MPs. Co-Author: Jennifer Showalter

Results

Consistent with recent FDA guidance, common trial elements were identified in the CPT. Sections unique to each investigation were placed in the investigation specific addenda (ISA). The statistical analysis plan (SAP) includes details on implementation of Bayesian or other methods used. When combined, the MP, ISA, and the SAP complete an investigational plan. Each of the three documents are unable to stand alone in supporting an investigation. Consultation from all stakeholders is a necessity when adjusting the CPT. The MP consists of the • master document, which defines the platform concept and overall structure, as well as the common elements across all investigations, • ISA, which define study specific hypotheses and investigational requirements. New ISAs will be implemented at any given time, as hypotheses emerge and new agents become available, compelling new investigations. Each ISA will describe the study population, rationale for evaluating the proposed treatment, and endpoints and analyses specific to each investigation. Findings will be reported in ISA-specific or combined study report(s). Once all patients for a particular investigation have met study completion (as defined in that ISA), that ISA will be closed. The MP end of study will occur when all ISAs have individually completed and no new investigations are planned. Investigations of common scientific interest may leverage information across ISAs to maximize learning and minimize redundancy. Examples of this include placebo/comparator control arms of common interest. Statistical analyses relevant to the specific hypothesis will be found in the relevant ISA and the more detailed addendum SAP. Correct identification of content modules as common or as intervention-specific is critical to the success of the writing project, as is correct assignment of modules to the MP, ISAs, or SAPs. Misidentification or misplacement of content could lead to reader error or complex protocol amendments.

Conclusion

A MP enables investigations of unique study drug(s) and patient populations with distinct endpoints through ISAs, while standardizing structure and operational components. This standardization helps facilitate review (regulatory, institutional review boards, and investigative sites), ease site participation and study execution burdens under one master construct, speed access to the latest treatments, and optimize resources through elimination of redundancy at the sponsor and site level. The establishment of a centralized database to gather data in a standardized fashion across investigations and over time, is an invaluable resource for hypothesis-generation and study planning, especially in rare patient populations. The flexibility of the standard overarching structure with ISAs allows for rapid implementation or closing of individual ISAs without jeopardizing the other ongoing ISAs being investigated. Furthermore, by utilizing innovative designs and adaptive analytics, there is an opportunity to maximize learnings via integration of relevant evidence in specified related ISAs. Leveraging data across ISAs increases the opportunity for patients to receive novel treatments while minimizing the number of patients required to meet endpoints. We hypothesize that implementation of a MP using the CPT as well as compliance of the FDA draft guidance, Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics Guidance for Industry, is obtainable. By using the CPT, we maintain our commitment to the industry for a standardized approach to clinical trial development while using innovative modern designs.