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Review 2: "Cost-effectiveness of Vector Control Strategies for Supplementing Mass Drug Administration for Eliminating Lymphatic Filariasis in India"

Reviewers have highlighted that this is an important study but raised major concerns related to the methods and data section, recommending the inclusion of robustness and sensitivity analysis.

Published onMar 04, 2024
Review 2: "Cost-effectiveness of Vector Control Strategies for Supplementing Mass Drug Administration for Eliminating Lymphatic Filariasis in India"
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key-enterThis Pub is a Review of
Cost-effectiveness of vector control strategies for supplementing mass drug administration for eliminating lymphatic filariasis in India
Cost-effectiveness of vector control strategies for supplementing mass drug administration for eliminating lymphatic filariasis in India

Abstract Background/Methodology Despite progress using mass drug administration (MDA), lymphatic filariasis (LF) remains a major public health issue in India. Vector control (VC) is hypothesized as a potentially useful addition to MDA towards LF elimination. We conducted cost-effectiveness analysis of MDA alone and augmented by VC single (VCS) or integrated VC approaches (VCI). Data came from historical controls and a 3-arm cluster randomized trial of 36 villages at risk of LF transmission in Tamil Nadu, India. The arms were: MDA alone (the standard of care); VCS (MDA plus expanded polystyrene beads for covering the water surface in wells and cesspits to suppress the filariasis vector mosquito Culex quinquefasciatus), and VCI (VCS plus insecticidal pyrethroid impregnated curtains over windows, doors, and eaves). Economic costs in 2010 US$ combined government and community inputs from household to state levels. Outcomes were controlled microfilaria prevalence (MfP) and antigen prevalence (AgP) to conventional elimination targets (MfP<1% and AgP<2%) from 2010 to 2013, and disability adjusted life years (DALYs) averted.Principal Findings The estimated annual economic cost per resident was US$0.53 for MDA alone, US$1.02 for VCS, and US$1.83 for VCI. With MDA offered in all arms, all reduced LF prevalence substantially and significantly from 2010 to 2013. MDA proved highly cost effective at $112 per DALY, a very small (8%) share of India’s then per capita GDP. Progress towards elimination was comparable across all three study arms.Conclusions The well-functioning MDA was effective and very cost-effective for eliminating LF, leaving little scope for further improvement. Supplementary VC demonstrated no statistically significant additional benefit in this trial.Authors’ Summary Lymphatic filariasis (LF) is one of the twenty neglected tropical diseases (NTDs) that affect more than one billion people worldwide. As part of the effort toward global elimination of LF, the Indian State of Tamil Nadu government has implemented mass drug administration (MDA) repeatedly since 1996. Despite their efforts, LF had not yet been eliminated. Although vector control (VC) is proposed to augment regular MDA to help eliminate LF, little is known about the increased impact or costs. Our study compares the costs of MDA alone to the combination of MDA with alternative VC interventions. We calculated both program operating costs and costs to communities. We found MDA to be very cost-effective for eliminating LF. Against low levels of LF endemicity (≤10%), the study had limited ability to detect further improvements and found no significant incremental improvements from VC.

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.


Review: The paper presents a detailed analysis of the cost-effectiveness of mass drug administration (MDA) supplemented with single vector control (VCS) strategies, or integrated vector control (VCI) for the elimination of lymphatic filariasis (LF) in Tamil Nadu. It employs a three-arm cluster randomized trial and economic evaluation, to assess the impact and cost-effectiveness of MDA alone versus MDA combined with either VCS or VCI approaches. The study finds that the addition of either vector control strategy to MDA alone does not enhance cost-effectiveness.

Major revisions: The following concerns should be thoroughly addressed before the findings of this analysis are used to inform programs or policy:

  1. Other, non-LF benefits of VC. In this study, the quantified benefits of VC are confined to reductions in the prevalence of MfP and AgP through MDA.  No statistically significant reductions beyond what was achieved through MDA were detected. However, VCS and especially VCI is presumably effective against the Anopheles mosquito in addition to the Culex quinquefasciatus mosquito. As is pointed out by the authors in the Discussion section, VCI thus also controls other (Anopheles) mosquito-transmitted diseases such as malaria and perhaps also non-mosquito transmitted diseases. Isn’t it plausible that including these non-LF benefits would tip the cost-effectiveness scales in favor of MDA plus VCI? In addition, as the authors acknowledge, VC campaigns may enhance compliance with MDA. If so, these benefits should be added to the VC side of the ledger.

