Ethics at NIH

The National Institutes of Health are home to many top-notch scientists. It is therefore not surprising that companies seeking sound scientific advice in the biomedical sciences look to them for help. In return for their advice, these scientists often receive monetary compensation or stock options.

The question of whether it is appropriate for NIH scientists to participate in this type of outside consulting activity has gained a lot of public attention as a result of a Dec. 7 Los Angeles Times article (C&EN, Dec. 15, 2003, page 10). The article, which reported the collection of millions of dollars in fees and stock options by high-level scientists at the agency for consulting activities in connection with research on potential drugs and therapies, also sparked congressional concern. Consequently, both the House and Senate launched inquiries into the conflict-of-interest allegations.

The first congressional hearing on NIH conflict of interest was held late last month by the Senate Appropriations Committee's Subcommittee on Labor, Health & Human Services & Education. At the hearing, subcommittee Chairman Sen. Arlen Specter (R-Pa.) warned NIH officials present that allegations like those appearing in the LA Times article "will give fuel to those who want to cut your funding."

Sen. Tom Harkin (D-Iowa) joined Specter in expressing concern for what these allegations might mean for the NIH budget, which completed a five-year doubling in 2003. NIH "has an unparalleled reputation for honesty and integrity," Harkin said. "I want to make sure it stays that way."

In his testimony, NIH Director Elias A. Zerhouni acknowledged the seriousness of the allegations and stressed the importance of tackling the issue "as quickly, transparently, and aggressively as possible." To that end, he reported that NIH has initiated an investigation, which has not "identified any situations where outside activities resulted in undue influence on grant approvals or other decisions." Zerhouni said, however, that he would reserve final judgment until all reviews are complete.

An important part of the investigation will be the findings of a blue-ribbon task force being set up by Zerhouni to take a systematic look at the agency's ethics practices and to recommend changes to policies and procedures. He announced that the panel will be headed by Bruce Alberts, president of the National Academy of Sciences, and Norman R. Augustine, chairman of the executive committee of Lockheed Martin. The cochairmen will be joined by eight yet-to-be-named members. Once formed, the panel will have 90 days to complete its report.

BY TAKING STEPS to review the process, Zerhouni has made it clear that NIH is willing to make any necessary changes to avoid conflicts of interest but indicated that he believes scientists should continue to have the opportunity to consult. According to Zerhouni, these relationships--currently involving about 200 scientists, or less than 3% of the staff--are key to recruiting the best scientists to NIH. They also provide a mechanism for knowledge transfer from research labs to the private sector, where basic research is applied to yield medical advances.

To ensure that these consulting relationships do not result in real or perceived conflicts of interest, they must pass through a series of checks by various offices within both NIH and its parent, the Department of Health & Human Services, several witnesses testified at the hearing. The process is guided by policies set up by the independent Office of Government Ethics (OGE), which oversees conflict-of-interest concerns across the federal executive branch agencies.

As part of the process, an evaluation is made to determine if the proposed activity will conflict with the scientist's official duties and if recusals from matters associated with the outside company would impair the individual from doing his or her job. Scientists who consult are not allowed to share details of ongoing, unpublished NIH research but can share advice based on their global understanding of their area of expertise.

Once a consulting relationship is established, the scientist must comply with governmental rules about reporting related income. Under the current law, certain top-level positions within the agency are required to fill public financial disclosures. However, OGE has the authority to designate additional positions into this class, explained Marilyn L. Glynn, acting director of OGE. Scientists not included in this class must report financial information to the agency, but the information is not publicly available.

Glynn also stated that OGE has initiated a 2004 review of NIH's ethics program--a practice done every five or six years. The review "will focus on the structure and staffing of NIH's ethics program, the public financial disclosure system, the criteria and process for approving outside activities, the criteria and process for approving the acceptance of awards, and other basic ethics systems," she told the committee.

This issue of public versus private reporting drew criticism from both Specter and Harkin. Harkin noted that 80 to 90% of those involved with outside consulting activities don't have to make any financial information public.

