Assessing Intervention Effectiveness in Longitudinal Trials of Antipsychotic Medi

描述（由申请人提供）：精神分裂症是导致残疾的主要原因，在生命的早期就发生，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大的机会来恢复他们在社会中的功能地位。然而，持续减少精神病症状和预防复发的可能性在很大程度上取决于处方药物的治疗依从性。早期停药不仅使治疗本身效果降低，而且对评价长期有效性试验也构成重大挑战。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，与真实的世界实践一样，参与者经常停止药物治疗，无论是缺乏疗效、副作用、社会耻辱还是更微妙的焦虑。停药的原因因不同的抗精神病药物而异。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 et al.，2005; Lieberman等人，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，并仔细评估纵向疗效和成本指标（例如精神病症状严重程度、生活质量、药物和医疗保健费用）中的患者结果。）由于治疗依从性的差异可能会被停药的竞争原因破坏。此外，在纵向抗精神病药物试验中，参与者甚至在停止治疗之前经常错过一个或多个预定的测量，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。这是第一个R21，将审查的影响，研究中止和间歇性错过测量的评价成本/效果在实际的抗精神病药物试验。这也是我们所知道的第一个同时解决有效性问题的方法，如通过上述纵向测量和特定原因治疗中止评估的。CATIE试验是NIMH有史以来资助的规模最大、时间最长的研究，但其结果一直存在争议，因为上述结局中的高脱落率和间歇性缺失测量妨碍了对研究结论达成共识。人们普遍认为，数据缺失的原因是，症状的重新出现未经计量，资源利用和成本相应增加，因此可能严重扭曲研究结果。这个R21是高度相关的抗精神病药物的评价和大型纵向试验分析的方法学文献的发展。

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.