ArticlesThe uncertainty principle and industry-sponsored research
Introduction
There is concern that clinical trials sponsored by the pharmaceutical industry result in biased findings.1, 2 Two reasons have been suggested. First, the quality of research sponsored by profit-making firms may be poor. For example, low-quality trials overestimate therapeutic benefit by an average of 34%.3 Second, it could be that industry will sponsor only those research projects that are likely to be positive, thus violating the uncertainty principle—a fundamental scientific and ethical principle for running randomised clinical trials.4, 5 The uncertainty principle, or equipoise, states that the patient should be enrolled in a randomised controlled trial only if there is substantial uncertainty ("equal bet”)4, 5, 6, 7, 8, 9 about which of the trial treatments would benefit a patient most. To distinguish between these possibilities we assessed the influence of the source of funding on the quality of randomised trials and whether the uncertainty principle was adhered to in their conduct.
Section snippets
Trials
We reviewed therapeutic studies in patients with multiple myeloma. By focusing on one disease, existing knowledge that plays a key role in the planning and design of the study can be better ascertained. Using the Cochrane search strategy, we identified all randomised trials for multiple myeloma from the period from 1996 to 1998.10 113 articles on 136 trials were identified. The quality of each trial was assessed with the scale of Jadad and colleagues.3, 11 This scale has a score from 0 to 5 and
Results
The overall quality of the randomised trials was poor (mean Jadad score 2·5 [SD 1]). 53 (39%) and 45 (33%) of the trials had scores of 2 and 3, respectively, accounting for 98 (72%) of the trials. Only seven trials (5%) had the maximum score of 5.
Figure 1, Figure 2 show the rating scores for all trials, with 56% of the studies reporting success for innovative treatments and 44% favouring standard therapy (p=0·170). The mean evaluation score was 3·7 (SD 1) with a median rating of 4, slightly
Discussion
Chalmers17 previously asked “what is the probability that new treatments will be superior to standard ones?” Gilbert and colleagues14 reviewed 46 randomised trials that compared surgical and anaesthesia treatments. 49% of innovations were successful when compared with standard treatment. Colditz and colleagues15 examined 36 randomised trials and found a 61% chance that a patient who received the new therapy would fare better than a patient receiving standard therapy. Machin and colleagues18
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2022, Journal of Clinical EpidemiologyCitation Excerpt :If such uncertainty does not exist, as in case when there is a high likelihood (say, greater than 80-90% [10,11]) that one treatment is predictably better than the other, scientifically no meaningful results would be generated, it would be unethical to enroll people in such a trial, [9,5] ethical committees would likely not approve it [10,11] and well-informed patients would likely refuse to participate in the studies where the results are predictable in advance[5,9]. However, this unpredictability of the results at the level of individual trial led to hypothesis that there is a predictable relationship between the uncertainty requirement (the moral principle) on which trials are based and the distribution of treatments effects at the group level of cohort(s) of clinical trials [5,9,12–14]. That is, it can be predicted that when overall distribution of all treatment effects is evaluated, the probability of finding that a new treatment is better than a standard treatment is about 50% [5,9,12-14].