Off-label prescribing: Comparative evidence, regulation, and utilization

药物的标签外处方是医生的常规做法。食品药品 美国食品药品监督管理局（FDA）根据新药对特定适应症的有效性批准新药，但一旦 当药物进入市场时，医生可以为他们认为合适的其他适应症开药。 有时，这种处方是基于严格的随机试验数据，尚未导致正式的FDA 特定适应症的批准;其他标签外使用基于不太完善的证据。因为 出于对护理成本和/或质量的担忧，私营和公共部门的付款人都试图禁止 标签外使用，限制其覆盖范围，和/或要求患者承担其成本的增加部分。 因此，标签外药物使用涉及可能是或可能不是合理治疗的处方，可能涉及 这可能会给患者带来不必要的风险，并且可能是成本效益或成本效益不佳的-或者三者兼而有之。虽然 据估计，超说明书使用占某些药物使用的近四分之三， 仍然知之甚少。很少有研究详细说明新批准的药物在多大程度上用于 标签外使用或支持此类使用的证据。此外，关于患者或 医生或药物特征，预测何时更可能发生超说明书使用。虽然促进 药品的标签外使用是严格管制的，最近有几个高调的违反 本规定没有研究系统地评价了营销或其他法律的、监管的影响， 或经济力量对超说明书药物使用的影响。 我们建议制订一套全面的研究计划，研究标签外药物的使用情况， 不同类型的标签外使用及其临床、经济和政策影响。我们将应用这种类型学 评价三个重要类别的标签外药物使用的频率和模式：肿瘤药物， 神经精神药物和其他罕见病药物。我们将确定目标药物，并审查医疗 关于每种产品的具体用途的文献以及专家意见，以确定证据的质量 支持每种标签外使用。然后，我们将评估大规模人群中超说明书用药的特征 处方和诊断数据库，包括医疗补助患者、医疗保险患者和承保患者 一家大型健康保险公司。使用这些数据集，我们将使用多变量回归来确定 使用特定的标签外药物用于特定目的，并确定患者，医生和 与标签外使用相关的药物。最后，我们将使用时间趋势分析来确定 影响超说明书使用的法律的、监管或财务因素变化的影响。 更好地理解标签外使用的性质和预测因素可以为循证医学提供信息。 处方这些产品。研究与此类用途相关的效益-风险-成本关系， 在这一争议日益激烈的领域，采取更开明的方法来制定处方和政策决定。

Off-label prescription of drugs is a routine practice among physicians. The Food and Drug Administration (FDA) approves new drugs based on their effectiveness for a particular indication, but once a drug enters the market, physicians can prescribe drugs for other indications that they deem appropriate. Sometimes, such prescribing is based on rigorous randomized trial data that has not (yet) led to formal FDA approval for a given indication; other off-label use is based on less well-established evidence. Because of concerns about cost and/or quality of care, payors in both the private and public sectors have sought to prohibit off-label use, limit its coverage, and/or require patients to assume an increasing fraction of its cost. Off-label drug use thus involves prescriptions that may or may not be sound therapy, that may involve unnecessary risk to patients, and that may be cost-effective or cost-ineffective-or a mix of all three. Though off-label use has been estimated to account for nearly three-quarters of the use of some drugs, the practice remains poorly understood. Few studies have detailed extent to which newly approved drugs are prescribed for off-label uses, or the evidence supporting such utilization. In addition, scant data exist regarding the patient or physician or drug characteristics that predict when an off-label use is more likely to occur. Though promotion of drugs for off-label uses is strictly regulated, there have been several recent high-profile instances of violation of these regulations. No studies have systematically evaluated the impact of marketing or other legal, regulatory, or financial forces on the practice of off-label drug use. We propose to develop a comprehensive scheme for studying off-label drug use to categorize the different types of off-label use and their clinical, economic, and policy implications. We will apply this typology to evaluate the frequency and patterns of off-label drug use in three important categories: oncology drugs, neuropsychiatric drugs, and drugs for other rare diseases. We will identify target drugs and review the medical literature, as well as expert opinion, regarding specific uses of each product to define the quality of evidence supporting each off-label use. We will then evaluate the characteristics of off-label drug use in large population databases of prescriptions and diagnoses, including Medicaid patients, Medicare patients, and those covered by a large health insurer. Using these datasets, we will use multivariable regression to determine predictors of use of specific off-label drugs for particular purposes, and identify characteristics of patients, physicians, and medications that are associated with off-label use. Finally, we will use time-trend analysis to determine the impact of changes in legal, regulatory, or financial factors that impact off-label use. A better understanding of the properties and predictors of off-label use can inform evidence-based prescribing of these products. Studying the benefit-risk-cost relationships associated with such uses can lead to more enlightened approaches to prescribing and policy decisions in this increasingly contentious area.