    Please add a passage that persuasively disposes of these objection; or alternatively, and preferably, formally includes a recalculation of the incremental cost effectiveness of VCI added to MDA that reflects these benefits. I understand that this would be likely be modeled based on data from outside the study area, but even this would be far preferable to ignoring these considerations. In this context, please also refer to the suggestions below regarding sensitivity and scenario analyses.

  2. Might the lack of incremental impact of VC be due to implementation problems in this particular program rather than inherent limitations of the VC approach? The authors write,

    The reason why VC failed to demonstrate incremental impact might be attributable to the presence of numerous untreated breeding sites for Culex quinquefasciatus, such as blocked drains, buckets, discarded containers and obscure disused cesspits, which yielded sufficient mosquitoes for continuing LF transmission. To address this challenge the NVBDCP has relied on more integrated VC strategies similar to VCI [58] but we are not aware of any cost-effectiveness evaluation.

    Isn’t it possible that with a modest increase in cost, these shortcomings of the VC program could be addressed? Elsewhere, the article mentions that the MDA intervention appears to have improved over the last few years. My concern is that this study compares  a high-quality MDA program with a lower-quality VC program yet broad conclusions are being drawn about the incremental cost-effectiveness of VC per se.

  3. Sensitivity and scenario analyses. Sensitivity analysis is critical in health economics and outcomes research for assessing the robustness of the study's conclusions against variations in key assumptions or parameters. It is not as a “nice to have” but a” must-have” feature of any cost effectiveness analysis intended to guide public health policy decisions. (Sanders, JAMA, 2016), In addition to the usual one-way sensitivity analyses using key mode inputs, this paper needs scenario analyses that portray plausible estimates of higher VCI efficacy combined with the quantified value of the non-LF related benefits of VCI.  It is stated that the success of MDA “ . . . leaves little scope for further improvement.” I would like to see the results if most of the incremental potential improvement was in fact realized by VCI. If these scenarios still show continued encouraging cost-effectiveness of MDA alone, this would do much to reassure the reader.

  1. Data are from 2011 and earlier. The author should address the fact that this analysis is based on data that are at least 13 years old. Haven’t there been advances in both MDA and VC methods that make the study’s these results less pertinent now?  If this is not the case, and the technologies used in the 2011 era are essentially unchanged, this should be discussed. In addition to advances in technology, might there be secular trends such as better housing, and sanitation that might have reduced the addressable burden of LF since 2011?

  2. WHO CE Threshold. For a wide variety of reasons the WHO threshold for cost-effectiveness based on per capita GDP is a poor method for gauging the value of a potential intervention. (Marseille, 2019). It typically leads to the result that any intervention that is effective in the developing country context is likely to be cost-effective, and thus is of little value in guiding constrained allocation choices. Rather than using the WHO threshold, please compare the cost-effectiveness results found in this study with the cost-effectiveness of other public health interventions in India. This would provide a far better picture of where MDA for LF is situated in the priority rankings of feasible options.

  3. Generalizing to India. The data are drawn entirely from Tamil Nadu, yet the title of the paper mentions India. I recommend that following implementation of the revisions discussed above that the analysis be reframed as pertinent to Tamil Nadu. It might then be appropriate to add a paragraph in the Discussion that evaluates the pros and cons of generalizing to India as a whole. Presumably, there are large variations among the States in LF prevalence and in the capability of delivering MDA or VC.

Minor revision:

  1. Potential impact of new VC technologies. It would be a useful, (although not strictly necessary), addition to this paper to include an acknowledgement that new VC technologies such as genetically modified mosquitoes are under development and that they could change the balance of the cost-effectiveness estimate.

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