Clinical Data Transparency a Big Challenge for Smaller Sponsors

Biopharma companies with the most effective and robust clinical trial disclosure programs often have one thing in common: a leadership that recognizes the importance of transparency beyond mere regulatory compliance.

By Thomas Wicks

Robust transparency and compliance with evolving regulations demand a united commitment from executives at companies of all sizes. Biopharma companies with the most effective clinical trial disclosure programs often have one thing in common: a leadership that recognizes the importance of transparency beyond mere regulatory compliance.

These companies — primarily some of the largest pharmaceutical firms such as GSK — have an executive commitment to, for example, publish their disclosure policies, register protocols and disclose results, provide plain language summaries (PLS), and share a broad range of clinical documents, even when these may not be required by regulation. The trial sponsors meet their commitments by investing in technologies and developing robust operating procedures.

However, smaller companies have often delayed investing in the dedicated systems and processes needed for even the modest goal of regulatory compliance and providing a global overview of disclosure activities. For example, these companies often use manual, spreadsheet-type approaches that can be challenging to scale and share across the organization. Since the repercussions of having a less effective program can go well beyond just regulatory penalties, investing in effective solutions to manage the evolving requirements and ensure compliance is crucial. 

Smaller trial sponsors are also more likely to be noncompliant without a commitment to meeting clinical trial disclosure requirements. Based on current data from ClinicalTrials.gov (CTgov) and the FDAAA TrialsTracker, industry trial sponsors with 200 or more trials on CTgov are over 99% compliant with the disclosure requirements for US clinical trial results. In comparison, industry sponsors with only one to five trials on CTgov are compliant with only 48% of their trials (see graph below). This noncompliance can lead to reputational damage, loss of investor confidence, and even legal consequences. 

Figure 1 – Industry sponsor trial results disclosure noncompliance

Source: ClinicalTrials.gov, the FDAAA TrialsTracker, and Citeline analysis, June 2024

Developing a transparency culture

Publishing any clinical trial data requires effort and introduces some risks to the organization. There is often a concern about inadvertently releasing confidential company or patient health information, tipping off competitors, or jeopardizing the ability to file patents. The culture at many biopharmaceutical companies is to hold data very closely, especially data about unapproved products or indications. Kim Green, transparency expert and founder of ClaritiDox, said that “smaller companies focused on rare diseases or highly competitive therapeutic areas are particularly reluctant to share clinical trial results, especially if these are not promising.” Ironically, seeking to disclose the least possible data required by law typically requires more effort to parse the regulations and question every requirement, leading to companies erring on the side of nondisclosure.

However, a properly managed process efficiently mitigates the potential risks of disclosure, brings an organization into full compliance, and prepares the data for valuable secondary uses. High-quality study data that is ready for the public can be leveraged beyond disclosure, including patient engagement initiatives through intuitive trial-finder websites and streamlined recruiting efforts that rely on timely trial, site, and status information.

Awareness and coordination

Figure 2 – Protocol registration requirements 

Source: TrialScope Intelligence, June 2024

The clinical trial disclosure space is rapidly evolving, with around 75 countries requiring the public disclosure of study information on one of over 50 trial registries. Not only are there about two new trial registries starting up every year, but the requirements evolve continuously. For example, our TrialScope Intelligence team recorded over 193 disclosure-impacting changes in the last 12 months, primarily in the European Union/European Economic Area (EU/EEA), Japan, and the UK. Government agencies and health authorities published approximately 130 new disclosure-related documents between June 2023 and June 2024, of which newer versions have already replaced 36. This rapid change has been a consistent trend for the last three years (see tables below).

Table 1 – New trial disclosure guidelines, regulations, laws, and related documents published in the past 36 months

Source: TrialScope Intelligence, June 2024

Table 2 – Disclosure document types published by government agencies and health authorities in the past 36 months

Source: TrialScope Intelligence, June 2024

Over the past two decades, mandatory clinical trial disclosure has evolved from providing summary protocols to publishing trial results and, more recently, the full clinical study report. Trial sponsors must make PLS of results available and, increasingly, protocol PLS.

Maintaining compliance can be complex, with a growing number of countries requiring the public availability of clinical data. Although the company is ultimately responsible for compliant and consistent global disclosure, many organizations delegate local affiliates’ responsibility. This delegation, however, means there is little corporate awareness of what data are publicly disseminated or whether they are made public in compliance with local law.

While global disclosure regulations tend to have some commonality, typically requiring, at minimum, the registration of Phase II and III interventional trials around the time of study start, local variations make it more complicated. “Companies planning their first Phase I/II or Phase II trials are often unprepared for or unfamiliar with the new disclosure requirements and may lack internal expertise,” said Green. Adding to this complexity is that initial registration timing can vary, as do the frequency and types of data updates expected and whether results are mandatory.

A further difficulty is ensuring consistent public dissemination of information when every registry has unique data and local language requirements. In organizations without a central disclosure function, each affiliate, partner, or CRO makes editorial decisions to conform the data to the local registry standards. However, public data may be inconsistent without a coordinated editorial approach, potentially leading to questions from industry critics. Additionally, because data privacy laws vary across regions, local editorial decisions may inadvertently result in disseminating personally identifiable information in violation of privacy laws in another country.

Finally, even when the decentralized approach complies with local disclosure regulations, there is an increased risk of publishing company confidential information absent a central review-and-approval process. There are examples of the European Medicines Agency (EMA) denying proposed redactions of sensitive information in submissions under its policy for the publication of clinical data for products for human use because the information was already publicly available and at least one instance of a rejected patent filing due to such inadvertent disclosure of company information.

Systems and data

Many smaller organizations have not yet implemented a specialized clinical trial disclosure system. Instead, they rely on a manual approach, perhaps tracked through various spreadsheets. With a manual approach, it can be difficult for companies to adapt to ever-changing policies or respond to tightened deadlines and more frequent update requirements. Spreadsheets and manual disclosure processes also make it harder to respond to inspections and rarely provide a global transparency perspective to company executives.

Companies with smaller trial portfolios often lack a system to track the dates, trial statuses, and metadata that must be disclosed to trial registries. Frequently, these data are managed by CROs or partner organizations and may not be aggregated in a central database or system.

In contrast, study sponsors with more extensive trial portfolios typically implement guidelines and templates for documentation related to clinical data sharing and disclosure requirements, including protocols, clinical study reports (CSRs), and SAS clinical datasets. Considering downstream data-sharing requirements facilitates efficient trial transparency and helps ensure global consistency of the data made public.

The first step to addressing the challenges of regulatory complexity and evolving transparency expectations is to recognize that disclosure is not merely an administrative function. Executives leading regulatory affairs, clinical operations, and medical writing should collaborate with the chief medical officer to establish a transparency policy that aligns with patient engagement and corporate communication strategies. Understanding global requirements, which have changed substantially in recent years, is the foundation for establishing the processes and systems to ensure compliance and avoid negative assessments by transparency advocates.

Thomas Wicks is head of transparency operations at Citeline, a Norstella company. He has over 23 years of experience with performance and content management approaches in the life sciences, mainly focusing on clinical trial transparency.