NIH Rebuffed, Rethinks New Ethics Regulations

Following a storm of criticism, HHS chief Sullivan asks for another plan to stem conflicts of interest. WASHINGTON--As soon as he read them, James Wyngaarden knew that there would be problems. The former National Institutes of Health director expected the agency to propose guidelines to eliminate potential conflicts of interest by government-funded university scientists who are carrying out clinical trials. But instead of directing a surgical strike against questionable financial relationships among that group of researchers, NIH had issued a sweeping proposal that shocked and angered nearly every segment of the biomedical community (The Scientist, Oct. 16, 1989, page 1). "I was astounded," says Wyngaarden, who left NIH six weeks before the guidelines were issued on September 15 and is now associate director for life sciences at the White House Office of Science and Technology Policy. "I called Bill Raub right away," says Wyngaarden, referring to his former deputy and the man who is now acting NIH director, "and told him these guidelines are going to kick up a firestorm." He was right. Over the next 90 days NIH received almost 800 letters from university administrators, biotech executives, professional societies, and individual scientists. Their objections went to the heart of the proposed guidelines, which would have prohibited any grantee from having any financial ties to companies with links to the research being conducted, banned any discussions of preliminary results with any such company, and required exhaustive disclosure of all financial interests by scientists and their families, reviewers, and anyone in a position to influence the research. In a rare example of democracy in action, the government listened to those complaints. Two weeks after the close of the official comment period, a December 29 order from Health and Human Services Secretary Louis Sullivan effectively buried the guidelines. The secretary told NIH officials to start over, this time taking an approach that recognizes the value of ties between federally funded university scientists and private industry. "I have instructed the NIH to submit to me options for addressing potential conflicts of interest that properly treat potential abuse while keeping the research process free of unnecessary burden and disincentives," declared Sullivan in what amounted to a stinging rebuke of the work by an internal NIH committee. Sullivan gave NIH a tall order that could take more than a year to fill. The agency has several options: to preserve the status quo that permits a broad range of such ties, to require universities to police their faculty and weed out self-identified conflicts, to submit a new proposal with a narrower focus, or to request legislation that would give the government the ability to tightly regulate interactions between scientists and industry. Officials have already begun an analysis of the formal comments submitted to the agency, and the next step could include the creation of an outside panel to look at the ethical, legal, economic, and scientific aspects of the issue. One way for the scientific community to anticipate what NIH will do next on the guidelines issue is to understand what happened the first time around. That means trying to figure out how NIH managed such a self-inflicted wound, and how it can prevent it from happening again. The December 11 meeting was only one of hundreds of such meetings that go on each week between a highly placed administration official and important constituents. But it was typical of the way that the scientific community informed the Bush administration that it wasn't happy with the proposed guidelines on conflicts of interest that had emanated from NIH last fall. "We met with C. Boyden Gray [special counsel to the president] because we knew that he was closely tied to [James] Wyngaarden and [Allan] Bromley," explains James Vincent, president and CEO of Biogen Inc., about how he and Richard Godown, president of the Industrial Biotechnology Association, expressed their views on a proposal that Vincent believes would stifle progress in the field. "They weren't at the meeting, but there is a reporting structure. We also talked with senior HHS officials." It wasn't the first time that the message had been sent. Michael Astrue, general counsel for the Department of Health and Human Services, notes that he heard the same thing last fall from various sources, as did Assistant Secretary of Health James Mason. In fact, Astrue's office had talked with NIH officials before the guidelines were issued to warn them that the extensive changes that they were proposing in the relationship between academic scientists and industry should be handled through a formal rule-making process that would require extensive review. "But NIH didn't properly understand our advice," he says. Once the complaints came rolling in, however, it became clear to the Bush administration that something had to be done. Astrue says that he and Mason agreed not to derail the process before the December 15 deadline for public comment because of the feeling that "there was value in receiving such comments." But on