International Push Under Way To Improve Drug-Trials Data

The World Health Organization (WHO) last month urged research institutions and pharmaceutical companies around the world to register all medical studies that test treatments on human beings, including the earliest phase of research, whether they involve patients or healthy volunteers.

The initiative—known as the International Clinical Trials Registry Platform— is framed around a set of 20 “key details” that must be disclosed at the time a study begins and is aimed at standardizing the way information on medical studies is made available to the public.

“Registration of all clinical trials and full disclosure of key information at the time of registration are fundamental to ensuring transparency in medical research and fulfilling ethical responsibilities to patients and study participants,” said Timothy Evans, M.D., assistant director-general of WHO.

Paul Appelbaum, M.D., a former APA president and director of the Division of Psychiatry, Law, and Ethics at Columbia University College of Physicians and Surgeons, agreed that registration of all clinical trials is a“ critical step,” one that would help assure “the integrity of the research process.” He added that comprehensive, advance registration of clinical trials would accomplish several goals.

“Not only does advance specification of outcome measures limit the potential for post facto manipulation of data, but public knowledge of every trial under way means that negative studies cannot go unacknowledged,” Appelbaum told Psychiatric News. “Physicians and patients are thus more likely to have access to the full array of information about medications before making prescribing decisions.”

Appelbaum also noted APA's long-standing commitment to transparency in clinical research. APA has been at the forefront of the issue, advocating for mandatory registration of all clinical trials and ensuring researchers' unencumbered rights to publication of all results from those trials. In 2002 APA looked favorably on calls for requiring that clinical trials be registered in order for their results to be published in peer-reviewed journals (Psychiatric News, February 1, 2002). In 2004 APA joined the American Academy of Child and Adolescent Psychiatry and others in winning approval of a new AMA policy calling for federal legislation mandating registry of all clinical trials (Psychiatric News, July 16, 2004).

The WHO Registry Platform is not a clinical trials register itself, but rather provides a set of standards for all registries around the world to use. Use of the standards is voluntary. The initiative not only aims to standardize what must be reported to register a clinical trial, but also will create a global trial identification system that will issue a standardized unique reference number for every qualified trial.

Currently, there are several hundred registries of clinical trials around the world, but little coordination among them. In the United States the predominant registry is the National Library of Medicine's<www.clinicaltrials.gov>. However, registration requirements for this site differ from WHO's (see box).

Other countries have also formed voluntary registries as well, including Canada, United Kingdom, Germany, Japan, and Australia. In addition, many large pharmaceutical companies have developed online registries devoted to their own clinical research.

Individual companies and institutions can adopt the new WHO standards at any time. While no countries have announced adoption yet, a WHO spokesperson noted that there is a vocal group of supporters calling on the United Nations to adopt the registry platform as a mandatory requirement of human research. Under current treaties, the spokesperson confirmed, a U.N.-mandated registry platform could be legally required for all sponsors initiating clinical trials in any U.N. member country.

Later this year, the WHO registry will launch a Web-based search portal through which scientists, patients, doctors, donors, and others can search among participating registers for clinical trials taking place or completed throughout the world.

WHO is recommending that 20 key details be disclosed at the time studies are begun. Basic identification information includes the primary registry in which the trial is registered and the identification number of the trial with that registry. In addition, source of funding, primary and secondary sponsors, and both the public and scientific titles of each clinical trial must be disclosed.

The WHO initiative also calls for disclosure of more specific trial information up front: The health condition(s) being studied, the specific intervention(s) being studied, key inclusion and exclusion criteria, and the primary and secondary outcomes to be measured.

WHO administrators said the initiative seeks to respond to growing public demands for transparency regarding all studies applying interventions to human participants.

“Our aim is to make clinical research transparent and enhance public trust in science, but we are engaged in a fair and open process with all stakeholders. We look forward to continued dialogue about trial registration and results reporting as we move forward with the registry platform,” said Ida Sim, Ph.D., the associate director for medical informatics at the University of California, San Francisco, and coordinator of the WHO Registry Platform initiative.

Before making the recommendations, the WHO initiative involved consultation over a period of nearly two years with a wide array of concerned stakeholders, including representatives from the pharmaceutical, biotechnology, and medical device industries; patient and consumer groups; governments; medical journal editors; ethics committees; and academia.

Some groups have raised concerns that the proposed requirements could jeopardize academic or commercial competitive advantage if they apply to preliminary trials of new interventions. Similar concerns have been voiced about the requirement to disclose certain items—such as the scientific title of the study, the specific name of the treatment being tested, and the outcomes expected from the study—at the time of registration.

WHO officials pointed out, however, that if all sponsors disclose all 20 key details outlined by the registry platform, no sponsor is left with a competitive advantage because the standards for disclosure are uniform.

More information on the WHO initiative is posted at<www.who.int/ictrp/en/>.▪