Making Small Numbers Add Up: The Challenge of Studying Rare Diseases

When you go to the doctor complaining of pain, numbness, lethargy, or other troubling signs, you expect to come away with a diagnosis and treatment plan. But some combinations of symptoms leave the doctors scratching their heads. If the problem is so uncommon that most doctors have never encountered it before, either personally or in the medical literature, it may take years for the patient to receive a correct diagnosis—and even then little may be known about appropriate treatment.

On the last day of February, PCORI joins organizations around the world in recognizing Rare Disease Day to raise awareness of uncommon diseases, their impact on patients’ lives, and the need for research to find and improve treatment options. Among the goals of Rare Disease Day are to strengthen the voice of patients and patient advocacy groups, provide information, promote equal access to care, and highlight the search for new therapeutics. Rare Disease Day was first observed in 2008 on February 29—the least common day of the year. This year Rare Disease Day focuses on encouraging everyone in the rare disease community to join together for better care, an idea well-aligned with PCORI’s outlook.

PCORI-funded Research Projects on Rare Disease

Major Public Health Impact

Rare diseases are surprisingly numerous. About 7,000 different types have been identified in the United States. Defined as affecting fewer than 200,000 people nationwide, rare diseases grouped together affect 30 million—or 10 percent of—Americans. (That’s similar to the number with diabetes, both diagnosed and undiagnosed.) Rare diseases are often genetic and can appear at any stage of life. They can be severe, chronic, progressive, disabling, or even fatal.

Most rare diseases have no effective therapy, and when treatments are available, they can be extremely expensive. About half of rare diseases are diagnosed during childhood, so they affect the patient for decades. But insurance frequently fails to cover long-term supportive care.

Patients with rare diseases can face more difficult challenges than patients with more common health problems. In addition to delays in diagnosis and misdiagnoses, rare-disease patients and their families may bear a greater psychological burden and receive less support.

Although research on most rare diseases is still very limited, it has increased in the two decades since the passage of the Orphan Drug Act, which provides financial incentives to pharmaceutical companies to develop effective treatments.

Previously, pharmaceutical companies considered it impractical to develop drugs to be used by only a few patients. Research on rare diseases remains challenging because when so few people are affected by a given condition, it is difficult to put together a sample large enough for standard study designs.

PCORI's Research Focus

Rare diseases are of special interest to PCORI. Our legislative mandate specifies an expert advisory panel focused on rare disease. This panel—approved by PCORI’s Board of Governors on November 18, 2013—will provide recommendations to PCORI on the conduct of patient-centered outcomes research (PCOR) in rare disease and facilitate productive collaboration and engagement with the rare-disease research community.

It will include people with rare diseases, their caregivers, and representatives of advocacy groups, as well as practicing and research clinicians, experts in scientific and health services research, and other healthcare stakeholders. PCORI is currently in the process of reviewing applications for the panel, and a kickoff is scheduled for May 1.

The charter of the PCORI Advisory Panel on Rare Disease was shaped, in part, by discussion at a PCORI-hosted roundtable in September 2013. At the roundtable, representatives from the rare disease community also expressed strong interest in the creation of registries for the many rare diseases that don’t currently have one. They noted, too, that international collaboration may be required to have large enough samples for robust clinical trials.

As of January 2014, PCORI had funded eight research projects on rare diseases. In one of these, a tool accessed through a tablet computer enables multiple sclerosis patients to learn about their current condition and what their future is likely to hold. In another, researchers are examining why the only disease-modifying therapy for sickle cell disease is vastly underutilized and patients tend not to adhere to the treatment. Multiples sclerosis and sickle cell disease are among the most common of the rare diseases. Another study is examining how supplemental oxygen—which is routinely prescribed for patients with pulmonary fibrosis, a less common disease—affects their symptoms, activity levels, and quality of life.

Coverage in PCORI's Data Networks

Rare diseases are also well represented in PCORnet, a PCORI-funded national network for clinical outcomes research currently being developed. PCORI recently approved awards to 29 health-data networks. Among the 18 Patient-Powered Research Networks (PPRNs), which are operated and governed by groups of patients and their partners, about half focus on one or more rare diseases.

Furthermore, each of the PCORnet’s Clinical Data Research Networks (CDRNs) has selected a specific rare disease and is developing methods for identifying and characterizing it, as well as recruiting patients. PCORI encourages the CDRNs to collaborate with organizations representing patients. The CDRNs originate in hospitals, health plans, and other healthcare systems that collect health information during routine patient care.

Research on rare diseases aims to help patients improve their health, decrease their rates of premature death, and increase their quality of life. Says Lucinda Shore, a patient partner in a PCORI Pilot Project documenting social and psychological burdens experienced by people with rare diseases, “I hope that future patients can avoid the worries, concerns, and hassles I have confronted.”