2Guideline development process

2.1. Guideline Development Group

A WHO guideline steering group, led by the Department of Mental Health and Substance Use Disorder, was established with representatives from WHO regional offices and relevant WHO departments and programmes. The guideline steering group provided overall support to the guideline development process. Two additional groups were established: a guideline development group (GDG) and an external review group. The GDG included a panel of academics and clinicians with multidisciplinary expertise on the conditions covered by the guidelines. Consideration was given to geographic diversity and gender balance (see Annex 1).

Potential members of the GDG were selected on the basis of their contribution to the area, as well as the need for regional and area of expertise diversity. As a respected researcher in the field, the Chairperson was selected for his extensive experience of guideline development methodology, and his participation in other guideline development groups. Each potential GDG member was asked to complete the WHO declaration of interest (DOI) form. These were reviewed by the steering group.

2.2. Declarations of Interest and Management of Conflicts of Interest

All GDG members, peer reviewers and systematic review team members were requested to complete the declaration of interest (DoI) form prior to the evidence review process for guideline development. Invitations to participate in the GDG meeting were sent only after the DoI had been reviewed and approved. The GDG members were also required to complete a confidentiality undertaking. Once received, the WHO Secretariat reviewed the DoIs as well as additional information (internet and bibliographic database search) and evaluated if there are any conflicts of interest and if so, whether these require a management plan. The group composition was finalized after this process.

In order to enhance its management of conflicts of interest as well as strengthen public trust and transparency in connection with WHO meetings and activities involving the provision of technical/normative advice, the names and brief biographies of members being considered for participation in the GDG were disclosed for public notice and comment prior to the meeting.

At the beginning of the GDG meeting, the DoI of each GDG member was presented and GDG members and external partners were asked to update their DoI with relevant changes by notifying the WHO Secretariat.

DoI were reassessed for potential conflict before the face-to-face meeting in Geneva. None of the members had major conflicts of interest. All decisions were documented (see Annex 2).

2.3. Collaboration with External Partners

The Centre for Global Mental Health, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, UK (WHO Collaborating Centre for Research and Training in Neurosciences) supported the development of the guidelines by conducting the evidence review and synthesis.

2.4. Identifying, Appraising and Synthesizing Available Evidence

A scoping review helped to identify the key questions that would establish the focus of the recommendations and consisted of the following steps:

1)

Initial broad focus on identification of risk factors for excess mortality and morbidity in people with SMD and specific interventions, guided by previous work by the WHO that has highlighted a number of physical health conditions and associated risk factors as critical factors in the excess mortality and morbidity in people with SMD;

2)

Review of existing WHO guidelines;

3)

Findings of the WHO consultation on the above topic and other relevant WHO documents and discussions with WHO steering group.

A total of one background question and seven key questions in PICO (Population, Intervention, Comparison, and Outcome) format were developed (Annex 3).

The background question provided the context and rationale for the guidelines and addressed the association of physical health conditions with SMD. It consisted of two sub-questions: What is the comorbidity between physical health conditions (NCDs and infectious diseases) and SMD? What is the impact of physical health conditions on the morbidity and mortality of people with SMD? The answer to this question was found in a wide range of information sources and summarised the growing body of evidence that has demonstrated the bi-directional relationships between SMD and physical health conditions. The evidence supporting the background question is presented in Annex 4.

Outcomes were rated by GDG members according to their importance as ‘critical’ for a decision, ‘important’ or ‘unimportant’. Those outcomes rated as critical and important were selected for inclusion into the PICO questions. Regular communication and discussions with the GDG were held by email and teleconferences, respectively.

The WHO steering group, in consultation with the guideline methodologist and GDG chair, proposed a framework based on the PICO questions to review the evidence. The process entailed the following steps: (i) review of evidence that exists for the interventions to manage physical health conditions in people with SMD; (ii) examination of the extent to which existing recommendations for the general population (especially from existing WHO guidelines) can be applied to people with SMD; (iii) examination of when and how these recommendations need to be adapted for people with SMD; and (iv) to provide recommendations that are specific to this population when needed.

