Study design
This study was a cost-effectiveness analysis to compare the iCCM delivery model utilizing drug sellers against the model using CHWs. A decision tree analytic model was employed in the economic analysis to construct and structure decisions.
Effectiveness data were obtained from a quasi-experimental study conducted in Southwestern Uganda [6] and the inSCALE cross-sectional household survey that was carried out in eight districts of mid-Western Uganda [12].
Unit costs for items were obtained from International Drug Price Indicator Guide (2014 edition), iCCM product selection UNICEF guide (2016 edition), Bugoye iCCM project budget, the iCCM costing report for Senegal, and other costing studies like [13–15]. The micro-costing (ingredients) approach was used to cost the iCCM interventions with the aid of the Community Health Planning and Costing Tool [16].
Cost and effect data were linked using a decision tree model and analysis was carried out with Amua modeling software [17].
Intervention
The iCCM intervention involved training health workers in the assessment, testing, classification, and treatment of malaria, pneumonia, and diarrhea among children under the age of five. Health care workers were taught how to detect malaria using mRDT, how to diagnose pneumonia using respiratory timers, and how to diagnose diarrhea based on the number of loose stools per day.
In the ICCM delivery model utilizing CHWs, the national iCCM trainer trains health workers (mainly staff from health centers II and III) and district health office staff as trainers of trainees (TOTs) in a six-day facilitator program. The TOTs then spend six days training CHWs chosen by their communities. Two trainers are assigned a class of between 25 and 30 VHTs.
Two VHTs are trained in the treatment of malaria, pneumonia, and diarrhea in each village. Free of charge, the trained VHTs received iCCM kits containing rapid diagnostic tests (RDTs) for malaria, respiratory timers, and supplies of artemether/lumefantrine (20mg/120mg tablets), amoxicillin (125mg dispersible tablets), low osmolarity ORS, zinc (20mg tablets), and rectal artesunate (50mg). Additionally, the VHTs received a job aid that included the iCCM diagnosis and treatment algorithms, as well as a register for documenting the nature and frequency of all VHT-related activities. Additionally, stock cards, medicine boxes, gloves, cotton wool, and methylated spirit are provided. VHTs were rewarded with raincoats, umbrellas, gumboots, solar lights, and hoes[18].
The iCCM trained-drug seller delivery model consisted of four different components, namely [6];
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Selection and training of drug sellers by the study manager, field supervisor, district drug inspector, and district health educator.
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Provision of materials for information, education, and communication (IEC).
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Subsidized distribution of prepackaged medicines (ACT, amoxicillin dispersible tablets (DT), and zinc sulfate/ORS) to pharmacies. Diagnostics (malaria rapid diagnostic test and respiratory rate counters) and other supplies, such as patient registers, referral slips, supply order forms, and treatment algorithms, were provided free of charge to drug sellers.
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Monthly support supervision is provided by a field supervisor who is either a pharmacist or a clinical physician, accompanied by the district drug inspector and district health educator on occasion.
To improve the community care-seeking practices that affect under-five child health, CHWs delivered messages on fever care-seeking, diagnostic testing, and treatment adherence through community meetings, workshops, radio talk shows, announcements, and word-of-mouth [18].
Estimation of effect
The effectiveness measure used was “U5 case of febrile illness appropriately diagnosed and treated.” The phrase mentioned earlier refers to any confirmed malaria, diarrhea, or suspected pneumonia case among U5s that received treatment according to treatment guidelines or any child without malaria, diarrhea, or suspected pneumonia that was not prescribed the recommended drugs to treat malaria, diarrhea, or pneumonia.
Appropriate treatment of uncomplicated malaria entails testing a child with fever or a history of fever with mRDT and administering the appropriate ACT regimen if positive. An afebrile child is not tested or prescribed ACT. Children who tested positive for mRDT were given artemether/lumefantrine 20/120 mg DT as follows: 6 tablets for children aged 4–35 months (one tablet twice daily for three days), 12 tablets for children aged 36–59 months (two tablets twice daily for three days).
A child with a cough and rapid breathing (checked using a respiratory timer to be ≥ 60 breaths per minute (bpm) for a child 0–7 days, ≥ 50 bpm for child 2–11 months, and ≥ 40 bpm for child 1–5 years) received an appropriate amoxicillin DT regimen. Amoxicillin DT was not prescribed to a child with a cough and normal breathing. Children with a cough and rapid breathing were given amoxicillin DT 125 mg as follows: 20 tablets for children aged 2–11 months (two tablets twice daily for five days); 30 tablets for children aged 12–59 months (three tablets twice daily for five days) [6].