December 11 he gave a speech to the Food and Drug Law Institute that described how a new special counsel for ethics within the department "will assist NIH in its efforts to promulgate regulations that will articulate new conflict of interest standards for grantees." That was a signal that the department was ready to step in. But HHS Secretary Sullivan still hadn't spoken. Perhaps the final straw was an article by a Boston Globe columnist that appeared in the Washington Post on December 27 that criticized NIH for "lashing out at the very industry it is meant to nurture." Notes one HHS official, when asked about the decision-making process: "I wouldn't underemphasize the power of the press. Besides, it only takes a minute to make a decision." In any case, the next day Bromley and Wyngaarden met with Sullivan. And the following day the secretary issued a four-paragraph statement that, in effect, asked NIH to start all over again. --J.M. Theories abound to explain the fiasco. The most popular says that NIH officials believed that they had to act quickly to show congressional critics that NIH wasn't ignoring the issue. In their haste, the theory goes, they produced a poorly written document so broad that it seemed to ban any contacts between university scientists and the private sector, and so comprehensive that it would require disclosure of every financial interest by anyone remotely connected to the investigator or the research itself. "Under the original NIH guidelines it was impossible to manage conflict," says Robert Anderson, deputy general counsel for the National Science Foundation. "Their proposal was all or nothing, and it failed completely to realize that there are ways to manage potential conflicts at the level of the principal investigator." NSF officials didn't hide their unhappiness with the guidelines, firing off a strongly worded, 14-page critique that suggested NIH's solution was much worse than the problem it was meant to eliminate. The need to please an important constituent was another reason the guidelines turned out as they did, say many observers. "NIH wanted to respond in an expeditious fashion to the concerns of Congress," notes Robert Charrow, a Washington lawyer and deputy general counsel of HHS during the Reagan administration. "It was a responsible thing for them to have done, but they did it all wrong." But some critics don't buy the "overreaction theory." They argue that NIH knew exactly what it was doing, and that it was counting on the university and business communities, along with the Bush administration, to torpedo the guidelines. According to this so-called conspiracy theory, NIH acted in an outrageous fashion so that it would be rescued from doing something it didn't want to do in the first place, namely, restrict the growing links between academia and business that profit both parties. "It was the best way they knew to mobilize their constituency and to get the guidelines pulled," says Leonard Minsky, executive director of the National Coalition for Universities in the Public Interest, a small Washington-based lobbying group. "They got the key people - medical school deans, vice presidents for research, and so on - to write and put pressure on the administration, and the result was that the guidelines got pulled." NIH officials insist that neither explanation is correct. They say that the conflict of interest issue is terribly complicated and that the proposed guidelines did not represent a consensus within the community or even within NIH. Rather, they were meant to elicit comments that would help officials do a better job the second time around. "We wrote something for people to react to," says Katherine Bick, deputy director for extramural affairs and the chief architect of the guidelines. "And the fact that we've received 790 comments means that it was a successful effort. We didn't go in with a preconceived idea that we knew the answers. In fact, my main concern was that people take it seriously, and work with us to come up with the best solution to the problem." There's no question that the community took the guidelines very seriously indeed. "It hit the streets like a grenade," recalls Samuel Thier, president of the Institute of Medicine within the National Academy of Sciences. "It caught people completely off guard, even at places that have been working on the problem for quite a while." It wasn't long before major figures from industry and academia began to converge on Washington, expressing their displeasure and their desire for something to be done (see story on page 12). The guidelines forced the scientific community to grapple with two basic issues: Are new rules necessary? And, if so, what should they look like? Most biotech industry executives don't see any problem with the status quo. "Why tinker with a system that has been working so well for all these years?" says James Vincent, president and chief executive officer of Biogen Inc., of Cambridge, Mass. "You've got a self-correcting mechanism now [to root out biased results] that makes additional regulations unnecessary." HHS lawyer Charrow agrees. "In order to go ahead with any type of rule-making, you need to show that the