Quality assurance in non-interventional studies

GMS German Medical Science — an Interdisciplinary Journal

Ferdinand Hundt²  Stefan Schinzel³  Marlis Herbold³  Müge Capan¹  Karlheinz Theobald³ 

[1] Technical University (TU) Berlin, Institute of Machine Tools and Factory Management, Dept. Quality Science, Berlin, Germany;SanofiAventis Deutschland GmbH, Clinical Operations, Berlin, Germany;SanofiAventis Deutschland GmbH, Clinical Operations, Frankfurt/Main, Germany

关键词: standard operating procedures (SOP);    study plan;    Good Epidemiological Practice (GEP);    quality management;    non-interventional studies;   

Others  :  869098

实施日期：2009-05-14，发布日期：2009-11-09

【 摘 要 】

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.

【 授权许可】

   
© 2009 Theobald et al.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

【 参考文献 】

• [1]Arbeitsgruppe Epidemiologische Methoden der Deutschen Arbeitsgemeinschaft für Epidemiologie (DAE). Leitlinien und Empfehlungen zur Sicherung von Guter Epidemiologischer Praxis (GEP). [Stand: April 2004]. Available from: http://www.gesundheitsforschung-bmbf.de/_media/Empfehlungen_GEP.pdf 
• [2]US Department of Health and Human Services, Food and Drug Administration; Center for Drug Evaluation and Research (CDER); Center for Biologics Evaluation and Research (CBER). Guidance for Industry – Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. March 2005. Available from: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126834.pdf 
• [3]International Society for PharmacoEpidemiology (ISPE). Guidelines for Good Pharmacoepidemiology Practice (GPP) [issued 1996, revised August 2004 & April 2007]. Bethesda: ISPE; 2009. Available from: https://www.pharmacoepi.org/resources/guidelines_08027.cfm 
• [4]International Epidemiological Association (IEA) European Federation. Good Epidemiological Practice (GEP) – IEA Guidelines for proper conduct of epidemiological research. November 2007.
• [5]Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Official Journal of the European Union 2001;L 121, 1/5/2001:34-44. Available from: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-1/dir_2001_20/dir_2001_20_en.pdf 
• [6]Gesetz über den Verkehr mit Arzneimitteln (Arzneimittelgesetz – AMG) Arzneimittelgesetz in der Fassung der Bekanntmachung vom 12. Dezember 2005 (BGBl. I S. 3394), das durch Artikel 1 der Verordnung vom 28. September 2009 (BGBl. I S. 3172) geändert worden ist. Berlin: Bundesministerium der Justiz; 2009. Available from: http://www.gesetze-im-internet.de/amg_1976/BJNR024480976.html 
• [7]Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM); Paul-Ehrlich-Institut (PEI). Gemeinsame Empfehlungen des Bundesinstituts für Arzneimittel und Medizinprodukte und des Paul-Ehrlich-Instituts zur Planung, Durchführung und Auswertung von Anwendungsbeobachtungen (Entwurfsfassung vom 9. Mai 2007 zur Kommentierung durch die Fachöffentlichkeit). 2007. Available from: http://www.bfarm.de/cln_012/nn_1198726/SharedDocs/Publikationen/DE/Arzneimittel/1__vorDerZul/klin-pr/nichtInterventPruef/EmpfAWBEntwurf,templateId=raw,property=publicationFile.pdf/EmpfAWBEntwurf.pdf 
• [8]Verband Forschender Arzneimittelhersteller e.V. (VFA). VFA-Empfehlungen zur Verbesserung der Qualität und Transparenz von nicht-interventionellen Studien [31. Januar 2007]. 2007. Available from: http://infomed.mds-ev.de/sindbad.nsf/0/f99eec1f4951d5c6c12572c800335eee/$FILE/VFA-Empf-NIS_070131.pdf 
• [9]de la Haye R, Herbold M. Anwendungsbeobachtungen, Leitfaden für die praktische Durchführung. 2nd ed. Aulendorf: Editio Cantor Verlag; 2006.
• [10]Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products. Official Journal of the European Union 2005;L 91, 9/4/2005:13-9. Available from: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-1/dir_2005_28/di r_2005_28_en.pdf 
