Assessing Clinical Equivalence for Generic Drugs Approved By Innovative Methods

摘要/摘要 仿制药约占所有药品处方的80%，价格较低的仿制药 促进患者坚持用药，减少浪费性医疗支出。这个 仿制药行业的成功与品牌名称和仿制药的互换性有关 药物，而这又依赖于FDA对仿制药生物等效性的认证。在最近 多年来，FDA采取了许多不同的创新方法来确定 由于特定药物的独特特性而产生的生物等效性。因为这些案件已经引发了 争议，这个项目的目标是使用不同的实证方法来研究临床 FDA生物等效性测定在6种特定情况下的含义：批准 仿制文拉法辛ER、降钙素鲑鱼鼻喷雾剂、依诺肝素、阿卡波糖、万古霉素 胶囊和葡萄糖酸铁钠。首先，我们将对患者进行全国调查，以 确定他们对仿制药安全性和有效性的看法，对 通过创新机制批准的生物等效仿制药，以及关于 与本申请中争议的六种特定模型药物有关的争议。我们将使用 对近125,000名患者进行基本人群调查，并调查那些开过处方的人 6种感兴趣的药物或用于相同条件的其他药物中的一种。第二，我们将 对医生进行一项全国性调查，以评估同样的结果。在本次调查中，我们将 在全国范围内随机抽取经过董事会认证的内科医生，并使用在线调查工具 以前受雇于这一人群的调查。第三，使用大型国家索赔数据库， 我们将确定与6种仿制药(患者接受 该药物的仿制版本，然后切换回品牌配方中 随后的处方)，并确定这些折返率是否有显著差异 从其他相关但没有争议的仿制药的回落。要确定 回转研究的可靠性，我们将把我们的结果与通用的替代分析进行比较 以及品牌药物的使用，这可能更好地解释了混淆。最后，我们将进行 对6种仿制药的研究进行系统评价和荟萃分析，以确定是否有 文献中有证据表明，它们的安全性或有效性与 名牌版本。这些数据将帮助FDA评估创新的 对这6种仿制药使用的监管方法，并评估类似的途径 可用于与未来药物相关的生物等效性测定。

Summary/Abstract Generic drugs make up about 80% of all drug prescribing, and less costly generic drugs promote medication adherence among patients and reduce wasteful health care spending. The success of the generic drug industry relates to the interchangeability of brand name and generic drugs, which in turn relies on the FDA's certification of generic drugs as bioequivalent. In recent years, the FDA has taken a number of different innovative approaches to determining bioequivalence due to unique characteristics of particular drugs. Since these cases have raised controversy, the goal of this project is to use different empirical approaches to study the clinical implications of the FDA's bioequivalence determination in 6 specific circumstances: the approval of generic venlafaxine ER, calcitonin salmon nasal spray, enoxaparin, acarbose, vancomycin capsules, and sodium ferric gluconate. First, we will conduct a national survey of patients to determine their opinions about generic drug safety and effectiveness, attitudes about bioequivalent generic drugs approved via innovative mechanisms, and knowledge about controversies relating to the six specific model drugs at issue in this application. We will use a base population of nearly 125,000 patients and survey those who have filled prescriptions for one of the 6 drugs of interest or other drugs indicated for the same conditions. Second, we will conduct a national survey of physicians to assess the same outcomes. For this survey, we will identify a random national sample of board certified internists, and use online survey tools previously employed in surveys of this population. Third, using large national claims databases, we will identify "switchback" rates related to the 6 generic drugs (episodes of patients receiving generic versions of the drug and then switching back to the brand name formulations in subsequent prescriptions), and determine whether these switchback rates differ significantly from switchbacks for other related but non-controversial generic drugs. To determine the reliability of switchback studies, we will compare our results to alternative analyses of generic and brand-name drug use that may better account for confounding. Finally, we will conduct systematic reviews and meta-analyses of studies of the 6 generic drugs to determine if any evidence exists in the literature of differences in their safety or effectiveness compared with the brand-name versions. These data will help the FDA assess the success of the innovative regulatory approaches used for these 6 generic drugs and evaluate whether similar pathways may be used for bioequivalence determinations related to future drugs.