How to Optimize Rare Disease Trials

As recognized experts in statistical methodology, the IDDI team not only implements a wide variety of established methodologies, but also actively participates in the development of novel approaches to clinical trial design. Most recently, this has manifested in the form of Generalized Pairwise Comparisons (GPC) which is a novel statistical methodology that allows for consideration of multiple endpoints at the same time in randomized control trials while simultaneously allowing for the rigorous capture of multiple benefits of a drug so long as these different endpoints can be put in an order of preference eg survival, quality of life, or symptoms. Such an approach can be beneficial in rare diseases or in other small populations as it allows for increased statistical power.

Due to the small patient populations, limited natural history data, and often heterogeneous manifestations of such rare diseases, the optimization of rare disease clinical trials poses a number of unique challenges. As a team of experts who not only understands the science behind the methodologies, but also the current statistical regulatory environment, IDDI is able to confidently focus on the following key considerations to enhance the efficiency and success of rare disease clinical trials:

Flexible Trial Design:

• Through the use of innovative statistical methods eg GPC to maximize the utility of small sample sizes.
• Wide expertise in the application and analysis of adaptive trial designs to allow for timely modifications based on emerging data.
• Ability to consider platform trials that allow for testing multiple treatments within the same infrastructure.

Global Collaboration:

• Engage with our community of expert individuals, international research networks and peer organizations.
• Understanding of the regulatory incentives for orphan drug development as specific to trial design and patient outcomes considerations.

Biomarkers and Surrogate Endpoints:

• Provide expert validation of identified biomarkers that may serve as surrogate endpoints.
• Accurately assess any treatment response of biomarkers and advise on the most efficient trial durations.
• Work confidently with regulatory agencies to establish the validity of surrogate endpoints.

Regulatory Support:

• Engage early and frequently with regulatory agencies as a confident partner to discuss and champion efficient and innovative trial design and endpoints.
• Understanding orphan drug designations and expedited pathways for regulatory approval as specific to the statistical considerations.

Data Sharing and Collaboration:

• Encourage data sharing among researchers, sponsors, and regulators.
• Participate in collaborations between academia, industry, and government agencies.

Technology and Digital Solutions:

• Use and comprehensively understand Electronic Data Capture to streamline data collection and mitigate potential for error.
• Implement dynamic Randomzation and Trial Supply Management Systems to flexibly meet the evolving needs of trial patients and their drug supplies.

Patient-Centric Outcomes:

• Through our broader network, include input on patient-reported outcomes (PROs) considerations to best capture the impact of the disease on patients’ lives.
• Develop endpoints that align with patients’ priorities and quality of life eg Generalized Pairwise Comparisons.

By addressing these considerations, sponsors can realize maximum efficiencies, strategically mitigate any risks to clinical data and, therefore, maximize the chances of success in rare disease clinical trials, while simultaneously improving the lives of patients by providing trial designs that increasingly address the direct preferences of the individual patient.