FDA Amendments Act requires clinical trial registration

October 15, 2008

The FDA Amendments Act of 2007 established requirements related to controlled clinical trials of drugs that ultimately would be subject to FDA regulation.

It has been a year since the passage of the FDA Amendments Act of 2007. As the annual meeting of the American Academy of Ophthalmology approaches and the Association for Research in Vision and Ophthalmology (ARVO) accepts abstracts for its 2009 annual meeting, compliance with registration rules once again becomes an immediate concern to researchers presenting trial data.

The FDA Modernization Act of 1997, the legislation preceding the FDA Amendments Acts of 2007, required registration of efficacy trials on drugs for serious or life-threatening diseases or conditions, but it did not include any means of enforcement. In fall 2004, legislators introduced a bill to Congress that called for the registration of all clinical trials as a condition of new drug application (NDA) approval, with a proposed penalty of $10,000 per day of non-compliance. That bill became the FDA Amendments Act of 2007.

In addition to mandating clinical trial registration and disclosure of results of trials of drugs, biologics, and devices as a condition of NDA approval, the act has the ultimate goals of offering complete transparency and open access of information to clinical researchers and the public. With the exception of phase I and small preparatory studies, all controlled clinical trials of drugs must be registered if the drugs ultimately are to be subject to FDA regulation. The penalties for failure to register are severe: as well as the potential fine of up to $10,000 per day of non-compliance, responsible parties also may lose grant funds. The responsibility for compliance rests with the sponsor or the principal investigator (PI), depending on who initiated the trial and who has ultimate control over the data.

What to report

The National Institutes of Health is charged with overseeing registration. In addition to registering a study, the sponsor or the PI also must update the information annually and each time a change occurs in the status of the trial. Study results also must be posted. When a sponsor is involved in a study, clear communication between the sponsor and the PI is necessary to define explicitly who is in charge of handling those responsibilities.

Numerous data elements must be disclosed, including information describing the study, recruitment procedures, location, administration, and contacts. Demographic and baseline characteristics of the patient sample, as well as primary and secondary outcome measures, also must be entered into the results data bank.

Submission of this information is required for ongoing clinical trials that were initiated after Sept. 27, 2007. Trials exempt from the 2007 act are those that involve a serious or life-threatening disease or condition, studies that were initiated before Sept. 27, 2007, and trials that were completed before Dec. 26, 2007. Proof of registration must be submitted as part of the NDA.

Other efforts

Although the FDA Amendments Act of 2007 applies only to research conducted in the United States, organizations elsewhere also are attempting to promote transparency. The World Health Organization (WHO), in an effort to provide unity and efficiency among clinical trial registries, introduced the International Clinical Trials Registry Platform (ICTRP) in 2006.

The platform, which includes the ICTRP search portal (a database of trial registration data sets), and the WHO Registry Network (designed to promote communication and exchange of information to bolster proper trial registration) was initiated to create a universal standard among registries. Researchers worldwide, in addition to medical journal editors, also have joined the collaboration for greater transparency. Further, since the 1978 introduction of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals by the International Committee of Medical Journal Editors, manuscripts submitted for peer review have been under increasingly stringent regulation with regard to author disclosures and data transparency.

Several ophthalmic conferences including ARVO require registration of trials if data are to be presented at a meeting. All studies and results-except phase I trials, individual case reports, or observational case series, retrospective analyses, and experimental treatments that were compared with historical control group-must be registered for them to be presented at ARVO annual meetings.

Because the 2007 act made full clinical trial registration mandatory, it also effectively rendered irrelevant any misgivings that pharmaceutical companies and industry sponsors might have had regarding increased disclosure. Not only are improved communication and accessibility of trial information coming with the new law, so is equality within the industry.

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