December 11, 2017
CWWeekly presents this biweekly feature as a spotlight on issues that executives in clinical research face. This week, writer Suz Redfearn spoke with Thomas Wicks, chief strategy officer at TrialScope. Wicks is responsible for leading TrialScope’s response to emerging trends and regulatory mandates, and championing the company’s strategic vision, which focuses on clinical transparency management.
Q: It’s been nearly a year since the final rule of FDAAA 801 (42 CFR Part 11) went into effect, expanding requirements for submitting clinical trial registration and results informa- tion to the FDA. Has this had an impact on the industry yet?
A: This has had a pretty significant impact in terms of the disclosure workload. There are two parts to the regulation. One, it affects the frequency with which registered protocols have to be updated. While the number of studies that have to be disclosed hasn’t changed much, the scope of information that has to be updated within 30 days rather than every 12 months has increased. That represents an additional workload to sponsors to make sure that they collect and report the changing data for a timely and accurate disclosure. The second shoe will drop on January 18th, when the new results disclosure regulation goes into effect. The biggest change is that until now, study results were not required until after the product was approved. Now, results of all studies must be posted within 12 months of completion. While a trial sponsor can request to delay the results disclosure, the maximum you can apply for is 24 months. The new regulation doesn’t change the volume of work, but it changes the timing which increases the pressure on everyone.
Q: What remains the biggest challenge for sponsors when it comes to disclosure?
A: On the results-disclosure side of the law, certain data elements that were previously not mandatory have become mandatory. For outcome measures, the statistical analysis is now required when that was optional before. It provides context, but does require additional work. Also, under the previous regulations, results were required within 12 months of the primary completion date, which is based on the last visit by the last patient for collecting data in support of the primary outcome, with a final update 12 months after the study was completed. The new regulation requires that results must be updated within 12 months of the last patient’s last visit of any outcome, which may require multiple results submissions for many trials.
The biggest challenge has to do with data maintenance. Under the previous version of the law, there were four data elements that had to be updated on ClinicalTrials.gov within 30 days if they were changed. Study enrollment status was one of those. Now, that has been increased to 13 pieces of information, some of which is labor intensive, for example requiring that the status of every single site in the study must be updated within 30 days. When you’re running global studies in remote corners of the world, sometimes the systems aren’t in place to collect site enrollment status updates that fast. It’s forcing change to meet compliance.
Other parts that remain a challenge even 10 years after the act was initially passed: The fact that perception of transparency and the legal requirements don’t necessarily line up. A company can be in full compliance with the law but the publicly available data does not give someone analyzing its transparency everything they need to know to verify legal compliance. That gap is one reason for the complaints that pharma companies aren’t as transparent as they must be.
Another perspective is that the disclosure laws don’t really go far enough. Transparency advocates with this view feel that all trials in humans must be made fully available, including phase I trials, which is a choice that some pharma companies are still struggling with internally. There are a fair number of pharma companies that agree, and are working on how to best communicate phase I results. The challenge is that since this is not a legal requirement, companies are trying to figure out the best approach to share data that provides good information for the public while they also struggle with what data should be disclosed and when transparency is taken too far without providing additional value to the public. These are evolving transparency policies within the industry.
In the long run, the requirements of the final rule are a good thing. It’s a bit like the Sarbanes–Oxley Act of 2002 in the finance world when it was passed. A lot of new work and a lot of changes at first, but in the long run it creates valuable clarity, transparency and efficiency at a level a company may have never quite have managed without the new regulations.
Q: What do you predict we’ll see when it comes to trial disclosure in 2018?
A: We’ll see the implementation of the final rule for results disclosure in the U.S. and that will have a big impact on the volume of results disclosures as people catch up and start reporting data for unapproved products or at least explaining why they’re not doing that by obtaining these certificates of delay. Since you’ll be able to see whether or not a company disclosed results or filed for a certificate of delay, it should improve the assessments of legal compliance, which has been a major contention in the past. I think that over time the perception that companies are not in compliance with the law will fade away.