To remedy the situation, Specter called for a reevaluation of who has to file public disclosures, adding that this should be the agency's "first line of defense" to avoid conflicts of interest. He also warned those in charge of designating who should file publicly that "we are prepared to do it if you don't."

Also on hand to testify before the committee were NIH scientists cited in the LA Times article. In all cases, the scientists testified that the allegations in the article were "misleading, grossly inaccurate, and filled with false innuendo."

For example, John I. Gallin, director of the Warren G. Magnuson Clinical Center at NIH, told the senators about a gene therapy study he was involved in during the mid-1990s. The work, done in collaboration with Somatix Therapy Corp., was completed and prepared for publication in February 1997. After the standard internal review, the paper was submitted for publication in July of that same year.

In the meantime, Somatix was purchased by Cell Gensys in June 1997. As the new parent to Somatix, Cell Gensys wanted its company recognized on the front of the submitted paper, which NIH was legally obligated to do. "In protest, we added a footnote at the end of the paper" explaining the situation, Gallin stated.

In the fall of that same year, Gallin was asked to join the scientific advisory board of a new company called Abgenix. Unbeknownst to him at the time, Abgenix was a spin-off of Cell Gensys--a relationship that the LA Times article cited as a conflict of interest with respect to his gene therapy study.

"Somatix Therapy Corp. and Cell Genesys were not affiliated at any time during our gene therapy study," Gallin said. "Therefore, there was no conflict between my consulting work for Abgenix and the clinical research study that my laboratory did with Somatix," he stated.

Stephen Katz, director of the National Institute of Arthritis & Musculoskeletal & Skin Diseases, was also named in the LA Times article for participating in a lupus study done in collaboration with Berlex, a U.S. subsidiary of Schering AG, a German company that Katz consulted for.

"NIH had no mechanism in place to identify subsidiaries or affiliated entities to the companies from which NIH staff recused themselves," Katz noted. In spite of the fact that Katz should have recused himself from any studies involving Schering AG's subsidiaries, he maintains that he "did not make any substantive decisions which affected Berlex or the lupus trial conducted with its drug," as alleged in the LA Times article.

When asked if they thought NIH would lose researchers if it stopped allowing outside consulting activities, the scientists agreed there would likely be negative effects. To see a scientific idea come to fruition gets to the passion of what scientists are about, Katz explained. Consulting enables that, he added.

As NIH continues to take steps to erase concerns that it is still worthy of the trust and confidence Congress has placed in it, Congress continues its investigations with more hearings to come. In addition to hearings, Reps. Henry A. Waxman (D-Calif.), John D. Dingell (D-Mich.), and Sherrod Brown (D-Ohio) have sent a letter to the General Accounting Office requesting an investigation into potential conflicts of interest at NIH.

RESEARCH

NIH Defends Human Sexuality Research

Conflict-of-interest questions are not the only ethical problems facing the National Institutes of Health. At a joint congressional hearing last fall, the agency came under fire for funding a number of grants related to the study of human behavior and societal pressures related to sex. In response to the concern over the appropriateness of funding this research, NIH Director Elias A. Zerhouni conducted a comprehensive review of all grants dealing with human sexuality studies, with emphasis on those cited by Congress.

On Jan. 26, Zerhouni delivered a summary of the review to the House Energy & Commerce Committee and the Senate Health, Education, Labor & Pensions Committee. In an accompanying letter, he wrote, "The constant battle against illness and disease ... cannot be limited to biological factors but has to include behavioral and social factors as well."

According to the summary, most of the grants at issue are "related to our efforts against HIV/AIDS and the at-risk populations we have targeted to prevent further spread of the disease. Understanding the risk factors posed by prostitution and illicit drug use, in addition to preventing initiation of sexual activity in teenagers, remain important to controlling the HIV/AIDS epidemic in the U.S."

Zerhouni pledged his continued support for research in this area. "I believe that the peer review process ... has worked properly and provided a level of valuable and independent review in this area of research," he said. He also reported that NIH institute and center directors are developing better ways to present these studies to the public.