By Ann Neuer
September 21, 2009 | Starting on September 27, sponsors of industry-, academic- and government-run clinical trials will have to begin reporting adverse events on www.clinicaltrials.gov. This is the latest in a series of requirements meant to extend the amount of publicly available information on clinical trials.
The various requirements are defined in the Food and Drug Administration Amendments Act of 2007 (FDAAA), which went into effect in September 2007. Since then, sponsors have been faced with yearly step-ups in what they must report. Effective December 2007, they had to start registering Phase II–IV drug and device trials on clinicaltrials.gov. September 2008 saw the beginning of the reporting of basic results for studies within twelve months of completion. And now, responsible parties submitting results will have to include adverse events (AEs) in order for the records to be accepted by the Protocol Registration System, the Web site’s data entry tool.
Suzanne Heyd, a consultant and clinical trial results analyst at Bristol-Myers Squibb, says the company is gearing up for this next step. “BMS is creating a process of XML feed to send AE data straight to the NIH. We have to report all serious adverse events, as well as all AEs with the frequency threshold of 5 percent or greater within any trial arm,” she says.
Complying with this latest reporting mandate, as well as previous requirements, is proving to be a very complex, labor-intensive process. There are multiple Web sites for stakeholders and detailed PowerPoint presentations put together by NIH to explain how data should be submitted to the results database. In addition, details surrounding how reports are to be prepared keep changing, as this is a work in progress. For example, there were two updates to information on AE reporting in the first half of September. Sponsors have to be very nimble because when NIH announces changes, they go into effect the same day.
Heyd comments, “This whole process is a huge drain on resources, no matter how you slice it. We have teams of people working on this, and we’ve spent hours and hours in meetings to do testing and to check the data. It’s a systemic change and it’s been an enormous undertaking.”
Once data are submitted, they go through a Quality Assurance process at NIH, which maintains clinicaltrials.gov. Data are scrutinized for validity, meaningful entries, internal consistency and logic, and format. Because of the massive volume of data now being submitted, there is a lag time between submission and posting on the Web site. According to Heyd, “NIH is taking about two months to review our records.”
As of mid-September, data from nearly 79,000 clinical trials from 171 countries appear on the Web site.
Being in compliance with clinicaltrials.gov submission requirements is serious business. There is a tough enforcement component. Thirty days after notification of a violation, violators face civil monetary penalties up to $10,000/day for each day the violation remains unresolved. In addition, there is public notice of the non-compliance, potential withholding of NIH funds, and possible sanctions from FDA.
The public hungers for transparency in clinical trials, and while NIH is working hard to satisfy this need, compliance requires an intense commitment by responsible parties. And the bar will be raised again next year. Effective September 27, 2010, requirements for expanded results reporting will go into effect.