Guiding Principles for Clinical Investigation
Henry K. Beecher and Human Subject Research
Oct 23, 2009
In January 1966, Dr. Henry K. Beecher published an editorial in the Journal of the American Medical Association (JAMA), “Consent in clinical experimentation: myth and reality.” Two months later, Beecher returned to this theme with “Some guiding principles for clinical investigation,” in which he tried to clarify his views about how research on human subjects should be conducted.
Should Patients Trust Responsible Investigators?
As he had in previous articles, Beecher insisted that following “rigid codes” of conduct was ineffective, and legal regulations should be avoided. Instead, Beecher relied on obtaining informed consent from patients before a study began. If consent were obtained, then patients would be aware that they were “involved in an experiment” and could withdraw at any time.
While he acknowledged the importance of informed consent, Beecher claimed that the principle could not be achieved in full. Not all contingencies were foreseeable by researchers, and there always would be occasions when patients would know less than they should.
In place of legal formalities, Beecher advised patients to put their trust in an “informed, able, conscientious, compassionate, responsible investigator.” Only an investigator having all those qualities would follow approved medical procedures, which was to provide treatment to a patient when required, or to inform the patient if experimental therapy was the only option.
According to Beecher, a patient had the ultimate power over giving consent, as the patient could simply “overrule the physician as to what factors [were] . . . relevant to his consent.” In practice, there are few instances where a patient would be more knowledgeable about a proposed therapy than an investigator. Thus, Beecher's suggestion was naïve at best, and ineffective at worst
Are Vulnerable Populations 'Martyrs for Science'?
Beecher then discussed circumstances under which experimentation on vulnerable populations (e.g., children, civil prisoners, people close to death) should be allowed. Although there were occasions when experimentation on the vulnerable was desirable, Beecher admitted that an investigator had no right to “choose martyrs for science.”
Curiously, Beecher's views are less noble than they first appear. For example, Beecher does not object to research on people close to death because of sensitivity issues. Rather, Beecher objects because a patient's death during an experiment would “cast a cloud on a careful investigator and on a meritorious project.”
Beecher Suggests Two Patient Safeguards
Beecher offered two possible safeguards to protect a patient's rights. First, he suggested that two physicians should be involved in every experiment — one to look after the patient’s welfare, and the second to serve as the investigator. In making this suggestion, Beecher recognized the conflict inherent in clinical trials, in which a single doctor tries to serve two different roles (i.e., personal physician and private researcher).
Second, Beecher recommended that ethical problems should be “presented to a group of the investigator's peers” for review. Peer review was not a new idea, but it was rarely used to block unethical research because it was ineffective.
For example, Lederer (2007) cites a case where the Journal of Experimental Medicine once received a peculiar manuscript for review. In the submission, the investigator stated that he had injected herpes virus into a one-year-old child, who he described as a 'volunteer.' The reviewing editor was outraged at how a baby could be considered a 'volunteer,' called the study an “abuse of power,” and refused to publish the manuscript
The investigator resubmitted the manuscript to the Journal of Pediatrics, where it was published without objection after peer review.
Beecher's Suggestions are Rebuffed
In an unusual move, JAMA added a disclaimer to Beecher’s article. Although staff members rarely discussed published articles, the editors declared that “the comments by Dr. Beecher have been prepared in his office with consultation as determined by him.” Inasmuch as the American Medical Association (AMA) had taken no position on the problems Beecher raised, the editors wanted to make it clear that Beecher was speaking for himself — not for the AMA, and certainly not on behalf of the journal.
The editors also claimed that “Appropriate councils and committees and the staff have this subject under study and will report at a later time.” The promised 'report' was never published.
Beecher Refuses to be Silenced
Stung by this reproof, Beecher nevertheless pressed onward. He became even more determined to publish a definitive review of clinical trials conducted after World War II. Beecher believed that the ethical principles set forth in the Nuremberg Code (1947) were not being followed.
Time would prove him right. Later that same year, Beecher published a landmark article in the New England Journal of Medicine, which he called “Ethics and Clinical Research.”
References
Beecher HK. 1966. Some guiding principles for clinical investigation. JAMA. 195:1135-1136.
Lederer SE. 2007 (26 September). Scandals and tragedies: Beecher, Tuskegee, Willowbrook and the rest. National Institutes of Health (NIH). Ethical and Regulatory Aspects of Clinical Research.
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