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

标签外处方：比较证据、监管和利用

• 批准号: 7929899
• 负责人: AARON SETH KESSELHEIM
• 金额: $ 15.87万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7929899
• 关键词: Off; label; prescribing; Comparative; evidence

DESCRIPTION (provided by the applicant): 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, payers 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. Many physicians prescribe drugs for non-FDA-approved reasons ("off-label uses"), but when this practice occurs without sufficient evidence basis, it raises important health policy concerns about patient safety and cost-effectiveness. We propose to study the characteristics of off-label drug use in three select classes-cancer drugs, neuropsychiatry drugs, and drugs for other rare diseases. Using expert interviews and pharmaceutical claims data from a variety of large databases, we will identify the predictors and frequency of off- label use and determine how the practice is affected by certain external scientific, market, and regulatory events.

描述（由申请人提供）：药物的标签外处方是医生的常规做法。食品药品监督管理局（FDA）根据其特定迹象的有效性批准了新药，但是一旦药物进入市场，医生就可以开出药物，以确定其认为适当的其他迹象。有时，这种处方是基于严格的随机试验数据，但尚未（尚未）导致FDA批准给定指示；其他标签的使用是基于较不公平的证据。由于担心成本和/或护理质量，私营部门和公共部门的付款人都试图禁止使用标签外，限制其覆盖范围和/或要求患者承担越来越多的成本。因此，使用标签的药物涉及可能或可能不是合理疗法的处方，可能涉及患者不必要的风险，并且可能是成本效益或成本效益或三种混合的成本效益。尽管据估计使用标签外的使用量将近四分之三，但这种做法的理解仍然很少。很少有研究详细规定了新批准的药物用于标签外用途或支持这种利用的证据。此外，关于患者或医师或药物特征的数据很少，这些数据预测何时使用标签的可能性更大。尽管严格规定了促进标签外使用的药物，但最近有一些违反这些法规的备受瞩目的实例。没有研究对营销或其他法律，监管或金融部队对标签非标签使用药物使用的影响的影响。我们建议制定一项全面的计划，用于研究标签外药物的使用，以分类不同类型的非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来评估三个重要类别中标签非标签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疾病的药物。我们将确定目标药物并审查有关每种产品的特定用途的医学文献以及专家意见，以定义支持每种标签外使用的证据质量。然后，我们将评估大型处方和诊断人口数据库中的标签外药物使用的特征，包括医疗补助患者，医疗保险患者以及大型健康保险公司所涵盖的患者。使用这些数据集，我们将使用多变量回归来确定用于特定目的的特定标签外药物的预测指标，并确定患者，医生和与标签外使用相关的药物的特征。最后，我们将使用时间趋势分析来确定影响标签外使用的法律，监管或财务因素的变化的影响。更好地了解非标签使用情况的属性和预测因素可以为这些产品的基于证据的处方提供信息。研究与此类用途相关的利益风险成本关系可能会导致在这个日益争议的领域中开处方和政策决策的更开明的方法。许多医生出于非FDA批准的原因（“标签不使用”）开出药物，但是当这种做法没有足够的证据基础上，这会引起对患者安全性和成本效益的重要关注。我们建议研究三种选择类药物，神经精神病学药物和其他罕见疾病的药物中使用标签外药物的特征。利用专家访谈和药品索赔数据来自各种大型数据库的数据，我们将确定使用非标签使用的预测因素和频率，并确定实践如何受到某些外部科学，市场和监管事件的影响。