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Characteristics and data reporting of rare disease clinical trials: Getting better but still room for improvement

Nina K. Mair

Nina K. Mair, Jürgen Gottowik, Raul Rodriguez-Esteban, Timothy J. Seabrook

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It is estimated that there are more than 7,000 rare diseases (RDs) worldwide, impacting the lives of approximately 400 million people and only 5% have an approved therapy. Facing special challenges, including patient scarceness, incomplete knowledge of the natural history and only few specialized clinical sites, clinical trials (CT) are limited, making the data from trials critical for research and clinical care. Despite the introduction of the U.S. Food and Drug Administration Amendment Act (FDAAA) in 2007 requiring certain CTs to post results on the registry within 12 months following completion, compliance has been reportedly poor. Here, we describe general characteristics of RD CTs, identify trends, and evaluate result reporting practices under the FDAAA aiming to draw awareness to the problem of non-compliance.


CTs conducted between 2008 and 2015 were extracted from the public U.S. trial registry using the text mining software I2E (Linguamatics). Disease names were matched with rare disease names from the Orphanet Rare Disease Ontology (ORDO, v2.5, Orphanet). Statistical analyses and data visualization were performed using GraphPad Prism 7 and R (v3.5). The Student’s t-test was employed to calculate significance using p-value cut-offs of <0.05 or <0.001.


We analyzed 1,056 RD CTs of which 55.7% were phase 2, 7.7% phase 2/3 and 36.7% phase 3 trials. The studies were mostly one- and two-armed experimental CTs with the majority (60.2%) being funded by industry. Cystic fibrosis and sickle cell disease represented the most frequently investigated diseases (25.0% and 16.5%). Industry-led phase 2 RD CTs were significantly (p<0.0001) shorter than their equivalent led by academia/non-profit (22 vs. 33 months). Screening CTs completed before the end of 2015, we found that of the 725 analyzed studies, 55.2% predominantly phase 2 CTs, did not report results. Taking their potential applicability to the FDAAA into account, 25.2% industry-funded and 28.0% academia/non-profit-funded trials failed to disclose results on


RD CTs tend to be comparatively small, industry-funded studies focusing on genetic and neurologic conditions. Sponsor-related differences in study design, duration, and enrollment were observed. There are still substantial shortcomings when it comes to result publication.

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