Findings of the International Subarachnoid Aneurysm Trial and the National Study of Subarachnoid Haemorrhage in context

Abstract

Concern has been expressed about the applicability of the findings of the International Subarachnoid Aneurysm Trial (ISAT) with respect to the relative effects on outcome of coiling and clipping. It has been suggested that the findings of the National Study of Subarachnoid Haemorrhage may have greater relevance for neurosurgical practice. The objective of this paper was to interpret the findings of these two studies in the context of differences in their study populations, design, execution and analysis. Because of differences in design and analysis, the findings of the two studies are not directly comparable. The ISAT analysed all randomized patients by intention-to-treat, including some who did not undergo a repair, and obtained the primary outcome for 99% of participants. The National Study only analysed participants who underwent clipping or coiling, according to the method of repair, and obtained the primary outcome for 91% of participants. Time to repair was also considered differently in the two studies. The comparison between coiling and clipping was susceptible to confounding in the National Study, but not in the ISAT. The two study populations differed to some extent, but inspection of these differences does not support the view that coiling was applied inappropriately in the National Study. Therefore, there are many reasons why the two studies estimated different sizes of effect. The possibility that there were real, systematic differences in practice between the ISAT and the National Study cannot be ruled out, but such explanations must be seen in the context of other explanations relating to chance, differences in design or analysis, or confounding.

Key words:

• Subarachnoid haemorrhage
• randomised controlled trial
• observational study
• surgical repair
• endovascular repair
• validity
• applicability

Notes

[1] This percentage is 6.7% (142/2133) if deaths before any procedure were omitted from Table 1.[4]

[2] The National Study coordinating team were not reliably informed about transfers, but were notified about some and identified others because the same patients were recorded as having been admitted to two units within a short period of time.

[3] This confidence interval was misreported in the version of the report originally published on the website of the Royal College of Surgeons of England. This error has now been corrected.[2]

[4] Note that the effect estimate reported in the ISAT was a risk ratio for coiling versus clipping, whereas the effect estimate reported in the National Study was an odds ratio for clipping versus coiling. The ISAT result has been recalculated as an odds ratio for clipping versus coiling so that the two estimates can be compared.