Spelsberg Angela, Prugger Christof, Doshi Peter, Ostrowski Kerstin, Witte Thomas, Hüsgen Dieter, Keil Ulrich
Transparency International Deutschland eV, Working Group on Health and Working Group on Freedom of Information, Alte Schönhauser Strasse 44, 10119 Berlin, Germany
Comprehensive Cancer Centre Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
BMJ. 2017 Feb 7;356:j337. doi: 10.1136/bmj.j337.
To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act.
Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10.
Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany.
Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions.
Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals.
Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor. High remuneration and strict confidentiality clauses in these studies could influence the physicians' reporting behaviours of adverse drug reactions.
调查德国三年期间上市后研究的开展情况，并评估这些试验是否符合德国药品法规定的目标。
对2008 - 2010年开展上市后研究前提交给德国监管机构的通知进行调查。
通过向德国负责登记上市后研究的三个当局提出信息自由请求获得通知。
上市后研究的描述性统计，包括所研究的产品、预期患者数量、预期参与医生数量、提议的报酬、研究计划和方案，以及相关科学出版物和药物不良反应报告的可得性。
从558项研究中获取了信息，每项研究的患者中位数为600名（平均2331名，范围2 - 75000名），参与医生中位数为63名（270名，0 - 7000名）。每位患者给予医生的报酬中位数为200欧元（441欧元，0 - 7280欧元）（170英镑，0 - 6200英镑；215美元，0 - 7820美元），在三年期间登记的558项研究的总报酬成本超过2.17亿欧元。每项研究中每位参与医生的报酬中位数为2000欧元（平均19424欧元），范围从0至2080000欧元。有广泛的药品和非药品产品，其中只有三分之一是最近批准的药物。在许多通知中，根据合同，数据、信息和结果严格保密，是各自申办者的唯一财产。在558项上市后研究中，没有一项能识别出单一的药物不良反应报告。不到1%的研究能被证实发表在科学期刊上。
上市后研究并未改善药物安全性监测。样本量通常太小，无法检测到罕见的药物不良反应，而且许多参与医生严格有义务对申办者保密。这些研究中的高额报酬和严格保密条款可能会影响医生对药物不良反应的报告行为。
