2017 will be a challenging year marked by public scrutiny of disclosure practices by regulators, stakeholders, and watchdog organizations. Expanded regulations require a significantly broader range of data to be disclosed within ever tighter timelines.
2016 saw renewed scrutiny of the transparency practices of industry and academic sponsors and the implementation of expanded disclosure regulations. 2017 is set to continue this trend as the new disclosure regulations become effective, inspections by regulatory agencies are likely to start, and new in-depth disclosure analyses and transparency indices are published. Enhanced transparency requirements will increase the effort to comply with regulations, while expectations for a broader scope of disclosure that exceeds regulatory requirements continue to grow.
2017 will see an increase of articles on disclosure across various media, based on two developments: regulatory requirements and the publication of key analyses and indices based on aggregated disclosure data.
1. Articles based on regulatory requirements
In the European Union (EU), the final batch of legacy studies dating back to May of 2004 are required to provide results on the EU Clinical Trials Register (EU-CTR) by December 21, 2016, which means that all studies registered on the EU-CTR that were completed by December 21, 2015 should have results posted. This creates a convenient baseline to assess results disclosure compliance in the EU, setting the stage for ongoing analysis and future articles. Industry watchdogs and other stakeholders will likely analyze the data on the EU-CTR and publish initial compliance assessments in the first half of 2017, naming and ranking trial sponsors on their results compliance.
Since October of 2016, the European Medicines Agency (EMA) has provided an open access Clinical Data Portal that includes information on new medicines for human use authorized in the EU. This portal provides public access to documents required under EU Policy 0070 including the Clinical Overview, Clinical Summaries, and the Clinical Study Report with the protocol and amendments, sample case report forms, and documentation of statistical methods. Researchers will have access to tens of thousands, if not hundreds of thousands, of pages of clinical data that was not readily available in the past. Articles based on this data are expected in 2017, potentially highlighting discrepancies between information disclosed on registries or in medical journals and the data available in the clinical reports on the portal.
In the U.S., Title VIII of the Food and Drug Administration Amendments Act (FDAAA), the regulation governing trial disclosure was updated in 2016 with 42 CFR Part 11, known as the “Final Rule,” clarifying the requirements, increasing the scope of disclosure, and tightening certain deadlines. This update is effective in January of 2017 with compliance mandated by April. The rule changes will improve the accuracy of future compliance analyses, although the updated regulation only applies to newer studies. However, some analysts may take the view that older trials should conform to the new requirements, which include the disclosure of results for unapproved products and indications and the need to file a certificate of delay if results are withheld for a limited period. This view will lead to articles that focus on the absence of results or certificates of delay in older trials without necessarily clarifying the difference between compliance with disclosure regulations and the ethical perspectives of the authors.
2. Articles based on the publication of key analyses and indices
While there are quite a few organizations and analysts assessing clinical trial disclosure practices, there are three groups that are particularly well recognized: Bioethics International, Sense about Science, and the Evidence-Based Medicine Data Lab (EBM Data Lab). When these organizations publish their findings, stakeholders across life sciences and healthcare pay attention. Their analyses are often accompanied by discussions in social media and reporting in business and general news publications. We expect to hear from all three organizations in early 2017, which will initiate further publicity and scrutiny of disclosure practices.
Bioethics International will publish the second edition of the Good Pharma Scorecard, which is currently focused on clinical transparency related to industry-sponsored trials of newly approved products. The transparency scorecard provides a rating of sponsors based on various aspects of compliance including different views of the regulatory requirements and assessments of disclosure practices based on ethical perspectives.
Sense about Science is expected to publish at least two articles on disclosure in the coming months, one is a review and ranking of industry sponsors based on their transparency policies and the other is a disclosure index that ranks sponsors by their disclosure practices. Sense about Science is one of the leads of the AllTrials initiative that has been joined by many organizations including asset managers that collectively represent over $3.5 trillion in assets, which suggest that this transparency index may factor in to future investment decisions
EBM Data Lab is conducting a few initiatives including TrialsTracker, COMPare Trials, and OpenTrials. In 2016, publications on these initiatives generated considerable interest in social and traditional media. OpenTrials, in particular, will likely be the source of future articles, as it has designed a repository of clinical data from a wide range of sources that may otherwise be difficult to access and analyze. For example, by pulling together information on trials across registries and publications it is possible to assess the quality and consistency of global data disclosure.
