A checklist for clinical trials in rare disease: obstacles and anticipatory actions—lessons learned from the FOR-DMD trial
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Crow, Rebecca A, et al. A Checklist for Clinical Trials In Rare Disease: Obstacles and Anticipatory Actions—lessons Learned From the For-dmd Trial. BioMed Central, 2018. https://doi.org/10.17615/g4yz-mf90APA
Crow, R., Hart, K., Mc Dermott, M., Tawil, R., Martens, W., Herr, B., Mc Coll, E., Wilkinson, J., Kirschner, J., King, W., Eagle, M., Brown, M., Hirtz, D., Lochmuller, H., Straub, V., Ciafaloni, E., Shieh, P., Spinty, S., Childs, A., Manzur, A., Morandi, L., Butterfield, R., Horrocks, I., Roper, H., Flanigan, K., Kuntz, N., Mah, J., Morrison, L., Darras, B., Von Der Hagen, M., Schara, U., Wilichowski, E., Mongini, T., Mc Donald, C., Vita, G., Barohn, R., Finkel, R., Wicklund, M., Mc Millan, H., Hughes, I., Pegoraro, E., Bryan Burnette, W., Howard, J., Thangarajh, M., Campbell, C., Griggs, R., Bushby, K., & Guglieri, M. (2018). A checklist for clinical trials in rare disease: obstacles and anticipatory actions—lessons learned from the FOR-DMD trial. BioMed Central. https://doi.org/10.17615/g4yz-mf90Chicago
Crow, Rebecca A, Kimberly A Hart, Michael P Mc Dermott, Rabi Tawil, William B Martens, Barbara E Herr, Elaine Mc Coll et al. 2018. A Checklist for Clinical Trials In Rare Disease: Obstacles and Anticipatory Actions—lessons Learned From the For-Dmd Trial. BioMed Central. https://doi.org/10.17615/g4yz-mf90- Creator
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Crow, Rebecca A
- Other Affiliation: John Walton Muscular Dystrophy Research Centre, Institute of GeneticMedicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK
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Hart, Kimberly A
- Other Affiliation: University of Rochester Medical Center, Rochester, NY, USA
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McDermott, Michael P
- Other Affiliation: University of Rochester Medical Center, Rochester, NY, USA
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Tawil, Rabi
- Other Affiliation: University of Rochester Medical Center, Rochester, NY, USA
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Martens, William B
- Other Affiliation: University of Rochester Medical Center, Rochester, NY, USA
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Herr, Barbara E
- Other Affiliation: University of Rochester Medical Center, Rochester, NY, USA
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McColl, Elaine
- Other Affiliation: NewcastleUniversity, Newcastle upon Tyne, UK
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Wilkinson, Jennifer
- Other Affiliation: NewcastleUniversity, Newcastle upon Tyne, UK
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Kirschner, Janbernd
- Other Affiliation: University Medical Center, Freiburg,Germany
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King, Wendy M
- Other Affiliation: University of Rochester Medical Center, Rochester, NY, USA
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Eagle, Michele
- Other Affiliation: John Walton Muscular Dystrophy Research Centre, Institute of GeneticMedicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK
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Brown, Mary W
- Other Affiliation: University of Rochester Medical Center, Rochester, NY, USA
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Hirtz, Deborah
- Other Affiliation: National Institutes of Health, Bethesda, MD, USA
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Lochmuller, Hanns
- Other Affiliation: John Walton Muscular Dystrophy Research Centre, Institute of GeneticMedicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK
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Straub, Volker
- Other Affiliation: John Walton Muscular Dystrophy Research Centre, Institute of GeneticMedicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK
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Ciafaloni, Emma
- Other Affiliation: University of Rochester Medical Center, Rochester, NY, USA
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Shieh, Perry B
- Other Affiliation: UCLA, LosAngeles, CA, USA
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Spinty, Stefan
- Other Affiliation: Alder Hey Children’s Hospital, Liverpool, UK
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Childs, Anne-Marie
- Other Affiliation: LeedsTeaching Hospitals, Leeds, UK
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Manzur, Adnan Y
- Other Affiliation: GOSH, UCL, London, UK
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Morandi, Lucia
- Other Affiliation: NeurologicalInstitute “Carlo Besta”, Milan, Italy
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Butterfield, Russell J
- Other Affiliation: University of Utah, Salt Lake City, UT,USA
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Horrocks, Iain
- Other Affiliation: Greater Glasgow and Clyde NHS Yorkhill Hospital, Glasgow, UK
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Roper, Helen
- Other Affiliation: Birmingham Heartlands Hospital, Birmingham, UK
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Flanigan, Kevin M
- Other Affiliation: Nationwide Children’sHospital, Columbus, OH, USA
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Kuntz, Nancy L
- Other Affiliation: Ann and Robert H. Lurie Children’s Hospital,Chicago, IL, USA
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Mah, Jean K
- Other Affiliation: University of Calgary, Calgary, Canada
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Morrison, Leslie
- Other Affiliation: University of NewMexico, Albuquerque, NM, USA
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Darras, Basil T
- Other Affiliation: Boston Children’s Hospital, Boston, MA,USA
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von der Hagen, Maja
- Other Affiliation: Children’s Hospital, Technical University Dresden, Dresden, Germany
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Schara, Ulrike
- Other Affiliation: University of Essen, Essen, Germany
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Wilichowski, Ekkehard
- Other Affiliation: Children’s University Hospital,Göttingen, Göttingen, Germany
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Mongini, Tiziana
- Other Affiliation: University of Torino, Turin, Italy
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McDonald, Craig M
- Other Affiliation: UC DavisMedical Center, Sacramento, CA, USA
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Vita, Giuseppe
- Other Affiliation: University of Messina AOU PoliclinicoGaetano Martino, Messina, Italy
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Barohn, Richard J
- Other Affiliation: University of Kansas Medical Center, KansasCity, KS, USA
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Finkel, Richard S
- Other Affiliation: Nemours Children’s Hospital, Orlando, FL, USA
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Wicklund, Matthew
- Other Affiliation: Penn StateCollege of Medicine, Hershey, PA, USA
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McMillan, Hugh J
- Other Affiliation: Children’s Hospital of EasternOntario, Ottawa, Canada
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Hughes, Imelda
- Other Affiliation: Royal Manchester Children’s Hospital, Manchester,UK
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Pegoraro, Elena
- Other Affiliation: University of Padova, Padua, Italy
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Bryan Burnette, W.
- Other Affiliation: Vanderbilt Children’s Hospital,Nashville, TN, USA
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Howard, James F
- Affiliation: School of Medicine
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Thangarajh, Mathula
- Other Affiliation: Children’s National Medical Center, Washington, DC, USA
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Campbell, Craig
- Other Affiliation: Children’s Hospital London Health Sciences Centre, London, Canada
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Griggs, Robert C
- Other Affiliation: University of Rochester Medical Center, Rochester, NY, USA
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Bushby, Kate
- Other Affiliation: John Walton Muscular Dystrophy Research Centre, Institute of GeneticMedicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK
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Guglieri, Michela
- Other Affiliation: John Walton Muscular Dystrophy Research Centre, Institute of GeneticMedicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK
- Abstract
- 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.
- Date of publication
- May 10, 2018
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- The Author(s).
- Language
- English
- Bibliographic citation
- Trials. 2018 May 10;19(1):291
- Publisher
- BioMed Central
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