Trial registry may be new policy for literature

November 1, 2005

Ophthalmologists who are clinical investigators will likely be affected by new trial registration policies if they intend to publish research in top-tier journals.

Allegations of selective publication and biased reporting of clinical trials have led to the demand for full disclosure and transparency in clinical research. Clinical trial registries are one way to provide this transparency.

In the last year, influential medical journal editors, including editors of prominent ophthalmic journals, have instituted a new policy that helps establish trial registration as a prerequisite for publication.

These initiatives are motivated by a desire to improve clinical research and provide greater transparency. At this time, there is agreement about all but four registry data elements. The remaining are viewed by PhRMA as details that could compromise intellectual property rights and competition.

Should clinical trials be registered in a public database? Should registration be voluntary or mandatory, and what trials should be included? There has been an increase in support for mandatory registration because of concerns about the effect of concealing negative data, a desire to protect research subjects, and a desire for open access to information on the part of researchers, physicians, and the public.

There have been disease-specific clinical trial registries since the 1960s. There are currently hundreds of clinical trial databases, some run by governmental agencies (such as the National Library of Medicine's [NLM] http://www.clinicaltrials.gov/) and some by industry (such as PhRMA's http://www.clinicalstudyresults.org/).1 In 1997, the FDA Reform Act mandated registration of all trials involving serious and life-threatening diseases, but since there was no enforcement mechanism it amounted to a voluntary system. In fact, in 2002 the FDA found that only 48% of trials of cancer drugs had been registered, and for some other serious diseases the compliance rate was in the single digits.2

In fall 2004, legislators introduced bills in the U.S. House and Senate that would require registration of all clinical trials as a condition of ethics board approval and with civil penalties of $10,000 per day for non-compliance. The legislation, called the Fair Access to Clinical Trials (FACT) Act, has bipartisan support in the Senate. The Senate and House versions are similar but not identical; both versions are being reviewed by congressional committees.3

S. 470 was introduced by Sen. Christopher J. Dodd (D-CT) on Feb. 28 and was referred to the Senate Committee on Health, Education, Labor and Pensions. H.R. 3196 was introduced by Rep. Henry A. Waxman (D-CA) on June 30 and was referred to the House Energy and Commerce Subcommittee on Health.

No further action has occurred on either legislation.

The requirement to register trials has been added to the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, which more than 200 journals are reported to follow (see sidebar, "Do ophthalmologists need to register their clinical trials?").