Challenges in Designing Rare Disease Clinical Trials

Due to the complex nature of many rare diseases, researchers must come up with strategic and innovative ways to design trials that can deliver the results in a reasonable amount of time to meet the needs of the rare disease community. Recently, guest
columnist of the Clinical Leader, Sharon H. Hrynkow, Ph.D., chief scientific officer of Cyclo Therapeutics, discussed how to overcome the 3 major challenges in conducting rare disease trials:

  1. Defining The Primary Outcome Measures: Many times, primary outcomes are not easily defined for a rare disease that did not have many prior studies done on it. Researchers may have to rely on what they know about the disease and try to look for certain "markers" associated with the disease and establish clinical outcome measures by evaluating disease progression or severity of disease symptoms.
  2. Patient Avoidance Of Being In The Placebo Group: For patients with rare diseases, learning that they may be randomized into the placebo arm could be a determining factor of whether or not they would want to participate in a trial. To address this challenge in recruitment, as well as on an ethical standpoint, placebo-controlled studies should have an open-label period to give all participants an opportunity to receive the investigational product.
  3. Deciding On The Trial Duration: The length of a trial is important for researchers to collect sufficient data to prove the effectiveness and safety profile of an investigational product; however, too long of a trial could become an added stress on the patients, their families, and the research team alike. Dr. Hrynkow suggests that developers should include critical time points during the trial when the study data could be evaluated. If the efficacy and safety of the product could clearly be seen, the study may be concluded early; otherwise, the study will continue through the designed duration.

Through thoughtful designs and collaborations with all parties involved, hopefully, we can find the perfect balance that makes clinical trials a success to benefit the rare disease community that we serve!

(From Hrynkow, Sharon. "How To Overcome The 3 Major Challenges In Conducting Rare Disease Clinical Trials.” Clinical Leader, November 30, 2021. Accessed Jan 2, 2022.)