Pharmaceutical companies are being required to be more transparent through the timely disclosure of more clinical trial data on more registry platforms such as Clinicaltrials.gov in the US and CTIS (Clinical Trial Information System, formerly EUDRA-CT) in Europe. You can read more about the changes that come with the rollout of CTIS in this blog.
Initially, clinical trial registries only required the registration of key trial data. Since then, the requirements have been expanded to include the disclosure of clinical trial results with financial penalties for non-compliance. Expanding requirements and an increase in the number of public registries create challenges for sponsors. Here are a few tips that can help ensure long-term success in meeting sponsor obligations.
What are the requirements for clinical trial registries?
As already complex requirements continue to expand (e.g., the Clinicaltrials.gov Final Rule), sponsors struggle to adhere to them. A major challenge for sponsors is populating and maintaining the registry data fields using internal trial documentation. Since the data fields are registry specific and contain their own definitions, limitations, and expectations, completing them successfully requires significant knowledge.
Focus your time and energy on tasks that support your regulatory objectives! Learning through experience and sharing your learnings should be part of the process. Internal reference documents should be created and updated periodically to focus on addressing key areas of concern, along with ensuring long-term consistency of reporting. Feedback from health authorities and internal stakeholders should be used to build in external requirements into internal templates to ensure the efficient reuse of information across systems. A small (but capable) team should review the registry submissions since the data on it are largely available through already reviewed documents. For example, the clinical trial protocol template could be updated with feedback from NIH reviewers on the registry protocol registration summary.
Gathering Appropriate Data
Sponsors can miss compliance deadlines if they fail to gather all appropriate data in a timely manner. Sponsors must set up policies, systems, and processes that facilitate data sharing. Disclosure teams must be able to engage appropriate delegates and stakeholders consistently to support the disclosure process. To be more proactive, sponsors can also consider incorporating registry data requirements into clinical study report (CSR) tables or automated solutions that always create the registry specific data for disclosure.
Another common issue faced by sponsors is the mandatory disclosure of data they consider to be exploratory in nature. Review teams may wish to remove listed clinical trial endpoints that don’t have results available for various reasons. It is important to account for such requests in your trial documentation to ensure that it can be removed lawfully. Strategic protocol and statistical analysis plan (SAP) development ensures alignment of expectations across the board upfront and reduces any downstream confusion at the time of results disclosure.
Clinical Trial Registry Data Entry
A major challenge faced by sponsors is the large volume of data that must be entered into clinical trial registries. Data entry slows down the regulatory document authoring process as well as the review/approval process. A better and progressive solution is the use of technology to automatically generate digital outputs (e.g., XML files) to populate the registry fields and free time for authors to focus on the overall quality of the posting.
Consistency and accuracy of data reporting
The data that is posted on public registries is scrutinized by various health authorities and academic publications. Thus, it’s important to maintain consistency of data formats across registry platforms and publications. Sponsors may be surprised to learn about the inconsistency of their data through various academic publications which could pose a reputational risk for them.
One way to ensure consistency of reporting is by leveraging approved content. Data that has already been posted to the registries is public information, and medical writing teams can consult them to draft additional registry postings. After all, the information on platforms such as clinicaltrials.gov has often been through several rounds of quality review by internal and external reviewers.
Another possible strategy is the simultaneous data entry and review for different registries. Any major comments raised by study teams, or by the regulators, can be addressed at the same time and will ensure that results posted across registries are consistent.
Often sponsor team members who are most knowledgeable about a study move on to other projects when a study ends. To ensure the accuracy of data reporting, it is also advisable to complete the disclosure process as soon as possible and while those team members are still available.
Improving quality of clinical trial postings while reducing review cycles
A lot of resources can be wasted in iterative cycles of review and approval based on regulator feedback. Sponsors interested in improving the quality of their submissions should focus on reducing the number of edit/review/approve cycles. One way to accomplish this is to categorize and keep track of all the QA comments received to identify any major quality concerns. For example, if the team is consistently receiving comments on a particular section, a knowledge gap could be easily identified, and actions undertaken to close it. These will be gradual but targeted improvements which will continue to yield larger benefit over time.
Another approach is developing and maintaining collaborative relationship with the National Institutes of Health as the US National Library of Medicine (NLM) at the NIH oversees Clinicaltrials.gov. NIH reviewers can be consulted to address how best to resolve a situation. If the reviewers are on-board even before a submission is made to them, it is much less likely to receive QA comments. NIH standards tend to be more stringent than other registries (CTIS, EU-PAS, or WHO-ISRCTN) so early engagement with them can even help avoid issues with other registries.
Final Thoughts
It is helpful to think about the challenges faced by any transparency and disclosures team from a study life cycle and volume perspectives. Regulatory requirements during the initial stages of a study are different than those that have been completed. At early stages, the requirements are not as burdensome. However, since the requirements are the same across drug development projects, they need a standardized management approach.
Do you need help with your clinical trial postings?
Certara can support you throughout your study lifecycle to meet your registry needs. We start by registering your protocols before the start of the trial, maintaining them through minor and major updates, and submitting the primary and final results. We help our clients understand the registry requirements, gather appropriate data, and ensure consistency of data reporting to ultimately provide a high-quality work product.
Learn more about we’ve supported sponsors with thousands of trial postings to global disclosure databases.