Forgotten Voices in the Transparency Debate

During the past two years, we have been enamored with the disclosure of trial information online. All stakeholders—among them the pharmaceutical industry, medical journal editors, the American Medical Association, the Association of American Medical Colleges, patient advocacy groups, the U.S. Congress, and the World Health Organization—actively and openly support improving information transparency and disclosure. What specifically is disclosed, how it is disclosed, and how to ensure compliance are the issues now stoking the flames of debate.

Kenneth A. Getz

Under the 1997 FDA Modernization Act, disclosure of clinical trial information for serious or life-threatening conditions on clinicaltrials.gov has been required of all research sponsors. Yet compliance and enforcement of this nearly decades-old mandate has been lax. Heightened attention and urgent debate around clinical trial and trial results registries has been prompted most recently by serious allegations that the lack of transparency and accountability, and the appearance of concealment, has compromised patient safety and public health. Recently, in an effort to stimulate higher levels of compliance, the International Committee of Medical Journal Editors began requiring that sponsors register their clinical trials, before enrollment of the first patient, as a condition of consideration for publication in major peer-reviewed journals. Legislators want to go even further by forcing sponsors to publicly post the details of their clinical trials, including results, on the National Library of Medicine's Web site (clinicaltrials.gov). Some have suggested that the failure to do so should carry substantial monetary penalties.

At the center of the "trial transparency" debate is whether or not disclosure is best accomplished via either one central registry—with clinicaltrials.gov the seemingly obvious choice—or at many different online locations. More than 1500 organizations —including private sector research sponsors, investigative sites, general and health information publishers, and disease-specific groups—are now listing clinical trials on the Internet, and the rate of proliferation of these autonomous Web sites is accelerating.

Although disclosure and transparency of clinical research information via online registries is primarily intended for use by the public, to date the debate has not had input from the public and patient communities. Shamefully, no one has bothered to inquire what registry users think about all of this. Had they asked, they would learn that the public isn't concerned about the volume and sophistication of clinical trials data they can find online. What the public wants is easy access to summary information and some sense of what to do once they find it.

In the absence of information on the attitudes and behaviors of registry users, The Center for Information and Study on Clinical Research Participation (CISCRP)—a nonprofit organization—conducted an online survey in late 2005 among nearly 5000 registry users. This initial CISCRP study begins to amplify a voice that is too often unheard and forgotten. It is critically important that clinicaltrials.gov and other well-established publishers of registries also make efforts to share what they have learned about their users to better inform the debate.

Multi- or single sources sought

According to the CISCRP survey, at this time the public does not want a single registry. They don't trust one source for information—regardless of whether a government or private-sector organization is sponsoring the site. Users would prefer to browse multiple locations to support their desire to self-advocate their health care decisions. Eventually, registry users want the convenience offered by a single source—but their trust in that source needs to be better established.

Approximately 40% of users access clinical trial and trial results registries through links from other Web sites such as those listing general or disease-specific health information. Another 40% of respondents access registry information through major search engines such as Google and Yahoo. Very few users report book-marking (i.e., capturing a favorite Web page for future reference) a given clinical trial or trial listing registry. Users are visiting an average of four registries per search, and it does not appear that they discriminate between general, disease-specific, and company-specific content. Each visit averages less than five minutes since registry users are looking for very specific information. This harried and brief browsing behavior is not conducive to dense, highly technical and detailed clinical research and medical information. Indeed, users don't want that much information.

Registry users most want easy-to-process, summary trial information; details on whether the trials are being conducted in conveniently accessible locations; and investigative site contact information. Investigator and staff credentials, highly detailed study requirements, glossaries of terms, and compensation amounts are of far less interest to users at this stage of their search. Individuals want summary descriptions of trial outcomes and short listings of relevant citations from peer-review journals.

The typical registry user is a middle-aged female with some college education. They are not university-trained scientists who subsist on footnoted, highly technical peer-reviewed literature. Many intelligent, would-be research participants don't understand exactly what a clinical trial is all about. The majority of registry users positively rate the amount and quality of information that is provided on a registry, but such ratings may be largely explained by users having no context or basis with which to compare information quality and quantity. One-out-of-five users report that finding information is very difficult, and one-out-of-six users report that registry information is very hard to understand.

Users appear somewhat lost and confused. Clinical trial registries do not elicit strong calls to action. Among those who succeeded in finding a clinical trial, most never bothered to contact the research center. Approximately 10% of users initially emailed registry information to a family member or friend. Only 1% of registry users report initially emailing the information to their health care provider. Eventually, half of all registry users report showing the information to a family member or friend, and one-in-four showed the information to their physician or nurse.

Most telling, 87% of respondents said that they want suggestions on what to do with information once they find what they're looking for. And more than eight-out-of-ten (84%) users said that they would like registries to teach them how to evaluate the information in order to determine the appropriateness and risk/benefit of a given clinical trial. This feedback captures the high importance of providing more than just clinical trial and results information on registries. Users are asking for hand-holding and guidance.

Inherent limitations

And all this is to say nothing of the limitations of the medium itself. Forty-two percent of Americans don't use the Internet, and about a quarter of them don't have access to the Web. This includes a disproportionate share of English-speaking Hispanics and African-Americans, the lesser educated, and the disabled. Of those who use the Internet regularly, a recent Harris Interactive poll finds that one-fifth would prefer not to use the Web to access registry information anyway. If the intent of disclosure and transparency is to be fully embraced, then research sponsors and registry information publishers must entertain using coordinated offline and online communication and dissemination vehicles.

In the real world of clinical trials, the gap between knowledge and personal action remains huge. Americans by and large believe in the importance of clinical research, yet lack a fundamental understanding of why and how it is conducted and feel severely ill-equipped to find and evaluate trial information on their own. They consider their physician the most trusted source for health-related information, yet few of them learn about trials this way. And while they are receiving promotional messages about clinical trials, they rarely consider a clinical trial when faced with a serious, life-threatening or debilitating illness for which limited or no viable treatments exist.

Do registries foster trust?

Loading up the Internet with increasing numbers of independent Web sites containing mind-dizzying amounts of clinical trial and results data will not raise awareness, aid decision-making or build trust among those who currently enjoy Internet access. Less than 20% of registry users believe that the listing of clinical trials and trial results on a public Web site would greatly increase their trust in information received from clinical research professionals. Public distrust of clinical research is the result of lapses in integrity on the part of stakeholders on all sides of the debate—academia, medical journals, regulatory organizations, government agencies, industry, and other members of the research community. None of these stakeholders are licensed to drive the debate alone. They must collectively address the rising level of public distrust with the benefit of input and insight from the public.

Clinical trial registries, in and of themselves, are not the answer. Grassroots and national awareness building, education, and outreach must be essential ingredients of any and all attempts to disclose information. In the interim, the trial transparency debate would be enriched by amplifying the largely forgotten voices browsing the Internet in search of information and hope for treatment options.

Kenneth A. Getz, MS, MBA, is a Senior Research Fellow at the Tufts CSDD and Chairman of CISCRP, both in Boston, MA, email: kenneth.getz@tufts.edu