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A checklist for clinical trials in rare disease: obstacles and anticipatory actions-lessons learned from the FOR-DMD trial.

Crow, Rebecca A and Hart, Kimberly A and McDermott, Michael P and Tawil, Rabi and Martens, William B and Herr, Barbara E and McColl, Elaine and Wilkinson, Jennifer and Kirschner, Janbernd and King, Wendy M and Eagle, Michele and Brown, Mary W and Hirtz, Deborah and Lochmuller, Hanns and Straub, Volker and Ciafaloni, Emma and Shieh, Perry B and Spinty, Stefan and Childs, Anne-Marie and Manzur, Adnan Y and Morandi, Lucia and Butterfield, Russell J and Horrocks, Iain and Roper, Helen and Flanigan, Kevin M and Kuntz, Nancy L and Mah, Jean K and Morrison, Leslie and Darras, Basil T and von der Hagen, Maja and Schara, Ulrike and Wilichowski, Ekkehard and Mongini, Tiziana and McDonald, Craig M and Vita, Giuseppe and Barohn, Richard J and Finkel, Richard S and Wicklund, Matthew and McMillan, Hugh J and Hughes, Imelda and Pegoraro, Elena and Bryan Burnette, W and Howard, James F and Thangarajh, Mathula and Campbell, Craig and Griggs, Robert C and Bushby, Kate and Guglieri, Michela (2018) A checklist for clinical trials in rare disease: obstacles and anticipatory actions-lessons learned from the FOR-DMD trial. Trials, 19 (1). p. 291. ISSN 1745-6215. This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs

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Abstract

BACKGROUND

Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of these deliberations require time to be operationally in place. FOR-DMD (Finding the Optimum Steroid Regimen for Duchenne Muscular Dystrophy) is an academic-led clinical trial which aims to find the optimum steroid regimen for Duchenne muscular dystrophy, funded by the National Institutes of Health (NIH) for 5 years (July 2010 to June 2015), anticipating that all sites (40 across the USA, Canada, the UK, Germany and Italy) would be open to recruitment from July 2011. However, study start-up was significantly delayed and recruitment did not start until January 2013.

METHOD

The FOR-DMD study is used as an example to identify systematic problems in the set-up of international, multi-centre clinical trials. The full timeline of the FOR-DMD study, from funding approval to site activation, was collated and reviewed. Systematic issues were identified and grouped into (1) study set-up, e.g. drug procurement; (2) country set-up, e.g. competent authority applications; and (3) site set-up, e.g. contracts, to identify the main causes of delay and suggest areas where anticipatory action could overcome these obstacles in future studies.

RESULTS

Time from the first contact to site activation across countries ranged from 6 to 24 months. Reasons of delay were universal (sponsor agreement, drug procurement, budgetary constraints), country specific (complexity and diversity of regulatory processes, indemnity requirements) and site specific (contracting and approvals). The main identified obstacles included (1) issues related to drug supply, (2) NIH requirements regarding contracting with non-US sites, (3) differing regulatory requirements in the five participating countries, (4) lack of national harmonisation with contracting and the requirement to negotiate terms and contract individually with each site and (5) diversity of languages needed for study materials. Additionally, as with many academic-led studies, the FOR-DMD study did not have access to the infrastructure and expertise that a contracted research organisation could provide, organisations often employed in pharmaceutical-sponsored studies. This delay impacted recruitment, challenged the clinical relevance of the study outcomes and potentially delayed the delivery of the best treatment to patients.

CONCLUSION

Based on the FOR-DMD experience, and as an interim solution, we have devised a checklist of steps to not only anticipate and minimise delays in academic international trial initiation but also identify obstacles that will require a concerted effort on the part of many stakeholders to mitigate.

Item Type: Article
Additional Information: This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs
Subjects: WE Musculoskeletal. Orthopaedics
Divisions: Womens and Childrens > Paediatrics
Related URLs:
Depositing User: Mrs Semanti Chakraborty
Date Deposited: 12 Jun 2018 15:38
Last Modified: 12 Jun 2018 15:38
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1669

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