Methodology

AGREE

This guideline has been developed conforming to the requirements of the report of Guidelines for Medical Specialists 2.0 by the advisory committee of the Quality Counsel (www.kwaliteitskoepel.nl). This report is based on the AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II) (www.agreetrust.org), a broadly accepted instrument in the international community and based on the national quality standards for guidelines: “Guidelines for guidelines” (www.zorginstituutnederland.nl).

Identification of subject matter

During the initial phase of the guideline development, the GDG identified the relevant subject matter for the guideline. The framework is consisted of both new matters, which were not yet addressed in part 1 and 2 of the guideline, and an update of matters that were subject to modification (for example in case of new published literature). Furthermore, a stakeholder consultation was performed, where input on the framework was requested.

Clinical questions and outcomes

The outcome of the stakeholder consultation was discussed with the GDG, after which definitive clinical questions were formulated. Subsequently, the GDG formulated relevant outcome measures (both beneficial and harmful effects). The GDG rated the outcome measures as critical, important and of limited importance (GRADE method). Furthermore, where applicable, the GDG defined relevant clinical differences.

Search and select

For clinical questions, specific search strategies were formulated, and scientific articles published in several electronic databases were searched. First, the studies that potentially had the highest quality of research were reviewed. The GDG selected literature in pairs (independently of each other) based on the title and abstract. A second selection was performed by the methodological advisor based on full text. The databases used, selection criteria and number of included articles can be found in the modules, the search strategy in the appendix.

Quality assessment of individual studies

Individual studies were systematically assessed, based on methodological quality criteria that were determined prior to the search. For systematic reviews, a combination of the AMSTAR checklist and PRISMA checklist was used. For RCTs the Cochrane risk of bias tool and suggestions by the CLARITY Group at McMaster University were used, and for cohort studies/observational studies the risk of bias tool by the CLARITY Group at McMaster University was used. The risk of bias tables can be found in the separate document Appendices to modules.

Summary of literature

The relevant research findings of all selected articles were shown in evidence tables. The evidence tables can be found in the separate document Appendices to modules. The most important findings in literature were described in literature summaries. When there were enough similarities between studies, the study data were pooled.

Grading quality of evidence and strength of recommendations

The strength of the conclusions of the included studies was determined using the GRADE- method. GRADE stands for Grading Recommendations Assessment, Development and Evaluation (see http://www.gradeworkinggroup.org) (Atkins, 2004). GRADE defines four levels for the quality of scientific evidence: high, moderate, low, or very low. These levels provide information about the certainty level of the literature conclusions (http://www.guidelinedevelopment.org/handbook).

The evidence was summarized in the literature analysis, followed by one or more conclusions, drawn from the body of evidence. The level of evidence for the conclusions can be found above the conclusions. Aspects such as expertise of GDG members, local expertise, patient preferences, costs, availability of facilities and organisation of healthcare aspects are important to consider when formulating a recommendation. These aspects are discussed in the paragraph justifications. The recommendations provide an answer to the clinical question or help to increase awareness and were based on the available scientific evidence and the most relevant justifications.

Appendices

Internal (meant for use by scientific society or its members) quality indicators were developed with the guideline and can be found in the separate document Appendices to modules. In most cases, indicators were not applicable. For most questions, additional scientific research on the subject is warranted. Therefore, the GDG formulated knowledge gaps to aid in future research, which can be found in the separate document Appendices to modules.

Commentary and authorisation phase

The concept guideline was subjected to commentaries by the involved scientific societies. The list of parties that participated in the commentary phase can be requested from the Kennisinstituut van de Federatie Medisch Specialisten (secretariaat@kennisinstituut.nl). The commentaries were collected and discussed with the GDG. The feedback was used to improve the guideline; afterwards the GDG made the guideline definitive. The final version of the guideline was offered to the involved scientific societies for authorization and was authorized.