2nd NIH Researcher to Become Part of Conflict Probe : Health: Federal investigators want to examine scientist’s role in government’s diabetes study of Rezulin and his financial ties to drug firm.
Federal investigators examining whether the top diabetes researcher at the National Institutes of Health had a conflict of interest while overseeing a $150-million government study of diabetes will be asked to review a second scientist’s financial ties to the drug Rezulin.
A spokeswoman for NIH Director Harold E. Varmus said that officials want to determine whether proper procedures were followed in the government study of Rezulin concerning the role of Dr. Jerrold M. Olefsky, a diabetes researcher based in San Diego.
Olefsky, who held prominent leadership positions in the NIH Diabetes Prevention Program study beginning in 1994, is listed on three separate patents as either the sole or the first-named inventor of Rezulin’s potential use for preventing diabetes. Officials at the NIH said previously that they had been aware of just a single patent.
“We would be very concerned if someone who was giving us advice misled us about their conflicts of interest,” said R. Anne Thomas, spokeswoman for the NIH director. “I don’t know if that’s the case” with Olefsky.
Viewed as a Leader in His Field
Olefsky, an endocrinologist at UC San Diego, has declined to return numerous telephone calls seeking comment. Olefsky is regarded as a leader in his field and has been honored by the American Diabetes Assn.
The NIH will ask the inspector general of the Department of Health and Human Services to review certain documents and, if deemed necessary, question those familiar with the matter, Thomas said. The NIH director’s office is acting in response to questions submitted by The Times.
Varmus early this year sought to underscore his sensitivity to potential conflicts of interest at the NIH, which works closely with pharmaceutical companies in development of new drugs.
Selecting Rezulin for the diabetes prevention study in effect provided the NIH’s endorsement of the compound--before it was submitted for approval to the Food and Drug Administration. Warner-Lambert Co., maker of Rezulin, immediately touted the NIH approval.
Others involved with the NIH study--launched in 1994 to determine whether certain drugs or lifestyle changes could prevent adult-onset diabetes--said that Olefsky advocated selecting Rezulin from the start. And one of the scientists told The Times that Olefsky protested in a conference call in the spring of 1998 when researchers were informed that Rezulin would be banished from the study because of the liver failure and death of a participant.
“Dr. Olefsky wanted to continue with the use of the drug in the study,” said Dr. Mohammed F. Saad, a UCLA diabetes specialist who remains a member of the NIH study’s Steering Committee. At the outset, Saad said, Olefsky “was the major advocate. . . . He fought vigorously for the use of Rezulin in the study.”
Olefsky maintained that it was unclear Rezulin caused the death, Saad said.
Rezulin Spurred ‘Intense’ Debate
Senior NIH officials have acknowledged that the decision to keep Rezulin in the prevention study had been a matter of “intense” debate since the fall of 1997, when the first patients in general medical practice began dying of drug-induced liver failure.
Because of Rezulin’s propensity to cause liver failure, the FDA and Warner-Lambert have narrowed its recommended use. On four occasions since the drug went on the market in March 1997, the FDA has altered Rezulin’s safety labeling.
Olefsky, 56, has long promoted Rezulin. He co-authored a medical journal article in 1994 that first raised the hope that Rezulin might prevent diabetes. A paid consultant to Warner-Lambert, Olefsky spoke on Rezulin’s behalf to an FDA advisory committee that endorsed Rezulin in December 1996. Olefsky also was the founding co-chairman of the National Diabetes Education Initiative, a group created by Warner-Lambert that encouraged doctors to prescribe the drug.
Public records do not identify how much, if any, compensation Olefsky would receive as an inventor. Applications were submitted for two patents in late 1994, in the United States and in Europe. The third patent, listing Olefsky as the only inventor, was filed in April 1995. The patents were issued from December 1995 to January 1998. Rezulin was selected for the NIH study in the wake of votes taken among the researchers in 1994, 1995 and, finally, in 1996.
The inspector general over the last eight months has conducted a conflict-of-interest investigation of Dr. Richard C. Eastman, director of the NIH’s diabetes division. Eastman, while overseeing the NIH study of Rezulin, became a paid consultant in late 1995 to Warner-Lambert. During a two-year period, Eastman accepted $78,455 in compensation from Warner-Lambert and its affiliates, records show. Eastman has said that he received advance permission from his NIH superiors.
Both Eastman and Olefsky have played seminal roles in the emergence of Rezulin, which vaulted from obscurity to a billion-dollar sales blockbuster for Warner-Lambert. Eastman acknowledged last year that Rezulin first came to his attention on the basis of work done at “Olefsky’s lab.”
After NIH officials approved Olefsky as one of 22 principal researchers for the diabetes study in 1994, he was installed as chairman of the “interventions” committee, the panel that first reviews which drugs would be used. In late 1994, the 22 researchers overwhelmingly rejected a proposal to administer Rezulin to study participants, according to Saad and others.
However, by about mid-1995, after assurances of the drug’s safety, sentiment shifted. By the final vote, the use of Rezulin was endorsed unanimously.
In the summer of 1995, Olefsky was replaced as chairman of the interventions panel because of concern over the “appearance” of his potential conflict, said Sanford A. Garfield, an NIH administrator who serves as project director of the study. Olefsky was allowed to remain as a member of that panel and the study’s Steering Committee.
Officials said that renewed concern emerged in 1997--this time about the nature of Olefsky’s involvement with what was understood to be a single Rezulin patent. At this point, both Eastman and a colleague conferred with Olefsky about the matter, according to Eastman’s boss. That official, L. Earl Laurence, has told The Times that he and Eastman relied on Olefsky’s assurance that he did not have a “financial interest” in that single patent.
Eastman, despite having filed a recusal in which he pledged to abstain from any actions affecting Warner-Lambert’s role in the study, continued to participate in matters concerning Rezulin. In late 1997, Eastman participated in discussions among the study’s executive committee of concerns raised privately about Olefsky’s potential conflict of interest, officials said. Reached Friday, Eastman declined to comment.
The inspector general’s office oversees federal health programs and is empowered to subpoena documents and question witnesses. The office may impose civil or administrative penalties or refer matters to the Justice Department for criminal prosecution.
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Researcher Janet Lundblad in Los Angeles contributed to this story.
