Clinical Trial Disclosure and Data Transparency

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Overview

In most countries, the disclosure and transparency of clinical trials is a regulatory requirement. While specific requirements vary, at minimum trial sponsors are required to register and publish trial results on public databases. In the United States, drug products, biological products and device product manufacturers are mandated by the Public Health Services Act (PHS)^[2] to submit clinical trial registration and/or result information within the ClinicalTrials.gov data bank. 

The first U.S. Federal law to require trial registration was the Food and Drug Administration Modernization Act of 1997 (FDAMA)^[7]. FDAMA required the National Institutes of Health (NIH) to create a public information resource, which came to be called ClinicalTrials.gov, to track federally and privately funded clinical trials regulated by the Food and Drug Administration (FDA). The primary purpose of this amendment was to improve public access to information on clinical trials for various diseases and conditions. All sponsors must register clinical trials in ClinicalTrials.gov database no later than 21 days after enrollment of the first participant.  

Following the retraction of several drugs due to toxicity tracking concerns, the Food and Drug Administration Amendment Act (FDAAA) of 2007 ^[6][5] mandated the expansion of ClinicalTrials.gov with new requirements for trial sponsors to publish results, protocols and statistical analysis plans within 12 months of trial conclusion. 

In July 2013, the Pharmaceutical Researchers and Manufacturers of America (PhRMA) and the European Federation of Pharmaceutical Industries and Association (EFPIA) jointly published “Principles for Responsible Clinical Trial Data Sharing”^[3] to detail industry commitments to data sharing. The principles support enhanced data sharing while safeguarding patient privacy, respecting the integrity of national regulatory systems and maintaining incentives for investment in biomedical research. In 2020, the FDA issued a guidance on “Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank”^[4], which defines the penalties for parties that fail to register and publish results of applicable clinical trials. Current penalties include a maximum of $ 10,000 for the first 30 days of delay and up to a maximum of $ 10,000 per day for any further delay. 

In April 2021, the FDA issued its first Notice of Noncompliance to Acceleron Pharma^[8] for failing to submit trial results to ClinicalTrials.gov. According to a 2020 analysis ^[9], less than half of all clinical trials publish results within a year of completion. Government and academic sponsors have the lowest rates of compliance, with only 33.8% of studies fully compliant within 12 months of trial conclusion.

Objective and Need

The need for enhanced data sharing will ultimately improve industry collaboration and public access to information on clinical trials. The discovery of new trends, insights and hypotheses have potential to support future research and faster approvals of drugs – which is in the best interests of patients, clinicians, researchers and the industry as a whole. While complying with the principles established by PhRMA and EFPIA, safeguarding the privacy of patients and respecting the integrity of regulatory systems, biopharmaceutical companies commit to the following:

• Enhance data sharing with researchers: Upon request from qualified scientific and medical researchers, companies will share patient-level data, study-level data and the necessary protocols for conducting legitimate research.
• Enhance public access to clinical study information: To help patients and physicians understand trial results and evidence for new drugs, companies will make a synopsis of the clinical study report publicly available.
• Sharing of results with the research participants: Companies will provide a factual summary of trial results with participating patients.
• Publish clinical trial results: Companies will publish trial results in scientific literature -regardless of the results being positive or negative.

Benefits

Patients, physicians and researchers significantly benefit from the timely disclosure of clinical trial data. Patients can review results of past trials and research about current trials to make an informed decision on participating. Physicians who are aware of the latest research and can better help their patients by providing the best treatment options and researchers can design more effective studies by leveraging past trial designs and data. 

Barriers and Challenges

Regardless of trial size, sponsor or regulations, full compliance is fraught with barriers and challenges that have yet to be overcome: 

1. Competitive Pressures: While sponsors typically comply with the trial registration requirement, they are reluctant to publish trial results out of hesitancy to share data with competition. In this context, there’s even more hesitancy to share trial results considered poor or “negative.”
2. Minimize risk to the privacy and confidentiality of participants: The industry has a significant need for a viable approach that balances transparency and patient privacy. Sponsors need a formal approach to anonymizing patient-level data and redacting privacy information before publicly sharing information.
3. Reduce and minimize effort, time, resources and cost: Compliance with registration and publishing trial results require sponsors to exert additional effort, time and resources.

Way Forward

As early as 2015, forward-thinking companies like GSK, Johnson & Johnson and Bristol-Meyer Squibb took the lead in widely sharing trial data. Since then, almost all major pharmaceutical companies have established Clinical Trial Disclosure/Transparency policies and publicly post results of their clinical trials, regardless of outcome.

Concerns regarding the privacy and confidentiality of participants have been addressed by the TransCelerate Clinical Data Transparency (CDT) Initiative^[1], which provides guidance and model approaches for redacting privacy information, anonymizing patient-level data, preparing and distributing layperson summaries to both the public and study participants. 

Across Europe and the US, transparency and compliance within clinical trials is increasing as companies recognize the benefits to the patients, physicians, researchers and overall industry. As the industry moves forward in a post-pandemic world, the path to complete disclosure and data transparency is by no means simple. There are barriers and challenges aplenty, but companies have an overwhelming opportunity to overcome them and create immense value in the clinical trial space. 

Sources

1. Clinical Trial Data Transparency & Patient Data Privacy. TransCelerate. (2021, April 23). https://www.transceleratebiopharmainc.com/initiatives/clinical-data-transparency/.
2. Code of Federal Regulations (2017).
3. European Federation of Pharmaceutical Industries and Associations. (2013, July 18). Principles for Responsible Clinical Trial Data Sharing. Brussels, Belgium.
4. FDA. (2020, August 12). Civil Money Penalties ClinicalTrials.gov Data Bank. U.S. Food and Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/civil-money-penalties-relating-clinicaltrialsgov-data-bank.
5. FDAAA 801 and the Final Rule. ClinicalTrials.gov. (n.d.). https://clinicaltrials.gov/ct2/manage-recs/fdaaa.
6. Food and Drug Administration Amendments Act (FDAAA) of 2007 (2007).
7. Food and Drug Administration Modernization Act (FDAMA) of 1997 (1997).
8. McMeekin, J. (2021, April 27). ACRA Signed Notice of Noncompliance 4-27-2021. Cambridge; U.S. Food and Drug Administration.
9. O’Riordan, M. (2021, May 13). Most Clinical Trial Sponsors Fail to Report Data as Mandated by FDA. TCTMD.com. https://www.tctmd.com/news/most-clinical-trial-sponsors-fail-report-data-mandated-fda.

About the Author

Harpreet Kanwar is a VP of Technology and part of Life Sciences business unit at Emids. With over 25+ years of experience in the IT industry,  he holds expertise in enterprise architecture, digital transformation, IT strategy, innovation and emerging technologies such as Cloud, DevSecOps, Automation/RPA, AI/ML, IoT and Blockchain. His in-depth understanding of the Pharma industry supports successful client relationships and digital solutions for Life Sciences and Medtech companies. Be sure to connect with Harpreet on LinkedIn.