Theobald Karlheinz, Capan Müge, Herbold Marlis, Schinzel Stefan, Hundt Ferdinand
Sanofi-Aventis Deutschland GmbH, Clinical Operations, Frankfurt/Main, Germany.
Ger Med Sci. 2009 Nov 9;7:Doc29. doi: 10.3205/000088.
Nowadays, drug research and surveillance after authorisation becomes more and more important for several reasons. Non-interventional studies (NIS) investigate various aspects of drug use including efficacy and safety under real life conditions. Such kind of health services research should be on a high scientific, methodological and organisational level. Therefore accompanying measures to improve or to keep the quality are highly recommended. The aim of quality management is: first to avoid bias of results by using an appropriate study design and an adequate data analysis, second to assure authenticity, completeness and validity of the data and third to identify and resolve deficiencies at an early stage. Basic principles are laid down in corresponding guidelines and recommendations of authorities, institutes and societies. Various guidelines for good epidemiological practice (GEP) were published by the U.S. Food and Drug Administration (FDA) and international and regional societies for epidemiology. In addition in Germany the Federal Institute for Drugs and Medical Devices (BfArM) together with the Paul Ehrlich Institute (PEI) and the German Association of Research-Based Pharmaceutical Companies (VFA) have published respectively recommendations dealing with quality aspects of non-interventional observational studies. Key points are the advanced publishing of information about the project, developing of a study plan/protocol containing the scientific objectives, a sample size justification and a description of the planned analyses and the publishing of a summary of the results timely after completion of the study. The quality of the data can be improved by using standardized case report forms (CRF) and the CRF should be reviewed and tested before start of study by some participants. A source data verification (SDV) should be performed in randomly selected centres - in between 2% and 5% of the centres depending on the number of participating centres. Before start of statistical analysis a statistical analysis plan (SAP) should be created. The use of standardized tables and figures is highly recommended. The basis of the report writing should be the STROBE-statement "Strengthening the Reporting of Observational studies in Epidemiology Initiative" containing a checklist of 22 points to be covered in the report. The development of own standard operating procedures (SOP) describing the processes during planning, conduct and evaluation of a non-interventional study as well as the quality management and the regular training of all involved people is also highly recommended. All accompanying measures to improve or to keep the quality of the NIS should not violate the concept of non-intervention.
如今，由于多种原因，药物研发及上市后监测变得越来越重要。非干预性研究（NIS）在现实生活条件下调查药物使用的各个方面，包括疗效和安全性。此类卫生服务研究应具备较高的科学、方法和组织水平。因此，强烈建议采取相应措施来提高或保持质量。质量管理的目标是：首先，通过采用适当的研究设计和充分的数据分析避免结果偏差；其次，确保数据的真实性、完整性和有效性；第三，在早期识别并解决缺陷。相关当局、机构和协会的相应指南和建议中规定了基本原则。美国食品药品监督管理局（FDA）以及国际和地区流行病学协会发布了各种良好流行病学实践（GEP）指南。此外，在德国，联邦药品和医疗器械研究所（BfArM）与保罗·埃利希研究所（PEI）以及德国研发型制药公司协会（VFA）分别发布了关于非干预性观察性研究质量方面的建议。要点包括提前公布项目信息、制定包含科学目标、样本量合理性说明以及计划分析描述的研究计划/方案，以及在研究完成后及时发布结果总结。使用标准化病例报告表（CRF）可提高数据质量，并且CRF应在研究开始前由部分参与者进行审核和测试。应在随机选择的中心进行源数据核查（SDV）——根据参与中心的数量，核查中心数量占比为2%至5%。在开始统计分析之前，应制定统计分析计划（SAP）。强烈建议使用标准化表格和图表。报告撰写应以“加强流行病学观察性研究报告倡议”（STROBE）声明为基础，该声明包含一份报告中应涵盖的22点清单。还强烈建议制定自己的标准操作规程（SOP），描述非干预性研究规划、实施和评估过程以及质量管理，并对所有相关人员进行定期培训。所有提高或保持NIS质量的配套措施均不应违反非干预概念。
