Researchers are often interested in estimating the effect of sustained use of a treatment on a health outcome. However, adherence to strict treatment protocols can be challenging for individuals in practice and, when non-adherence is expected, estimates of the effect of sustained use may not be useful for decision making. As an alternative, more relaxed treatment protocols which allow for periods of time off treatment (i.e. grace periods) have been considered in pragmatic randomized trials and observational studies. In this article, we consider the interpretation, identification, and estimation of treatment strategies which include grace periods. We contrast natural grace period strategies which allow individuals the flexibility to take treatment as they would naturally do, with stochastic grace period strategies in which the investigator specifies the distribution of treatment utilization. We estimate the effect of initiation of a thiazide diuretic or an angiotensin-converting enzyme inhibitor in hypertensive individuals under various strategies which include grace periods.

翻译：研究人员通常关注评估持续使用某种治疗对健康结局的影响。然而在实践中，个体严格遵循治疗方案可能具有挑战性，且当预期存在不依从性时，持续使用效果的估计值可能对决策无益。作为替代方案，务实随机试验和观察性研究中已考虑了允许治疗中断时段（即宽容期）的更宽松治疗方案。本文探讨了包含宽容期的治疗策略的解读、识别与估计方法。我们将自然宽容期策略（允许个体按自然方式灵活用药）与随机宽容期策略（研究者规定治疗使用分布）进行对比。基于包含宽容期的多种策略，我们评估了高血压患者启动噻嗪类利尿剂或血管紧张素转化酶抑制剂治疗的效果。