4 Ways Home Visits Support Successful Rare Disease Clinical Trials
The Orphan Drug Act, which was enacted in 1983, has been largely responsible for advancing the quality and quantity of rare disease research over the past 40 years. It has…

4 Ways Home Visits Support Successful Rare Disease Clinical Trials

The Orphan Drug Act, which was enacted in 1983, has been largely responsible for advancing the quality and quantity of rare disease research over the past 40 years. It has driven the approval of more than 600 therapies to treat serious diseases affecting fewer than 200,000 patients in the U.S. According to the British Journal of Dermatology, over the last three to four decades, the number of designated orphan drugs for rare diseases has increased more than fourfold, which is a reflection of the expansion of novel drugs and biologics for an array of rare conditions. By the end of the first quarter of 2023, the FDA has already approved two notable rare disease treatments.

Despite such progress, FDA officials acknowledge continued challenges in testing, approving, and producing new treatments for critical conditions affecting small patient populations. These added obstacles are key reasons why “less than 5% of the estimated 7,000 rare diseases currently have an effective treatment” and why only 12% of clinical trials are focused on rare diseases.

What makes rare disease trials so challenging?

Trial design and delivery in the rare disease arena are accompanied by specific considerations and added potential pitfalls for researchers, patients, pharma and regulators. What are the special considerations that make rare disease trials more challenging?

  • The first challenge of rare disease trials is the most obvious: it’s hard to find patients. Around 5%-5.9% of people have a disease classified as rare (which in the U.S. is defined as a disease affecting fewer than 200,000 people). An even smaller percentage will have the specific disease that a clinical trial is attempting to study. But that’s only part of the mathematical considerations that limit the chances of success of a rare disease clinical trial. In combination with the smaller enrollment numbers, there is high inter-individual variability in clinical course observed in many rare diseases which diminishes a study’s power.
  • It’s also difficult to establish specific criteria for participation. That’s because there is often a desire to study patients with early disease for disease-modifying agents or, in contrast, those with advanced disease when the intervention risk is high. Yet, where patients are few, it may not be feasible to significantly narrow entry criteria based on disease stage or other characteristics.
  • Rare disease clinical trials are further complicated by the fact that there is seldom access to large industry research to support critical hypotheses or provide a starting point for treatment. There are several requirements for therapeutic study of human diseases, including appropriate trial design and analysis to answer the research question, appropriate measurements to complement the trial design, selection of the correct sample, and knowledgeable study staff to execute the study. In rare diseases, the limitations that come with studying a small population can transform these requirements into monumental challenges.
  • Then there’s the geography factor. Low numbers of people with a particular disease means it’s difficult to identify enough patients to participate in a trial within a specific region. To reach sufficient prospective participants, sponsors and CROs often need to conduct studies in multiple US states, or countries. The low volume of potential participants spread thousands of miles apart creates additional problems for patient recruitment. This can challenge protocol harmonization, ethical review, indemnity, organization of clinical services, standards of care and cultural diversity. Language differences and working across varied time zones can add complications.
  • Another consideration is the lack of financial incentives, despite the advances made by the Orphan Drug Act. Since rare disease clinical trials serve a smaller portion of the population than more mainstream trials focused on cancer or infectious disease, for example, they also suffer from less funding. This creates the need to identify more creative, less traditional approaches for recruiting participants and gathering data in order to lower costs.
  • Working with pediatric patients brings about a new set of complications, as children and, more importantly, the parents who must approve the enrollment of their children in a clinical trial, often require more support and special handling to remain in a trial long-term. The Centers for Disease Control (CDC) estimates that 30 million people in the United States have a rare disease, of which roughly half are children.
  • While a double-blind placebo-controlled randomized trial remains the gold standard, limited potential participants and phenotypic heterogeneity in rare diseases may limit the ability to conduct such a trial. In rare diseases, in particular (many of which cause a shortened lifespan), there are ethical concerns about placebo-controlled trials. Furthermore, parents may be reluctant to enroll their child in a trial where he or she may receive a placebo rather than the intervention under study.

In-home nurse visits address many rare disease trial challenges

Using a research partner who has the knowledge, experience and proven track record to adapt to the unique needs of rare disease clinical trials can directly impact the results of a study. At PCM Trials, more than half of the study protocols delivered by our Certified Mobile Research Nurses are for rare diseases, and we’re proud of the role we play in bringing services to these underrepresented patient communities. Deploying mobile research nurses in rare disease trials has been shown to be effective in overcoming the various cost, operational and retention challenges that plague many rare disease clinical trials.

  1. By visiting patients in their homes, workplaces or other locations that are convenient for them, mobile research nurses ease the burden of trial participation which leads to higher recruitment and retention. Such convenience is especially attractive to patients suffering from diseases characterized by significant physical impairments. For example, PCM Trials was honored to carry treatment the last mile as part of the first FDA-approved treatment for Rett Syndrome.
  2. A mobile research partner with deep experience in conducting rare disease research possesses the capabilities and resources necessary to manage a clinical trial in multiple countries, overcoming language barriers and understanding varying regulatory guidelines. At PCM Trials, we employ and/or manage our nurses via the most direct model in order to ensure that they all have consistent training and the necessary skills to meet trial-specific protocols. This makes it easier for us to provide services for trials that span multiple countries and continents, and we are currently able to deliver in-home visits in more than 70 countries around the world.
  3. The use of mobile research nurses has additionally been shown to result in lower costs and faster startups—two primary challenges of rare disease clinical trials. A recent Tufts study documented that decentralized trial methods, including the use of mobile research nurses, can result in as much as a five-fold increase in ROI over centralized models by reducing clinical phase cycle times, screen failure rates and the number of substantive protocol amendments. That same study suggested that decentralized trial methods can reduce Phase II and Phase III durations by at least 10%, or three months. PCM Trials achieves consistent start-up times of eight weeks in an industry where 80% of clinical trials don’t complete the enrollment phase on time.
  4. Mobile research nurses can additionally help improve participant retention and compliance by providing needed human interaction and social support—the kind that can’t be replicated through the use of digital devices and wearables. This is especially relevant in the case of rare diseases. In fact, the social isolation that comes from having a rare disease is often discussed as a challenge unique to people with a rare disease.


The key to being able to bring more rare disease treatments to market relies on the ability to make trial participation easier. Mobile research nurses have proven to be an effective approach to creating more patient-centric trials. The end result is successful trials that advance more quickly due to faster startups, face less risk of being delayed or cancelled due to low patient retention, are more cost effective, and overcome the many logistical challenges typical of a multinational study. Because of PCM Trials’ unique approach to these challenges, to date, 17 protocols we have supported with home visits have received regulatory approval upon submission to the FDA.

These benefits in the rare disease space can also be applied to advance trials focused on diseases that impact a broader patient population, including Alzheimer’s and Parkinson’s, to name two, as well as trials that led to the development of multiple COVID pharmacologic treatments. For these trials, mobile research nurses performed a wide array of protocol-specific procedures, including blood draws for pharmacokinetic sampling and administration of intravenous drugs, as well as GCP-compliant documentation of trial results.

To learn more how mobile research nurses could help advance your next rare disease clinical trial, call (303) 253-7470 or visit pcmtrials.com.