aHUS

A comprehensive search for guidelines was undertaken to identify the most relevant guidelines to consider for adaptation.

Inclusion/ exclusion criteria followed in the search and retrieval of guidelines to be adapted:

• Selecting only evidence-based guidelines (guideline must include a report on systematic literature searches and explicit links between individual recommendations and their supporting evidence)

• Selecting only national and/or international guidelines

• Specific range of dates for publication (using Guidelines published or updated in 2015 and later)

• Selecting peer reviewed publications only

• Selecting guidelines written in English language

• Excluding guidelines written by a single author, not on behalf of an organization to be valid and comprehensive, a guideline ideally requires multidisciplinary input

• Excluding guidelines published without references as the panel needs to know whether a thorough literature review was conducted and whether current evidence was used in the preparation of the recommendations

All retrieved guidelines and consensus statements relevant to atypical Hemolytic Uremic Syndrome (aHUS) were screened and appraised using the AGREE II instrument (www.agreetrust.org) by at least three independent members of the Guideline Development Group (GDG). A threshold was set whereby only guidelines scoring above 50% in the ‘rigour of development’ domain were retained. Based on this appraisal, the GDG decided to adapt the recommendations derived from the KDIGO Controversies Conference on aHUS and C3 Glomerulopathy [12]  and the role of complement in kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference [13], along with other high-quality international sources, to formulate context-specific guidance for the diagnosis and management of aHUS

Evidence assessment

According to WHO Handbook for Guidelines, we used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to assess the quality of a body of evidence, develop and report recommendations. GRADE methods are used by WHO because these represent internationally agreed standards for making transparent recommendations. Detailed GRADE information is available on the following sites:

• GRADE working group: http://www.gradeworkingroup.org

• GRADE online training modules: http://cebgrade.mcmaster.ca/

• GRADE profile software: http://ims.cochrane.org/revman/gradepro

Table 2: Quality and Significance of the four levels of evidence in GRADE:

Table 3: Factors that determine how to upgrade or downgrade the quality of evidence

The strength of the recommendation

The strength of a recommendation communicates the importance of adherence to the recommendation.

Strong recommendations

With strong recommendations, the guideline communicates the message that the desirable effects of adherence to the recommendation outweigh the undesirable effects. This means that in most situations the recommendation can be adopted as policy.

Conditional recommendations

These are made when there is greater uncertainty about the four factors above or if local adaptation has to account for a greater variety in values and preferences, or when resource use makes the intervention suitable for some, but not for other locations. This means that there is a need for substantial debate and involvement of stakeholders before this recommendation can be adopted as policy.

When not to make recommendations

When there is lack of evidence on the effectiveness of an intervention, it may be appropriate not to make a recommendation.