Another method proposed to control for unmeasured confounding is the Prior Event Rate Ratio (PERR) adjustment method, in which the effect of exposure is estimated using the ratio of rate ratios (RRs) from periods before and after initiation of a drug exposure as discussed in Replicated studies of two randomized trials of angiotensin‐converting enzyme inhibitors: further empiric validation of the ‘prior event rate ratio’to adjust for unmeasured confounding by indication (Pharmacoepidemiol Drug Saf. 2008;17:671-685). For example, when a new drug is launched, direct estimation of the drugs effect observed in the period after launch is potentially confounded. Differences in event rates in the period before the launch between future users and future non-users may provide a measure of the amount of confounding present. By dividing the effect estimate from the period after launch by the effect obtained in the period before launch, the confounding in the second period can be adjusted for. This method requires that confounding effects are constant over time, that there is no confounder-by-treatment interaction, and outcomes are non-lethal events.
Performance of prior event rate ratio adjustment method in pharmacoepidemiology: a simulation study (Pharmacoepidemiol Drug Saf. 2015;24:468-477) discusses that the PERR adjustment method can help to reduce bias as a result of unmeasured confounding in certain situations but that theoretical justification of assumptions should be provided.
|Annex 1.||Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes|