The advent of more flexible clinical trial design brings a promise of greater hope in alleviating the challenges rare and orphan patients face in accessing clinical trials. However, just as creating a diagnosis and treatment plan is a slow and complex process, there is no simple path to innovation in clinical trials, and patient populations continue to struggle with availability, access, and exclusion/inclusion criteria.

Challenge #1: Barriers to Innovation

Within the larger study of trial design, interest in nontraditional clinical trial models in the development and application of drug therapies is growing; two such examples are basket trials and umbrella trials. Basket trials are useful for diseases which have common molecular alternations. In a basket trial, a targeted therapy is evaluated on multiple diseases or disease subtypes. Umbrella trials evaluate multiple targeted therapies for a single disease that is stratified into subgroups by molecular alteration.

While both basket and umbrella trials are being used minimally in the disease market, they are used even less frequently in the rare disease space. Research from Clinical Trials Arena’s December 2021 analysis revealed there were approximately 42 basket trials and seven umbrella trials initiated in 2021 as compared to more than 5,000 rare disease trials started in the same year. According to the article, “Basket and umbrella trial designs could open new doors in therapeutic rare disease research, but they remain largely underutilized outside of cancer.”

Challenge #2: Access and Availability

With a limited population size that’s geographically dispersed, the challenges presented by rare disease trials are frustrating for both patients and manufacturers. Because the population is so small, it’s difficult to identify, recruit, and retain the number of patients needed for trial.

Often, patients must travel far from home to participate in the few clinical trial sites set up by the manufacturer. Understandably, this results in rare disease patients opting out or dropping out of a trial – for a patient living with a rare disease, the effort and expense of travel simply may be too much to bear.

To add further complexity, rare disease physicians are uncommon and are geographically separated, creating a situation in which even the most dedicated physician teams are thwarted by logistical challenges.

Challenge #3: Exclusion and Inclusion Criteria

Because of the small size of rare and orphan disease groups, the endpoints needed to meet exclusion and inclusion criteria must be tight. There is no room for error; just one or two patients can make or break that endpoint. Many patients will not meet the inclusion points and will, therefore, be ineligible to participate. Although frequently this challenge results in the expansion of program access later on – thus creating more viability for patients and physicians alike – it’s still a barrier to participation in trials which might, in fact, be more productive.

Diligence Will Make a Difference

There’s no shortage of obstacles when it comes to rare disease trials. Our biggest challenge may be the one we make ourselves to remain both curious and diligent in seeking solutions.

• Push for inclusive, patient-first care. For rare disease trials – just like everything else with rare disease – we cannot rest on what works for other populations.

• Pharmaceutical companies must embrace new trial designs in terms of how they are designed, what they can accomplish, and how information is submitted to the FDA. Continued innovation in trial design will be worth the effort.

• CRO partners must be held to a higher standard. It’s not enough to simply choose the largest CRO or default to the known provider. We must adopt relationships with CRO partners who are successfully creating trials for small patient populations.

• Think creatively about access. In response to Covid-19, the corporate world had to reimagine how work gets done. What big-picture concepts have we learned that now could be applied to clinical trials?

At Optime Care, we prioritize our patients above all else, which is why it is vital that we continue to advocate for their best interest. That means pushing past the barriers and looking toward solutions that meet the needs of those afflicted with rare disease.