Evolving Disclosure Regulations
January 18, 2017 is the effective date of the new regulations related to Title VIII of the FDAAA. This new Clinical Trials Registration and Results Information Submission rule, commonly referred to as the ‘Final Rule,’ is intended to clarify the requirements for disclosing data on ClinicalTrials.gov. The most significant aspects of this rule are the requirements to disclose results data for unapproved products and uses, as well as new deadlines for updating information.
When FDAAA went in to effect in 2007. Results for completed studies were required either within one year of the primary completion date or within 30 days of approval of the product or new use, whichever was later. Under the expanded regulation, results for studies will be required within 12 months of primary completion date irrespective of approval status, with additional results required within 12 months after completion of each secondary outcome. In certain circumstances, it will be possible to apply for a 24-month delay in publishing results, but only by filing a certificate of delay before results would otherwise be due.
The final rule increases the frequency of mandatory updates to disclosed information. Under the new rule, changes to 13 study registration data elements will require updates on ClinicalTrials.gov within 30 days, including data on trial sites outside of the U.S. For medical device trials, there is an additional requirement that clearance status change or approval for a device must be updated within 15 days.
Data submitted to ClinicalTrials.gov goes through a quality review process before publication on the website. Sponsors are given only 15 days to address comments made by the quality reviewers for protocol registrations and 25 days to address those for results disclosures. This may be challenging for sponsors that have rigorous review and approval processes.
These changes mean that studies which fall under the original version of FDAAA will have different disclosure requirements than studies under the new regulation. This nuance will make future assessment more complex and may lead some analysts to apply the new requirements incorrectly to older studies.
The Technology Imperative
With the increased workload and tighter timelines of the new clinical trial regulations and the focus of disclosure articles shifting to global data consistency and overall transparency, sponsors are moving to automation and centralization to manage global transparency. This move helps ensure a uniform and compliant disclosure of study data. Disclosure automation addresses four key issues:
- Understand, track, and manage global disclosure requirements
- Ensure timely and compliant data disclosure
- Harmonize the disclosed information for a consistent, accurate, and complete view of trials
- Eliminate duplicative effort, minimize required resources, and inform stakeholders promptly
While decentralized manual work or home-grown systems may have helped sponsors meet their local disclosure requirements in the past, these approaches are unable to scale to meet the mandates for a globally consistent and compliant disclosure that will stand up to scrutiny by regulatory agencies and watchdog organizations. In 2016, there was a 30 percent increase in trial sponsors that rely on commercial disclosure solutions, which now includes smaller biopharmaceutical companies. Academic and medical device sponsors are also considering disclosure systems since the regulations for these sponsors have are becoming considerably more complex with the passage of the new regulations and expanded disclosure requirements for government funded studies. Based on current trends, 2017 will see a significant increase in the number of sponsors that are adopting commercial disclosure solutions, both to remain compliant with regulations and disclosure policies and to gain control over global disclosure requirements.
Recommendations for 2017
2017 will see the publication of new analyses of disclosure practices, as well as new transparency indices and public rankings of trial sponsors. While sponsors must be compliant with global regulations, this represents the ‘low bar’ for disclosure. Sponsors should consider the growing transparency expectations and shift their focus from mere legal compliance to the ethical obligation for broader transparency.
Centralized disclosure groups were once the domain of large pharma and biotech. New regulations, policies, and public scrutiny are motivating academic institutions and smaller industry sponsors to recognize that disclosure must be managed at an organization level, rather than at a study level. Many will create or enhance centralized disclosure groups with the responsibility to make sure global disclosure meets legal requirements and market expectations.
Consider disclosing all results on ClinicalTrials.gov within two years of the primary completion date. ClinicalTrials.gov is the de facto global clinical trial repository with over 232,000 studies registered as of December 2016. Because ClinicalTrials.gov provides data in a way that can be easily analyzed, this is the first, and often only, stop for many researchers and article authors. Organizations that embrace transparency and voluntarily register protocols on ClinicalTrials.gov may still look bad if they do not also provide results there. Sponsors who voluntarily post results on their website may not receive credit for the disclosure, even when those results are linked from ClincalTrials.gov.
Start preparing for FDA inspections. The new clinical trial requirements effective in early 2017 largely resolve ambiguities in determining which trials fall under the US regulation. It is widely anticipated that this will result in inspections by the FDA of clinical trial disclosure activities.