ClinicalTrials.gov is a publicly available registry and database for clinical trials. Publicly and privately supported studies that involve human subjects research are required to register on the site (and provide the design of the study) before patient enrollment begins and provide summary results no less than 12 months after the study ends.

As part of the registration process, users are asked to indicate if they will share individual participant data, explain what exactly will be shared, or explain why it won’t be shared. Users are also asked to provide a URL of where the data will be shared and include supporting information, such as the

• protocol
• statistical analysis plan
• informed consent form
• clinical study report
• analytic code

To enhance use of these data, the Clinical Trials Transformation Initiative created the Aggregate Analysis of ClinicalTrial.gov (AACT) database so that researchers could easily access and analyze these data.

In 2016, the U.S. Department of Health and Human Services clarified and codified Section 801 in a final rule governing the registration and data reporting for clinical trials with ClinicalTrials.gov. Recently, the National Library of Medicine has launched a multi-year initiative to modernize and enhance the user experience of this public resource, and a beta ClinicalTrials.gov website was released in late 2021 (Fine 2021). The new website will acknowledge the different users, including patients and caregivers, data providers, and data researchers:

“We aim to ensure that:

1. Clinical trial information is current, complete, and reliable.
2. All users can easily find and use information about clinical trials.
3. Clinical trial information, resources, and tools provide value to the research ecosystem.” — Rebecca Williams, PharmD, MPH, acting director of ClinicalTrials.gov at the National Library of Medicine, National Institutes of Health (Williams 2021).

The rule requires sponsors or principal investigators to register clinical trials and report key data about the trial design, study population, and outcomes.

The registry was developed to help ensure information about human subjects research is expediently added to the public knowledge base and to enable a full understanding of the effectiveness of interventions and therapies. The registry also provides a platform to document the frequency and severity of side effects, prevent duplicating studies, and help prospective researchers plan future studies. Because journals often reject papers with negative results, small studies, and trials stopped early, ClinicalTrials.gov is a critical dissemination strategy that fills in these gaps (Piller 2015a). However, this registry was created with a traditional explanatory trial in mind, and is not ideally suited to the reporting of pragmatic trials or implementation research. An improved structure for reporting ePCTs would be beneficial for this type of research.

Although reporting all results—including negative results—is critical to the scientific process, overall compliance with FDA requirements is poor (Anderson et al. 2015; Miller et al. 2015; Piller 2015b); about half of clinical trial results go unreported (Anderson et al. 2015), and most research institutions fail to report some of their trials (Piller 2015a). (For more, see this interactive map.) Although the government can levy a fine of up to $10,000 a day or suspend research funding for failure to report results, it has not penalized any institution (Piller 2015a). Reasons for low reporting include: lack of money set aside in budgets for reporting, time burden, lack of incentive, delay for the creation of a journal article, or pressure from sponsors.

Before an FDA law requiring investigators to publish summaries of trial results on ClinicalTrials.gov went into effect in December 2007, some participants in clinical research were unable to find the results of the research in which they participated, as this article in the Atlantic describes (Yasinski 2016). Although the majority of patients want to know the results of the clinical trial in which they participated (Shalowitz and Miller 2008), fewer than 10% of them actually receive this information (Getz et al. 2012). Patients may not know of the existence of ClinicalTrials.gov, and even if they do, the language is often written for audiences other than for patients, and consequently, the information provided may not be written in a clear, plain language that is understandable to average readers.