5.5.5. Low event rates with large sample size: an exception to the need for OIS

In the criteria we have offered so far, our focus has been on relative effects. When event rates are very low, CIs around relative effects may be wide, but if sample sizes are sufficiently large, it is likely that prognostic balance has indeed been achieved, and rating down for imprecision becomes inappropriate.

The decision regarding the magnitude of effect that would be important is a matter of judgment. When control rates are sufficiently low, CIs around relative effects can appear very wide, but CIs around absolute effects will nevertheless be narrow. Thus, although one would intuitively rate down for imprecision considering only the CI around the relative effect, consideration of the CI around the absolute effect may lead to an appropriate conclusion that precision is adequate. Note that the inference of unimportance requires a low incidence of events over the desirable duration of follow-up; short follow-up will generate a low incidence of events that may be misleading.