Clinical trials require a unique approach to public dissemination. Because clinical trials often involve the collection of sensitive information, sharing clinical trial data should always be conducted through formal and secured media. However, because access to certain key information from these trials is in the public interest, a reasonable level of transparency is not only expected but is legally required.
Since 1997, Sponsors of clinical trials conducted in the US have been required to register clinical trials (with some exemptions) with the FDA. Sponsors can refer to this checklist to determine whether their trial is an “applicable clinical trial” requiring registration. This requirement, including the eventual creation of ClinicalTrials.gov in 2000, was a meaningful first step towards advancing clinical trial transparency. Through ClinicalTrials.gov, key facts about registered trials, including study design, administrative information, and results summaries (for completed trials), are now readily available to researchers, medical professionals, potential trial participants, and the public at large.
In general, Sponsors typically embrace and comply with trial registration requirements. However, when it comes to publishing trial results, many Sponsors have been slow to adopt the same level of adherence. There may be several reasons for this. One of the greatest reasons is likely simple economics (e.g., protecting key data from competition, allocation of limited resources, and needing to protect the ability to secure additional funding). In this context, there can be significant hesitation about publicly disclosing clinical study results at all and a temptation to limit any data that are shared to “positive” results only.
Viewed solely through an economic lens, these practices may appear reasonable and even desirable. However, there remains an undeniable ethical argument for transparency. Aren’t all clinical trial results—positive, negative, or neutral—worth sharing to promote understanding of a drug candidate or disease? All clinical trial results should be shared in order to strengthen pharmaceutical advancement and optimize utilization of clinical trial participants and other critical and often limited resources.
When it comes to the question of clinical trial transparency, it is clear that effective, timely, and transparent disclosure of clinical trial results benefits everyone. Given that appropriate protections are in place to preserve intellectual property and reward innovation.
Benefits of Public Disclosure of Clinical Trial Results
Each group of key stakeholders benefits differently from the timely public disclosure of clinical trial data. Some of the key stakeholders impacted by clinical trial transparency include:
- Patients (whether or not they go on to participate in a clinical trial)
- Clinical trial participants
Patients with serious conditions or diseases can review the results of past trials, and then can research and register for trials investigating potentially lifesaving therapies. The ability to access this vital information can allow these patients to be more informed about current treatment options (even if they are still investigational) and can allow them to communicate more effectively with their doctors. This can further empower patients and/or their caregivers to be advocates for their own health.
Clinicians can stay abreast of the state of ongoing clinical research in their field, which may help them provide informed advice to their patients. This includes whether clinical trial participation may be appropriate for a given patient and, if so, what the potential risks and benefits of participating in a trial might be, what alternative therapies are available, and so forth. Furthermore, when clinicians are better informed, they can participate more productively in dialogue with the research community to better align medical and research goals. These clinician-researcher interactions can result in meaningful contributions to improving healthcare overall.
Researchers can design and conduct studies more efficiently when they are presented an unbiased picture of past trial designs and results. This saves time, money, and other resources and reduces the possibility of running redundant or ineffective trials. Furthermore, with an increased focus on systematic literature reviews and machine learning technologies, having all clinical trial results presented in a standard format within the same database could prove especially valuable for next generation in silico analyses.
Clinical Trial Participants
Clinical trial participants can gain a better understanding of the trial in which they are participating and the context in which it is being conducted. Once the trial is completed, the participant can review study results and compare them to those from other studies, which may help inform their own future healthcare decisions. It may also provide them satisfaction that their personal contributions extend beyond that single trial toward the larger goal of advancing medical research.
Regulatory Policies for Clinical Trial Transparency
Both the World Health Organization (WHO) and the World Medical Association (WMA) have issued strict expectations for the public disclosure of clinical trial results. WHO advises that summary methods and results of all interventional trials involving humans (including Phase I through Phase IV drug trials) should be posted on a free, public website within 12 months of study completion (Goldacre et al., 2017). In this context, “study completion” is defined as the final data collection date for the primary outcome measure. The WMA etched similar language into the Declaration of Helsinki—an important medical ethics code borne out of the atrocious human experiments conducted during World War II—making it only the seventh revision to the document since its adoption in 1964.
Mirroring these proposals, the Food and Drug Administration Amendments Act (FDAAA) of 2007 also pushed for the publication of summary results, protocols, and statistical analysis plans on the ClinicalTrials.gov website within 12 months of trial conclusion (as defined under 42 CFR 11.10(a)), with certain exceptions. Nearly all Phase I trials are excluded, and Sponsors can request a deadline extension if data analysis is ongoing after one year or for other qualified extenuating circumstances. More than 10 years after FDA proposed these changes, the Final Rule mandated that results from all applicable U.S. clinical trials be made public from January 2018 and onward.
The European Medicines Agency (EMA) enacted similar rules in 2014. The EMA requires protocol information and results from clinical trials, including Phase I trials, to be submitted to the publicly accessible EU Clinical Trials Registry within one year of study completion (EMA Statement).
Issues with Compliance
Coinciding with the new rule, FDA indicated that violators would face a penalty of up to $12,000 per day after the one-year submission deadline passed until trial results were submitted to ClinicalTrials.gov. There is no evidence that the Agency has imposed these fines, and compliance with these regulatory policies has been mixed (DeVito et al., 2020).
Government and academic Sponsors seem to be out of compliance most frequently. Just 33.8% of non-industry-sponsored studies are fully compliant at 12 months after trial conclusion (TCTMD). Industry Sponsors tend to do a better job overall. Some industry Sponsors even have an impressive track record of submitting close to 100% of non-exempted study results on time (ScienceMag.org).
There is some indication that larger companies are more compliant because they have more resources to devote to timely reporting. Whereas government entities, academic Sponsors, and smaller companies often lack these resources. Hesitancy to report negative results may also play a role in delays and noncompliance, especially for smaller Sponsors.
How to Access More Detailed Clinical Trial Data
The ClinicalTrials.gov results reporting system can be a useful resource for drug developers, especially those exploring the 505(b)(2) pathway. If this ends up being the right path for your product, some of your initial research into past trials can begin with these publicly disclosed results. However, if there is a potential weakness in the current system, it is that public data tend to lack the depth necessary to be useful for researchers beyond the initial “idea” phase.
For additional insight, researchers might consider consulting clinical study reports (CSRs), which provide greater detail than the summary results presented on ClinicalTrials.gov. One glaring issue with this strategy, however, is that CSRs are not available for many clinical trials. Regulatory authorities have been seeking ways to remedy this. While some regulatory authorities, like the FDA, have tested the idea of publicly disclosing redacted CSRs for approved products in their Clinical Data Summary Pilot Program, others, such as the EMA, already include CSR release as part of their standard approval process.
While CSRs might provide enough information to support your research, individual patient data (IPD) remains the most complete source of results from any given clinical trial. Accessing IPD can be even more difficult than accessing redacted CSRs because of the need for controlled access to these potentially sensitive data—but this does not mean that these data are inaccessible. On the contrary, there are ways of obtaining this information, but doing so requires careful planning.
If you decide to pursue clinical trial information in this way, you will need to generate a comprehensive proposal that includes details about your research and about how you will use any data from these studies. Once you have fully considered your plan for the data, you can provide your proposal and request access via the Sponsor’s preferred portal. Two examples of external portals are the Yale University Open Data Access (YODA) System and ClinicalStudyDataRequest.com (CSDR). Either the Sponsor will directly evaluate your request or a third-party decision-making panel (approved by the Sponsor) will determine the fate of your request. Access might be denied for any number of reasons including:
- Patient privacy concerns
- Case narratives
- Practical constraints to providing access
- Conflicts of interest
- Out-licensing agreements
If granted access, you will likely need to handle IPD in a controlled sandbox environment to prevent privacy breaches. Furthermore, data must only be used for explicitly agreed-upon purposes. Once you have used the data for its intended purpose, the Sponsor will expect you to publish the results of your efforts.
While many larger pharmaceutical companies have committed, through online policy statements, to sharing detailed clinical trial data, remember that the ultimate responsibility is on the requesting party to construct a strong research proposal and utilize the proper channels to gain access.
Clinical trial transparency is important for patients, clinicians, researchers, clinical trial participants, and the public at large for numerous reasons. Sharing sensitive clinical trial data should always follow the guidelines laid out by regulatory authorities.
If you are the Sponsor of a clinical trial, remaining compliant with the law requires understanding how clinical trial reporting rules and policies apply to you, budgeting adequate resources for publishing clinical trial results, and staying organized throughout the process. If you are interested in reviewing and analyzing clinical trial data from other Sponsors, it is important to consider what sources of information are available, the processes required to gain access, and how to generate an effective proposal.
Nuventra can help with any of these tasks and many others, including study design, study management, data analysis, and results publication. We can also help you register and maintain your trial on clinicaltrials.gov. Contact us to speak with one of our veteran consultants about our many clinical trial-related services.
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