The Price of Failing to Register Clinical Trials
By now researchers should be aware of a 2007 law that expanded the types of clinical trials that must be registered on clinicaltrials.gov, the federal registry established in 2000. They should also be aware of a 2004 policy instituted by the editors of leading journals requiring trials to be registered in a public database in order for studies to be considered for publication. Since failure to do so will result in the study's being rejected for publication—as happened recently at Yale—it's worth reviewing the rules.
While the Food and Drug Administration Amendments Act of 2007 (FDAAA) and the International Committee of Medical Journal Editors (ICMJE) policy both require the registration of clinical trials, the ICMJE policy is more stringent. By law, most trials of drugs, biologics, and devices under FDA jurisdiction must be registered, although phase I trials are excluded. According to the ICMJE policy, however, all interventional studies, regardless of phase or intervention type, must be registered. Many journals adhere to the ICMJE requirements, including such top-tier publications as the Journal of the American Medical Association, The Lancet, and The New England Journal of Medicine. Yale researchers are therefore advised to register all trials on clinicaltrials.gov in order to comply with ICMJE policy and meet eligibility requirements for publication in peer-reviewed journals.
Timing is another important issue. According to the FDAAA, the registration deadline is 21 days after the first subject is enrolled for clinical trials that were initiated after September 27, 2007 or were ongoing as of December 26, 2007. But the ICMJE's policy, which went into effect in 2004, requires registration before the first subject is enrolled. The ICMJE will accept registration in any of the dozen or so WHO-approved primary registries: however, because registration on clinicaltrials.gov is a legal requirement and meets the ICMJE criteria, investigators fulfill both requirements by registering on it.
The FDAAA states that as of September 27, 2008, clinical trial results must be reported within 12 months of final data collection and as of 2009, adverse events must be included. It also requires that information be updated at least every 12 months. The ICMJE requires updates at least every six months. Recognizing that the FDAAA mandates the posting of summary results data on clinicaltrials.gov, the ICMJE does not consider posting results data there to be prior publication.
While noncompliance with the ICMJE policy may preclude publication of a study in a peer-reviewed journal, the penalty is steeper for failing to register on clinicaltrials.gov. It includes fines of $10,000 per violation and the withholding or recovery of grant funds for federally funded trials.
When the ICMJE policy was announced in 2004, only about 13,000 trials were registered on clinicaltrials.gov. Today the registry includes over 112,000 trials from 175 countries and the website receives over 50 million page views per month. But that doesn't mean that compliance is 100 percent.
"We're aware of many academic medical centers where there seems to be a lot less reporting of results than would required under the law," said Deborah Zarin, MD, director of clinicaltrials.gov. According to an update in the Journal of Clinical Research Best Practices, the NIH has found that academic institutions are compliant with FDAAA regulations for posting trial results less than five percent of the time. "I think academic medical centers have a responsibility to their human volunteers to make sure that research conducted in their centers is compliant with all prevailing standards, so clinical trials should not be done that aren't registered," said Zarin, who has visited Yale two years in a row to educate investigators on complying with the FDAAA.
YCCI can assist investigators with setting up registration on clinicaltrials.gov. Please click here or contact Kevin Palmer at 203.785.3482, or firstname.lastname@example.org if you need help or have questions. Additional information is also available at http://www.clinicaltrials.gov.