# How to guarantee finding a statistically significant difference: the use and abuse of subgroup analyses

In 1988 the Lancet published a very large randomised clinical trial of intravenous streptokinase, oral aspirin, both, or neither for treatment of suspected acute myocardial infarction [1]. The ISIS-2 trial recruited 17,187 patients from 417 hospitals. The authors concluded that there were benefits both from streptokinase and from aspirin. This paper contained a complex table reporting subgroup analyses, and rather intriguingly, the first analysis was by astrological birth sign. The results suggested that for people born under the star signs Gemini and Libra, aspirin was no better than placebo; for others, aspirin had a strongly beneficial effect. Why, one might wonder, did a highly respected journal publish such arrant nonsense?

The use of patient reported outcomes (PROs) in clinical trials can lead to problems with ‘multiple testing’, that is, the testing of multiple hypotheses and the associated problem of how to interpret resultant *P* values [2]. Most commonly, this problem arises...

## Keywords

Migraine Subgroup Analysis Streptokinase Rizatriptan Interaction Test## References

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