Appropriate treatment for non-bloody diarrhea included administering zinc 20mg DT and ORS sachets to a child who had non-bloody diarrhea (3 or more loose stools with no blood seen in 24 hours. Zinc sulfate was administered as follows: 5 tablets for children aged 2 to 6 months (half tablet once daily for ten days), ten tablets for children aged 7 to 59 months (one tablet once a day for ten days). Each of these children was given two sachets of ORS, and the drug seller or CHW demonstrated how to reconstitute them to the caregiver. Each child should drink at least half a 300ml cup of water following each loose stool [6].
Appropriate diagnosis and treatment of U5 febrile illnesses serve as a proxy indicator of the potential for child mortality associated with these illnesses. Malaria cases can rapidly progress to complications and death if treatment is not initiated within the first 24–48 hours of symptom onset[19]. Prompt treatment with a complete course of effective antibiotics is critical for pneumonia mortality reduction [20]. ORS and zinc are both effective interventions for reducing diarrhea-related mortality [21].
The effectiveness data of the drug seller-based delivery model was determined through a quasi-experimental study conducted in Southwestern Uganda. This study is detailed elsewhere [6]. According to the previously mentioned study, the iCCM intervention utilizing drug sellers increased the appropriate treatment of uncomplicated malaria, pneumonia symptoms, and non-bloody diarrhea by 80.2% (95% CI 53.2–107.2), 65.5% (95% CI 51.6–79.4), and 31.4% (95% CI 1.6–61.2), respectively.
Effectiveness data for the CHW-based delivery model were obtained from the inSCALE cross-sectional household survey conducted in eight districts of mid-Western Uganda. The Malaria Consortium supported the above-mentioned iCCM project through a grant from the Canadian International Development Agency (CIDA). The study's details are available elsewhere [22]. According to Soremekun et al., the coverage rates of appropriate treatment increased 80.4%, 51%, and 21.5% for uncomplicated confirmed malaria, suspected pneumonia, and non-bloody diarrhea, respectively.
Estimation of costs
Economic costing was done from the societal perspective using a micro-costing approach (ingredients approach). The societal perspective is broader than the health care or government perspective and allows comparison with previous studies. Costs that were considered in the societal perspective included health sector costs, costs borne by CHWs or drug sellers, and household costs. It was essential to consider household costs because they can be significant and may deter caregivers from utilizing the iCCM service and cause poverty [23].
Data on the cost of medicines and other health supplies were collected from the International Drug Price Indicator Guide (2014 edition) and iCCM product selection UNICEF guide (2016 edition). Costs for implementation of the iCCM program were estimated based on the budget of the iCCM project in the Bugoye sub-county and the iCCM costing report for Senegal. Household costs were obtained from costing studies like [13–15]. Overhead costs were distributed among the three illnesses based on the prevailing burden of malaria, pneumonia, and diarrhea within the community.
All costs were adjusted to the 2018 price level. For tradable resources, costs in the Ugandan shillings (UGX) were exchanged to US dollars (US$) and inflated with US inflation rates. In contrast, the costs of non-tradable resources in UGX were inflated using local inflation rates and then exchanged to US$ [24]. The inflation rates were calculated based on the World Bank GDP implicit price deflators between 2010 and 2018 [25]. The average exchange was UGX3727 = US$1 by the end of 2018 [26].
Health sector costs
The total costs of resources for training drug sellers or CHWs, supervision, community sensitization, and management of the iCCM programs utilizing drug sellers or CHWs were considered health sector costs because the government would need to fund these activities if any of the intervention was to be implemented at scale. The health sector costs mentioned above were estimated based on the budget for the iCCM project being implemented in the Bugoye sub-county in the Kasese district, and the iCCM costing report in Senegal [27]. The training of trainers/supervisors and initial training of drug sellers or CHWs, including the first three months of close support supervision, were considered capital items since their useful lifespan lasted more than one calendar year. These capital costs were annualized at a real discount rate of 3% assuming a useful lifespan of 5 years (annualization factor of 4.58) [28]. The less intense routine supervision and management costs incurred on an annual basis were considered recurrent costs. Costs for community sensitization were similar in both delivery models, thus eliminated.
Medicines including artemether-lumefantrine, rectal artesunate, amoxicillin, ORS, and zinc were supplied free of charge to the CHWs, and at subsidized prices (mark-up of 50–80%) for drug sellers, hence also considered health sector costs. Costs for medicines were obtained from the International Drug Price Indicator Guide (2014 edition). A recommended 10% was added to supplier price to cater for shipping cost (freight & insurance) [29] and the wastage rate was assumed to be 10% [30].
