07 Mar Many But Not All Results of Clinical Trials on Rare Diseases Reported

MedicalResearch.com Interview with:

Dr. Agnes Dechartres

Dr. Agnes Dechartres MD, PhD
Centre de Recherche Epidémiologie et Statistique
Paris, France

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Dechartres: In general, the availability of trial results is not optimal, with about half of the results from clinical trials, especially those with negative results, not being published in journals. To improve the availability of results, the FDA Amendment Act (FDAAA) requires results to be posted at ClinicalTrials.gov for all trials evaluating FDA-approved drugs, devices, or biologics within one year of trial completion. However, some previous methodological studies showed poor compliance with this law^1-3.

Rare diseases are defined by a prevalence of fewer than 200,000 people, but overall, they may affect up to 25 million people in North America. The limited number of patients affected by each rare disease makes this research particularly challenging, and the access to information on all trials conducted and their results is even more necessary.

In this study, we aimed to describe the characteristics of completed phase 3 or 4 trials of rare diseases registered at ClinicalTrials.gov and assess whether their results were publicly available.

We found a substantial proportion of single-group trials and trials not randomized. Many trials were also conducted in a single-center.

Concerning the availability of results, 36 months after trial completion, results were posted at ClinicalTrials.gov for 35% of trials, published in journals for 47%, and publicly available (ie, posted at ClinicalTrials.gov or published in journals) for 63%.

Among the trials likely subject to the FDAAA, 68% had results posted at ClinicalTrials.gov: 4% had results posted at 12 months and 57% at 36 months. We also found that 21% of studies not concerned by the FDAAA had results posted.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Dechartres: The methods of trials on rare diseases are not always optimal, which can compromise the validity of their results.

Many trials are performed in a single center, but there is need for more collaborative research.

Concerning the availability of results, results are rather encouraging, because compliance with the FDAAA seems to be higher than in other areas^1-3. Also, many trials not concerned by the FDAAA have results posted, which suggests that some researchers are willing to share results for the purposes of transparency and not just because it is mandatory.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Dechartres: Although research on rare diseases is challenging because of the limited number of patients, treatments must be evaluated rigorously. Some innovative methods have been developed to overcome the methodological challenges inherent to the assessment of rare diseases and should be promoted^{4 5}.

The development of collaborative projects and the dissemination of information among patients and health care professionals could help accelerate research on rare diseases_ENREF_27. A major advance could come from the development of online communities of patients allowing for connections between patients, researchers and health care professionals. A relevant example is Reg4all, a cross-disease health registry platform where people can share the information they specify with the researchers and research organizations they choose⁶. Such platforms could also be helpful to conduct efficacy trials in real-life conditions⁷ and to monitor adverse events.

Finally, concerning the availability of results, although our results are encouraging, there is a need to do more. The compliance with the mandatory posting of results could be improved by a better knowledge of the legislation and the applicable trials. Also, deadline reminders sent by email may help improve posting of results⁸.

Data sharing of individual patient data should also be promoted because these data can contribute to the testing of other hypotheses and performing individual patient-data meta-analyses. The ORDR, NCATS, and NIH have launched a pilot project to establish a data repository of de-identified patient data, aggregated in a standardized manner by using common data elements and standardized terminology, to be available to all investigators for analyses across many rare diseases and for facilitating various biomedical studies including clinical trials⁹.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Additional references

1. Anderson ML, Chiswell K, Peterson ED, Tasneem A, Topping J, Califf RM. Compliance with results reporting at ClinicalTrials.gov. N Engl J Med. Mar 12 2015;372(11):1031-1039.
2. Nguyen TA, Dechartres A, Belgherbi S, Ravaud P. Public availability of results of trials assessing cancer drugs in the United States. J Clin Oncol. Aug 20 2013;31(24):2998-3003.
3. Prayle AP, Hurley MN, Smyth AR. Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study. BMJ. 2012;344:d7373.
4. Tudur Smith C, Williamson PR, Beresford MW. Methodology of clinical trials for rare diseases. Best Pract Res Clin Rheumatol. Apr 2014;28(2):247-262.
5. Gagne JJ, Thompson L, O’Keefe K, Kesselheim AS. Innovative research methods for studying treatments for rare diseases: methodological review. BMJ. 2014;349:g6802.
6. So D, Joly Y, Knoppers BM. Clinical trial transparency and orphan drug development: recent trends in data sharing by the pharmaceutical industry. Public Health Genomics. 2013;16(6):322-335.
7. Wicks P, Vaughan TE, Massagli MP, Heywood J. Accelerated clinical discovery using self-reported patient data collected online and a patient-matching algorithm. Nat Biotechnol. May 2011;29(5):411-414.
8. Maruani A, Boutron I, Baron G, Ravaud P. Impact of sending email reminders of the legal requirement for posting results on ClinicalTrials.gov: cohort embedded pragmatic randomized controlled trial. BMJ. 2014;349:g5579.
9. Groft SC. Rare diseases research: expanding collaborative translational research opportunities. Chest. Jul 2013;144(1):16-23.Citation:

Dechartres A, Riveros C, Harroch M, Faber T, Ravaud P. Characteristics and Public Availability of Results of Clinical Trials on Rare Diseases Registered at Clinicaltrials.gov. JAMA Intern Med.Published online March 07, 2016. doi:10.1001/jamainternmed.2016.0137.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Dr. Agnes Dechartres (2016). Many But Not All Results of Clinical Trials on Rare Diseases Reported MedicalResearch.com

Last Updated on March 7, 2016 by Marie Benz MD FAAD