Industry anger over stringent trial disclosure requirements

Arguments over the WHO's request to register early-stage trials You have full access to this article via your institution. Download PDF Improving transparency: The World Health

Organization's guidelines for clinical trials registries demand that companies must post details of Phase I trials. Credit: WHO In response to a series of recent scandals involving

clinical trials, companies and organizations have launched several voluntary registries to increase transparency. But these have also created confusion, with registration requirements

differing markedly among initiatives. In an attempt to harmonize the process, the World Health Organization in May published universal standards for disclosing clinical trial data. The new

standards urge registration of all trials from their inception, and list 20 data requirements that the WHO says should be posted as part of registration (see _Lancet_, 367, 1631–1633; 2006).

Although most stakeholders welcomed WHO's commitment to improving transparency, industry has objected to several aspects of the new standards. And drug company officials and lobbyists

say bluntly that they have no plans to abide by the provisions with which they disagree. “We already have in place a very solid policy with regard to disclosure which we believe meets the

key needs of patients and physicians. And we don't currently have any plans to revise it,” says Caroline Loew, the senior vice president for scientific and regulatory affairs at the

Pharmaceutical Research and Manufacturers of America (PhRMA), which launched its own clinical trials database in September 2004. One standard that has clearly irked the industry is

WHO's request that Phase I studies be registered. Industry representatives contend that there is little public value, and great proprietary risk, in posting details of Phase I studies.

They note that Phase I trials generally involve small numbers of patients and are only designed as preliminary dose and toxicology studies. They also point out that around 80–90% of

molecules fail at this stage. “The fact that [the WHO] would take on clinical trial registries and data disclosure is very good for the transparency movement,” says Alan Breir, the Chief

Medical Officer at Eli Lilly. “But the value of a Phase I trial to the public is very, very limited, so there's just not a compelling argument to post all Phase I trials at their

inception.” Proponents of the new standards say, however, that a recent Phase I trial that went badly wrong clearly shows the value of disclosing these first-in-human trials. In March, six

healthy volunteers at Northwick Park Hospital in London suffered multiple organ failure when they were injected with TGN1412, a monoclonal antibody made by TeGenero (see _Nature_ 440,

388–389; 2006). If the TeGenero trial was registered, other investigators considering developing a similar antibody in future would have access to “very important information in making a

decision as to whether to go ahead,” argues Tim Evans, the WHO Assistant Director-General who co-authored the standards. Beyond their resistance to registering Phase I trials, industry

officials also argue that 5 of the 20 data points that the WHO is urging be made public could cause proprietary harm later in drug development: the scientific title of the study; the target

sample size; the key inclusion and exclusion criteria; and the primary and secondary outcomes. For instance, publishing the title of the study could alert competitors to the fact that a firm

is working on a novel application of an already-approved drug, they say. Companies, says PhRMA's Loew, would be discouraged from making investments in innovation “by knowing

there's a relatively high risk of a competitor leveraging their research.” In their guidelines, the authors argue that some companies already disclose all outcomes and that proprietary

information on investigational drugs is often available in databases for a fee, or through trial participants and consumer websites. “It's not a secret that companies spend a tremendous

amount trying to find out what others are doing,” says WHO's Evans. “If these trial-registration processes are respected, companies might spend an awful lot less trying to figure out

what's in each other's pipelines.” > It's important to look at the cup as half full. I see only good > things coming out of this. Brier, who served on the Scientific

Advisory Group for the guidelines, thinks that arguments over the 5 data points are a smokescreen, because the main value of a registration standard lies in the very publicizing of a

trial's existence. “What's critical is the acknowledgement that the trial exists, and to connect it later with the trial results,” says Brier. “If you fill out 15 versus 20 [data

points], that's not the critical question.” Brier says that Lilly posts the results and all the methodology of Phase I trials for its drugs that do make it to market. The difficulty in

moving forward from this apparent impasse is that the WHO standards lack an enforcement mechanism, and at present there is little indication that the industry intends to embrace them in

their entirety. “If WHO had been able to show more flexibility with regard to what information it provided on what trials at what time, we would have found ourselves in much more of a

position to be able to consider implementing their policy proposal,” says Loew. But although the WHO standards aren't legally enforceable, they do carry considerable moral and political

weight. Their backers are hopeful, for instance, that university and hospital-based ethics committees will begin requiring registration of WHO's 20 data points before signing off on

proposed trials. And Richard Horton, editor of The Lancet and co-chair of the WHO Scientific Advisory Group, notes that clinical trials are increasingly being conducted in developing

countries, where standards can be lax, so a registration standard that has global reach is of great importance. Despite the differences in opinion, Brier remains hopeful that the stumbling

blocks can be overcome. He believes that the areas of agreement between the industry and WHO are much greater than the few areas of disagreement. “It's important to look at the cup as

half full,” he says. “I see only good things coming out of this.” Authors * Meredith Wadman View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Wadman, M. Industry anger over stringent trial disclosure requirements. _Nat Rev Drug Discov_ 5, 527–528 (2006).

https://doi.org/10.1038/nrd2103 Download citation * Issue Date: 01 July 2006 * DOI: https://doi.org/10.1038/nrd2103 SHARE THIS ARTICLE Anyone you share the following link with will be able

to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing

initiative