Elsevier

The Lancet

Volume 357, Issue 9254, 10 February 2001, Pages 455-462
The Lancet

Review
Reliable assessment of the effects of treatment on mortality and major morbidity, II: observational studies

https://doi.org/10.1016/S0140-6736(00)04017-4Get rights and content

Summary

Observational studies and randomised trials can contribute complementary evidence about the effects of treatment on mortality and on major non-fatal outcomes. In particular, observational studies have an important role in the identification of large adverse effects of treatment on infrequent outcomes (ie, rare, but serious, side-effects) that are not likely to be related to the indications for (or contraindications to) the treatment of interest. Such studies can also provide useful information about the risks of death and disability in particular circumstances that can help to generalise from clinical trials to clinical practice. But, due to their inherent potential for moderate or large biases, observational studies have little role in the direct assessment of any moderate effects of treatment on major outcomes that might exist. Instead, sufficiently large-scale evidence from randomised trials is needed to assess such treatment effects appropriately reliably. Wider appreciation of the different strengths and weaknesses of these two types of epidemiological study should increase the likelihood that the most reliable evidence available informs decisions about the treatments doctors use— and patients receive—for the management of a wide range of life-threatening conditions.

Section snippets

Assessment of adverse effects of treatment

Observational studies can have an important role in the identification of large adverse effects of treatments, particularly on infrequent outcomes that are not likely to be related to the indications for, or contraindications to, the treatment of interest (Panel 1). Perhaps one of the best illustrations of this is the detection of increased risks of abnormal fetal limb development after maternal use of thalidomide.2 A decade later, observational studies also detected the many-fold increased

CONCLUSIONS: Improving health care by the appropriate use of epidemiological evidence

Both randomised trials and observational studies can contribute important evidence about the effects of treatment on mortality and major non-fatal outcomes. The appropriate role for each type of study is determined primarily by the extent to which random error and bias can be guaranteed to be sufficiently small for the question posed to be answered reliably. Observational studies can often reduce random error substantially by involving very large numbers of individuals with a specific disease

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      For this reason, although 51/78 studies reported no adverse effects (or reported ‘no serious adverse effects’, 2 studies), it was often not possible to confidently distinguish between studies where no adverse effects occurred, where no adverse effects were identified or where adverse effects might have been identified but not reported in the manuscript. It should also be noted that most studies were not powered to detect rare adverse effects, which requires large trials or observational studies.104 Only 6 of 47 studies reported separate numbers for adverse effects in the active intervention versus control condition, limiting conclusions.

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