As every biopharma company knows, rare disease trials may be among the most difficult projects to plan and deliver. The patient populations are small and scattered and some may be located in pockets in remote areas or regions where clinical research is not traditionally conducted and others are only identified after sophisticated molecular testing. Additionally, some rare conditions have a limited number of experts, often little to no peer reviewed research and a virtual absence of key opinion leaders to access for guidance and advice. This all creates a trial environment that is fraught with uncertainty and a risk of failure to meet objectives.

We need to think about things in a different way and we need to be creative in the ways we approach these perceived difficulties. As we reflect on Rare Disease Day this week, it is time to start thinking differently about how we do rare disease research.

Rare disease research needs forward-thinking project teams who recognize the inherent challenges these projects face – and are willing look for unorthodox ways to overcome them. Fortunately, the biopharma industry, patient advocacy groups and regulators are working collaboratively to make rare disease research opportunities more abundant for patients and their families and more attractive for biopharmaceutical companies. For patients suffering from a rare disease, development cannot come soon enough. In some cases teams are drawing on best practices from within the healthcare delivery system itself in others they are drawing lessons from outside industries to find better, faster and economical ways to meet the needs of patients.

Thinking differently for rare disease research
Often the first thing parents and families do when a diagnosis is made is head to the internet. Harnessing this powerful tool is really at the center of good strategy from trial concept to recruitment. One of the things I’ve increasingly learned about is social listening. The best way to approach a clinical trial is to first understand who the thought leaders are, where patients go for information, and what their key concerns are about treatment and trial participation. All of this information can directly inform trial protocol development and efforts to recruit patients. Social listening addresses all of these issues, enabling researchers to gather valuable data in a matter of days.

Social listening involves running an algorithm or online query to scan the internet for discussions, research, key opinion leaders and advocacy efforts related to the disease. The results are then compiled into a report that outlines where discussions are taking place, where patients are finding advice and treatment information, and what are the ‘patient important outcomes’ that will determine whether or not a patient will participate in a trial. This information allows investigators to tweak their trial design, find advocates to collaborate with, and target their efforts to be most accessible to patients. All of this will help them make the best use of their recruiting resources and more efficiently attract these hard-to-find patients to their trials.

We try to keep the patient at the heart of everything we do. This involves making things as convenient and complication free as possible. Incorporating patient concierge servicesas part of the clinical trial planning process should certainly be considered. One of the biggest challenges in rare disease research is finding the patients and making sure they have the opportunity to participate thus transportation to the trial sites can be a barrier.

Even if there are numerous possible participants, they are often scattered all over the world. If sponsors can’t track them down and offer a trial site that they can get to, they face a high risk of trial failure due to insufficient patient accrual. Many sponsors attack this challenge by opening dozens of sites around the world, each of which may serve one or two patients, if any at all. In some cases this is an incredibly expensive and inefficient approach and we need to carefully consider changing this embedded tactic.

Instead of opening sites near the patients where the potential for recruitment is low and expertise with clinical trials may be as well, they are bringing the patients to the trial. Once sponsors identify a patient who meets the inclusion criteria for the trial they provide door-to-door services, transporting that patient, and their family if appropriate, directly to one of a few trial sites set up via partnerships with highly respected research facilities adept at rare disease care. This shift dramatically reduces infrastructure and costs, while aligning the trial with a renowned institution where leading physicians are already treating patients with a variety of rare diseases. Inherent with this approach is smart trial design including patient-driven input allowing for remote visits on a more frequent basis eliminating the need for excessive travel.

It is a surprisingly cost efficient approach that could be a game changer for rare disease trials. Not only does it eliminate the geographical barriers to this research, it ensures trial sites are led by physicians who understand both the disease and the trial process, and are eager to participate in research.

Once a sponsor recruits patients to the trial, they need to do everything they can to keep them engaged. Making participation easier and more convenient can go a long way toward achieving this goal. With that in mind, some sponsors are taking advantage of telemedicine technology, remote monitoring devices, and localized services to meet the patient’s needs in their own community or even in their own home. This may include sending home health nurses to conduct lab work, having patients see their own physician for treatments with the trial physician overseeing the appointment via Skype, capturing patient data via remote monitoring, and using sub-investigators located near the patient’s community to conduct non-critical visits, reducing the frequency of visits to a distant trial site to a few times per year. By harnessing local healthcare resources, sponsors can cut costs and reduce attrition without sacrificing the quality of the data. And the patients’ lives are much less disrupted by the trial experience.

Most rare diseases have related patient advocacy groups, and there are differences between them in terms of overall capabilities and organization. This creates a valuable opportunity for sponsors to support a strong voice in the disease community, and to get their support and feedback in return. One mutually beneficial way a sponsor or CRO can support an advocacy group is by helping them build a patient registry. The group can use this information to support their advocacy efforts, to track long term progress of their members, and to chart the course of the disease. At the same time it creates a valuable data source for the biopharma sponsor, who can use those real world outcomes to support regulatory approval of their treatment, and to track outcomes post approval, or as part of an adaptive pathway approval process.  Another way to foster a sense of community between biopharma, CROs, patient advocacy groups and investigators is to directly connect the PAGs with the investigators.  These connections may enhance support for the patient during the course of the trial and beyond.

These are few examples that demonstrate how by thinking beyond the traditional trial model we can overcome obstacles to rare disease research to the benefit of patients and biopharma companies alike.  Doing rare disease clinical research should not be thought of as difficult or impossible just different and we need to challenge ourselves to think outside our normal processes. After all, it really is all about the patient.


Cynthia Jackson, D.O., is vice president and head of the Pediatric Center of Excellence. In that role, she leads strategy and consulting around all aspects of pediatric clinical development. She also serves as a consulting assistant professor in the Division of Pediatric Infectious Diseases at Duke University. Throughout her career, Dr. Jackson has served as a medical advisor for clinical trials in therapeutic areas related to pediatric patients, including asthma, allergies, migraines, nutrition and vaccines. In addition, Dr. Jackson has experience with infectious diseases indications such as antivirals, anti-HIV compounds, tuberculosis, vaccines, antifungals and antibacterials.