Section 801 of the US Food and Drug Administration (FDA Amendments Act (FDAAA) of 2007 is the baseline regulation defining clinical trial disclosure in the US.
The regulation was refined in 2016 with the issuance of 42 CFR Part 11 for Clinical Trials Registration and Results Information Submission – commonly referred to as the “Final Rule.”
In the US, the Final Rule went into effect in January 2017, with the requirement to share clinical trial results coming into effect earlier this year. As per the new rule, the FDA is able to levy fines of more than $10,000 a day against clinical trial sponsors who fail to publish trial results in ClinicalTrials.gov.
The FDA recently released a draft guidance on the enforcement of US regulations on clinical trial disclosure and certification regulations.
Following the release of the guidance, we caught up with TrialScope VP of Global Transparency Francine Lane to discuss further the challenges to disclosure and what has been driving calls for reform.
Outsourcing-Pharma (OSP): What are the historical challenges to transparency in the clinical trial process?
Francine Lane: Clinical trial transparency has some complexities because there are various regulations and policies that drive which studies are in scope, even in the US.
I would say that the challenges are that there is no one answer to what must be disclosed. There are multiple different regulations and policies that may have a different scope of which studies are included.
Some organizations have a better understanding of these requirements and the resources and experience to meet the requirements.
As a general rule, large pharma has more resources and dedicated team to meet their compliance obligations and have done a much better job in disclosing data.
Smaller organizations and academia have less experience and may not have dedicated teams to understand the requirements and assist their study teams in disclosing properly.
OSP: How have these challenges evolved with the industry?
Lane: Larger organizations (typically large pharma) that conduct more studies have devoted resources that have allowed them to have a better understanding of the requirements, better tools to disclose the data, more scrutiny on their performance, and better visibility into what needs to be done.
Smaller organizations or investigators that conduct few studies lack many of these resources and may not even recognize that they lack and understanding of the various requirements.
OSP: What has been driving the calls for increased transparency?
Lane: Beyond regulatory requirements, there are various transparency advocates, researchers, and journalists who have used their visibility to push for more transparency.
Calls for more transparency have shaped the level of public demand for clinical trial data, and in some cases influence regulatory requirements.
OSP: How does the lack of clinical trial disclosure affect patients?
Lane: One of the basic arguments for more transparency lies in the ability for a health care provider to have the information necessary to make a good decision for the care of a patient.
Clinical trial disclosure is supposed to improve information by reducing publication bias (only publishing clinical trial results that show positive outcomes) and increasing trust in peer reviewed publications as they have access to better data upon which to conduct their review.
To date, I am not aware of any studies that have researched the impact of disclosure on patient care.
OSP: And the industry as a whole?
Lane: The pharmaceutical industry is often not perceived by the public as trustworthy. Clinical trial disclosure is one avenue where, if done well, can show that sponsors are working towards building more trust.
OSP: What is the FDA’s current thinking on the topic?
Lane: FDA’s current thinking on disclosure enforcement is that it will be part of their existing Bioresearch Monitoring Program (BIMO) and will be assessed during BIMO inspections.
If issues are found during an inspection, the sponsor will be informed and will have 30 days to remediate the findings.
If the issues are not remediated in that 30-day period, the FDA will seek monetary penalties. Sponsors can enter into an appeal process at this point, if they disagree with the findings.