Statin-related side effects: the recent Lancet publication is biased toward false-negatives

Adverse events (AEs) are adverse clinical events which occur at some point after a patient has taken a drug. Unlike the term “Adverse Drug Reaction, ” the term “AE” does not imply that the drug necessarily caused the event. For example, traumatic injuries sustained by a clinical trial subject who happened to be a passenger in a motor vehicle accident would be classified as “adverse events.”

A wide variety of AEs is recorded during clinical trials. At the end of the trial, an observed between-arm imbalance in the rate of a given AE might constitute a “safety signal” for that AE. The imbalance provides a hint that the drug might be capable of causing that AE. However, since AE rates are generally much lower than the rates of the primary outcome for which the trial was powered, definitive group-level inferences regarding causality for an AE are not usually possible at the end of a trial. Caveat: some trial AE imbalances are potentially so concerning (e.g., mortality imbalances favouring placebo) that they might jeopardize approval, even if causality has not been definitively established.

The number of patients exposed to statins in the context of clinical trials is by now so large that we have accrued a large number of reports for a very wide spectrum of AEs. And since the vast majority of these AEs have occurred at roughly equal rates among statin-treated patients and placebo-treated patients, we can infer that statins do not likely “cause” these AEs- at least not through a mechanism that is common enough to manifest as a measurable between-group difference.