Objective
The overall objective of this proposal is to continue the ongoing work of T1DC, to expand its value to community, and to increase the efficiency in which the consortium is able to operate. T1DC is a public-private partnership that aims to provide a neutral pre-competitive space for those with an interest in developing new products for people living with T1D, including the biopharmaceutical industry, academic and clinical researchers, patient-advocacy organizations, philanthropic organizations, and regulators, to share expertise, identify unmet needs in product development, and develop solutions to overcome these unmet needs.
To enhance and streamline the T1D community’s abilities to develop regulatory grade solutions to pressing unmet needs in T1D, T1DC has proposed a restructuring of the current consortium. This proposed construct utilizes a hub and spoke model, with a ‘core’ consortium component and separate specific workstreams for each individual project the consortium undertakes. This will provide a more collaborative space for the consortium to achieve its overall goals, while ensuring the specific projects pursued by the consortium have the resources necessary to achieve those goals. Initially, the consortium will consist of the Core component and a T1D prevention workstream.
The objectives of the T1DC Core will be to provide a collaborative and engaging working space for consortium members to collectively advance medical product development in T1D. The Consortium Core will facilitate discussion across T1D stakeholders, including regulatory agencies, with a focus on identifying and addressing the most pressing barriers and unmet need to new product development.
The overall goal of the T1D prevention workstream is develop and obtain regulatory endorsement of a T1D prevention clinical trial simulation tool. This tool will build upon completed and ongoing T1DC consortium activities to expand the utility and value of the consortium’s work to the drug development community and, ultimately, to patients. This tool is intended to facilitate the design of optimized T1D prevention clinical trials. Regulatory endorsement of the tool will be obtained from US and European regulators (i.e., FDA and EMA), in order to ensure the tool is acceptable to regulators. Regulatory endorsement provides significant confidence to drug sponsors that the tool should be implemented into drug development programs, thereby increasing the overall impact of the tool. Regulatory endorsement also streamlines the regulatory review process of individual products by ensuring regulatory agencies have deep knowledge and data-driven understanding of the tool before receiving regulatory submissions that include trials designed with support from the tool.
Background Rationale
There are currently no disease-modifying therapies available for use in T1D. As the global incidence and prevalence of T1D rises, there is a growing unmet medical need for new therapies that target the underlying disease process. Despite several recent successes, product development in T1D remains costly, lengthy, and high-risk for product developers. When also considering the relatively small target population (compared to other chronic autoimmune diseases, for example rheumatoid arthritis), many product developers have turned attention and resources towards other areas of unmet need. To ensure new products become available for patients at risk for or currently living with T1D, the community must collaborate to improve the efficiency and likelihood of success of new product development in T1D.
To this end, T1DC was established in 2017 as a pre-competitive public-private partnership with members representing the biopharmaceutical industry, patient-advocacy groups, philanthropic organizations, clinical and academic researchers, government institutions (i.e., the National Institutes of Health), and regulatory agencies. T1DC is managed and operated by C-Path, an independent non-profit organization with a mission to support collaborations that streamline and advance medical product development.
T1DC members initially focused on improving trial design in T1D prevention trials by improving the community’s ability to enrich T1D prevention trials for subjects likely to rapidly progress to T1D diagnosis. The overall goal of this work was to reduce the required length of clinical trials by enrolling an enriched population. To achieve this goal, T1DC undertook a global data sharing initiative to develop an aggregated database that could be used to provide regulatory evidence regarding the use of islet autoantibodies for trial enrichment. A substantial modeling initiative, leveraging the aggregated database, was completed and submit to the regulatory agencies. This effort resulted in formal EMA endorsement of the islet autoantibodies as enrichment biomarkers, when used with additional relevant clinical features (such as sex, baseline age, baseline HbA1c, and baseline 120-minute glucose from an OGTT). Review of this work by FDA is ongoing.
While this work substantially improves trial design for T1D prevention trials, additional opportunities exist to further optimize trial design. Importantly, during the regulatory review process, EMA indicated they believed the aggregated databases developed by T1DC could be used to address additional unmet needs. Thus, through this research proposal, T1DC intends to build upon its completed work by addressing additional unmet needs in trial design.
Description of Project
The Critical Path Institute (C-Path) proposes to continue and expand ongoing efforts to facilitate the development, regulatory approval, and dissemination of regulatory science solutions that inform medical product development in type 1 diabetes (T1D). C-Path's current collaborations with the T1D community include product developers, patient advocacy organizations, philanthropic organizations, clinical and academic researchers, and regulatory agencies. These groups work together in the pre-competitive space to advance the development of medical products for T1D. By obtaining regulatory endorsement of the specific tools generated through these collaborations, medical product developers, researchers, and regulatory agencies are aligned on the appropriate use of the tool, and all have confidence to implement the tool in the development and review of new therapeutics.
This proposal includes the continuation of the core component of the T1D Consortium (T1DC) and the T1D prevention workstream. The T1DC Core provides a regulatory and scientific forum for all T1DC members to discuss updates regarding ongoing consortium activities, regulatory and scientific advancements and news in T1D, and other T1DC activities that could be undertaken to advance medical product development. Examples of Core Consortium activities include discussing new regulatory guidelines of interest and relevance to T1D (e.g., the U.S. Food and Drug Administration (FDA)’s recent draft guidance titled, “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations”) and to potentially provide public comments to the Agency on behalf of T1DC. Other activities may include discussion of new potential workstreams for the consortium, guest presentations from experts across the T1D and regulatory science fields covering topics of interest to the consortium (e.g., updates from other T1D initiatives or examples on the use of real-world evidence), and the development of publications that will support the overall consortium’s goals of advancing the product development landscape in T1D.
The T1D prevention workstream will build upon work already completed by T1DC during its recent qualification of the islet autoantibodies as enrichment biomarkers for T1D prevention trials. During this important work, the European Medicines Agency (EMA) indicated they believe there may be substantial untapped value in the datasets aggregated by the consortium. As such, T1DC identified early opportunities to develop a clinical trial simulation tool to further aid in the design of T1D prevention clinical trials. The development of such a clinical trial simulation tool requires substantially more data than the consortium’s initial work on the islet autoantibodies as enrichment biomarkers. Thus, the consortium expanded its data sharing initiative and has begun efforts to initiate regulatory pathways to obtain endorsement of the to-be-developed clinical trial simulation tool. In short, the clinical trial simulation tool will support trial design by allowing sponsors to simulate the results of clinical trials with different designs prior to initiating real-world trials. This will allow sponsors to optimize enrollment criteria, trial size and duration, endpoint selection, and other factors while still maintaining adequate trial power. Sponsors will also be able to individually determine appropriate and acceptable risk-benefit trade-offs for their drug development programs when considering the likelihood of trial success with the size, duration, and likely costs of such a trial. Overall, the clinical trial simulation tool will allow sponsors to develop more efficient trials with higher confidence in trial success.
The T1DC Core work will provide a broad foundation for the consortium to carry out its current and future efforts, and the T1DC prevention workstream will focus on delivering a specific tool that will significantly enhance the product development landscape in T1D prevention.
Anticipated Outcome
The anticipated outcomes of this effort are as follows:
1) Continuation of the T1D Consortium with a new ‘hub-and-spoke’ model, consisting of a Consortium Core and individual project workstreams
2) Establishment of the initial project workstream, focused on T1D prevention
3) Expansion of the existing curated, standardized, and integrated patient-level database of longitudinal observational studies and clinical trials in T1D prevention by acquiring and aggregating additional studies of interest
4) Development of a T1D prevention clinical trial simulation tool
5) Achievement of regulatory endorsement of the T1D prevention clinical trial simulation tool through appropriate regulatory review pathways at FDA and EMA
6) Development and public release of a user-friendly graphical user interface to allow product developers and regulators to implement the tool into the design and review of T1D prevention clinical trials
Relevance to T1D
The overall goal of this work is to facilitate the development of new products for individuals at risk or currently living with T1D by leveraging the resources, data, and expertise of the entire T1D community through a pre-competitive public private partnership. This effort will apply the foundation of excellence in data science, quantitative modeling, and regulatory science of the Critical Path Institute to the T1D community and expand upon work already completed by T1DC.