Observational Research, Randomised Trials, and Two Views of Medical Science

The lecture text was amended because of comments by discussants and three reviewers of PLoS Medicine. The first seven pages of this longer version are close to the main paper in PLoS Medicine. Thereafter, the longer text treats more topics and gives more examples. 2 Two views of medical science Two views about medical research seem to have split ever more apart over the past decades. One view is that of medical researchers who rejoice in discoveries and explanations of causes of disease. Discoveries happen when things are suddenly seen in another light. Ideas strike by seeing the odd course of a disease in a patient, the strange results of a lab experiment, a peculiar subgroup in the analysis of data, or some juxtaposition of papers in the literature. Researchers continuously have masses of ideas. They get enthusiastic about one idea, and will try to find data to see whether there is " something in it ". For first exploration, they will preferably use existing clinical or epidemiologic data, do a quick additional lab experiment, a quick search for more literature, or look for some more patients. As soon as there is a hint of confirmation, a paper is submitted. The next wave of researchers reads this paper and immediately tries to check this idea, using their own existing data or their trusted lab experiments. They will grill the idea by looking at different subgroups of diseased persons, by varying the definition of exposures, by taking potential bias and confounding into account, or by varying the lab conditions to explain why the new idea holds – or why it is patently wrong. In turn they swiftly submit their results for publication. These early exchanges may lead to strong confirmation or strong negation. If not, new studies are needed to bring a controversy to resolution. The other view is that of medical researchers whose aim is to set up studies to evaluate whether the patient's lot is really improved by the new therapies, diagnostics and insights that looked so wonderful in the lab or on initial testing? The most developed branch of evaluation research is randomised trials of drug therapy, which I will use as its prototype in this paper. One major condition for credibility of such trials is complete preplanning of every aspect of the trial, and nowadays even advance registration and documentation of everything that was preplanned [1]. This …