An Epidemiologic Evaluation of Adverse Events of 5-Alpha-Reductase Inhibitors

5-α-还原酶抑制剂不良事件的流行病学评估

• 批准号: 8916105
• 负责人: Hozefa Divan
• 金额: $ 10.78万
• 依托单位: NEW ENGLAND RESEARCH INSTITUTES, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8916105
• 关键词: 5 Alpha-Reductase Inhibitor; Accounting; Address; Adrenergic alpha-Antagonists; Adverse effects; Adverse event; Aging; Area; Awareness; Behavioral; Benefits and Risks; Benign; Benign Prostatic Hypertrophy; Boston; Breast; Breast Diseases; Chemoprevention; Chibro-Proscar; Clinical; Clinical Treatment; Cohort Studies; Collaborations; Computerized Medical Record; Data Analyses; Data Set; Databases; Decreased Libido; Development; Disease; Dose; Drug Utilization; Drug user; Dutasteride; Epidemiologic Studies; Epidemiology; Erectile dysfunction; Evaluation; Event; Finasteride; Foundations; Functional disorder; General Practices; GlaxoSmithKline brand of dutasteride; Goals; Health; Healthcare; Heterogeneity; Incidence; Label; Libido; Male Pattern Baldness; Malignant - descriptor; Malignant neoplasm of male breast; Malignant neoplasm of prostate; Medical; Medical Records; Medicine; Mental Depression; Methods; National Institute of Diabetes and Digestive and Kidney Diseases; Neurosecretory Systems; Orgasm; Outcome; Patients; Peyronie Disease; Pharmaceutical Preparations; Pharmacoepidemiology; Population; Prostate; Prostate Cancer Prevention Trial; Psychosexual Disorders; Public Health; Reporting; Research; Research Design; Resources; Risk; Risk Factors; Safety; Sex Functioning; Sexual Dysfunction; Stanolone; Surveillance Program; Survival Analysis; Symptoms; Syndrome; Testosterone; Time; Validation; active method; aged; arm; base; cancer chemoprevention; clinical practice; comparison group; cost; design; drug market; experience; follow-up; innovation; interest; longitudinal design; lower urinary tract symptoms; male; men; novel; public health relevance; young man

DESCRIPTION (provided by applicant): We propose a harmacoepidemiologic study of 5-alpha-reductase inhibitors (5ARIs) to address emerging safety concerns (permanent sexual side effects, depression) with use of these marketed drugs, presently being considered for expanded use in healthy men as agents of prostate cancer chemoprevention. In order to cost- efficiently deliver needed safety information, this research will examine the occurrence of adverse events (AEs) via analysis of a large electronic medical records database, the UK-based Clinical Practice Research Datalink (CPRD). The CPRD is the most widely-used resource for pharmacoepidemiologic research in the world. In preliminary analyses of this very large database (11M patients, 45M patient-years), we have identified over 58,000 users of the drug class in question with on average approximately 10 years of follow-up time. In addition to studying risk of events, the proposed study will be the first to study symptom persistence in relation to both types of drugs in the class (finasteride and dutasteride), and will be the largest epidemiologic study of its kind to date. We propose to examine the occurrence of 4 thematic groups of AEs: 1) erectile dysfunction (ED); 2) non- ED sexual dysfunction (ejaculatory and psychosexual dysfunction, low libido, Peyronie's disease); 3) breast outcomes (benign/malignant breast diseases), and 4) depression, using longitudinal epidemiologic approaches. In addition to a retrospective cohort study focused on incident events, we will examine the persistence/permanency of sexual dysfunction outcomes and depression following drug cessation, and risk factors for permanency. Our analyses are designed such that men under various drug treatments for benign prostatic hyperplasia (BPH) are compared (finasteride, dutasteride, and alpha-blockers) to account for the underlying influence of BPH on outcomes. We will examine potential confounding in our analysis using the wide variety of medical and behavioral factors available in CPRD, including use of novel methods such as high-dimensional propensity score analysis. Our research team is comprised of experts in the epidemiology of male aging, pharmacoepidemiology relating to sexual function and lower urinary tract symptoms, and clinical treatment of BPH. The PI has immediate access and >25 years of experience in pharmacoepidemiologic utilization of the CPRD. Other strengths of our proposed study include its large size, use of medical records (avoiding the need to rely on patient recall o prescriptions and avoidance of problems with use of medical claims), longitudinal design, the ability to compare 5ARIs to other treatments, and the richness of the underlying dataset for confounder control. The public health contribution of the study is to quickly to inform the safety profile of the 5ARI class for currently-approved indications before further expansion to healthy men for chemoprevention.

描述（由申请人提供）：我们提议对 5-α-还原酶抑制剂 (5ARIs) 进行危害流行病学研究，以解决使用这些市售药物时出现的安全问题（永久性性副作用、抑郁），目前正在考虑扩大在健康人群中的使用男性作为前列腺癌化学预防剂。为了经济有效地提供所需的安全信息，本研究将通过分析大型电子病历数据库（位于英国的临床实践研究数据链（CPRD））来检查不良事件（AE）的发生情况。 CPRD 是世界上最广泛使用的药物流行病学研究资源。在对这个非常大的数据库（1100 万患者，4500 万患者年）的初步分析中，我们已经确定了超过 58,000 名相关药物类别的使用者，平均随访时间约为 10 年。除了研究事件风险外，拟议的研究还将是第一个研究与该类药物（非那雄胺和度他雄胺）相关的症状持续性的研究，并且将是规模最大的研究 迄今为止的此类流行病学研究。 我们建议检查 4 个主题组 AE 的发生情况：1) 勃起功能障碍 (ED)； 2)非ED性功能障碍(射精和性心理功能障碍、性欲低下、佩罗尼氏病)； 3) 乳腺结局（良性/恶性乳腺疾病），4) 抑郁症，采用纵向流行病学方法。除了针对事件事件的回顾性队列研究外，我们还将检查停药后性功能障碍结果和抑郁症的持续性/永久性，以及永久性的危险因素。我们的分析旨在对接受各种良性前列腺增生 (BPH) 药物治疗的男性（非那雄胺、度他雄胺和 α 受体阻滞剂）进行比较，以解释 BPH 对结果的潜在影响。我们将使用 CPRD 中可用的各种医学和行为因素来检查分析中潜在的混杂因素，包括使用高维倾向评分分析等新颖方法。 我们的研究团队由男性衰老流行病学、性功能和下尿路症状相关药物流行病学以及 BPH 临床治疗方面的专家组成。 PI 可以立即访问 CPRD，并在药物流行病学应用方面拥有超过 25 年的经验。我们提出的研究的其他优点包括其规模大、使用医疗记录（避免依赖患者回忆或处方并避免使用医疗索赔的问题）、纵向设计、将 5ARIs 与其他治疗进行比较的能力，以及用于混杂控制的基础数据集的丰富性。该研究对公共卫生的贡献是，在进一步扩展到健康男性进行化学预防之前，快速告知 5ARI 类药物目前批准的适应症的安全性。