Key challenges within rare disease clinical trials

Yaffa Rubinstein

National Institute of Health

Continuing our clinical trials theme, and leading us into our rare disease focus for August, we speak with Yaffa Rubinstein, from the Office of Rare Diseases Research at the National Institute of Health.

One of the biggest challenges in rare diseases is clinical trials patient recruitment. But with the rise in public awareness, online patient advocacy groups and government funding, investigations into rare disease clinical trials have provided insight, not only into unique diseases, but also into common disorders, too.

Yaffa Rubinstein works at the Office of Rare Diseases Research, which is part of the National Institute of Health (NIH). We speak with her about her experiences working within clinical trials and the challenges of patient recruitment for rare diseases.

HB: Hello Yaffa, it’s lovely to speak with you. What is your current role at the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS) at the National Institute of Health?

YR: My main role at the ORDR (as the Director of Patient Resources for Clinical and Translational Research) is to direct the office activities on patient registries and biospecomens / Biorepositories. These two fields are associated with many other topics which are also under my direction which includes: standard vocabulary and terminology (e.g. developing Common data Elements (CDEs), disease related and disease specific questions) and ethical and legal issues (e.g. Inform consent / patient privacy and ownership of data). The two main projects that I am in charge of are: the Global Rare Diseases Patient Registry and Data Repository (GRDR) and the Biorepositories / Biospecimens database and website, RD-HUB.


“Unless patients are organized in advocacy groups and have their specific disease registry, there is a difficulty to identify and locate the patients.”


HB: What is the definition of “rare disease”?

YR: In the USA, a rare disease is any disease or condition where the prevalence is less than 200,000 patients.

HB: What is the main goal of the ORDR?

YR: The goals of ORDR are:

• To stimulate and coordinate research on rare diseases and to support research,

• To respond to the needs of patients who have any one of the more than 6,800 rare diseases known today,

• To leverage its resources, stimulate rare diseases research activities, and foster collaboration,

• To coordinate and encourage cooperation and collaboration in rare diseases research,

• To build international research collaborations,

• To educate and provide information to patients to organize their advocacy groups and establish their disease specific patient registry,

• To provide opportunities for patient support groups to become partners with the NIH, in order to better understand NIH research programs,

• To gain better access to NIH research opportunities.

HB: What are some of the key challenges rare disease community faces?

YR: At the moment, there is no accurate figure for the prevalence of each rare disease. Unless patients are organized in advocacy groups and have their specific disease registry, there is a difficulty to identify and locate the patients. The fact that there are a small number of patients for each disease, scattered over large geographical area and around the globe, it requires developing new models for conducting clinical, and other studies, with small patient population.

In addition, we don’t have the proper tools to diagnose many of the rare diseases and not enough specialized clinicians for the treating patients suffering from various rare diseases.

Also, there is a need to increase pharmaceutical’s involvement in developing drugs for rare diseases.

HB: How can these issues be overcome?

YR: Some ways to overcome these issues are by:

• Educating the community, especially the rare disease community, that patients need to get organized into advocacy groups,

• Advocacy groups need to establish their disease specific registry,

• Better collaboration and sharing of information, knowledge and resources,

• Developing Common Data Elements (CDEs),

“…there is a need to increase pharmaceutical’s involvement in developing drugs for rare diseases.”

• Disease specific questions and standardized vocabulary to be shared and accepted by the community,

• Discovering and developing new biomarkers and genetic testing, respectively, to diagnosed rare diseases,

• Training young clinicians in diagnosing and treating patients with rare diseases.

Plus, there needs to be the realization by pharmaceutical companies that understanding rare diseases and developing drugs for rare diseases may also help other common diseases.

HB: Within your responsibilities, what steps is the ORDR taking to address these issues?

YR: ORDR has conducted a large meeting and workshop to bring together all the stakeholders in the rare disease community to discuss these issues and develop recommendations and future plans. ORDR is working to bring the community together and accept a common set of standards. We have developed CDEs that can be by any patient registry and are currently working on developing disease-related and disease-specific questions. ORDR has also developed an informed consent form template for participating in patient registry. ORDR launched the Global Rare Disease Patient Registry and Data Repository (GRDR), in February 2012, which aims to collect and aggregate de-identified patient information in a standardized way to facilitate different types of studies, including clinical trials, translational research and analyses across many diseases and ultimately drug developments and therapeutics for the millions of rare disease patients.

In addition, GRDR will work to link patient clinical information to biospecimens data using unique coded identifiers. ORDR has developed a searchable database / website for rare diseases biorepositories / biospecimens around the globe RD-HUB with the ability to link the two sets of data (patient clinical information and biospecimens data) using a coded global unique identifiers (GUID).

HB: Who are the organizations participating in the GRDR program and how were they selected?

YR: ORDR selected 34 (based on the review process) patient organizations with and without registries representing different diseases and patient group size.

HB: How will the GRDR help generate research on rare diseases and recruit patients for clinical trials?

YR: Once the de-identified data is aggregated, investigators can access the data to develop hypothesis, clinical trials or any other studies.


“Biospecimens are the key to understanding the pathogenesis of any disease.”


HB: Who will have access to the data and how will the privacy of the patient be protected?

YR: The GRDR data repository will be available to all stakeholders to mine the data. GRDR will not collect any identifiable patient information and will not have any access to such information. The individual registries will have to code to the patient identifiable information, they will own the data and only through them anyone can have access to the patient, assuming the patient gave their consent to be contacted.

HB: The ORDR website also mentions the link to biospecimens. What is the importance of biospecimens for studying rare diseases?

YR: Biospecimens are the key to understanding the pathogenesis of any disease. They are needed to validate diseases testing and treatment developed biomarkers to determine appropriate treatment, diagnostics, genetic testing. Biospecimens are a key for personalized medicine.

HB: Thanks for your time today, Yaffa, it has been really interesting.


About the author:

For additional information, please contact Yaffa Rubinstein at or on 301-402-4338.

How can pharma better support the rare disease patient community?