The systematic review team developed protocols to review the evidence that existed for the interventions to manage physical health conditions and their risk factors (as outlined in the PICO questions) for people with SMD (Annex 5). Existing relevant systematic reviews were identified for each of the PICO questions. The steering group assessed the quality of existing reviews using the assessment of multiple systematic reviews (AMSTAR) checklist. Systematic reviews found to be of high quality were also assessed for timeliness to ensure that the most current evidence was used. In addition, drug-drug interaction searches were conducted between medicines relevant for each PICO question and medicines used for SMD (Annex 5).

The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (Guyatt et al., 2011) was used to develop the evidence profiles as well as the WHO Handbook for Guideline Development. The quality assessment of the evidence was performed according to GRADE considering study design (randomized controlled trials or observational studies), risk of bias, inconsistency, indirectness, imprecision and risk of reporting bias. Evidence was characterised as either high, moderate, low or very low. The evidence profiles are available at the WHO website (http://www.who.int/mental_health/evidence/guidelines_physical_health_and_severe_mental_disorders/en/index.html).

2.5. Decision-Making During the Guideline Development Group Meeting

The GDG met at the WHO headquarters in Geneva, 9 – 10 May 2018. The evidence reviews were sent out in advance and summarized in a presentation during the meeting. The GDG members discussed the evidence, clarified points, and interpreted the findings in order to develop recommendations based on the draft prepared by the WHO Secretariat. The GDG considered the relevance of the recommendations for people with SMD based on the GRADE-DECIDE framework (Alonso-Coello et al., 2016):

• the balance of benefit and harm of each intervention;
• values and preferences of people with SMD and their carers;
• costs and resource use;
• acceptability of the intervention to healthcare providers in low- and middle-income countries;
• feasibility of implementation;
• impact on equity and human rights.

The discussion and assessment of values and preferences was based on the knowledge and experience of GDG members. Similarly, no surveys or formal cost-effectiveness studies to determine resource constraints were conducted but discussions of these domains were informed by the combined expertise and experience of the GDG members. Equity and human rights were considered by specifically searching databases that include studies from LMIC, examining data for disaggregation for specific subgroups of people with SMD and when direct evidence for the relevant subgroup was not available, evaluating the indirectness of evidence obtained from other populations. Potential differential effects of the interventions on different subgroups of people with SMD related to economic status, employment or occupation, education, place of residence, gender or ethnicity were considered by the GDG. Equity and human rights considerations were applied to the other criteria in the framework described above by:

• assessing both desirable and undesirable effects for different subgroups of people with SMD;
• examining if some subgroups may value the main outcomes differently than the general population;
• balancing treatment costs with effectiveness;
• varied acceptability of the intervention in different subgroups.

Taking into account these considerations, when making a strong recommendation, the GDG was confident that the desirable effects of the intervention outweighs any undesirable effects. When the GDG was uncertain about the balance between the desirable and undesirable effects, the GDG issued a conditional recommendation. Strong recommendations imply that most individuals would want the intervention and should receive it while conditional recommendations imply that different choices may be appropriate for individual patients and they may require assistance at arriving at management decisions. In some instances even when the quality of evidence was low or very low, it was agreed that if the recommendation would be of general benefit, and this was seen to outweigh the harms, it may still be rated as strong. In the event of a disagreement, the chair and the methodologist would ascertain whether the dispute was related to the interpretation of the data or to the way that the recommendation was formulated. If a consensus agreement was not reached, the GDG members agreed to a majority vote of 70% to determine a decision The WHO staff members present at the meeting, as well as other external technical experts involved in the collection and review of the evidence, were excluded from voting. The GDG members reached a consensus agreement on all recommendations and ratings and voting was not needed.

In addition to recommendations, best practice statements were formulated which did not rely on systematic reviews of the evidence but rather on good clinical care and were consensus-based from the GDG.

2.6. Document Preparation and Peer Review

In addition to the GDG members, an external review group (ERG) provided expert inputs. The draft guideline and evidence profiles prepared by WHO staff and the GDG were circulated to the external review group and the steering group. The role of the ERG was to identify any errors or missing data and to comment on clarity, setting–specific issues and implications for implementation rather than changing the recommendations. All inputs and remarks were discussed and agreed with the GDG by email.