Why Do I Get Side Effects? Personalized (N-of-1) Trials for Statin Intolerance and the Nocebo Effect

Abstract

The ability of statins to reduce the morbidity and mortality of cardiovascular disease has ensured that they are among the most prescribed drugs in modern medicine. Unfortunately, most patients who start taking statins will end up stopping them, most commonly due to side effects. Confusingly, however, in blinded placebocontrolled trials, side effects appear no more common in those taking statins than those taking placebo. One possible explanation is that ever-present background symptoms are being falsely attributed to statins. However, another explanation is the nocebo effect, where the act of just taking a tablet (even a placebo) causes genuine side effects in patients.Two recent randomized placebo-controlled personalized (N-of-1) trials have been reported: StatinWise and SAMSON. In these trials, each participant was randomized to multiple periods of statin and placebo, with regular symptom burden assessments. Together, these trials support the existence of a significant nocebo effect from taking statins. Possibly even more importantly, they demonstrate the ability of personalized trials to inform and empower patients: up to half of the patients in these trials were able to successfully restart statins after taking part, despite previously having been statin intolerant. StatinWise and SAMSON have raised public awareness of the nocebo effect in statin intolerance. However, they also demonstrate a potential role for the personalized design outside of clinical trials. If taking part in these personalized experiments allows half of our patients to successfully restart life-saving medications, maybe we should be able to prescribe personalized experiments to our patients in the clinical setting?

Introducing Data Sciences to N-of-1 Designs, Statistics, Use-Cases, the Future, and the Moniker ‘N-of-1’ Trial

“…Importantly, this issue concludes with use cases of personalized trials that range from presentation of results to patients, medication side-effect testing, lower back pain management, and multimorbidity disease management (D'Angelo et al, 2022;Howard et al, 2022;Butler et al, 2022;.…”

“…Best practices for reporting, ethics, and conduct of personalized trials comprise the next section ( Porcino & Vohra, 2022 ; Samuel & Wootton, 2022 ; and Kravitz & Duan, 2022 ). Importantly, this issue concludes with use cases of personalized trials that range from presentation of results to patients, medication side-effect testing, lower back pain management, and multimorbidity disease management ( D’Angelo et al, 2022 ; Howard et al, 2022 ; Butler et al, 2022 ; and Suls et al, 2022 ).…”