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The randomized ISAT demonstrated the superiority of endovascular treatment in patients with ruptured intracranial aneurysms considered suitable for either clipping or coiling. A later publication proposed a second look at the results, demonstrating that older patients with ruptured MCA aneurysms appeared to benefit from clipping, in disagreement with the general findings of the trial. Subgroup analyses in randomized trials and observational studies examine whether effects of interventions differ between subgroups according to the characteristics of patients. However, many apparent subgroup effects have been shown to be spurious. Misleading subgroup effects can result in withholding efficacious treatment from patients who would benefit or can encourage ineffective or potentially harmful treatments for patients who would fare better without. Some guidelines for the prudent interpretation of subgroup findings are reviewed.

The Problem of Subgroup Analyses: An Example from a Trial on Ruptured Intracranial Aneurysms