6 Tips For Collaboration In Rare Disease Clinical Research


By Ankit Mehta, MD, program director for the Department of Internal Medicine, Baylor University Medical Center


It is well known that designing and executing clinical trials at any stage takes a village, involving stakeholders including manufacturers, patients and their families, clinicians, trial site teams, study coordinators, and regulators. For clinical trials of rare disease drugs, the involvement of disease specialists — whether nephrologists, cardiologists, endocrinologists, or others — is also essential given a therapeutic area may be beyond most general healthcare practitioners’ purview, as they are often not exposed to any of the 7,000 known rare diseases on a daily basis. The unique insights of disease specialists can help identify patients who may be interested in and appropriate for rare disease clinical research.

Patients living with Fabry disease, a rare lysosomal storage disorder that occurs in only about one person per 40,000 to 60,000, are considered some of the “lucky few” rare disease patients who have approved treatments available to them. For decades, people living with Fabry disease had no treatment options and suffered daily from symptoms including severe pain, kidney problems, heart complications, and digestive difficulties. Many patients never even received an accurate diagnosis due to the broad range of symptoms caused by Fabry, many of which overlap with more common conditions, and a lack of broader disease awareness in the medical community.

After years of research and development, in 2003, the FDA approved the first on-label treatment option, an enzyme replacement therapy (ERT), for Fabry disease. But for many patients, the treatment did not address all their symptoms and presented its own burden by requiring time-consuming infusions every two weeks. Since 2003, the FDA has approved a few additional treatments for Fabry disease, including one recently approved in both the U.S. and EU in May 2023. But there is a continued need for new clinical trials evaluating more advanced therapies, as first-generation ERTs present limitations and, despite having several treatment options available, not every therapy is right for every patient.

Given the multifaceted nature of Fabry disease, what are best practices for designing clinical trials, identifying patients, and thus determining the best treatment options for them? After more than 15 years of treating adults living with Fabry disease, I have found that key factors are industry communication and collaboration.

What Does It Mean To Collaborate With Industry In Clinical Research?

As a nephrologist, my instinct is to first address the kidney problems associated with Fabry disease. But Fabry also can cause EKG changes, strokes, pain crises, and other symptoms. One key takeaway that I have learned over the course of my career is that nephrologists must take a holistic view of patients to diagnose Fabry disease accurately and as early as possible. This holistic mentality must also be used by drug developers when conducting research and designing clinical trials for many rare diseases.

Diagnosis and treatment of patients with Fabry disease often requires collaboration among nephrologists and other specialists including cardiologists, neurologists, and pain management physicians, all of whom a patient might visit given the range of their symptoms. While this can make areas of responsibility and decision-making pathways complex in terms of patient management, clinical trials present a unique opportunity to bring these specialists together to share their knowledge and insights. Drug developers will need these collective insights to be able to determine optimal trial design and access and to identify eligible patients quickly.

Drug developers also can leverage relationships with clinicians, including disease specialists, to communicate with rare disease patients and caregivers more directly and effectively. Patients or caregivers who may be less inclined to trust industry executives or who are not able to independently learn about available clinical trials and their eligibility and enrollment criteria may be more likely to participate in research efforts if they can discuss them directly with their trusted physicians. In addition, physicians may also have established relationships with patient advocacy groups and can help make connections with drug developers as a way to communicate about clinical trial opportunities and research advances with larger patient communities.

I regularly work with clinical operations teams to learn about the latest research and clinical trial eligibility criteria so that I can make the appropriate recommendations to patients and provide them with the information they need.

In one recent example, I worked with another Fabry disease care provider and a pharmaceutical company’s clinical operations team to identify Fabry disease patients appropriate for a promising research effort. Together, we screened eight patients and enrolled six of them in a pivotal Phase 3 active-control, randomized, double-blind, 24-month study of a novel plant-based ERT being evaluated as a treatment for adults with renal function impairment caused by Fabry disease, which has since been approved. We also  screened three additional patients and enrolled one in another Phase 3 clinical trial of the same plant-based ERT in treating Fabry disease. This trial was a multicenter, multinational, open-label, switchover study designed to evaluate the safety and efficacy of the investigational ERT in adults previously treated with a commercially available ERT. Our cross-collaboration with industry was key in identifying patients quickly who might benefit from this clinical research and enroll them in the trial.

