Assessing Intervention Effectiveness in Longitudinal Trials of Antipsychotic Medi

描述（由申请人提供）：精神分裂症是早期致残的主要原因，导致高昂的医疗和心理健康服务费用。非典型抗精神病药物的出现为患者提供了更多的机会来恢复他们在社会中的功能地位。然而，精神病症状持续减轻和预防复发的可能性在很大程度上取决于对处方药的治疗依从性。早期停止治疗不仅使治疗本身的效果降低，而且对评估长期疗效试验提出了重大挑战。在具有里程碑意义的临床抗精神病药物干预有效性试验（CATIE）中，正如在现实世界的实践中一样，参与者经常因为缺乏疗效、副作用、社会耻辱或更微妙的焦虑而停药。停药的原因因抗精神病药物的不同而不同。停药时间通常是主要的研究结果，因为它被认为反映了阻碍有效治疗的多种因素(Kemmler等人，2005；Lieberman et al., 2005)，然而，我们需要充分了解处方抗精神病药物与不同停药原因之间的关联，并仔细评估患者的纵向疗效和成本措施（如精神病症状严重程度、生活质量、药物和医疗成本），这些措施是由治疗依从性的差异引起的，可能被停药的竞争原因打乱。此外，在纵向抗精神病药物试验中，参与者经常在停止治疗之前错过一次或多次预定的测量，这也可能与有效性本身有关，并进一步使研究结果的解释复杂化。本R21是第一个将在实际抗精神病药物试验中检查研究中断和间歇性遗漏测量对成本/有效性评估的影响的R21。这也是我们所知道的第一个方案，它将同时解决上述纵向措施所评估的有效性问题和针对具体原因停止治疗的问题。CATIE试验是NIMH资助的规模最大、时间最长的研究，但其研究结果存在争议，因为上述结果的高损耗率和间歇性错过测量妨碍了对研究结论达成共识。人们普遍认为，缺失的数据来自并代表了未测量的症状重新出现以及相应的资源利用和成本增加，因此可能严重扭曲研究结果。该R21与抗精神病药物的评估和大型纵向试验分析的方法学文献的发展高度相关。

DESCRIPTION (provided by applicant): Schizophrenia is a leading cause of disability striking relatively early in life, incurring high medical and mental health service costs. The emergence of atypical antipsychotic medications has offered patients greater opportunity to regain their functional status in society. However, the likelihood of sustained reduction in psychotic symptoms and prevention of relapse are largely dependent on treatment adherence with prescribed medications. Early treatment discontinuation not only renders treatment itself less effective, it also poses a major challenge in evaluating long term trial of effectiveness. In the landmark Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), as in real world practice, participants often discontinue medication whether for lack of efficacy, side effects, social stigma, or subtler kinds of dysphoria. Reasons of discontinuation vary between different antipsychotic medications. Time to discontinuation was usually the primary study outcome because it was thought to reflect multiple factors that impede effective treatment (Kemmler et al., 2005; Lieberman et al., 2005), however, we need to fully understand the association between prescribed antipsychotic medications and different reasons of discontinuation and to carefully assess patient outcomes in longitudinal efficacy and cost measures (such as psychotic symptom severity, quality of life, drug and health care costs) resulting from the differences in treatment adherence that can be disrupted by competing causes of discontinuation. Furthermore, participants often miss one or more scheduled measurements before they even discontinue their treatment in longitudinal antipsychotic trials, which may also be related to the effectiveness itself and further complicates the interpretation of study results. This R21 is the first one that will examine the impact of both study discontinuation and intermittently missed measurements on the evaluation of cost/effectiveness in practical antipsychotic trials. It is also the first of which we are aware, that would simultaneously address the issues of effectiveness as assessed by the above longitudinal measures and cause- specific treatment discontinuation. The CATIE trial was the largest, longest study ever funded by NIMH but its findings have been contested because high attrition rate and intermittently missed measurements in the above outcomes have precluded reaching consensus on study conclusions. It is widely believed that the missing data results from and represents the unmeasured re-emergence of symptoms and corresponding increases in resource utilization and cost and thus can deeply distort study findings. This R21 is highly relevant to both in the evaluation of antipsychotic medications and to the development of methodological literature on the analysis of large longitudinal trials.