Our study demonstrates that the potential of ClinicalTrials.gov registry to address selective publication and better inform the public and professionals about the results from completed clinical trials is limited because critical information from trial registration, such as study contact, trial end date, and primary outcome, were not consistently reported. Moreover, publication rates among completed trials registered within ClinicalTrials.gov were low, even among trials with at least 4 y documented since study completion. Low publication rates were widespread among differing trial sponsors, conditions studied, study types, and locations. However, we also found significantly different publication rates among study types and primary sponsors, consistent with prior research 
. Even when trials were found to be published, for the majority the citation was not available within ClinicalTrials.gov, which would have made it easy for the public and professionals to access results.
We expected that the trials we examined were likely to have been published in that they were recently completed after being registered at ClinicalTrials.gov within the past decade, ensuring that thet trial was in compliance with ICMJE requirements if the results were publishable. However, the recent nature of our sample is a possible explanation for our finding low rates of trial publication. Although we allowed at least 2 y after the study ended for publication, consistent with FDAAA legislation, rates were higher among those that ended longer ago. Nevertheless, publication rates reached only 60% among trials documented as having ended prior to 2004, an allowance of at least 4 y for trial publication. Importantly, all the trials included in our study had their registration updated to notify ClinicalTrials.gov that the trial had been completed.
Many studies have attempted to evaluate the extent of selective publication in the biomedical literature and found similarly low rates of publication 
, although none have used, to our knowledge, as large and as broadly representative a registry as ClinicalTrials.gov, particularly with regards to condition studied and study location, with the exception of two recent studies focused on the publication of trials submitted to the FDA 
. Other evidence concerning selective publication is anecdotal, such as the absence of 6 mo of trial data from a key publication describing the efficacy of celecoxib 
, the delay of publication for two early trials of rofecoxib until after the medication was withdrawn from the market 
, and the aforementioned studies of rosiglitazone 
, erythropoiesis-stimulating agents 
, and antidepressants 
However, as described, low publications rates were not limited to specific trial sponsors, suggesting that selective publication is an issue among trials sponsored by both industry and government and reinforcing the importance of registries like ClinicalTrials.gov for addressing this problem. Selective publication may occur for several reasons, although our study was not designed to evaluate its causes. If trial results put either investigators or the study's sponsor at financial risk, they may be delayed or suppressed 
. In addition, if trial results contradict investigators' beliefs, providing unexpected support (or lack of support) for a particular clinical practice, they may not be submitted for publication 
. This may be exacerbated by investigator reluctance to publish negative results given the need to highlight “positive, promising” findings for grant applications. Finally, researchers, reviewers, and editors have historically been more enthusiastic about positive or equivalence trials and less excited about negative trials 
; accordingly, these latter trials are submitted and accepted for publication less often 
. Suggestive of this, 70% of published manuscripts in our study from intervention-placebo or intervention-active trials were reported as positive, although we are unable to determine what proportion of the unpublished trials found positive results.
Although the FDAAA now requires reporting of trial results within 1 to 2 y after study completion within ClinicalTrials.gov, selective publication may not be fully remedied. The quality of the information provided for some data elements within ClinicalTrials.gov varied widely. It is not clear whether or how often the accuracy of the data is verified by the NLM, although those responsible for the conduct of the clinical trial are principally accountable for its quality and accuracy. Even though nearly all trials reported mandatory data elements, many entries were of poor quality and provided limited information, particularly the principal investigator/study contact. Reporting of optional data elements ranged widely and, similar to the mandatory data elements, many were of poor quality and provided limited information. As had been shown in prior research 
, only 66% of trials reported their primary outcome measure, and outcomes were often vague and poorly specific among those that did, making it difficult or impossible to detect outcome reporting bias. Given the documented presence of outcome reporting bias among trials studied in other settings 
, the potential impact of ClinicalTrials.gov on outcome reporting bias deserves further research. Just as significant progress has been made with regards to improved reporting of the study intervention (i.e., drug name) within ClinicalTrials.gov 
, progress can be made by mandating the registration of all information that is necessary for the public and profession to access and interpret trial results, including primary and secondary outcomes, study location, and enrollment, with clear field requirements to prevent vague reporting and improve data quality. Furthermore, we propose that either the NLM or another specified agency be given sufficient power of enforcement, including the capacity to assess fines or other penalties to sponsors or investigators who are not compliant with requirements.
One limitation of our study was that nearly half of the 10% subsample of trials among which we determined publication status did not report a trial end date, and those that did not were published at the lowest rates, preventing an assurance that all trials were allowed at least 2 y after study completion for trial publication. In addition, although all the trials included in our study had their registries updated to notify ClinicalTrials.gov that the trial had been completed, the date on which this specific notification was made was not available. This low rate of reporting of an optional data element (“study end date”) in itself suggests that reporting of information needed to comprehensively assess trial progress and completion must be required and verified. In addition, we cannot be certain of the relationship between not reporting trial end date and publication. Not reporting an end date may indicate that study officials had determined that the trial would not be submitted for publication and thus made minimal efforts to fully update the trial's registration within ClinicalTrials.gov, such as by providing the actual trial end date, outside of providing notification that the trial had been completed. Similarly, the low response rate among investigators surveyed about completed yet unpublished registered trials may indicate that the trials were not published and investigators were instead focused on current study efforts. Nevertheless, rates of publication were low among both trials that did and did not report end dates.
There are other limitations to our study. Relevant publications may not have been identified in our review, partly because we limited our study to MEDLINE and did not search other databases, such as EMBASE or research conference proceedings (abstracts). However, EMBASE is not publicly accessible, requiring a subscription for access. Moreover, research abstracts are often preliminary and rarely provide all relevant efficacy and safety findings. Our search for publications was extensive, involving two independent investigators using a systematic method to query MEDLINE. If we were unable to identify a trial publication, it is unlikely that others using PubMed to find results from a trial from ClinicalTrials.gov would be able to consistently do so. In addition, some studies may have been made publicly available elsewhere. In response to criticism about selective publication, several pharmaceutical companies and their US trade association (Pharmaceutical Research and Manufacturers of America) have established registries to report results of their clinical trials 
. Although a useful step, these registries do not adequately address the issue of selective publication since the results are not subject to peer review and provide no assurance of complete reporting of efficacy and safety. Secondly, our sample size may have been too small for our analyses to have sufficient power to identify true differences in publication rates between trial subcategories, such as sponsorship or study purpose. Finally, many changes may have already been or will be made to ClinicalTrials.gov in response to addressing the new requirements enacted as part of the FDAAA. However, an important purpose of our study was to inform these efforts and future work will need to examine whether changes made the registry more effective.
The scientific community should be prioritizing the timely and accurate publication and dissemination of clinical trial results, regardless of the strength and direction of trial results. Current, up-to-date evidence is critical for clinicians, researchers, and patients, and late publication can impair and undermine evidence-based clinical practice almost as effectively as nonpublication. In addition, investigators have an obligation to ensure that the efforts of patients who volunteer as trial subjects are shared to advance science. Publication rates among completed trials registered within ClinicalTrials.gov were low, even among trials with at least 4 y since the study had ended. Critically, even among published trials, few reported the citation within ClinicalTrials.gov, a small but necessary step that should be required in order to make it easy for the public and the profession to have access to the trial results. The FDA needs a coordinated strategy for oversight and enforcement of the new requirements of the FDAAA, along with a commitment from industry, government, and all other trial sponsors, as well as the scientific community, to minimize selective publication of trials and ensure timely public and professional access to trial results.