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BMJ No 7102 Volume 315 Letters Saturday 26 July 1997 Informed consentInformed consent is not always obtained in United StatesEditor,A code of silence and a spirit of denial surround one of the oldest and most perplexing conundrums in medical research: how to recruit large numbers of fully consenting subjects. So it was refreshing to note the BMJ's pioneering willingness to devote much of the issue of 12 April to questions of informed consent. 'Rather than restrict the debate to ourselves,' as the editor, Richard Smith, put it, the BMJ dared to display publicly what institutional review boards and healthcare professionals usually handle with discretion or denial. Our own analysis, published in The (Cleveland, Ohio) Plain Dealer and other American newspapers late last year, suggests the extent to which questions of consent persist.(1) This is despite the American government having apologised formally recently to survivors of a study of the natural course of syphilis in black men in Tuskegee, Alabama.(2) President Clinton has diverted the mandate of the National Bioethics Advisory Commission (which was formed to grapple with issues such as informed consent) to take up the more sensational if speculative topic of human cloning. Headlines have overtaken the issue before; in 1995, on the day that the Advisory Committee on Human Radiation Experiments warned of questions of consent in contemporary medical research, public interest focused on the verdict in the case of O J Simpson. In the past few months, disclosures in Augusta, Georgia, and Orange County, California, raised questions of consent, illustrating that the topic is more than a matter of distant history.(3, 4) Since 1977 the US Food and Drug Administration (FDA) has
conducted 4154 inspections of clinical trials. Our analysis of records
of those inspections showed that 53% of the investigators were cited
by the FDA for failing clearly to disclose the experimental nature of
their work. In 46 t We also found evidence that the US government, which makes annual
payments to survivors of the study in Tuskegee, has sponsored
experiments on unsuspecting subjects well into the 1990s. Among our
case studies were tests by the Centers for Disease Control and
Prevention, begun in 1990 in Los Angeles, of the immunogenicity and
efficacy of the Edmonston-Zagreb measles vaccine, which the centres
knew had earlier caused excess mortality in Africa; and a study in 1991
of hepatitis A vaccine, conducted on a Sioux reservation, in which the
letterhead on the consent form implied an established prevention
programme rather than the safety and efficacy trial it was.
Nor does the record overseas appear any better. Foreign and internal
FDA documents that we reviewed contained accounts of fraud, concealed
side effects, experiments diverging from protocols, and questions of
consent. Consent forms were incomplete or inadequate in 65 of 137
inspections by the FDA of trials conducted in countries other than the
US. In Canada, consent forms were inadequate in 21 of 36 inspections.
Verifiable scientific data were missing from 53% of the international
research submitted to support a US new drug application.
Our analysis of FDA data also showed that internal review boards, the
front line in protecting test subjects, cannot be counted on to ensure
that people know they are being used in medical research. At 942
internal review boards between 1990 and 1996, FDA inspectors found
multiple violations: no evidence of continued safety monitoring (at
20% of the review boards); no copies of consent forms, injury reports,
or protocols (19%); and that patients were not clearly told when
procedures were experimental (16%), not offered proved alternative
treatments (13%), not informed of expected risks and pain (10%), and
not told of likely benefits (6%).
Some people-among them US senator John Glenn and Gary Ellis,
director of the office for protection from research risks at the
National Institutes of Health-have argued for stronger controls. Glenn
has proposed legislation to close many regulatory gaps. But until more
researchers and their publications are willing to come out publicly
about what they know and what they believe should be done to better
advance medical research without sacrificing-and documenting-consent
of the fully informed test subject, prospects appear dim for meaningful
reform. And questions of consent can be expected to recur with
disturbing frequency.
Keith Epstein
Bill Sloat
The (Cleveland) Plain Dealer,
References
1 Epstein K, Sloat B. Drug trials: do people know the truth
about experiments? The (Cleveland) Plain Dealer 1996 Dec
15-18:a1. [Articles and charts are posted at
http://www.spj.org/sdxawards/03invrptg/index.htm#top or can be requested from:
epstein@dgsys.com]
2 Harris J F, Fletcher M A. Six decades later, an apology.
Washington Post 1997 May 17:a1.
3 Teegardin C, Whitt R. FDA inspection finds violations in Augusta
studies. Atlanta Constitution 1997 May 11:a3.
4 Marsh B, Romney L. Hospital accused of violating consent rules.
Los Angeles Times 1997 May 30:a3.
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