Background
Since 1 January 2017, WHO implements a new process for evaluating vector control products. The process aims to provide enhanced assurance regarding product safety, quality and efficacy (both entomological and epidemiological) to better meet the needs of WHO Member States. The assessment of individual products for their quality, safety and entomological efficacy is overseen by the WHO Prequalification Team for Vector Control Products Assessment, while the WHO technical departments, namely the Global Malaria Programme (GMP) and the Department of the Control of Neglected Tropical Diseases (NTD), review epidemiological data to assess the public health value of new vector control interventions, informing WHO recommendations. The latter process is supported by the WHO Vector Control Advisory Group (VCAG) and provides the underpinning of the WHO guidelines process that is overseen by the Guidelines Review Committee.
In parallel with WHO’s move to a new evaluation process for vector control products, GMP revised its process for the development of recommendations and companion documents. This revised process provides better predictability, enhanced clarity on what malaria interventions are recommended and how they should be deployed, and supports uptake of guidance. One of the outputs of this process, the first edition of WHO’s consolidated Guidelines for malaria, was released in 2021 and has been updated and expanded since. A series of preferred product characteristics (PPC) documents were developed to communicate identified unmet public health needs and associated evaluation requirements. The present data call relates to the PPCs on insecticide treated nets (ITNs) and on indoor residual surface treatments (IRS).
Since 2017, the evaluation process for vector control products has continued to evolve to incorporate implementation experience and meet the emerging needs associated with a flow of new interventions that are being submitted for evaluation to WHO. As part of this evolution, WHO/GMP and WHO/NTD, with the support of the VCAG, reviewed and reduced the overall number of intervention classes. With fewer intervention classes that are broader in scope, the number of epidemiological trials to inform WHO recommendations is reduced. Product diversity within a class, however, increases considerably, raising the question as to whether products grouped within a specific class perform similarly to the ‘first-in-class’ product that established the class. In turn, this raises questions regarding the relative value of such products in the fight against malaria, and how resources for vector control would be used most effectively. This uncertainty was recognized by WHO early on and based on technical consultation, WHO embarked on a process to explore the use of comparative effectiveness to address it. A notice of intent to this effect was published by WHO in 2018, accompanied by a study protocol, and further explored by means of generating 2 sets of data for mosquito nets treated with a pyrethroid insecticide and the synergist piperonyl butoxide (PBO). For IRS, comparative effectiveness data were used to expand the relevant WHO recommendation to neonicotinoid insecticides in 2017 and the need for these types of data were explicitly referenced in the preferred product characteristics.
Based on these encouraging practical experiences, and in the context of an ever-increasing diversity of vector control products, the WHO Malaria Policy Advisory Group (MPAG) recommended that WHO further progress the implementation of comparative effectiveness assessments (now termed ‘non-inferiority assessments’) to expand on this exploratory area (October 2021 and October 2022 meetings). The present call for data on comparative evaluations of ITN and IRS products serves to update the current evidence-base and inform the next steps in this area, including further potential extensions of WHO’s IRS recommendation for fast-acting insecticide classes.
Data call
WHO is rolling out the implementation of non-inferiority assessments of vector control products as an exploratory approach, drawing on entomological data (e.g. mosquito mortality, mosquito blood-feeding inhibition). To provide an update on the status of comparative evaluations conducted by manufacturers and researchers, WHO requests the submission of data packages that focus on ITNs treated with pyrethroid-PBO, pyrethroid-chlorfenapyr and pyrethroid-pyriproxyfen and on new insecticide classes for IRS not currently covered by WHO’s recommendation on IRS for malaria control. (Note: presently covered insecticide classes for IRS are i) pyrethroids, carbamates, organophosphates, neonicotinoids and, with considerable caveats, the organochlorine DDT). Any data submitted should have been generated in line with WHO’s guidance including i) the identified need for data from at least 2 independent experimental hut trials to inform an assessment, ii) the data having ideally been generated different geographical regions, and iii) data from each trial having been analysed separately. Where there are deviations from the recommended study designs, these should be indicated as part of the submission in sufficient detail.
The overarching goal of the WHO/GMP assessment of non-inferiority is to provide reassurance to WHO Member States and their procurement partners regarding the applicability of a WHO recommendation, as referenced in the WHO Guidelines for Malaria, to new products where these fall into established intervention classes and/or to clarify open questions as to which class may be applicable (e.g. fast vs slow acting IRS). The findings from non-inferiority assessments will be used in furtherance of WHO/GMP’s work in supporting WHO Member States and their procurement partners in their complex resource prioritization exercises and the associated sourcing of vector control products.
It is expected that data may be provided by manufacturers of vector control products, research institutions or individual researchers who have generated comparative data.
→ WHO cover sheet for data submission to allow comparative assessment
The deadline for submission of data under the present data call is 19 May 2023.
Next steps
During Q1 & Q2 2023, WHO intends to conduct a literature search for published comparative effectiveness/non-inferiority assessments in the area of malaria vector control, as well as collate any data submitted in response to this data call. The data will be used to re-assess the evidence-base in this area and will ultimately be included in a WHO report on the third technical consultation on non-inferiority planned for 2023. Previous reports on this topic provide examples of the currently envisaged communication on this topic. The meeting will, amongst other points, consider explicit extensions of WHO recommendations to new classes of insecticides for IRS. The findings will be presented to MPAG for their review. WHO may, at its sole discretion, invite manufacturers, researchers and other stakeholders to attend the open sessions of the technical consultation and of the MPAG meeting as observers. Open sessions may be convened by WHO for the sole purpose of the exchange of non-confidential information and views.
The evidence from the literature review and data collation exercise will also be used to inform the ongoing revision of WHO’s guidance.
A session on non-inferiority assessments has been scheduled for the upcoming MPAG meeting on 18–20 April 2023. Registration is now open for virtual participation at the following link: https://who.zoom.us/webinar/register/WN_AtV6M8XPTjCK7pkwUCwpZA
Where possible, data and/or results from non-inferiority assessments should be submitted electronically to vc-noninferiority@who.int. Alternatively, data may be submitted in hardcopy to:
Vector Control & Insecticide Resistance Unit
Global Malaria Programme
World Health Organization
Avenue Appia
1211 Geneva 27
Switzerland
Manufacturers and researchers submitting data are assured that all data not already available in the public domain will be treated as confidential.