A leading scientist and a drug company have asked federal regulators to keep information secret about the death and illnesses of patients undergoing experimental gene therapy, stirring controversy in a field of medical research that has prided itself on openness.
In one case, the researcher provided sketchy details of a patient's recent death and his conclusion, in a letter to the National Institutes of Health, that it was not caused by the experimental treatment. But he asked that "this letter be kept confidential and not part of the public record," even though that office has traditionally made all such reports public.
The death notification, which is required under federal regulations, and the accompanying request for confidentiality came just two weeks after the biotechnology company the scientist founded had filed for an initial public offering of stock.
Details of his request, and separate ones from a drug company, Schering-Plough Corp., came to light through interviews and documents obtained by The Washington Post, after weeks of grumbling by NIH insiders concerned about a growing number of secrecy requests from researchers. NIH officials objected to the confidentiality claims, but government lawyers concluded that the regulations insisting that researchers make such reports public were imperfectly worded, and so might not be enforceable.
The revelations come at a time of increased interest in the safety of gene therapy, an experimental field in which genes are given to patients to correct inherited disorders and treat cancer. Last month, researchers at the University of Pennsylvania reported the first publicly acknowledged death thought to be caused by gene therapy. Scientists and federal officials praised those researchers for their speedy and open reporting of that tragedy.
Ronald Crystal, the New York gene therapist who sought to keep his patient's death confidential, said yesterday that the death was not caused by his widely publicized gene experiment, which aims to grow new blood vessels around blocked ones in patients' hearts.
Crystal said the 61-year-old man died from his preexisting heart condition 40 days after undergoing the therapy and a bypass operation.
He said he reported it promptly in May 1998 but did not want the details disclosed until he had more time to investigate it. He said he was not trying to keep news of the death from hurting the pending stock offering of the company he founded, GenVec, based in Rockville.
The company later dropped plans to offer stock. And Crystal said he has openly discussed the death at scientific meetings over the past year. Two months ago he described the death and two others in the same experiment in a scientific journal. He said there has been a fourth death, but none have been related to the gene therapy.
"I'm stunned by all this," he said yesterday. "I'm caught up in someone's agenda. I'm one of the few senior people in this field that have been supportive" of the government's policy of openness about gene therapy experimentation.
NIH regulations require that any serious illnesses or deaths involving patients getting gene therapy be reported to the NIH Office of Recombinant DNA Activities (ORDA), the Food and Drug Administration and local review boards at the institution where the research was conducted. Researchers can make a preliminary determination as to whether the death was caused by the therapy, but the FDA has the final say.
Crystal said he does not know if the FDA has concurred with his determination that the deaths in his study were unrelated to the treatment, and the FDA has not yet decided whether it will act on requests by The Washington Post for that documentation. Crystal said his heart study is now sponsored by another drug company, Parke-Davis, which is responsible for dealing with the FDA and other regulators.
Officials from Parke-Davis and Schering-Plough could not be reached late last night, when The Post obtained details about the confidentiality requests. The Schering-Plough cases involved two patients who became seriously ill while participating in a gene therapy study. No additional details were available.
The first gene therapy experiment, in 1990, was held up for years while scientists, government officials, ethicists and others debated the medical and ethical implications of so radically intervening in a person's molecular identity.
To ease public concern, the NIH created within ORDA the Recombinant DNA Advisory Committee, or RAC, a panel of geneticists, theologians, patient advocates and others to review every proposed gene therapy protocol and be told of any serious adverse outcomes.
The issue of confidentiality requests was a major topic of discussion at last month's RAC meeting, which has watched over the years as gene therapy has shifted from a publicly funded venture led by university and government scientists to a field largely sponsored by private companies with strong proprietary interests.
Members received a few details of the death and two illnesses at that meeting, but could not get further details or discuss the events outside the meeting. Expressing their frustration with the situation, members proposed new language for the NIH guidelines that would remove any doubt about the public accessibility of all reports to the RAC. That language is to be finalized at the RAC's December meeting.
Openness about adverse events has scientific value, too, said Amy Patterson, an ORDA official. "This field is a new science where the experience with one patient should inform the experiments performed on the next. And in this day and age when we can communicate in a nanosecond, there's no excuse to keep repeating the same adverse events if we can prevent them," Patterson said.