ccess to reliable, complete, accurate information on clinical trial results will inform the best treatment options for patients and instill greater trust between patients, healthcare providers, clinical research professionals, and the public.

Until relatively recently, information about clinical trial results was not provided in language that is clear, accessible, and easy to understand (plain language) to most patients. Instead, information was only available in scientific and technical language (e.g., peer-reviewed medical journals, professional society presentations and proceedings, and scientific and research-oriented websites).

During the past two decades, research indicates that clinical research sponsors—in the private sector and to a lesser extent in the public sector—have been slowly improving transparency and access to technical clinical trial results summaries. According to a 2018 study, for example, more than two-thirds of industry-funded clinical trials have included technical results on the EU Clinical Trials Register.

Although the proportion of clinical research sponsors providing plain language trial results summaries is substantially lower than the above (estimated at less than 20 percent in 2019), this proportion has been expected to rise largely in response to the EU Clinical Trials Regulation 536/2014 which went into effect in January 2022. This regulation requires research sponsors to publish a plain language results summary on the Clinical Trials Information System (CTIS) of any clinical trial conducted in an EU member state within a specified timeframe. Although the US FDA has yet to issue a similar regulation, many drug development sponsors must comply with EU CTR 536/2014 because the majority of phase 2 and 3 clinical trials are conducted in global locations that include EU member states. Many research sponsors are also publishing their clinical trial results summaries on ClinicalTrials.gov as well as private websites.

Rising compliance with the EU regulation is a hollow achievement if the clinical trial results listings themselves cannot be accessed or if they lack the information essential to informing treatment decisions and the assessment of treatment risks and benefits. A 2020 study found that plain language clinical trial results listings on the EudraCT system could not be easily accessed. The listings could not be found using a commercially available and widely adopted search engine (e.g., Google) unless the unique sponsor company identifier or a specific EudraCT number was included in the search term.

In another 2022 study, the Center for Information and Study on Clinical Research Participation (CISCRP) conducted an initial qualitative assessment of clinical trial results listed on ClinicalTrials.gov and found wide inconsistencies in the presentation of the information, and more importantly, critical information missing. Specifically, the clinical trial results listings typically did not provide reference to whether the study endpoints were met, nor did they provide information on any adverse reactions (only adverse events, even though adverse reactions are required under the EU CTR 536/2014) to the investigational drug.

In late 2022 and into 2023, CISCRP conducted a follow-up study to gather more quantitative information on the substance of clinical trial results summaries on ClinicalTrials.gov. The primary aim of this follow-up study was to evaluate and inform the communication of clinical trial results summaries to promote higher levels of utility and value consistent with the intent of both the regulation and ethical obligations.

Methods

To obtain the listings to be sampled, CISCRP filtered all listings on ClinicalTrials.gov to only include completed trials with results posted and then downloaded the top 10,000 (the maximum number allowed without downloading all results meeting this criteria). Using the Excel randomization formula, 50 listings were randomly selected. CISCRP staff manually evaluated each of these listings using the framework introduced in the 2022 study to ensure that the summary results communicated basic yet essential and valuable (i.e., useful and meaningful) information for patients, their families, and care providers. This included:

• Study title and identification.
• Background on why the clinical research is needed (i.e., medical condition, how the study drug works, objectives of the clinical trial).
• Inclusion and exclusion criteria.
• Description of the study design and participant subgroups.
• Results of the clinical trial (i.e., primary and secondary endpoints, adverse events and reactions to the study drug).
• Information directing patients to places and resources where they can learn more about the clinical trial and its findings.

Based on their extensive experience reading, writing, and user-testing plain language clinical trial results, the CISCRP team assessed whether the trial results qualified as plain language communications: the information was compiled and displayed at an 11- to 13-year-old reading level, with defined technical terms, and in a format and design that was easy to read.

Results

Every one of the 50 clinical trial results evaluated provided basic background information about the study, though rarely in plain language (Table 1). Study title, location, point of contact, and medical condition were present in all evaluated trial results summaries. Less than two-thirds (60 percent) of the results provided an explanation of how the study drug might treat the medical condition, and in all cases the explanation provided was in technical language.

Table 1: Background and Additional Information

Table 1: Background and Additional Information

The information specific to the clinical trial protocol and its results was poor, and virtually no plain language was provided. Although all the evaluated clinical trials provided at least a partial description of the study design, only 16 percent discussed whether the primary endpoint had been met and only 13 percent discussed whether key secondary endpoints had been met. In no instance were these study outcomes presented in plain language (refer to Table 2).

Table 2: Protocol Descriptions and Discussion of Trial Results

Table 2: Protocol Descriptions and Discussion of Trial Results

Six out of 10 evaluated clinical trial results presented discussion of adverse and serious adverse events observed. In no instance, however, was this discussion presented in plain language. None of the trial results provided information about adverse reactions to the study drug.

Discussion

Study results suggest that patients, their care community, and the public do not have access to useful and valuable clinical trial results information on ClinicalTrials.gov at this time. Although compliance with the EU CTR regulation is encouraging global research sponsors to provide publicly accessible clinical trial results summaries, our evaluation found that the summaries largely lacked essential information—and little of the limited information provided was presented in plain language.

In particular, although the clinical trial results provided general background information, only a small percentage provided discussion about whether primary and secondary endpoints had been met, and none of the results summaries discussed adverse reactions to the investigational treatment. These findings are consistent with those observed in the 2022 study and suggest that ClinicalTrials.gov is not being used as intended by professional or patient audiences.

Given high and rising public and patient demand for greater transparency and disclosure, it is critical that research sponsors take steps to address shortcomings in their published trial results summaries. Ensuring that the most basic and essential information is provided in plain simple language is a good place to start. Specifically, results summaries would provide patients as well as professionals far more value and relevance if they included discussion about whether primary and key secondary outcomes were met and whether adverse reactions to the investigational treatment were observed.

Of note, ClinicalTrials.gov has made recent updates to improve the user experience, visual layout, and navigability of trial listings. However, much of the information posted is still not written in accessible language.

To shorten timelines and reduce cost, some sponsors are considering automating the preparation of clinical trial results summaries including the use of artificial intelligence/machine learning. At this time, given the poor and incomplete state of trial results summary content, moving hastily in this direction would seem to be a mistake. In addition to advising companies on best plain language trial results summary practices, CISCRP is forming a working group to develop responsible automation and AI usage guidelines.

The CISCRP team intends to continue to monitor the quality and utility of trial results summaries on ClinicalTrials.gov. Future research will also look at summaries published on the EU’s Clinical Trials Information System to evaluate compliance as well as quality, utility, and value.

There is much room for improvement and a clear opportunity for research sponsors to support higher levels of patient engagement by providing essential and useful clinical trial results summary information in plain, easy-to-understand language.

Funding Statement

The authors received no grant or financial support for this research and manuscript development.

Conflict of Interest Disclosure

At the time of writing this paper, the authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed. This includes employment, consultations, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.