6 Lessons Learned Through Collaborating With Industry

By working with multiple professionals and executives in clinical research and drug development, I have recognized the essential role industry collaboration plays in designing and executing meaningful clinical trials, removing barriers of care, building broader disease awareness, and advancing research efforts so that new, safe, and effective treatment options may become available to patients. Several lessons learned along the way include:

  1. Some clinical trials require longer time frames than others. When designing clinical trials, it is important that the study’s duration is commensurate with the endpoint(s) being evaluated. In Fabry disease and other rare diseases, measuring clinically meaningful results might take longer than the usual two, three, six, or 12 months required of trials in disease indications with larger patient populations. Improvements in left ventricular mass index, estimated glomerular filtration rate (eGFR), and other measures associated with Fabry disease progression often must be observed over the long term to determine a pattern and get robust data. Rare disease drug developers should go into the next phases of clinical research understanding that, depending on the disease and patient population, they may not see meaningful results for several months or years.
  2. Focus on outcomes — like quality of life — that matter most to patients. In discussions with other specialists, we realized that many patients are most interested in the impact an investigational drug may have on their quality of life and daily function, which may not have quantifiable measures. Researchers, clinicians, and drug developers tend to focus on biomarkers and endpoints that are quantifiable and better indicate a drug’s impact on the underlying biology of a disease rather than the patient’s quality of life, especially if these markers are important to regulators. But we must consider the outcomes that matter most to patients, even though they might not be as easily measured. For people with Fabry disease, these include improvements in gastrointestinal symptoms and overall pain levels. Given this feedback, drug developers should consider using available pain and symptom evaluations including the MAINZ Severity Score Index (MSSI), Brief Pain Inventory (BPI), and Multidimensional Symptom Index (MSI) in future clinical trials.
  3. Collaborate with multidisciplinary specialists. In the past, care plans for those with Fabry disease were typically managed by geneticists. However, shortages of these specialists have led other specialists, including nephrologists and cardiologists, to take the lead as primary points of care. However, the lead care provider is not always consistent and may differ for each patient. This presents challenges in patient access to clinical trials and in fully understanding a patient’s medical history. Drug developers must consult with all of a patient’s care providers, not just the lead provider, to get a holistic and accurate picture of the patient’s symptoms.
  4. Patients must understand the consequences of clinical trial participation. While patients who consider participating in clinical research are always made aware of the potential risks regarding side effects of treatments, they don’t always know that participation may exclude them from enrolling in subsequent clinical trials. For example, a patient who plans to participate in a gene therapy trial should be clearly informed that they will likely be excluded from future studies because it is impossible to evaluate efficacy of other treatments on patients who have already undergone gene therapy. Patients need all relevant information up front before entering a clinical trial.
  5. Use the trial design process as an opportunity to provide patients with standard care. For rare diseases, especially those that impact multiple organ systems like Fabry disease, patients often have difficulties accessing standard testing and care related to their condition. For example, it is typically recommended that patients with Fabry disease undergo cardiac MRIs every two to three years, but it can be difficult to get insurance to cover the tests. Offering patient participants standard testing and care may give them an additional incentive to participate as well as provide researchers and clinicians with important insights.
  6. Talk about your collaborative experience with others. Use every opportunity to discuss your collaborative experience in clinical research with colleagues, peers, industry executives, and others. Spreading the word about the benefits of industry communication and collaboration, whether in person, in written communications, at medical meetings, at clinical trial sites, during webinars, or in other venues or platforms, may result in more researchers taking this approach when conducting clinical trials. This may help lead to more optimal trial design in the future. In addition, cross-collaboration may help educate more patients about opportunities to participate in clinical research.

Progress cannot be achieved alone. Close collaboration among industry stakeholders, including drug developers, clinicians, specialists, researchers, and others, allows us to provide targeted support and engage in communication that can continually optimize patient outcomes. Healthcare providers and drug developers alike must work to improve their understanding of all the different manifestations of diseases, such as Fabry disease, to identify patients quickly as well as fully understand disease burden and continued unmet needs.

About The Author

Ankit Mehta, MD, is a fellowship-trained and board-certified nephrologist and internal medicine specialist. He is also program director for the Department of Internal Medicine at Baylor University Medical Center in Dallas and is involved in research at Baylor Scott & White Health’s research institute as well as its renal disease research institute. He practices nephrology with Dallas Nephrology Associates. He began seeing patients with Fabry disease during his training and has continued treating them for more than 10 years. Mehta attended medical school at Grant Medical College in Mumbai, India, before completing an internship and internal medicine residency at Baylor University Medical Center and a fellowship in nephrology at Baylor, Dallas.


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