rule is needed. And I think that will be a very difficult thing for NIH to do. They must show that significant conflicts of interest already exist, that they are adversely affecting research, and that they are having a detrimental effect on the federal research enterprise. To do that, you need concrete examples - a few anecdotes will not cut it." The original proposal was submitted not as a formal rule but rather as a more informal guideline. "We wanted to take a kinder, gentler approach," says one NIH official, "because we didn't want people to think we were forcing something down their throats." They also wanted to save time. "I can understand NIH's frustration with the formal rule-making process," says Michael Astrue, HHS general counsel. "It's a long and difficult process, and there's a natural tendency to want to do it differently." Bick feels strongly that changes are needed. And she believes that the next time around it will be in the form of a rule. "There is general agreement that the current statement [on conflict of interest] is sufficiently old and doesn't deal with the contemporary world," she says. "And the secretary has made it clear that whatever is done should be handled through formal rule-making." But process is only part of the problem. There's also the question of substance. And nobody thinks that it's going to be easy for NIH to define a conflict of interest, much less how it should be avoided. Many people argue that such conflicts are the price that society must pay to receive the improved health, higher economic productivity, and better standard of living that are promised from allowing companies to profit from government-funded research. As NSF wrote in its comment, "precluding spin-off commercial ventures [by precluding the holding of an equity interest in a startup company] would cancel very considerable benefits to the country, for reasons that seem unobvious and insufficient. . . After all, in most cases the public can only benefit from research if some firm exploits the results commercially." One important criterion, say many observers, is whether the research is basic or applied. Scientific work that deals with fundamental biological processes doesn't need to be regulated, according to that argument, while efforts to find new drugs to treat or cure patients must be beyond reproach. "You start where the problem is greatest," says Thier. "In cases where you have a population of individuals who have placed their trust and their lives in the outcome of certain research, then you have to be sure that the people doing the research aren't deriving any financial benefit from sources that could skew their judgment. It comes down to making sure that people aren't placed at risk because of a potential conflict of interest." That, in essence, is what Wyngaarden said to Rep. Ted Weiss (D-N.Y.), the chairman of a House Government Operations Committee subpanel on human resources and a leading proponent of more stringent measures. He testified June 12 that the problem lay chiefly with those engaged in clinical trials, and that NIH was taking steps to address the issue. Two weeks later, at a two-day public symposium at NIH, Cleveland Clinic vice president Bernadine Healy proposed that such scientists should disclose all relevant ties and be prohibited from the most obvious sources of conflict. That would include the holding of stocks and any position in a company whose products were being tested. In fact, Healy is part of a group of investigators, engaged in a large NIH-funded trial of coronary bypass patients, who have declared that they will abstain from such financial relationships while the trial is under way. That's why Wyngaarden was so surprised when the September 15 guidelines made no distinction among the types of research being conducted. "I would like to think that had I still been there, they would not have been issued," he says. Others believe that the broad scope of the guidelines reflected a sincere attempt by NIH officials to cover all possible areas of conflict. Indeed, notes Janet Newburgh, head of NIH's institutional liaison office, which issued the guidelines, "it's hard to know where to draw the line [between basic and applied research]." Whatever happens next, it's a safe bet that lots of people will know about it. "It's clear that we need to have the opportunity for further public input before we get to the stage of proposed rule-making," says Bick. She suggests that a committee composed of public members representing various outside perspectives might advise administrators working on the issue. NSF's Anderson notes that his agency has already offered to help NIH informally on its next draft. In addition, the rule-making process includes formal notification of every agency with any interest in the subject, along with extensive debate within HHS and the Office of Management and Budget. "These are complicated issues," says HHS's Astrue. "At the same time, there's a great deal of concern about the issue. I would hope that [the department] would have made significant progress by the end of the year."

NIH Rebuffed, Rethinks New Ethics Regulations

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