Guidelines for intensified tuberculosis case-finding and isoniazid ...

from the evidence are close to the actual effects ofinterest. The usefulness of an estimate of the effect (ofthe intervention) depends on the level of confidence inthat estimate. The higher the quality of evidence, themore likely a strong recommendation can be made;however, the decision regarding the strength of theevidence also depends on other factors. Althoughthe GRADE evidence assessment process was usedfor all of the questions, it was not always possibleto calculate GRADE profiles for all the questionsbecause there was a lack of data and information tocalculate the necessary risk ratios. The initial rankingof the evidence for each question was collectivelydone by the consultants of the systematic review andmembers of the WHO Steering Group, which was laterpresented and discussed by the Guidelines Group.In the GRADE profiles, the following levels ofassessment of the evidence were used:Evidence levelHighModerateLowVery lowRationaleFurther research is very unlikely to change our confidence in theestimate of effect.Further research is likely to have an important impact on ourconfidence in the effect.Further research is very likely to have an estimate of effect and islikely to change the estimate.Any estimate of effect is very uncertain.Reports were also commissioned from people livingwith HIV and affected communities regarding the keyquestions and the summary of the evidence (Annex 4).The final recommendations also take into considerationthe quality of the evidence, cost, feasibility, and valuesand preferences of the community, and health-careworkers. The Guidelines Group, which included twoGRADE methodologists, assessed the evidence alongwith the risks and benefits of each recommendation,and determined their recommendations and thestrength of the evidence. The Group used open votingand discussion to arrive at a consensus for each of therecommendations. After the initial draft was reviewedby the Guidelines Group, the comments wereincorporated into a draft that was then sent to over200 people for peer review. The Coordinators of theprocess, representing the two technical units of WHO(HIV/AIDS and Stop TB Departments), incorporatedcomments from around 30 internal and external peerreviewers to finalize the recommendations.1.5 Strength of recommendationsThe strength of the recommendations reflects thedegree of confidence of the Guidelines Groupthat the desirable effects of adherence to therecommendations outweigh the undesirable effects.Desirable effects considered include beneficial healthoutcomes (e.g. prevention and early diagnosis of TB,reduced TB-related morbidity and mortality), lessburden and savings, whereas undesirable effectscan include harms, more burden and costs. Burdensconsidered include the demands of adhering tothe recommendations that programmes, patientsor caregivers (e.g. family) may have to bear, suchas having to undergo more frequent test, takingadditional medications or opting for a treatment thathas a risk for toxicity.The recommendations in these guidelines weregraded into two categories as follows:A strong recommendation is one for whichthe Guidelines Group is confident that the desirableeffects of adherence to the recommendationoutweigh the undesirable effects. This can be eitherin favour of or against an intervention.A conditional (weak) recommendation isone for which the panel concludes that the desirableeffects of adherence to the recommendation probablyoutweigh the undesirable effects, but the panel isnot confident about these trade-offs. Reasons fornot being confident can include: absence of highqualityevidence, presence of imprecise estimates ofbenefits or harms, uncertainty or variation regardinghow different individuals value the outcomes,small benefits, and benefits that may not be worththe costs (including the costs of implementing therecommendation).13