03322nas a2200241   4500000000100000008004100001260003700042653005700079653002400136653001400160653001400174100001600188700001500204700001600219700001600235700001500251245020600266856009900472300001300571490000700584520247500591022001403066       2020                            d  bPublic Library of Science (PLoS)10aPublic Health, Environmental and Occupational Health10aInfectious Diseases10asnakebite10aTreatment1 aAinsworth S1 aMenzies SK1 aCasewell NR1 aHarrison RA1 aCalvete JJ00aAn analysis of preclinical efficacy testing of antivenoms for sub-Saharan Africa: Inadequate independent scrutiny and poor-quality reporting are barriers to improving snakebite treatment and management  uhttps://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0008374&type=printable  ae00085790 v143 aBackground<br>
The World Health Organization’s strategy to halve snakebite mortality and morbidity by 2030 includes an emphasis on a risk-benefit process assessing the preclinical efficacy of antivenoms manufactured for sub-Saharan Africa. To assist this process, we systematically collected, standardised and analysed all publicly available data on the preclinical efficacy of antivenoms designed for sub-Saharan Africa.<br>

<br>Methodology/Principal findings<br>
Using a systematic search of publication databases, we focused on publicly available preclinical reports of the efficacy of 16 antivenom products available in sub Saharan Africa. Publications since 1999 reporting the industry standard intravenous pre-incubation method of murine in vivo neutralisation of venom lethality (median effective dose [ED50]) were included. Eighteen publications met the criteria. To permit comparison of the several different reported ED50 values, it was necessary to standardise these to microlitre of antivenom resulting in 50% survival of mice challenged per milligram of venom (μl/mg). We were unable to identify publicly available preclinical data on four antivenoms, whilst data for six polyspecific antivenoms were restricted to a small number of venoms. Only four antivenoms were tested against a wide range of venoms. Examination of these studies for the reporting of key metrics required for interpreting antivenom ED50s were highly variable, as evidenced by eight different units being used for the described ED50 values.<br>

<br>Conclusions/Significance<br>
There is a disturbing lack of (i) preclinical efficacy testing of antivenom for sub Saharan Africa, (ii) publicly available reports and (iii) independent scrutiny of this medically important data. Where reports do exist, the methods and metrics used are highly variable. This prevents comprehensive meta-analysis of antivenom preclinical efficacy, and severely reduces the utility of antivenom ED50 results in the decision making of physicians treating patients and of national and international health agencies. Here, we propose the use of a standardised result reporting checklist to resolve this issue. Implementation of these straightforward steps will deliver uniform evaluation of products across laboratories, facilitate meta-analyses, and contribute vital information for designing the clinical trials needed to achieve the WHO target of halving snakebite morbidity and mortality by 2030.  a1935-2735