Guest Column | May 25, 2021

Best Practices For Designing And Running Clinical Trials For Patients With Rare Diseases

By L. Mary Smith, Ph.D., SpringWorks Therapeutics

Hands Up In Class

Most people agree that drug development is risky and challenging, and as an industry, we are constantly searching for ways to improve the drug development process – particularly in the rare disease space.  SpringWorks Therapeutics works hard to develop patient-centric clinical trials for rare diseases and has found success through fostering collaborative partnerships with patient advocacy organizations and allowing for new flexibilities in trial design. Let’s begin by exploring the role that patient advocacy organizations can play in clinical trial design and implementation and discuss ways to stay connected to the needs of patients and their families.

Patient Advocacy Groups Offer Multiple Avenues To Gain Insights

Patient advocacy groups play a critical role for the rare disease patient community.  These groups are active in fundraising for research, designing and managing patient registries, providing information on clinical trials, and connecting rare disease communities so patients and their families feel less isolated and more informed. They can also be extremely helpful in providing input on clinical trial designs, patient-reported outcomes (PRO) tools, and raising awareness of the trial to help with recruitment.

Patient advocacy groups also often host conferences that present opportunities to share information about clinical trials. Participating in scientific sessions enables interaction with the medical community and, oftentimes, these conferences also have sessions for patients and their caregivers.

Sponsors of a rare disease clinical trial can host patient advisory boards to help guide a successful clinical trial. This can be done in conjunction with existing patient advocacy conferences to optimize scheduling and access to patient advocates. For example, the patient community can describe what matters to them, give input on PRO tools, help identify other potential hurdles to participation in a study, and give feedback on how often they would be able or willing to travel to a treatment site for study visits. While this may sound basic, the voices of patients are often overlooked in designing clinical trials.

Sponsors can collect feedback about the clinical trial consent forms, which can be incredibly valuable to learn if there is certain language that people do not understand or may discourage them from participating. One example I recall from a previous company was feedback from a family that if a biopsy was going to be collected during the trial, they wanted the consent form to clearly indicate if their child could have a scar from the procedure. Particularly when conducting studies in pediatric populations, this type of information is important for parents as they weigh the risks and benefits of participating in a clinical trial.

Create Opportunities To Stay Connected To Patients Throughout The Trial

Sponsors should make every effort to stay closely connected to patient needs throughout the trial. While sponsors cannot interact directly with patients, it is important to maintain close relationships with patient advocacy organizations and proactively share study updates whenever possible.

It is critical to work with the clinical research organizations (CROs) to provide support and ensure that patients can remain on study. This is even more important in the rare disease space, given the small patient population and limited number of study sites with expertise in the indication being studied. Examples of this collaboration may include sponsor representation at study monitoring visits, sponsor-led study training with the CRO, and partnership with the CRO when discussing trial participation with study investigators.  Close collaboration with CROs has never been more important than during the COVID-19 pandemic. Especially in rare disease trials, each participant is incredibly important, and COVID-19 has presented a risk to study compliance and retention.

Flexibility in trial design, including expanded visit windows, virtual health visits, use of local facilities for blood draws, and direct-to-patient shipping of study medication have been critical in addressing the challenges presented by the COVID-19 pandemic, particularly among patients with rare diseases who may have to travel greater distances to participate in clinical studies. Given the broad uptake and success of these changes during COVID-19, these measures will likely remain in place after the pandemic to improve the overall patient experience in clinical studies.

What’s The Patient Advocacy Role In The Regulatory Process?

The role of the patient advocate in rare diseases extends beyond execution of clinical trials and into the regulatory approval process. Over the last few decades, regulatory agencies have increasingly included patient advocates in regulatory review committees, such as the FDA Patient Representation Program, a flagship program that offers patients and caregivers the opportunity to provide critical advice to the agency as it regulates medical products — drugs, biologics, and devices. Collaboration with patient advocacy groups early in the development process will help build relationships required to support potential regulatory reviews.  


As the biopharmaceutical industry continues to develop innovative treatments for the 300 million individuals who are living with rare diseases globally, more challenges to delivering innovative treatments are expected to be encountered. Although the task seems daunting, it can be accomplished through close partnerships with advocacy organizations and by implementing new flexibilities when needed. Understanding the patient experience is critical, and sponsors need to commit to incorporating these best practices into clinical trials as they work to develop life-changing medicines for people living with rare diseases and cancer. The answers are waiting…let’s go find them!

About the Author:

Mary SmithMary Smith, Ph.D., is responsible for clinical development and operations, regulatory, manufacturing, and quality as chief development officer at SpringWorks Therapeutics. Prior to joining the company, she was the executive vice president of gene therapy at Bamboo Therapeutics, a wholly owned subsidiary of Pfizer, where she led several key gene transfer programs for rare genetic diseases. Prior to joining Bamboo, she was vice president of product development at United Therapeutics, with responsibility for biological development in oncology, as well as regenerative medicine and virology. Smith earned a Ph.D. in microbiology from the University of New Hampshire and received her postdoctoral training at Emory University under an NIH research fellowship.