Medical research can have big rewards—both in gratifying discoveries and in potentially turning them into profitable treatments. To achieve the former, researchers work hard. Very hard. To obtain the latter, they can start companies or sign commercial funding agreements—well before testing is over. So, do patients undergoing clinical trials for new treatments have a right to know about these monetary interests?

Legally, no. And no empirical data has tied researchers' financial interests in a study to negative outcomes for patients. In the past several years, however, more findings suggest that, ethically, patients should be informed prior to participating in a trial.

Various federal agencies, including the U.S. Food and Drug Administration and the Department of Healthe and Human Services, have made general recommendations that institutions review and consider conflict-of-interest notification policies. More pragmatic guidelines remain elusive.

A new letter, published yesterday in The New England Journal of Medicine, brings together data from the five-year Conflict of Interest Notification Study backed by the National Heart, Lung and Blood Institute, along with broader reports on conflict of interest in medicine released by the Institute of Medicine (IOM) and the Association of American Medical Colleges (AAMC) to examine the practical goals and challenges of presenting this information to possible trial participants. The paper's lead author is Kevin Weinfurt, an associate professor at Duke University in Durham, N.C. He asserts that making this information available to patients should help achieve the following: ensure patient welfare, promote informed decisions, respect assumed right to know, create trust, decrease legal liability, and ultimately discourage financial conflict of interest.

The impact of being informed
After finding out about a conflict of interest, who would trust a coach who was betting on the game?

Most patients, it turns out.

A 2003 survey, led by Scott Kim, an associate professor in the bioethics program at the University of Michigan at Ann Arbor, showed that if participants were told that a researcher or institution testing a treatment was being funded by the pharmaceutical company that made the drug, 40 percent would be more willing to participate—a finding Kim chalks up to an appreciation for up-front honesty. If the financial arrangement were switched, however, and a researcher had an equity investment in a company that owned the treatment method (and their share of earnings would increase if a treatment went to market and did well), more than a third of patients said they would be less willing to participate.

That sizable minority alone, says Kim, should indicate that investigators and institutions have an ethical obligation to disclose financial information to patients.

Making such a disclosure beneficial to all involved might be trickier than simply adding a line to the informed consent forms, the authors of the new paper point out. Some worry that bogging down already lengthy consent documents with details about financial arrangement could confuse patients. Weinfurt and others note that there's "a worry that patients already tune out and don't pay attention to what's there," he says. "Any decision to add length to the consent form is potentially going to make patients tune out even more." In focus groups, he found that many patients still weren't entirely clear on the implications of certain financial arrangements after hours of discussion, and he worries that even simple statements might not be understood or taken into account properly when patients are deciding whether or not to participate in a clinical trial.

"Informed consent is a huge problem," Kim also says. "The language is written by lawyers, [not] by psychologists. [And] rather than an opportunity to truly help people make difficult decisions, it mostly operates on institutional efforts to comply with federal regulations."

Differentiating between doctors and researchers
Beyond presenting the consent statement itself, the underlying challenge may be addressing the public perceptions about the people and institutions involved in the research process. "They want to trust that the doctor is doing only things that would improve their health," Weinfurt says about patients who might enroll in a clinical trial. "It's also confusing for patients because they have a hard time differentiating between a doctor and a researcher…; [the latter's] primary goal is to generate generalizable knowledge…, not to improve the health of this patient right here."

Doctors are also often presumed to already be well-paid, which, like an independently wealthy politician, could theoretically render them immune to financially driven conflicts of interest, a notion that some focus group conversations supported, Weinfurt says.

Disclosure can increase that trust, but it could also give researchers a moral carte blanche to take more risks in search of financial riches, according to research published in 2003 in JAMA The Journal of the American Medical Association. "Look, it's not enough to say, 'disclose, disclose, disclose.' You have to have some good idea of what effect disclosing will have, because it could be counterproductive," Kim says.

Reconceiving academia
Weinfurt acknowledges that it is extremely difficult to pinpoint the financial relationship as a cause of poor patient outcome. Many point to the Jesse Gelsinger case, in which a teenager died during a gene therapy clinical trial. But, as Weinfurt notes, "That trial had one of the better disclosure statements." And the resulting lawsuit was settled out of court, leaving a dearth of precedent to establish the legal strength of financial disclosure's role in the safety or consent for a clinical trial.

Finding the best way to present financial information will require more research into patient decision-making and interests, but, Kim notes, in the bigger picture, the topic of informed consent is "a very narrow focus."

"What really matters," he says, is "that we understand conflict in the conception, design and implementation of the research—and the presentation of the data."

"Society has put so much trust into academia as a disinterested, objective, honorable, above-the-fray institution—and researchers are like that, too," he continues. But, he notes, "most people don't realize that these institutions have tremendous incentives to behave like for-profit institutions." And changing that perception—and current regulation—could take a major overhaul. "Do we need to now reconceive these institutions and individuals? Where do we draw the line?"

Recent hullabaloo over drug companies paying for ghostwritten medical journal articles—that doctors later sign their names to—has raised questions about a wealth of hidden financial arrangements in the medical research community. "Nonprofit academic institutions and individuals now have a tangled web of incentives that we had not had 30 years ago," Kim says.

Reining in all of these manifestations of conflict of interest that have surfaced will take distinct approaches for mitigating them, Weinfurt says, adding, "They…stem from a profit-driven medical technology industry, but I think they're fairly separate in how we manage them."

In most cases, Weinfurt asserts, financial conflicts of interest have no need to be in clinical trials in the first place. Letting someone who doesn't have equity in a company conduct the trial is an alternative that shouldn't present "a big challenge in terms of getting the science done," he says. On rare occasions, someone who has perfected the techniques of using a new surgical device might be the best and safest candidate for operating on patients, but, he explains, that's for institutional review boards to decide.

The bottom line is that "virtually everybody wants to know," Kim says. "That's just nature." But figuring out how people use that information? "It's going to be tricky," he adds.