General Methodsa Version 4.2 of 22 April 2015 a This translation is based on the German document Allgemeine Methoden (Version 4.2) of 22 April 2015. Please note: The translation is provided as a service by IQWiG to English-language readers. However, solely the German original text is absolutely authoritative and legally binding. General Methods Version 4.2 of 22 April 2015 Address of publisher: Institute for Quality and Efficiency in Health Care Im Mediapark 8 (KölnTurm) 50670 Cologne Germany Tel.: +49 (0)221 – 35685-0 Fax: +49 (0)221 – 35685-1 E-mail: [email protected] Internet: www.iqwig.de Institute for Quality and Efficiency in Health Care (IQWiG) - i- General Methods Version 4.2 of 22 April 2015 Preamble The Institute for Quality and Efficiency in Health Care (IQWiGb) is an establishment of the Foundation for Quality and Efficiency in Health Care. IQWiG is a professionally independent scientific institute. Information on the structure and organization of the Foundation and the Institute is available on the website www.iqwig.de. The General Methods explain the legal and scientific basis of the Institute. Its tasks are described in this document, as are the scientific tools applied in the preparation of its products. Hence the Institute’s methods paper provides an important contribution towards transparency in the Institute’s mode of operation. The General Methods are primarily directed at researchers. In order to make the information on the Institute’s mode of operation accessible to as many interested persons as possible, the authors have aimed to produce a comprehensible document. However, as with any scientific text, a certain level of prior knowledge on the topic is assumed. The General Methods aim to describe the Institute’s procedures in a general manner. What specific individual steps the Institute undertakes in the assessment of specific medical interventions depend, among other things, on the research question posed and the available scientific evidence. The General Methods should therefore be regarded as a kind of framework. How the assessment process is designed in individual cases is presented in detail for each specific project. The Institute’s methods are usually reviewed annually with regard to any necessary revisions, unless errors in the document or relevant developments necessitate prior updating. Project- specific methods are defined on the basis of the methods version valid at that time. If changes are made to the general methodological procedures during the course of a project, then it will be assessed whether project-specific procedures need to be modified accordingly. In order to continuously further develop and improve its mode of operation, the Institute presents its General Methods for public discussion. This applies to the currently valid version, as well as to drafts of future versions. bInstitut für Qualität und Wirtschaftlichkeit im Gesundheitswesen Institute for Quality and Efficiency in Health Care (IQWiG) - ii- General Methods Version 4.2 of 22 April 2015 What is new? In comparison with Version 4.0 of the Institute’s General Methods of 23 September 2011, in Version 4.1 minor errors were corrected and a few editorial changes made. The following changes to content were made: . description of the external review for preliminary reports as an optional step in Sections 2.1.1 and 2.2.3 . division of the previous Section 3.1.4 into the new Sections 3.1.4 and 3.1.5 and specification of the requirements for the evidence base to formulate conclusions on benefit with different certainties of conclusions . operationalization of the determination of the extent of added benefit, as well as the corresponding rationale, in Section 3.3.3 and in the new Appendix . use of prediction intervals for meta-analyses with random effects in Section 8.3.8 (previous section 7.3.8) In comparison with Version 4.1 of the Institute’s General Methods of 28 November 2013, in the present draft for Version 4.2 minor errors were corrected, editorial changes made, and current literature citations added. The following changes of content were made: . addition of a section on health economic standards in Chapter 1 (new Section 1.3) . addition of the new product “assessment of potential” according to § 137e Social Code Book V (SGB Vc), as well as the corresponding methods in Sections 1.1, 2.1, 2.2, 3.8, 7.2 (previously Section 6.2), 8.1.3 (previously Section 7.1.3), and 8.1.4 (previously Section 7.1.4) . revision of the text on health information after changes of formats following the relaunch of the website informedhealthonline.org (gesundheitsinformation.de) of 13 February 2014 in Section 2.1.7 and Chapter 6 (previously Chapter 5) . new version of Section 3.5 on diagnostic tests with integration of the old Section 3.8 on prognosis studies . integration of methods for health economic evaluations (HEEs) as new Chapter 4 and connected revisions in Section 3.1.5 . amendment on the handling of data provided without a prior request in Chapter 7 (previously Chapter 6) c Sozialgesetzbuch: regulates the statutory health care services. Institute for Quality and Efficiency in Health Care (IQWiG) - iii- General Methods Version 4.2 of 22 April 2015 . amendments on the hierarchy of evidence of non-randomized studies in Section 8.1.3 (previously Section 7.1.3) . amendment on patient-relevant outcomes in Section 8.3.3 (previously 7.3.3) Institute for Quality and Efficiency in Health Care (IQWiG) - iv- General Methods Version 4.2 of 22 April 2015 Table of contents Preamble ................................................................................................................................... ii What is new? ............................................................................................................................ iii Table of contents ....................................................................................................................... v List of tables ............................................................................................................................. xi List of figures .......................................................................................................................... xii List of abbreviations .............................................................................................................. xiii 1 The Institute for Quality and Efficiency in Health Care ............................................... 1 1.1 Legal responsibilities ................................................................................................... 1 1.2 Evidence-based medicine ............................................................................................ 4 1.2.1 Practical evidence-based medicine ......................................................................... 4 1.2.2 The relevance of evidence-based medicine for the Institute .................................. 5 1.2.3 Strategies of evidence-based medicine ................................................................... 5 1.2.4 The relevance of certainty of results ...................................................................... 6 1.2.5 The connection between certainty of results and proximity to everyday conditions ............................................................................................................... 7 1.2.6 Benefit in individual cases ..................................................................................... 9 1.3 Health economics ....................................................................................................... 10 1.3.1 Relevance of health economics for the Institute .................................................. 10 1.3.2 The international standards of health economics ................................................. 11 1.3.3 Methodological standards in health economics .................................................... 12 1.4 Evidence-based decision-making in health care ..................................................... 13 2 The Institute’s products .................................................................................................. 14 2.1 Product-specific procedures ..................................................................................... 14 2.1.1 Report ................................................................................................................... 17 2.1.2 Rapid report .......................................................................................................... 21 2.1.3 Dossier assessment ............................................................................................... 22 2.1.4 Health economic evaluation according to §35b SGB V ....................................... 23 2.1.5 Assessment of potential ........................................................................................ 26 2.1.6 Addendum ............................................................................................................ 27 2.1.7 Health information ............................................................................................... 28 2.1.8 Working paper ...................................................................................................... 30 2.2 General aspects in the preparation of products ..................................................... 32 2.2.1 Selection of external experts ................................................................................ 32 2.2.2 Guarantee of professional independence .............................................................