There are myriad challenges to conducting clinical research which are exponentially greater in the rare disease space. Part 2 of this article brief series explores additional obstacles, proposed solutions and outcomes.

“The main problem is that there are fewer patients with rare diseases, so you have to go outside of the established trial site network to meet the required subject numbers,” explained Elvin Thalund, Director, Industry Strategy, Oracle Health Sciences.

Multi-country studies introduce another level of complexity to an already complicated process. It is more expensive than a domestically located study. There are barriers with language, global time difference and issues of regulatory compliance. While there are approximately 50,000 research sites worldwide, there is often a lack of staff, study coordinators and other trained technicians, space to conduct trials and an understanding of how to navigate affiliated paperwork. Additionally, funding is limited in the rare disease space. Scaled back financial resources makes it difficult to engage CROs with the necessary background and expertise. As a result, trials must be managed centrally with limited, local, high-level professional guidance. 

The funding that is available through the United States government comes with regulatory guidelines that are stringent and specific. Overseas sites, while under the purview of another nation’s laws, are subject to these requirements, as well, which include:

  • US specific, GCP (Good Clinical Practice) training that is only offered in English
  • Obtaining a FWA (Federal Wide Assurance) number to ensure compliance with the federal regulations for protecting the welfare and rights of human subjects
  • Acquiring a DUNS (Data Universal Numbering System) number which enables the tracking of all organizations doing business with or funded by the United States government
  • Having a SAM (System Award Management) code which combines the federal procurement system with a central contracting agency

Other challenges faced with the conduct of clinical trials internationally include patient insurance and indemnification, contracting and legal requirements, delays driven by the delivery of expired medication and changing cost due to fluctuating exchange rates. There are, however, solutions to these pressuring hindrances.

 Ways to address the challenges of rare disease conduct internationally include:

  • Using analytics to identify optimal study countries, sites and protocols
  • Inventorying all steps to include in the site activation process to understand the extent to which government funding will assist with the given budget
  • Sharing resources across all rare disease areas with other organizations to address the lack of a local CRO
  • Focusing on how to attract the most patients within the least harmonized regulatory regions
  • Evaluating the available patient population versus the regulatory complexity and number of languages and translations required

“You want to minimize the number of study amendments. The more submissions you end up doing in other countries, or if you try to go to institutions in the US who have their own local IRB (Institutional Review Board), you’ll have more reviews of your study. Even if changes to the study are few, you’ll end up with amendments that require study submissions across all authorities. Find sites with the fewest competent authority reviews,” Elvin advised.

In the United States, the NIH (National Institute of Health) and the Department of Health and Human Services Common Rule states that in the United States, performance sites must use a sIRB (single Institutional Review Board). The effective date per the NIH is January 25, 2018 and the DHHS effective date is January 20, 2020. A single IRB review means less review and less overhead in changing studies.  A similar regulation is going into effect in Europe with a planned implementation date of sometime in 2020.

Another challenge is identifying research sites with optimal country locations and patient pools for a given study. One way to avoid issues of time delays and language barriers is to build a centralized, deidentified registry pool of patients which has accurate and timely code indications.

Global legal and contractual harmonization of data can drive the costs down for rare disease study start-up and clinical research trial management.  The use of analytics and strategic coordination of resources can provide further context and validate what Sponsors and CROs are hearing from sites. While there is no one-size-fits-all approach, it’s abundantly evident that technology drives rare disease research.

When you need direct access to physicians and their known patients or research practice management solutions to accelerate your clinical trials, there’s Only Elligo.

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