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Uncertainty in Clinical Research

Published online by Cambridge University Press:  28 April 2021

Extract

“It is a fact of life that human beings find it difficult to maintain a consistent, self-conscious appreciation of the extent to which uncertainty accompanies them on their daily rounds and to integrate that uncertainty with whatever certainties inform their conduct. Physicians are not exempt from this human proclivity.”

—Jay Katz

Type
Autonomy and Risk-Taking
Copyright
Copyright © American Society of Law, Medicine and Ethics 1988

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References

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Although this is the typical form of expression of the null hypothesis, it would be more accurate to say “therapy A = therapy B in the accomplishment of objective O in population P,” where objective O is the endpoint under examination (e.g., lowering of blood pressure) and population P is a subset of those patients with disease D (e.g., essential hypertension) who have the necessary attributes (inclusion criteria and lack of exclusion criteria) to be eligible for participation in the RCT.Google Scholar
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Actually, most consent forms for placebo-controlled RCTs which I have seen do not use the expression, “it is not known.” Many of them provide information based upon which prospective subjects could make either of two seemingly inconsistent inferences: 1) The consent form usually refers to preliminary evidence that the active drug is effective and labels the placebo as “an inert substance.” In presenting the risks of placebo, it may also refer to the perils of withholding active therapy. From such information the prospective subject could reasonably infer that the investigator already believes that the active drug is more likely than not to prove superior to placebo. 2) Institutional Review Boards (IRBs) generally constrain investigators from making clear statements that the investigational drug is likely to be effective, reasoning that if this were already known, it would invalidate the null hypothesis used to justify the RCT. Following this reasoning, grounded in the concept of theoretical equipoise, it is considered unethical to tell subjects that a new drug is likely to be effective until the RCT demonstrates that it is. IRBs generally require that subjects be informed that “the purpose of this study is to determine whether the drug is effective.” Since in order to do this it will be compared with placebo, the subject could infer that “it is not known whether the new drug is better or worse than placebo.”Google Scholar
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