Rare disease isn’t rare. As a whole, more than 350 million people in the world have at least one rare disease – more than the population of the United States. Exactly what qualifies as a rare disease is another story. The statistical definition of “rare” varies by country. Officials in the European Union require that no more than 1 in 2,000 people have a disease for it to be considered rare, while in the US, a condition is rare if fewer than 200,000 people in the country have it. Overall, there are roughly 7,000 rare diseases recognized worldwide and even more that simply don’t have names yet.
Quantifying the Problem
Treatments for rare diseases are just as rare as the incidence of the conditions themselves. Current estimates put the number of rare diseases with a recognized treatment option at less than 5 percent. The reality is that rare diseases have comparatively few people impacted (as opposed to non-rare conditions). With so few people having a disease, developing treatments or even merely conducting a natural history study of a condition can be challenging. Furthermore, over 50 percent of rare diseases impact children, and afflicted people may be in various locations around the world.
Novel approaches to patient recruitment can help bridge the gap. Something as simple as employing social media in study recruitment efforts and adding a website pre-screener can simplify and streamline recruitment efforts. However, site location still plays into the success of rare disease studies. There are several considerations outside of recruitment that are influenced by geography.
Regulations can be a barrier to site initiation. In one study, over 40% of clinical research organizations said that obtaining regulatory approval was difficult for rare disease trials. Researchers found that regulators were more flexible and even often willing to provide advice during meetings that happen post-Phase II as opposed to drug applications. Almost 90% of respondents said that population size was to blame for the difficulties.
Retention is another complication. Population sizes for rare and orphan drug studies could be as small as 20 for a Phase 3 study, so losing even a single subject could impact the research conclusions. Amongst rare diseases, the dropout rate is roughly 67% for site-only patients and 23% for all patients. While the reasons for so many dropouts are myriad, they tend to boil down to inconvenience. With rare disease patients being spread out, many study participants have to travel significant distances to reach site locations. The time and energy required to do so can be a burden, even with the lodging and reimbursement of travel expenses often seen in these trials.
In some cases, rare disease researchers are effectively forced to pursue relocation instead of travel reimbursements. In studies where remote visits are not possible, it can improve participation and retention to support subject and caregiver relocation for the trial duration. Obviously, this can come at a high cost and could impact study results. Relocated participants may experience new challenges that non-relocated participants do not share. For instance, social support may be different, or their diets may change with regard to the new location. Even if the impact is a placebo effect, the possibility of interference must be carefully considered, and the ethics committee overseeing the study would need to approve such a measure.
Finding a Solution
There are solutions to these issues. Advocacy groups, as well as medical networks/databases, can help bridge the gap. They can be leveraged to increase awareness about a study or bolster recruitment efforts, but many drug developers – as many as 75% – end up outsourcing their rare disease research. They choose CROs who have the local relationships needed to complete successful rare disease trial enrollment. Some contract research organizations have established patient recruitment departments and proven track records in meeting enrollment goals for rare disease clinical trials.
At Allucent, we have worked in the rare disease space for decades and have strong relationships with local investigators. We have provided CRO services for 14 drug approvals, and roughly 88% of our PMs and 92% of CRAs have Rare Disease experience. We also offer patient recruitment services.
Contact us to request a proposal.
Applequist, J., Burroughs, C., Ramirez, A., Jr, Merkel, P. A., Rothenberg, M. E., Trapnell, B., Desnick, R. J., Sahin, M., & Krischer, J. P. (2020). A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment. BMC medical research methodology, 20(1), 58. https://doi.org/10.1186/s12874-020-00926-y
Gelinas, L., Crawford, B., Kelman, A., & Bierer, B. E. (2019). Relocation of study participants for rare and ultra-rare disease trials: Ethics and operations. Contemporary clinical trials, 84, 105812. https://doi.org/10.1016/j.cct.2019.105812
Julkowska, D., Austin, C. P., Cutillo, C. M., Gancberg, D., Hager, C., Halftermeyer, J., Jonker, A. H., Lau, L., Norstedt, I., Rath, A., Schuster, R., Simelyte, E., & van Weely, S. (2017). The importance of international collaboration for rare diseases research: a European perspective. Gene therapy, 24(9), 562–571. https://doi.org/10.1038/gt.2017.29
Khaleel, S.L., (2014). Rare Disease Patient Recruitment and Retention. Clinical Leader. https://www.clinicalleader.com/doc/rare-disease-patient-recruitment-and-retention-0001
Mansell, P. (2013). Site selection complicates rare-disease trials: Premier Research. PharmaTimes Online. http://www.pharmatimes.com/news/site_selection_complicates_rare-disease_trials_premier_research_1004686
Ribbink, K. (2017). Rare recruitment. Pharma Voice, May 2017. https://www.pharmavoice.com/article/2017-5-rare-disease/