I’m not sure the nomenclature "Orphan Diseases" ever made sense.
Today, with so many biopharmaceutical companies ready to adopt compounds aimed at these disorders into their pipelines, the shift to the term Rare Diseases is most welcome—especially by the individuals and families affected by these conditions. In the United States, these disorders generally are defined as those affecting fewer than 200,000 people. In the European Union, a disease is considered rare when it affects not more than 1 person in 2,000. Although low prevalence is the common feature shared by all rare diseases, there are between 6,000 and 8,000 conditions that fall within this designation that affect or will affect an estimated 30 million people in the E.U. and 25 million in the U.S.
Within the clinical research arena, we are experiencing an explosion in the number of new rare disease studies. In January and February 2012 alone, the FDA designated 24 studies within this category—replete with all the benefits of this status. Yet tremendous progress brings new challenges—especially in recruiting physicians and patients to participate in clinical research studies for treatments of rare diseases. While research sponsors for chronic conditions may elect to conduct studies in multiple countries to expedite timelines or better manage costs, for most rare disease study teams there is no other choice. Rare disease studies require a multinational platform to achieve enrollment.
Success in these studies also requires different selection criteria for investigators. Academic research centers become increasingly important. Those with strong commitments from department heads and those with documented and well-established referral networks rise to the top. Multiple studies competing for the same patient population are more troublesome than usual. And the communications skills of investigators matter more, as there are fewer patients to approach.
Patients with rare disorders educate themselves about their diseases to the greatest extent possible. Because often there is limited information about these conditions’ causes or treatment options, study participants are likely to be nearly as well-versed in the science and research frontiers of their conditions as their physicians. Many of these patients and their family members—whether as individuals or through advocacy groups—go beyond monitoring research and propose new areas of study. I have seen patients even decline to participate due to their perception of flaws in the study design.
Now, layer the complexities of executing a rare disease study in eight or 12 countries on top of these challenges. My best advice: embrace flexibility.
■ For example, visit number three may not need to be in the clinic and could be conducted at home, by phone or in person. This would need to be drafted as such in the protocol. Each physician may have his or her own preference. Or this flexibility could be applied at the individual patient level.
■ The fewer the number of available patients, the greater the demand for capturing as much data as possible in every study. In the earliest stages of study design, strive to understand the daily lives of patients with the condition and incorporate this knowledge into the final protocol to find the right balance of patient sensitivity and data collection requirements.
■ Just because rare disease studies typically involve fewer sites and patients, doesn’t mean they demand less of the sponsor’s resources in trial management, monitoring and relationship efforts. Often, sponsors and sites need to rethink their standard allocation of resources to achieve success.
One other piece of advice: take care of every day.
■ Studies of rare diseases often require more time to identify optimal sites, conduct qualification visits, execute contracts, obtain regulatory ethics approvals and train site staff on protocol details. Don’t allow a single day to pass without knowing exactly where you are in these processes with each study site.
■ Once active, plan for periodic visits with study sites. Be prepared to participate in any or all intra-institutional activities the site may conduct to raise awareness and generate support for the study.
■ Even though you expect each site to enroll only two patients in two years doesn’t mean you should wait patiently until the end of year one before worrying about recruitment timelines. Rare disease studies also benefit from early enrollment within the first few months of site activation.
When we are disciplined about asking ourselves every Monday, “What could be done to make this study more successful?” and answer that question for every country and each site, we make the greatest contribution to advancing the knowledge and treatment of rare diseases.