National registry has grown to near 30,000 studies
Journal announcement started avalanche
Clinical trial registration rapidly is gaining acceptance and soon could be a standard for researchers and sponsors alike.
"It's moving towards becoming something that people will expect," says Deborah Zarin, MD, director of ClinicalTrials.gov at the National Library of Medicine, which runs the web site on behalf of the National Institutes of Health.
"We're hoping IRBs will start accepting and demanding it," Zarin says. "The more comprehensive it is, the more useful it is to everyone."
Patients, providers, and journal editors, who try to interpret medical literature, all should find it useful, she adds.
The NLM's ClinicalTrials.gov web site for registering clinical trials grew at a steady pace between its initiation in 2000 and 2005.
Then in the second half of 2005, its registration jumped in response to the implementation of the International Committee of Medical Journal Editors (ICMJE) policy requiring clinical trials to be registered as a prerequisite for publication.1
"The ICMJE said they wouldn't consider publishing a manuscript of a clinical trial unless it had been registered prior to registry of the first subject," Zarin says.
The NLM had a year's notice of the ICMJE's deadline, which was Sept. 13, 2005, and was able to handle a huge increase in registration, Zarin notes. (See table of ICMJE's registration requirement.)
"It has quadrupled the number of weekly registrations even now," Zarin says.
As of mid-May 2006, the web site has about 29,700 trials registered, making it the biggest clinical trials registry in the world, Zarin says.
Between May 20, 2005, and Oct. 11, 2005, the registry had a 73% increase in the number of registrants, from 13,153 to 22,714.1
Both investigational new devices (IND) and non-IND studies had increases, and non-industry data providers also changed their registration behavior near the ICMJE deadline. Also, there was a 195% increase in international registrants.1
Prior to the ICMJE announcement, there was little extrinsic incentive to register a trial, other than the minority of trials that were required to register under the FDA's Modernization Act, section 113, which mandated the registration of all private and public trials that test effectiveness for serious or life-threatening conditions submitted under an IND application.1
Budgeted at $3 million per year, NLM doesn't charge for clinical trials registration, Zarin says.
"We take advantage of a lot of the infrastructure at NLM, which runs Medline and Pubscan and GenBank," Zarin says. "So this fits well within our portfolio at NLM, and we have efficiencies."
The web site, which has 20 million hits monthly, including one-half a million unique users per month, was not created to provide study results, although there are links to published results and to other resources that might be useful, Zarin says.
Although some drug companies and research institutions have developed their own clinical trial registries, the ICMJE initially only accepted ClinicalTrials.gov because it met their criteria for a not-for-profit registry that also is inclusive and does not have conflicts of interest, she says.
For example, the University of Pennsylvania of Philadelphia, PA, started its own registration site called ClinicalTrials@Penn in August, 2005, but the ICMJE said it did not meet their criteria at the time the university presented the registry to ICMJE, says Adam P. Rifkind, Esq, associate director of corporate contracts in the office of research services.
ClinicalTrials.gov has a straightforward protocol registration system that was designed to encourage the registration of all clinical trials, Zarin says. "We encourage everyone to register all of their trials to improve transparency and as an ethical obligation to subjects in the trial," Zarin says. "It's important, in order to contribute to medical knowledge, that things have to be published."
People can't interpret published literature about trials without knowing the denominator, Zarin notes.
"If you read one study of a drug and missed nine others, then you've been mislead," she says. "Knowing how many trials were conducted on a drug helps you understand the context in which you are reading the results."
The original intent of ClinicalTrials.gov was to help potential subjects find trials in which they might be interested in enrolling, Zarin says.
"That's an important user group, but other uses have become clear, including IRB members, and anyone who would want to see what other studies are out there," Zarin adds.
Those who register trials are required to keep the information up to date, focusing in particular on the latest news about recruitment status, Zarin says. "If we don't hear from you, we bug you every six months," she says.
An international clinical trials registration site is an idea whose time has come.
"Experts in the field have been calling for registries for a long time," Zarin says. "And it didn't hit a critical mass of public understanding of the importance of registries until the human cry over Vioxx and Paxil."
The Journal of the American Medical Association published an editorial calling for trial registration in September, 2004, and the World Health Organization (WHO) also endorsed registration.
It wasn't until the ICMJE issued its announcement that the avalanche of registration began, Zarin says.
The registry is undergoing continuous improvement, largely to follow the ICMJE's policy regarding breadth and depth of the registry, Zarin says.
Reference
- Zarin DA, Tse T, Ide NC. Trial registration at ClinicalTrials.gov between May and October 2005. N Engl J Med. 2005;353(26):2779-2787.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content