Background/Aims The registry clinicaltrials.gov was created to provide investigators and patients an accessible database of relevant clinical trials. Methods To understand the state of sickle cell disease (SCD) clinical trials, a comprehensive review of all 174 “closed”, “interventional” sickle cell trials registered at clinicaltrials.gov was completed January 2015. Results The majority of registered SCD clinical trials listed an academic center as the primary sponsor and were an early phase trial. The primary outcome for SCD trials focused on pain (23%), bone marrow transplant (13%), hydroxyurea (8%), iron overload (8%), and pulmonary hypertension (8%). Fifty two trials were listed as terminated or withdrawn including 25 (14% of all trials) terminated for failure to enroll participants. At the time of this review, only 19 trials uploaded results and 29 trials uploaded a manuscript in the clinicaltrials.gov database. A systematic review of pubmed.gov revealed that only 35% of sickle cell studies completed prior to 2014 resulted in an identified manuscript. In comparison, of 80 thalassemia trials registered in clinicaltrials.gov four acknowledged failure to enroll participants as a reason for trial termination or withdrawal and 48 trials (60%) completed prior to 2014 resulted in a currently identified manuscript. Conclusion Clinicaltrials.gov can be an important database for investigators and patients with sickle cell disease to understand the current available research trials. To enhance the validity of the website, investigators must update their trial results and upload trial manuscripts into the database. This study, for the first time, quantifies outcomes of SCD trials and provides support to the belief that barriers exist to successful completion, publication, and dissemination of sickle cell trial results.

Background Clinicaltrials.gov was created in 2000 to comply with the FDA Modernization Act of 1997 and since 2007, Federal law (Section 801 of the FDA Amendments Acts) mandates registration of all applicable, prospective clinical drug trials of health outcomes. ICMJE journals also require registration of all intervention trials prior to publication. Clinicaltrials.gov offers patients and clinicians a valuable tool to identify open sickle cell disease (SCD) clinical trials by disease and results of closed trials with links to manuscripts. Objective To conduct a systematic review of all completed interventional SCD trials registered at clinicaltrials.gov and identify enrollment rates and reporting of trial results. Methods We performed a search of “sickle” in www.clinicaltrials.gov to identify every registered SCD clinical trial. (Last update: August 5, 2013). Every “closed” “interventional” registered trial was recorded in a database to include: trial name, trial identifier, start/stop date, sponsor/collaborator, primary objectives, enrollment age, expected enrollment, type of trial, and manuscripts. For trials without a manuscript in the registry, we performed a Pubmed search by keywords from the trial title, intervention, and/or PI. All manuscripts identified were reviewed to confirm trial enrollment numbers. Results Three hundred and fifty three SCD trials were registered, of which 212 (60%) were closed or completed. We performed a systematic review of 147 “interventional”, closed trials. (1983-2012). The primary sponsor or collaborator listed for these trials included an academic center (n=72, 41 unique centers registered trials), industry or pharmaceutical company (n=47), and/or NIH (n=45). Ninety trials (61%) were registered as either phase I or II, 29 (20%) registered as phase III, 8 (5%) registered as phase 4, and 20 trials did not provide a phase. Fifty two percent of trials were randomized. For trials that listed inclusion criteria for age, 41% were pediatric trials, 50% were adult, and 9% were both pediatric and adult. The most frequent outcomes of interest for these trials were pain (22%), bone marrow transplant (12%), pulmonary hypertension (7.5%), and endothelial function/dysfunction (5.5%). The reporting of trial results and manuscripts to clinicaltrials.gov was low. Nineteen of 147 (13%) trials completed the “trial results” section in clinicaltrials.gov. Twenty six trials downloaded their primary manuscript to clinicaltrials.gov despite 51 trials having manuscripts published on Pubmed. Eighty seven closed clinical trials registered on clinicaltrials.gov have not reported their trial results to clinicaltrials.gov or published their manuscripts as searched in Pubmed. Barriers to successful enrollment in SCD trials were evident in this review. Thirty two (22%) trials updated their registry to reflect “study termination” or “withdrawal”. For the 27 trials that listed the reason for this early termination/withdrawal, 17 (63%) were closed for slow enrollment. Barriers to enrollment in phase III trials were identified as 45% of phase III trials enrolled < 60% of their expected participants. The reporting of phase III trials was also low as only 16 (55%) of the registered phase III trials results have published manuscripts. Conclusion Clinicaltrials.gov can be a valuable tool for clinicians to identify SCD clinical trials, but in practice is limited by investigator reporting of trial results. SCD clinical trials that are under-enrolled or not published place subjects at risk for participation in a trial without a scientific benefit to their disease community. Research should continue to focus on identifying and overcoming barriers to enrollment in clinical trials and publication of trial results. Disclosures: No relevant conflicts of interest to declare.