- Diederick E Grobbee, professor of clinical epidemiologya (email@example.com),
- Arno W Hoes, associate professor of clinical epidemiologya
- a Julius Centre for Patient Oriented Research, Utrecht University Medical School, Academic Hospital, PO Box 80035, 3508 TA Utrecht, Netherlands
- Correspondence to: Professor Grobbee
- Accepted 28 May 1997
In research on the effectiveness of treatments, the randomised controlled trial is considered the best study design because it enables several sources of bias to be removed from the observation. The most important advantage of such a trial is that the baseline prognoses of patient groups are comparable so that unbiased estimates of the effects of a particular intervention can be obtained. In non-experimental (observational) studies allocation to drug treatment is, by definition, not random. This usually means that the prognoses of the patient groups are not comparable and any inferences drawn about the relative effects of treatment are therefore invalid.1 2 In studies of patients who are not randomly allocated to a treatment arm but receive treatment when their doctor decides to prescribe it, the onus is on the investigator to achieve comparability. We discuss the pitfalls of non-randomised comparisons of treatment effects. The results of a recently published study which suggested that hypertension should not be lowered too far by treatment and the subsequent debate provide an example of problems that may arise in validating the conclusions of such studies.
Confounding by indication
A sensible doctor prescribes drugs only to patients who need them—those who have indications that this treatment is required. Moreover, he or she will give priority to treating the most needy patients. When two patients seem to have indications but only one is being treated, the treated patient probably has more compelling indications than the second. The prognosis in any given group of treated patients will be different from that in untreated subjects because the latter will not generally have any indications for treatment. Furthermore, although many drugs can affect the course of a disease positively, the outcome in people with that disease compared with those who do not have it or have a less severe form …