Data often incomplete, unavailable, or difficult to access, panel says.

BOSTON -- Clinical trials lack transparency, and needed information is not getting to physicians. That was the consensus at a bioethics track session on increasing clinical trial transparency at the BIO annual meeting here May 7-9.

A pilot survey by the Tufts Center for the Study of Drug Development and Aptel Consulting was conducted recently, noted Kenneth Kaitin, director of the Center. The survey asked participating physicians three vital questions about clinical trials--where do physicians get information, to what extent do they access this information, and what is the accuracy and adequacy of the information--in three areas of clinical practice: oncology, cardiology, and infectious diseases.

The results showed that the top source of information for physicians surveyed is peer-reviewed journals, followed by email alerts, FDA and Department of Health and Human Services (HHS) websites, and continuing education. "What didn't show up," Kaitlin noted wryly, "was information from patients themselves."

The primary unmet need, as identified by survey respondents, is access to published results of negative trials, as well as a centralized web-searchable database, with guidelines attached to the clinical trial data.

This kind of trial registration and results reporting is what Clinicaltrials.gov is mandated to do. Two recent developments have spurred interest in the reporting of clinical trials: the new trial registration requirement of peer-reviewed journals, and the recent availability of publicly accessible archives on the site.

However, there are issues with availability of clinical trials data having to do with data access, according to Deborah Zarin, Assistant Director for Clinical Research at ClinicalTrials.gov. "It's not always easy to get information," she acknowledged. "Names and identifiers are critical. For example, search engines can only use known names and synonyms." Not only that, but "code names lead to hidden trials," which isn't the agency's intention. "We have no intention of keeping any of this secret," Zarin explained. "What we need are decoders."

One way of creating this transparency about the trials is to list all synonyms for drugs when they are marketed--the current procedure in Maine, the only state to have instituted any kind of law concerning clinical trials. The reporting of trial results, said Zarin, needs to include a link to PubMed/Medline, information from FDA, "and a clearly marked sponsor site."

"We're talking about a complicated set of issues with no industry consensus," explained John Alam, Executive Vice President, Medicines Development and Chief Medical Officer of Vertex Pharmaceuticals, which sponsored the bioethics track at the BIO meeting. "We're all talking about a clinical trials database but with no target audience agreement and no results agreement."

Negative or incomplete clinical trials results are not published for a variety of reasons including "a lack of time or resources, or an incomplete study," said Alam. The company may have "a need to focus on filing for successful disease indicators," or there could have been a failed trial, a lack of reward, journal ambivalence, investigator ambivalence, or an issue of disclosure of proprietary information.

Industry-sponsored clinical trials can be delayed in getting information out. There are higher publication rates when the issue concerns patient safety, and delayed publication in trials that are more centered on scientific progress.

The results of clinical trials in the pre-approval stage for drugs that are eventually approved may be published eventually, but are frequently delayed for intellectual property reasons. And the results of clinical trials in the pre-approval stage for drugs that are not commercialized are generally not published at all, as there is "no immediate impact on patient safety," said Alam; the results "may be presented at meetings but aren't published in peer-reviewed journals." There is competitive positioning that goes on "as well as IP issues in the timely dissemination of results."

Moreover, disclosure requirements can place smaller or midsized companies at a competitive disadvantage with regard to larger pharmaceutical and biotech companies. "What is sufficient disclosure?" Alam asked. "Publication, scientific presentations, regulatory submission, a clinical trials database, a press release? All of the above?"

Standardization opportunities, he points out, are available at regulatory authorities' websites. But standardization is not the only issue. "We have to decide what are objectives are," he concluded. "Which trial results should be published? What incentives or protection are we offering for scientific disclosure early in the drug development cycle?"

The Commission on the Future of Drug Safety has made some recommendation as part of its vision for overall drug improvement, said R. Alta Charo, Warren P. Knowles Professor of Law and Bioethics at the University of Wisconsin Law School and another member of the panel.

The first recommendation was a "return to the lifecycle approach," said Charo, with preapproval and post-approval no longer the paradigm for drug development. The other recommendations have to do with the FDA: improving its culture and credibility, giving the agency more authority, improving the surveillance system, and adding "extensive additional funding."

That's not what is happening now, Charo argued. "The process is unorganized and FDA postings are incomplete."

He said registration at ClinicalTrials.Gov should happen during phases II through IV if the company intends to file with FDA, and every completed trial should be submitted, with uncompleted trials stating why they were not finished. "This is not a trivial amount of work," Charo cautioned.

Speaking from the perspective of a patient advocacy group, Veronica Todaro, Director of National Programs, Parkinson's Disease Foundation, said there is a "low level of satisfaction with the available information on clinical trials," including a low reliance on physicians for information. "The peer group is more important to patients," she argued. "We need to incorporate the patient perspective in the clinical research process."

By Jeannette Cezanne New England Correspondent