7
he priority areas that were identiied included: management of selected neonatal conditions; management of cough or diiculty breathing; antibiotics for treatment
of dysentery; management of conditions with fever; antibiotics for severe acute malnutrition; and supportive care i.e. oxygen therapy, choice of intravenous luids,
and treatment of hypoglycaemia.
2.2 Evidence retrieval and synthesis process
hroughout 2010, the Department of Maternal, Newborn, Child and Adolescent Health coordinated eforts to review and synthesize the evidence on the various,
identiied priority questions. his process included targeted, systematic reviews of relevant literature, preparation of GRADE proiles, and analysis of the risk-beneits,
feasibility, and costs of implementation.
A literature search of the Cochrane Database and OVID-Medline was conducted in July 2010 to identify high quality, systematic reviews in the last two years that
were relevant to the priority PICO questions. Where data were not available or up-to- date from the two sources, systematic reviews were commissioned to various groups
to collate the evidence. he systematic reviews, meta-analyses, and GRADE proiles followed the methodology recommended by the GRC and as described in Version
5.1.0 of the Cochrane Handbook for Systematic Reviews of Interventions.
1
Where data were lacking, systematic searches were conducted from various electronic databases,
including MedlinePubMed, Embase, CENTRAL, NLM Gateway, and WHO regional databases.
For each question, data on critical and secondary outcomes were extracted and appraised by evaluating the quality, consistency, and external validity of the evidence.
hese were then graded from very low, low, medium, and high in tabular form using the GRADE methodology. Quality was deined as the extent to which one could be
conident that an estimate of efect or association is correct and was based on the following criteria:
n
study design;
n
limitations of the studies, in terms of their conduct and analysis;
n
the consistency of the results across the available studies;
n
the precision of the results wide or narrow conidence intervals;
n
the directness or applicability or external validity of the evidence with respect to the populations of interest, interventions, and low-resource settings where the
proposed intervention will be applied. Additional considerations included the magnitude of the efect, presence or absence
of a dose response gradient, and direction of plausible biases. he quality of evidence was then categorized as: high, moderate, low, or very low
as deined in Table 2.1
.
1
Higgins J and Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions, West Sussex, he Cochrane Collaboration and John Wiley Sons Ltd, 2008. Available at
http:www.cochrane- handbook.org
. Accessed on 29 August 2011.
8
GRADE tables from systematic reviews were cross-checked, and where relevant, risk-beneit analysis was produced by the GSC. Internal discussions were held to
evaluate the quality of the evidence presented to the GDG and needed to produce drat recommendations, beneits, harms and risks, costs of implementation, and
acceptability. Recommendations were then formulated and drated in accordance with procedures outlined in the WHO Handbook for Guideline Development,
1
and guided by the quality of evidence using the GRADE methodology.
In drating the recommendations, the WHO Secretariat used those summaries of evidence for the critical outcomes i.e. morbidity, mortality, disease progression and
sequelae, or adverse events for medicines; quality of evidence; risks and beneits of implementing the recommendations; acceptability; costs; and feasibility. he recom-
men dations were then were then ranked as strong or weak recommendation and research gaps or needs were identiied.
2.3 Consensus building and external peer review
Drat recommendations, along with the supportive evidence including summary of the evidence of the systematic reviews with risk-beneit analysis and GRADE tables
were circulated to selected expert external reviewers and some Pocket Book users for feedback
Annex 4 . his process was managed electronically through a EZcollab
site accessible to external reviewers. Results of the peer review process were used to modify the drat recommendations before presentation to the GDG panel.
To formulate the inal recommendations, these evidence summaries, with risk- beneit analysis and GRADE tables, were presented and discussed at an expert panel
meeting held at WHO headquarters in Geneva, Switzerland, in February 2011. he panel weighed the quality of evidence, risks, and beneits, including acceptability,
and placed emphasis on the values and feasibility of implementation in low-resource settings while ensuring that the recommendations are in line with international
standards of care. Although most decisions were based on the evidence from randomized clinical trials RCTs, or large efect observational cohort data, where the
panel determined that there was insuicient evidence, expert consensus was used.
TABLE 2.1
Assessment of strength of evidence
LEVEL OF EVIDENCE RATIONALE
High Further research is very unlikely to change confidence in the estimate of effect.
Moderate Further research is likely to have an important impact on confidence in the effect.
Low Further research is very likely to have an estimate of effect and is likely to change the
estimate. Very low
Any estimate of effect is very uncertain.
1
WHO Handbook for Guideline Development. Geneva, World Health Organization, March 2010.
Available at http:www.who.inthivtopicsmtctgrc_handbook_mar2010_1.pdf
. Accessed on 29 August 2011.
