Protocol of economic evaluation and equity impact analysis of mHealth and community groups for prevention and control of diabetes in rural Bangladesh in a three-arm cluster randomised controlled trial

Introduction Type 2 diabetes mellitus (T2DM) is one of the leading causes of death and disability worldwide, generating substantial economic burden for people with diabetes and their families, and to health systems and national economies. Bangladesh has one of the largest numbers of adults with diabetes in the South Asian region. This paper describes the planned economic evaluation of a three-arm cluster randomised control trial of mHealth and community mobilisation interventions to prevent and control T2DM and non-communicable diseases’ risk factors in rural Bangladesh (D-Magic trial). Methods and analysis The economic evaluation will be conducted as a within-trial analysis to evaluate the incremental costs and health outcomes of mHealth and community mobilisation interventions compared with the status quo. The analyses will be conducted from a societal perspective, assessing the economic impact for all parties affected by the interventions, including implementing agencies (programme costs), healthcare providers, and participants and their households. Incremental cost-effectiveness ratios (ICERs) will be calculated in terms of cost per case of intermediate hyperglycaemia and T2DM prevented and cost per case of diabetes prevented among individuals with intermediate hyperglycaemia at baseline and cost per mm Hg reduction in systolic blood pressure. In addition to ICERs, the economic evaluation will be presented as a cost–consequence analysis where the incremental costs and all statistically significant outcomes will be listed separately. Robustness of the results will be assessed through sensitivity analyses. In addition, an analysis of equity impact of the interventions will be conducted. Ethics and dissemination The approval to conduct the study was obtained by the University College London Research Ethics Committee (4766/002) and by the Ethical Review Committee of the Diabetic Association of Bangladesh (BADAS-ERC/EC/t5100246). The findings of this study will be disseminated through different means within academia and the wider policy sphere. Trial registration number ISRCTN41083256; Pre-results.


Comments:
1) The description of each arm of the intervention was clearly described. Table 1 clearly outlined the economic evaluation plan, which was nicely supplemented in the text.
2) In the introduction, the authors describe the epidemiological data surrounding diabetes in Bangladesh to form a strong argument that this is a significant health problem. Despite stating that there is a substantial economic burden of diabetes, a thorough description of the economic burden in Bangladesh is limited. Also, much of the protocol focuses on the intervention's economic outcomes associated with the patient, healthcare provider, and system. Highlighting the current economic state (and economic burden of diabetes) of each group would help put the intervention design and analyses into perspective.
3) In the methods (pg. 6; lines 55-56), "The interventions will be completed by the end of December and all data collection will be ongoing until May 2018." Please clarity December of which year. 4) Please justify why mHealth app intervention and communitybased intervention are compared to the control group, but not compared to one another. 5) A section should highlight potential limitations, and potentially challenges and attempts to overcome them.

REVIEWER
Sheyu Li Department of Endocrinology and Metabolism, West China Hospital, Sichuan University REVIEW RETURNED 02-Apr-2018

GENERAL COMMENTS
This is a cost-effective analysis of m-health for diabetes prevention and control based on a cluster-randomized trial. The study was well designed and the protocol was well presented. I have only some minor concerns before its publication.
1. How many people use smart mobile phones in rural Bangladesh? Is there any difference between the users and non-users? Will the equipment facility be concerned in the study? 2. I did not find QALY in the outcomes. How do the authors think about QALY? 3. Some critical information may be re-stated in the current protocol, such as the brief timeline of the trial (eg. the time when the first cluster/patient recruited) and the strategy of informed consent (or exempted). 4. I do suggest a brief discussion added following the methodology section. Some information could be discussed, such as the clinical and public expectation of the study as well as its expected strength and limitations.

VERSION 1 -AUTHOR RESPONSE
Reviewer: 1 Reviewer Name: Samantha Paige Institution and Country: University of Florida, USA Please state any competing interests: None.

Please leave your comments for the authors below
This submission presents a protocol to test the effectiveness of a diabetes mHealth and communitybased intervention in rural Bangladesh. Authors describe the mHealth app, community program, and control group. The mHealth app and community program will be compared to the control group, but not to each other. Primary and secondary outcomes of the intervention is described, as well as the cost-effectiveness and cost-consequence variables. Authors describe that mHealth is increasingly valued as a low-cost public health tool, yet there is limited evidence for their efficacy (both improving diabetes outcomes and cost-related) in low income populations. The submission is valuable and of interest to transdisciplinary teams conducting international research on diabetes, as it presents a theoretically-driven protocol to implement and evaluate innovative methods to alleviate the burden of diabetes.
Reply: We thank the reviewer for their kind appraisal of our work. Comments: 1) The description of each arm of the intervention was clearly described. Table 1 clearly outlined the economic evaluation plan, which was nicely supplemented in the text.
Reply: We thank the reviewer for their kind appraisal of our work.
2) In the introduction, the authors describe the epidemiological data surrounding diabetes in Bangladesh to form a strong argument that this is a significant health problem. Despite stating that there is a substantial economic burden of diabetes, a thorough description of the economic burden in Bangladesh is limited. Also, much of the protocol focuses on the intervention's economic outcomes associated with the patient, healthcare provider, and system. Highlighting the current economic state (and economic burden of diabetes) of each group would help put the intervention design and analyses into perspective.
Reply: We agree with the reviewer that there is limited description on the economic burden of diabetes in Bangladesh. We have now added few sentences in the introduction explaining the financial burden of the diabetes, globally and in Bangladesh (page 4, second and third paragraphs).
3) In the methods (pg. 6; lines 55-56), "The interventions will be completed by the end of December and all data collection will be ongoing until May 2018." Please clarity December of which year.
Reply: We thank the reviewer for spotting this. We have now clarified the year (2017) in the text (page 6, last paragraph). 4) Please justify why mHealth app intervention and community-based intervention are compared to the control group, but not compared to one another.
Reply: We thank the reviewer for the comment. The D-Magic trial is not powered to test the differences between mHealth and community mobilisation interventions due to the large sample size required and the resources available for this trial. We have now highlighted this in the strengths and limitation section of the paper (Page 13, last paragraph) 5) A section should highlight potential limitations, and potentially challenges and attempts to overcome them.