Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois2Division of General Internal Medicine and Geriatrics, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
JAMA Dermatol. 2015 Jun;151(6):600-6. doi: 10.1001/jamadermatol.2015.36.
Two meta-analyses conclude that finasteride treatment of androgenic alopecia (AGA) is safe but do not assess quality of safety reporting.
To assess safety reporting for clinical trial reports of finasteride for AGA.
MEDLINE, ClinicalTrials.gov, and a clinical data repository for an academic medical center.
Published clinical trial reports for finasteride treatment of AGA.
For each trial, we assessed quality of adverse event reporting, extracted the number and type of adverse events in treatment and placebo groups, and assessed duration of safety evaluation and adequacy of blinding. Two observers independently extracted the data; differences were resolved by consensus. We assessed generalizability in a large cohort of men prescribed finasteride, 1.25 mg/d or less, by assessing for eligibility in the finasteride-AGA pivotal trials.
Quality was assessed as adequate, partially adequate, inadequate, or no events reported. We used funnel plots of the hazard ratio to assess bias.
Of 34 clinical trials, none had adequate safety reporting, 19 were partially adequate, 12 were inadequate, and 3 reported no adverse events. Funnel plots were asymmetric with a bias toward lower odds ratio for sexual adverse effects, suggesting systematic underdetection. No reports assessed adequacy of blinding, 18 (53%) disclosed conflicts of interest, and 19 (56%) received funding from the manufacturer. Duration of drug safety evaluation was 1 year or less for 26 of 34 trials (76%). Of 5704 men in the clinical data repository who were treated for AGA with finasteride, 1.25 mg/d or less, for AGA, only 31% met inclusion criteria for the pivotal trials referenced in the manufacturer's full prescribing information and 33% took finasteride for more than 1 year.
Available toxicity information from clinical trials of finasteride in men with AGA is very limited, is of poor quality, and seems to be systematically biased. In a cohort of men prescribed finasteride for routine treatment of AGA, most would have been excluded from the pivotal studies that supported US Food and Drug Administration approval for AGA. Published reports of clinical trials provide insufficient information to establish the safety profile for finasteride in the treatment of AGA.
两项荟萃分析得出结论，非那雄胺治疗雄激素性脱发（AGA）是安全的，但并未评估安全性报告的质量。
评估非那雄胺治疗 AGA 的临床试验报告的安全性报告。
MEDLINE、ClinicalTrials.gov 和学术医疗中心的临床数据存储库。
已发表的非那雄胺治疗 AGA 的临床试验报告。
对于每个试验，我们评估了不良事件报告的质量，提取了治疗组和安慰剂组中不良事件的数量和类型，并评估了安全性评估的持续时间和盲法的充分性。两名观察者独立提取数据；通过共识解决差异。我们通过评估在接受非那雄胺治疗 AGA 的大型男性队列中是否符合条件，来评估一般化情况，这些男性的非那雄胺剂量为 1.25mg/d 或更低，该队列来自非那雄胺-AGA 关键试验。
质量评估为充分、部分充分、不充分或无不良事件报告。我们使用危害比的漏斗图来评估偏倚。
在 34 项临床试验中，没有一项具有充分的安全性报告，19 项部分充分，12 项不充分，3 项报告无不良事件。漏斗图不对称，性不良反应的优势比呈下降趋势，表明系统性漏检。没有报告评估盲法的充分性，18 项（53%）披露了利益冲突，19 项（56%）获得了制造商的资金。34 项试验中有 26 项（76%）的药物安全性评估持续时间为 1 年或更短。在临床数据存储库中，5704 名接受非那雄胺治疗 AGA 的男性中，1.25mg/d 或更低，只有 31%符合制造商完整处方信息中引用的关键试验的纳入标准，33%的患者服用非那雄胺超过 1 年。
从 AGA 男性的非那雄胺临床试验中获得的可用毒性信息非常有限，质量较差，并且似乎存在系统性偏倚。在接受非那雄胺常规治疗 AGA 的男性队列中，大多数人将被排除在支持美国食品和药物管理局批准 AGA 的关键研究之外。已发表的临床试验报告提供的信息不足以确定非那雄胺治疗 AGA 的安全性概况。
