We took the date of diagnosis as the index date because the precise
date of onset of muscle symptoms was not known for all cases. Potentially
this could have led to amisclassification of exposure status, and biased
estimates of relative risk, if a gradual onset of symptoms had led to
an early discontinuation of simvastatin or a reduction in dose. However,
this does not appear to have been a substantive issue; of the rhabdomyolysis
cases who were classified as current users, only three were dispensed
a different dose of simvastatin in the 90 day period before the
index date (a reduction in dose from 80 mg to 40 mg [32 days before
index date], a short-term reduction from 40 mg to 20 mg [57 days before
index date, resumed 40 mg 20 days later], and an increase from
20 to 40 mg [51 days before index date]). Moreover, the three rhabdomyolysis
cases whowere past users (including the current user of atorvastatin)
stopped simvastatin well before the index date (155 days,
16 months, 24 months).