Experimental studies JeanFranois Boivin 25 October 2010 2

Experimental studies Jean-François Boivin 25 October 2010

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N Engl J Med 1997; 337: 322 -8. 6

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Am J Public Health. 2009; 99: S 675–S 680. 8

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Method: Young children living in institutions in Bucharest were enrolled when they were between 6 and 30 months of age. Following baseline assessment, 136 children were randomly assigned to care as usual (continued institutional care) or to removal and placement in foster care that was created as part of the study. 10

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Unexpectedly, we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not 13

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Coronary Drug Project Five Year Mortality Clofibrate Placebo 20. 0 % 20. 9 % Clofibrate adherence Placebo adherence 15. 0 % 15. 1 % 20

Aspirin Myocardial Infarction Study Mortality Aspirin Placebo 10. 9 % 9. 7 % Aspirin adherence Placebo adherence 6. 1 % 5. 1 % Friedman et al. Fundamentals of clinical trials. Third edition. 1998. Page 290 21

Under the intent-to-treat principle, the primary analysis in a randomized trial should compare outcomes between the groups formed by randomization. In other words, each participant is categorized according to what intervention he or she was intended to receive. Koepsell-Weiss p. 327 22

The main reason for using the randomized-trial design in the first place is to form groups that can be assumed similar, even with regard to unmeasured factors that may affect outcomes. If the composition of one or more of those groups is altered, this property of randomization is lost. A study that began as a randomized trial would, in effect, be converted into an observational study in which confounding may be present. Koepsell-Weiss p. 327 23

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The chaplain’s secretary randomly assigned all new patients to either the usual care or prayer group based on the last digit of the medical record number; even numbers were assigned to the prayer group and odd numbers to the usual care group. 25

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There are many proscriptions (in the Old Testament, New Testament, and Koran) against “putting God to the test”; it is predictable that at least some patients will view the study as doing exactly that. Out of respect for autonomy, one should think long and hard before enrolling an uninformed, nonconsenting patient as a subject in a study that he or she might find blasphemous. 27

retracted 28

It is of the utmost importance , before undertaking a new study, to do a systematic review of the existing clinical research on that topic, not to risk both repeating work that has been done already and repeating its mistakes (Iain Chalmers) JNCI 1999; 91: 11 -12 29

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An RCT is permissible when there is no scientific consensus about the relative efficacy of two competing interventions. Freedman referred to this state of uncertainty in the expert community as clinical equipoise [4]. Clinical equipoise provides a justification for randomising individuals to competing therapies or to placebo. Clinical equipoise must be based on awareness of the existing medical evidence, which in turn requires the organized study of that evidence. 33

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LANCET 2005; 366: 107 -108 36

From August, 2005, we will require authors of clinical trials submitted to The Lancet to include a clear summary of previous research findings, and to explain how their trial’s findings affect this summary. The relation between existing and new evidence should be illustrated by direct reference to an existing systematic review and meta-analysis. When a systematic review or meta-analysis does not exist, authors are encouraged to do their own. 37