Adverse drug events (ADEs) account for a significant mortality, morbidity, and cost burden. Pharmacogenetic testing has the potential to reduce ADEs and inefficacy. The objective of this INGENIOUS trial (NCT02297126) analysis was to determine whether conducting and reporting pharmacogenetic panel testing impacts ADE frequency. The trial was a pragmatic, randomized controlled clinical trial, adapted as a propensity matched analysis in individuals (N = 2612) receiving a new prescription for one or more of 26 pharmacogenetic-actionable drugs across a community safety-net and academic health system. The intervention was a pharmacogenetic testing panel for 26 drugs with dosage and selection recommendations returned to the health record. The primary outcome was occurrence of ADEs within 1 year, according to modified Common Terminology Criteria for Adverse Events (CTCAE). In the propensity-matched analysis, 16.1% of individuals experienced any ADE within 1-year. Serious ADEs (CTCAE level ≥ 3) occurred in 3.2% of individuals. When combining all 26 drugs, no significant difference was observed between the pharmacogenetic testing and control arms for any ADE (Odds ratio 0.96, 95% CI: 0.78–1.18), serious ADEs (OR: 0.91, 95% CI: 0.58–1.40), or mortality (OR: 0.60, 95% CI: 0.28–1.21). However, sub-group analyses revealed a reduction in serious ADEs and death in individuals who underwent pharmacogenotyping for aripiprazole and serotonin or serotonin-norepinephrine reuptake inhibitors (OR 0.34, 95% CI: 0.12–0.85). In conclusion, no change in overall ADEs was observed after pharmacogenetic testing. However, limitations incurred during INGENIOUS likely affected the results. Future studies may consider preemptive, rather than reactive, pharmacogenetic panel testing.

药物不良事件 （ADE） 是导致大量死亡率、发病率和成本负担的原因。药物遗传学检测有可能减少 ADE 和无效性。这项 INGENIOUS 试验 （NCT02297126） 分析的目的是确定进行和报告药物遗传学面板测试是否会影响 ADE 频率。该试验是一项实用的随机对照临床试验，适用于在社区安全网和学术卫生系统中接受 26 种药物遗传学可操作药物中的一种或多种新处方的个体 （N = 2612） 的倾向匹配分析。干预措施是 26 种药物的药物遗传学检测小组，剂量和选择建议返回健康记录。根据修改后的不良事件通用术语标准 （CTCAE），主要结局是 1 年内 ADE 的发生率。在倾向匹配分析中，16.1% 的个体在 1 年内经历过任何 ADE。严重的 ADE （CTCAE 水平 ≥ 3） 发生在 3.2% 的个体中。当联合所有 26 种药物时，药物遗传学检测组和对照组之间在任何 ADE （比值比 0.96,95% CI： 0.78-1.18）、严重 ADE （OR： 0.91， 95% CI： 0.58-1.40） 或死亡率 （OR： 0.60， 95% CI： 0.28-1.21） 方面均未观察到显著差异。然而，亚组分析显示，接受阿立哌唑和血清素或血清素-去甲肾上腺素再摄取抑制剂药物遗传学分析的个体严重 ADE 和死亡减少 （OR 0.34,95% CI： 0.12-0.85）。总之，在药物遗传学检测后未观察到总体 ADE 的变化。然而，INGENIOUS 期间发生的限制可能会影响结果。未来的研究可能会考虑先发制人，而不是被动的药物遗传学面板测试。