Department of Psychiatry, New York University School of Medicine; and the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Int J Clin Pract. 2010 May;64(6):707-18. doi: 10.1111/j.1742-1241.2010.02344.x. Epub 2010 Feb 23.
To describe the contents of a Drug Approval Package and to describe the efficacy and safety of iloperidone for the treatment of schizophrenia.
Drug Approval Package from the US Food and Drug Administration available at http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022192s000TOC.cfm.
The Drug Approval Package contains several different sections that describe both the preclinical (animal) and the clinical (human) studies conducted that led to the approval of iloperidone, a second-generation antipsychotic medication. Most of this information has not been published in the peer-reviewed literature and much of it had not been previously publicly available. Iloperidone's indication for the acute treatment of schizophrenia in adults is supported by two of the four principal registration studies completed by the manufacturer. The documents made available reveal that there was disagreement between the Food and Drug Administration (FDA) and the manufacturer as to which study was considered 'positive' for iloperidone. There was additional controversy surrounding the appropriateness of combining patients with schizophrenia and schizoaffective disorder in the same study. Questions were also raised by the FDA about the relative efficacy of iloperidone vs. other antipsychotics; the need for an initial titration period was offered as a possible explanation as to why risperidone appeared to have superior efficacy. Moreover, there was disagreement as to what constitutes an appropriate study to test the long-term efficacy of an antipsychotic. Additional information is made available regarding the safety and tolerability of iloperidone, with the FDA acknowledging an overall attractive profile that includes less akathisia and extrapyramidal symptoms than other agents in its class. Of potential clinical utility are the results from FDA analyses of patients where clinical variables shifted from the normal to abnormal range.
Iloperidone is efficacious and reasonably tolerable. The information made publicly available in the Drug Approval Package from the US FDA allows a closer examination as to how the medication was approved and allows for outside clinicians and researchers to appraise the data more carefully. Safety signals generated by FDA analyses of outliers can provide the impetus for the conduct of additional studies and post hoc analyses of registration study data already collected.
描述药物批准文件的内容，并描述伊洛哌酮治疗精神分裂症的疗效和安全性。
可从以下网址获取美国食品和药物管理局的药物批准文件：http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022192s000TOC.cfm。
药物批准文件包含多个不同部分，描述了导致第二代抗精神病药物伊洛哌酮获得批准的临床前（动物）和临床（人体）研究。这些信息大部分尚未在同行评议文献中发表，而且其中许多信息以前并未公开。制造商完成的四项主要注册研究中的两项支持伊洛哌酮用于成人精神分裂症急性治疗的适应证。提供的文件显示，美国食品和药物管理局（FDA）与制造商之间对哪项研究被认为对伊洛哌酮为“阳性”存在分歧。在同一研究中将精神分裂症和分裂情感障碍患者合并在一起的适当性也存在争议。FDA 还对伊洛哌酮与其他抗精神病药的相对疗效提出质疑；提供起始滴定期的必要性可能是利培酮似乎具有更好疗效的原因。此外，对于测试抗精神病药长期疗效的适当研究也存在分歧。还提供了关于伊洛哌酮安全性和耐受性的更多信息，FDA 承认其总体上具有吸引力的特征，包括与同类药物相比，静坐不能和锥体外系症状更少。对临床变量从正常范围转变为异常范围的 FDA 分析结果可能具有潜在的临床应用价值。
伊洛哌酮具有疗效且具有良好的耐受性。美国 FDA 药物批准文件中公开的信息允许更仔细地检查药物的批准情况，并允许外部临床医生和研究人员更仔细地评估数据。FDA 对离群值进行分析产生的安全性信号可以为开展额外研究和对已收集的注册研究数据进行事后分析提供动力。
