By Ann Neuer
June 18, 2012 | eCliniqua | Clinical trial databases and registries will be upping the ante by requiring more disclosure from biopharmaceutical and medical device companies, but it’s not yet clear what additional information will be required or when compliance will be expected. Details are scarce, but what is known is that the next round of disclosures will expand the level of transparency in widely used databases such as ClinicalTrials.gov in the US and EudraCT in the EU due to legislation requiring industry, academia, and government to be more forthcoming with clinical trial specifics.
On the horizon for ClinicalTrials.gov is the potential for sponsors to provide more complete study results and greater details about protocols, possibly in non-promotional lay language, to enhance patient access and understanding of clinical trials. Originally these regulations were to have been issued by September 2010, but they don’t yet exist. Consequently, the anticipated changes have sponsors scrambling to comply with what is already required while trying to second-guess when the next round of requirements will go into effect.
Barbara Godlew, president of The FAIRE Company, an Illinois-based consultancy, comments that she and her colleagues frequently ask government representatives from the National Library of Medicine (NLM), the body that regulates ClinicalTrials.gov, when new rules will be issued. “There continues to be no definitive answer,” she says. According to information posted on the ClinicalTrials.gov web site, rulemaking is ongoing, but there is no timeline for release of draft rules, which would be circulated to various stakeholders during a public comments period, and then eventually finalized.
The source of the new rules and the earlier ones stem from requirements defined in the FDA Amendments Act of 2007 (FDAAA), which called for a series of disclosures. Starting in December 2007, the responsible party -- defined as either the sponsor or sponsor-designated principal investigator -- had to begin registering Phases II–IV drug, biologics, and device trials on ClinicalTrials.gov using the Protocol Registration System, a web-based system with complex formatting requirements. A year later, in September 2008, sponsors had to start reporting basic results for studies of approved products within twelve months of completion date. In September 2009 came the reporting of adverse events (AEs).
Penalties for non-compliance are serious. Violators face civil monetary penalties up to $10,000/day for each day a violation remains unresolved; there is public notice of the non-compliance on ClinicalTrials.gov; and the possibility of withholding grant funds from the NIH.
According to Godlew, “This whole process is very resource-intensive. Most companies have some processes in place to address the current rules and teams to comply, but this varies by size of company and complexity of the trials. Large companies may dedicate 10 to 15 full-time equivalents (FTEs) to this effort. Medium size companies will grab resources where they can, and for smaller companies, it can be really tough.”
Merete Jorgensen, director, Global Clinical Registry, Global Development, for Novo Nordisk, says her company has a dedicated unit. “My group has a total of eight people. As part of registering trials, we closely monitor our clinical trial management system to see when trials are going to be initiated and when the status of a trial changes, so we can make sure that we are posting at the right time,” Jorgensen notes.
Compliance is made more difficult by the growing number of trial registries across the globe, each with its own set of submissions requirements. Differences between requirements for ClinicalTrials.gov and EudraCT highlight how much work can be involved in meeting such requirements. For example, in Europe, clinical trial results must be disclosed for approved as well as unapproved products. Also, protocol-related information and results of studies with a pediatric population are to be disclosed for all phases of clinical trials. By comparison, Phase I drug trials with a pediatric cohort do not require results posting on ClinicalTrials.gov.
Another difference between the two registries will come with the release of EudraCT Version 9 late this year or early in 2013, calling for expanded results requirements. “We know there will be more fields required for EudraCT than for ClinicalTrials.gov. We understand they’ve proposed approximately 150 fields, which is about 50 more than what is currently required for ClinicalTrials.gov,” explains Godlew.
It is noteworthy that presently, clinical trial results from Europe are available only to regulators, not the general public. This will change once the latest version of EudraCT is implemented, as results of clinical trials will be made publicly available through the European Union Clinical Trials Register (EUCTR).
The US and the EU have among the world’s more developed registries, but as more countries develop their own, submitting data will pose a growing drain on resources. Although harmonizing this effort globally may be on the horizon, it remains a far-off reality.