Vector control and policy: systematic reviews
Funding source I am funded by UKAid to increase decisions based on reliable evidence in health in LMIC I am responsible for the WHO Collaborating Centre for Evidence Synthesis for Infectious and Tropical Diseases
Part 1. Background to evidence synthesis & GRADE In the 1980 s Reviews were opinion pieces GRIP/TRIP from single studies Association muddled with causality Guideline groups influenced by opinion & COI No transparency in policy development
Scientific principles When researchers come to reviews...
World Health Organization Guidelines and recommendations
GOBSAT Good Old Boys Sat Around A Table
Individual voices may dominate
"Most WHO guidelines did not meet most of the AGREE criteria Systematic reviews and concise summaries are rarely used for developing recommendations. Processes usually rely heavily on experts rather than representatives of those who will have to live with the recommendations
Systematic reviews Emphasis on trials and unconfounded comparisons Methods developed (Cochrane) Protocol driven by teams Methodologists and methodology central Conflicts of interest managed Effects take into account estimate reliability Guideline development methods Multidisciplinary panels Transparent methods Set procedures and appraisal (for example Sign )
Narrative Review Systematic Review Cochrane Review General topic Clear question Clear PICO No protocol Methods variable, not always clear Protocol completed before review started Clear methods Protocol refereed and published Standardized (Cochrane Handbook), supported by methods specialists Vague/no inclusion criteria Explicit inclusion criteria Explicit inclusion criteria in protocol, and reasons for excluding studies stated in review Risk of bias not assessed Strength of evidence not assessed Risk of bias and heterogeneity investigated Strength of evidence not usually assessed Systematic investigation of risk of bias and heterogeneity Current reviews use GRADE methods
Grading of Recommendations Assessment, Development and Evaluation An approach to formulating: Evidence-based recommendations Through a transparent and systematic process With an explicit link between evidence and recommendations www.gradeworkinggroup.org
The origin of GRADE: Which hierarchy? Recommendation for use of oral anticoagulation in patients with atrial fibrillation and rheumatic mitral valve disease Evidence Recommendation B Class I A 1 IV C Organization AHA ACCP SIGN
Grading of Recommendations Assessment, Development and Evaluation 5 factors to consider Risk of bias Inconsistency Indirectness Imprecision Other Were the studies unbiased? Are the trial findings consistent? Does the trial PICO address our question? Is the result statistically and clinically important? Is the result overestimated due to publication Bias?
WHO Guideline appraisal: Results AGREE II domain Mean scores (%) Mean Pre GRC (n=10) Post GRC (n=10) difference (%) Median change in domain score (%) Range Scope and Purpose 62.2 80.4 +18.2 +12.5-3 to +39 Stakeholder Involvement 49.8 61.2 +11.4 +18.0-33 to +47 Rigour of Development 30.7 68.3 +37.6 +53.5-26 to +76 Clarity of Presentation 60.9 78.2 +17.3 +23-47 to +52 Applicability 49.1 61.6 +12.5 +16.5-22 to +65 Editorial Independence 20.9 73.6 +52.7 +67-21 to +92 D Sinclair 2013. PlosOne
Part 2. Cochrane Infectious Diseases Group 400+ authors 20 editors 120 systematic reviews Supported by UK Aid Develop systematic reviews Contribute to methods
Cochrane and malaria Key reviews Amodiaquine vs. chloroquine 1996 ITNs 1998 ACTS 2004 DHAP 2014 PQ single dose for Pf 2012 & 2018 [pre-referral ACT 2014]
WHO Malaria guidelines 2015
Part 3. Adoption at country level Globalise the evidence, Localise the decision John Eisenberg UK AID short course for health advisers Liverpool 2018
Part 4. Cochrane and vectors Insecticide-treated bednets and curtains 1995 protocol: debates over generalisability 1998 ed: 81 trials- 22 included. Point estimate. 2004 ed: had confidence intervals About 5.5 lives (95% CI 3.39 to 7.67) can be saved each year for every 1000 children protected with ITNs (2004)
Update reviews where required Use quasi-experimental designs human & entomological outcomes Set up & support author teams Use latest methods
