Clinical trials: Active control vs placebo — what is ethical?

Science and Engineering Ethics 10 (1):73-79 (2004)

The quest for effective medicines is very old. In modern times two important tools have been developed to evaluate efficacy of drugs: superiority and non-inferiority types of clinical trials. The former tests the null hypothesis of μ (the difference between a tested drug and comparator) ≤ 0 against μ > 0; the latter tests the null hypothesis of μ ≤ - Δ against, μ > - Δ, where Δ is the clinical difference from the comparator. In a superiority trial, a new drug is tested against a placebo; in a non-inferiority trial, a new drug is tested against active treatment. In this paper, arguments are presented to show that a superiority trial against a placebo is scientifically sound but ethically unacceptable, whereas a non-inferiority trial against active treatment is ethically sound but scientifically not reliable. Switching from a superiority type of trial with placebo to a non-inferiority trial with an active-control — following the latest revision of Declaration of Helsinki — is in practice switching from the violation of the uncertainty principle to uncertainty of results. Given human and financial resources, it appears an academic question as to which is more unethical: to violate patients’ rights or to produce results without scientific value. All presented considerations lead to the conclusion that the use of a superiority trial of design with an active control instead of placebo will satisfy scientific needs, expectation of patients, and the ancient quest for effective medicines. In the era of Good (Clinical, Laboratory, Manufacture) Practice, the attention of those performing clinical trials is focused on the procedure, not always on its essence. However even the excellent performance of a trial which is not worth doing is fruitless.
Keywords placebo  active-control  superiority  non-inferiority  informed consent  uncertainty principle
Categories (categorize this paper)
DOI 10.1007/s11948-004-0065-x
Edit this record
Mark as duplicate
Export citation
Find it on Scholar
Request removal from index
Revision history

Download options

Our Archive

Upload a copy of this paper     Check publisher's policy     Papers currently archived: 41,481
External links

Setup an account with your affiliations in order to access resources via your University's proxy server
Configure custom proxy (use this if your affiliation does not provide a proxy)
Through your library

References found in this work BETA

Law and Medical Ethics.J. K. Mason - 2003 - Lexisnexis Uk.

Add more references

Citations of this work BETA

Add more citations

Similar books and articles


Added to PP index

Total views
46 ( #172,678 of 2,248,579 )

Recent downloads (6 months)
10 ( #125,276 of 2,248,579 )

How can I increase my downloads?


My notes

Sign in to use this feature