• [11]Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM). Empfehlungen zur Planung, Durchführung und Auswertung von Anwendungsbeobachtungen, 12. November 1998. BAnz. 1998;229:16884.
• [12]Koch A, Windeler J, Abel U. Anwendungsbeobachtungen: zu Begriff und Nutzen [Therapeutic indications: on the concept and applications]. Med Klin (Munich). 1996;91(2):103-5.
• [13]European Parlament. EudraLex – Volume 9: Pharmacovigilance guidelines [September 2008]. 2008. Available from: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol9_en.htm 
• [14]Kübler J, Vonk R, Beimel S, Gunselmann W, Hommering M, Nehrdich D, Köster J, Theobald K, Voleske P. Adverse Event Analysis and MedDRA: Business as Usual or Challenge? Drug Inf J. 2005;39(1):63-72.
• [15](Muster-) Berufsordnung für die deutschen Ärztinnen und Ärzte der Bundesärztekammer, – MBO-Ä 1997 – in der Fassung der Beschlüsse des 100. Deutschen Ärztetages 1997 in Eisenach […] geändert durch den Beschluss des Vorstands der Bundesärztekammer am 24.11.2006. 2006. Available from: http://www.bundesaerztekammer.de/downloads/MBOStand20061124.pdf 
• [16]Landesärztekammer Hessen. Satzung zur Änderung der Berufsordnung für die Ärztinnen und Ärzte in Hessen [geändert am 10. April 2007]. Hessisches Ärztebl. 2007;5:325-30. Available from: http://www.aerzteblatt-hessen.de/pdf/haeb07_325.pdf#search=%22berufsordnung%22&view=%22fit%22 
• [17]Bayerische Landesärztekammer. Berufsordnung für die Ärzte Bayerns: Bekanntmachung der Neufassung vom 1. August 2005. Bayerisches Ärztebl. 2005;60(Spezial 2). Availabe from: http://www.blaek.de/presse/aerzteblatt/2005/SD_Berufsordnung.pdf 
• [18]Ärztekammer Berlin. Neufassung der Berufsordnung der Ärztekammer Berlin vom 30. Mai 2005, zuletzt geändert durch den 2. Nachtrag vom 26.09.2006. [Stand 11.01.2007]. 2007. Available from: http://www.aerztekammerberlin.de/10arzt/30_Berufsrecht/06_Gesetze_Verordnungen/30_Berufsrecht/331_BerufsO.pdf 
• [19]Koyuncu A. Vertragsgestaltung und Ärztevergütung bei Anwendungsbeobachtungen und anderen nichtinterventionellen Studien. Dtsch Z klin Forsch. 2009;3/4:54-61.
• [20]Hahn M, Bethke TD, Hecht A, Henn D, Ruppert T, Hundt F. Qualitätssichernde Maßnahmen in nicht-interventionellen Studien: Ergebnisse einer Umfrage unter den Mitgliedsunternehmen des Verbandes Forschender Arzneimittelhersteller [Quality assurance measures in non-interventional studies: Results of a survey among the members of the Association of Research-Based Pharmaceutical Companies]. GMS Ger Med Sci. 2008;6:Doc12. Available from: http://www.egms.de/static/en/journals/gms/2008-6/000057.shtml 
• [21]European Medicines Agency. ICH Topic E9, Statistical Principles for Clinical Trials [Stand: September 1998]. London: EMEA; 2006. Available from: http://www.emea.europa.eu/pdfs/human/ich/036396en.pdf 
• [22]Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M; STROBE Initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Epidemiology. 2007;18(6):805-35. DOI: 10.1097/EDE.0b013e3181577511 
• [23]Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, Gøtzsche PC, Lang T; CONSORT GROUP (Consolidated Standards of Reporting Trials). The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med. 2001;134(8):663-94.
• [24]Plint AC, Moher D, Morrison A, Schulz K, Altman DG, Hill C, Gaboury I. Does the CONSORT checklist improve the quality of reports of randomised controlled trials? A systematic review. Med J Aust. 2006;185(5):263-7.
• [25]Schön, Theobald, Kallert, Schädlich. How to gain high data quality in a non-interventional trial taking the LIVE-COM study as example; Poster accepted for ISPOR 12th Annual European Congress; October 2009.