1. Review logic framework: the potential points in the Plasmodium parasite life cycle that could be impacted by PQ and the outcomes used to measure impact. Abbreviations: AUC: area under the curve. EIR: entomological inoculation rate; PQ: primaquine. Graves PM, Choi L, Gelband H, Garner P. Primaquine or other 8 aminoquinolines for reducing <i>plasmodium falciparum</i> transmission. Cochrane Database of Systematic Reviews 2018, 2. Art. No.: CD008152. DOI: http://dx.doi.org/10.1002/14651858.cd008152.pub5
Figure 2. Forest plot for experimental hut trials comparing LLIN or CTN versus UTN for blood feeding. Strode C, Donegan S, Garner P, Enayati AA, Hemingway J (2014) The Impact of Pyrethroid Resistance on the Efficacy of Insecticide-Treated Bed Nets against African Anopheline Mosquitoes: Systematic Review and Meta-Analysis. PLOS Medicine 11(3): e1001619. https://doi.org/10.1371/journal.pmed.1001619 https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001619
Figure 3. Forest plot for experimental hut trials comparing LLIN or CTN versus UTN for mosquito mortality. Strode C, Donegan S, Garner P, Enayati AA, Hemingway J (2014) The Impact of Pyrethroid Resistance on the Efficacy of Insecticide-Treated Bed Nets against African Anopheline Mosquitoes: Systematic Review and Meta-Analysis. PLOS Medicine 11(3): e1001619. https://doi.org/10.1371/journal.pmed.1001619 https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001619
Resistance and entomologic outcomes Our analysis suggests the potential for cumulative meta-analysis in entomological trials, but further field research will require specialists in the field to work together to improve the quality of trials; to standardise designs, assessment, and reporting of resistance outcomes; entomological outcomes 2014
Around 10,000 patients were enrolled in the trials we identified as potentially eligible for inclusion in this review. After application of our inclusion criteria approximately 5240 have been included in this review. Despite the large amount of clinical research that has been done, variation in study design and quality makes synthesis of the data problematic.
Vector control batch Consultative meeting 2015
Review Published Trials included Updat e Larvivorous fish for preventing malaria transmission Dec 2017 No studies in main analysis. 15 studies examine fish and larvae/pupae New New Mosquito repellents for malaria prevention Insecticide space spraying for preventing malaria Feb 2018 Nov 2018 10 RCTs. topical repellents, insecticide treated clothing, spatial repellents 2 interrupted time series from India Updat ITNs for preventing malaria Nov 2018 23 trials e New PBO + pyrethroid vs. pyrethroid for preventing Dec 2018 (intended) 15 trials including 5 cluster-rct field trials malaria New Combining IRS with ITNs vs. Jan 2019 6 cluster-rcts ITNs to prevent malaria (intended) New Larviciding to control malaria Jan 2019 (estimate) 1 cluster-rct, 2 controlled before and after studies, 1 crossover trial New IRS for controlling malaria Protocol being finalized Quasi-experimental designs will be included in update New Housing for preventing malaria Protocol being written Quasi-experimental designs will be included
ITNs-update November 2018
Larvivorous fish No studies in main analysis (examining malaria outcomes) 15 studies examining fish and effect on larvae/pupae in water sources
Repellents Topical repellents Insecticide treated clothing Spatial repellents
PBO nets 15 trials including 5 cluster RCTs Due for publication Dec 2018
Space spraying
Analysis of time series data If effective, the intervention s effect on the outcome would be both a step change and a gradual change in the gradient We calculated: - Rate ratio of the step change - Rate ratio of the slope change The two studies in India report the incidence over time for at least a year prior to space spraying implementation. We can therefore calculate the effect whilst adjusting for the seasonality in the data.
India (Narayansamy): Malaria incidence
India (Tewari): Melpallipatu village Malaria incidence
India (Tewari): Sathanur Dam Malaria incidence
India (Tewari): Vanapuram Malaria incidence
India (Tewari): Pudupettai Malaria incidence
Malaria incidence (step rate ratio)
Malaria incidence (slope rate ratio)
Other Cochrane reviews Combining IRS with ITNs Larviciding update Both to be published January 2019
Reviews in progress IRS Housing
In summary VCAG examines public health value of new vector control tools CIDG prepare and update independent systematic reviews of evidence, mainly around effects/public health Reviews are relevant to policy and help identify gaps in research We are happy to continue the collaboration with this field, building on work started 20 years ago.