Challenges, opportunities of clinical trial transparency

Public disclosure of the results of clinical trials is important for everyone — trial participants, researchers, patients and the healthcare professionals who care for them. The critical evidence that clinical trial transparency provides about the safety and effectiveness of proposed treatments and devices makes it an important brick in the foundation of biomedical research and useful for clinical care officers who oversee these efforts. As the pharmaceutical industry encounters growing scrutiny and calls for increased transparency and accountability, the need for greater attention to ensuring public disclosure of clinical trial results is more critical than ever.

Clinical trial sponsors in the U.S. have been required to register their trials with the FDA since 1997 and, today, clinicaltrials.gov serves as a storehouse of a wealth of data about registered trials. While most sponsors submit the registration requirements for their upcoming trials, many have been slow to comply with the need to publish trial results. With pressure mounting for organizations to share their data, more organizations have made public commitments to post and share their clinical data.

The tide is beginning to turn, yet challenges remain. Globally, regulations affecting the disclosure of clinical trial data exist in approximately 90 countries, each with their own health authority and requirements about the level of detail, scope and timing of disclosures. Currently, there are more than 30 clinical trial registries, with an average of two new registries launched every year. The continued growth in M&A activity and the appearance of new licensing agreements in the pharmaceutical and life sciences industry are prompting questions about the entity responsible for disclosure.

Additionally, regulators face growing pressures to report noncompliance to oversight committees, and are responding with increased inspections and audits of clinical trials.

Considerations for clinical trial sponsors

Clinical trial disclosure and transparency benefit sponsors in a variety of ways. They provide an opportunity to demonstrate the quality of research and product development. They can facilitate recruitment of trial participants. And by demonstrating the commitment to providing access to clinical trial results, they can improve the perception of the organization with patients and the public.

To reap the benefits — and meet the challenges — of a dedicated practice of publishing clinical study results, there are a number of steps that clinical trial sponsoring organizations can take now:

• Ensure organizational alignment. It is important to ensure that all regulatory personnel within the organization are in alignment with the organization’s clinical trial transparency policy. “For organizations hosting studies in multiple locations, it’s also very important for them to ensure they are in alignment with the requirements of the country in which they are hosting the study,” said Ivan Montoya, Grant Thornton Consultant, Life Sciences.
• Assure data quality. Sponsoring organizations must ensure the quality and integrity of the data generated by their clinical trials. The guideline developed by the International Conference on Harmonization has impacted the way clinical trials in Europe and Japan are conducted.¹ In the U.S., the FDA has also issued guidance on monitoring trials and maintaining electronic records.²
• Facilitate data sharing. Data sharing responsibly is a critical component of any clinical trial transparency initiative. Not only is it a key factor in accelerating new discoveries and innovations, it can also help inspire new areas for research and prevent duplication of efforts. “According to good clinical practice, trial sponsors are required to anonymize clinical study documents in order to protect the privacy of trial participants and many journals are requiring data sharing agreements with trial sponsors,” said Montoya. JAMA and the JAMA Network journals, for example, make publication of data sharing statements a condition of publication for clinical trials.³
• Avoid selective reporting and publication bias. Because clinicians often make prescribing decisions from published trials, reports that include inaccurate or incomplete data can be ethically troubling, with potentially detrimental effects on clinical decisions and patient outcomes.
• Protect your clinical trial results as intellectual property. Although the way in which clinical trials are conducted are governed by FDA regulations, they also are important business assets. It is critical to retain ownership of any intellectual property that is developed during a clinical trial and any data from the study that it wishes to retain as proprietary information.

Without taking all these factors into consideration, trial sponsors risk significant financial penalties. In the U.S., FDAAA Section 801 provides for penalties up to $10,000 per day of delay following receipt of a notice for noncompliance. After many years of nonenforcement, the FDA issued its first “Notice of Noncompliance” in April 2021 and followed with three more.⁴

Beyond regulatory penalties, the costs of inadequate disclosure of trial results can also result in delays in obtaining approvals and market access, increased regulatory scrutiny, and lost opportunities for partnerships and collaboration.

What’s ahead for clinical transparency

Changes in the offing promise to strengthen transparency, protect patient rights, foster scientific advancement and, ultimately, improve healthcare outcomes and public trust in the clinical research enterprise.

The number of clinical trial registries worldwide is expected to continue to grow, while regulatory bodies everywhere are expected to intensify their transparency requirements. This could include more rigorous enforcement of current regulations or new reporting requirements and increased penalties for noncompliance. It is also possible that regulatory agencies will expand their transparency initiatives to cover broader areas of clinical research, including noninterventional studies and medical device trials.

In addition, the ability of artificial intelligence, machine learning, and blockchain to automate data extraction from clinical trial reports promises to revolutionize data collection, analysis and reporting.

Regulatory bodies across the globe are now shining a new light on the need for global harmonization for disclosure policies and procedures. Initiatives such as the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use, an international nonprofit that is bringing together regulatory authorities and the pharmaceutical industry, is working to align data standards and transparency guidelines from region to region and streamline the compliance efforts of clinical trial sponsors that operate in multiple jurisdictions.

All the intensified efforts to ensure data harmonization, implement standardized data formats, and develop secure platforms for controlled access to individual patient-level data for secondary analysis are designed to ensure consistency in reporting and strike a clear balance between making data sharing easier and protecting patient privacy.

Navigating the clinical trial transparency landscape

More than enabling regulatory compliance, clinical trial transparency can go a long way in elevating public perception and trust in the trial sponsor and the pharmaceutical industry itself, advancing scientific knowledge, promoting a positive corporate image, and protecting patient safety.

Life sciences organization leaders can approach the challenges inherent in navigating this complex landscape by addressing these key areas:

• Assessing the regulatory landscape by conducting comprehensive audits that evaluate compliance with current transparency regulations. This assessment can help identify gaps and areas for improvement — with customized roadmaps for facilitating transparency in registering trials, reporting results and disclosing adverse events.
• Selecting and implementing secure, scalable data sharing platforms that can help streamline data collection, facilitate collaboration and data anonymization, control access and safeguard patient privacy.
• Developing strategies for enhancing communication among study sponsors, investigators, regulators, and patients — and for ensuring effective dissemination of trail results.
• Enabling responsible data sharing and developing strategies for proactive disclosure of data that are in sync with the principles inherent in leading global initiatives such as the WHO Trial Registration Data Set.