Furthermore, other health sector costs covered mRDT, respiratory timers, and health supplies like stock cards, iCCM registers, examination gloves, cotton wool, and methylated spirit. All these items were supplied free to both the drug sellers and CHWs. The prices for these previously mentioned items were obtained by the UNICEF supply catalog (2016 edition) with a 10% added to cater to freight costs [31].
In addition to these items, CHWs were also given medicine boxes, safety boxes, and incentives including raincoats, umbrellas, gumboots, solar lights, and hoes, which were valued at the prevailing local prices.
Costs borne by drug sellers or CHWs
Drug sellers and CHWs invested time in the iCCM program without any formal pay. Drug sellers or CHWs spent around 30 minutes per consultation. The median time per household visit was also estimated to be 30 minutes for CHWs. It was assumed that drug sellers did not perform household follow-up visits for their clients. According to Kasteng et al., the opportunity cost attached to this volunteer time was estimated to be around US$0.34/hour based on the median wage rate of alternative work for these volunteering communities [32].
Drug sellers received subsidized pre-packaged drugs (ACTs, amoxicillin, ORS, and zinc), which were sold at a mark-up of 50–80% [7].
Other out-of-pocket costs incurred by CHWs that were non-reimbursed included travel expenditure and mobile phone airtime expenditure of about US$2.4 and US$1.5, respectively [12].
Household costs for caregivers
Household costs incurred when visiting a drug seller or CHW were divided into direct medical, direct non-medical, and indirect costs. Direct medical costs included drug costs or diagnostic costs, while costs like transport to provider and costs for special food for the febrile child on treatment were considered as direct non-medical costs. Indirect costs related to productivity losses and referred to time spent traveling to a drug seller or CHW and time spent at or with the provider.
Concerning receiving care from CHWs, caregivers traveled for an average of 20 minutes. The waiting times were generally low with caregivers spending only 30 minutes receiving care from CHWs; the overall time was about 50 minutes [14]. It was assumed that caregivers who sought care from drug sellers spent about 30 minutes traveling to the provider and another 30 minutes receiving care from the drug seller [12]. The opportunity cost attached to the caregiver’s time was estimated to be around US$0.34/hour based on the median wage rate within the community [32].
The household costs were obtained from previously conducted household surveys [12, 14], with assumptions being made in cases where no cost data was available.
Cost-effectiveness analysis
Data on the costs and effects were linked through a decision analytical approach (Briggs et al., 2006). A decision tree was used to model delivery of the iCCM intervention via drug sellers or CHWs as shown in Fig. 1. The probabilities corresponding to the individual tree branches (chance nodes) were obtained from iCCM intervention studies conducted by[6, 7, 12, 15, 33] and are shown in Additional file 1. At the end of each decision tree branch, the treatment of a child with suspected malaria, pneumonia, or diarrhea was classified as appropriate or not.
Societal costs for each decision tree branch were calculated by populating the decision tree with corresponding costs per drug seller or CHW, assuming each saw about 100 febrile under-five cases per year. The overhead costs such program costs were divided among the three illnesses based on the annual prevalence rate of malaria, pneumonia, and diarrhea for 2017/2018[3].
The total societal costs and the number of appropriately treated under-five children were calculated by letting 100 children pass through the populated decision tree for each arm. The incremental cost was obtained by subtracting the total cost of the control (CHW) arm from that of the intervention (drug seller) arm. Incremental effect measured as the number of appropriately treated U5s was obtained by subtracting the total effect in the control arm from the total effect in the intervention arm. The incremental cost-effectiveness ratio (ICER) was then calculated as a ratio of the incremental cost (numerator) to the incremental effect (denominator). Therefore, ICER measured the extra cost per additional appropriately treated child when a drug seller is utilized to deliver iCCM instead of a CHW.
The results of this study were presented to guide policymakers, rather than presenting ICERs numerically. Based on the cost-effectiveness plane, the following classifications were used to explore in which circumstances it might be appropriate to support the drug seller- iCCM delivery model with public funds:
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iCCM trained-drug seller model dominates: iCCM trained-drug seller intervention is less costly and more effective.
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iCCM trained-drug seller model is more costly and more effective.
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iCCM trained-drug seller model is less costly and less effective.
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iCCM trained-drug seller model has been dominated: iCCM trained-drug seller intervention is more costly and less effective.
From a policymaker’s perspective, if the iCCM trained-drug seller delivery model dominated, it would justify the support of this strategy with public funds. However, this would not mean that the iCCM delivery model utilizing CHWs should be discontinued. The iCCM trained-drug seller model aims to complement the iCCM trained-CHW intervention —and not to substitute it—as a strategy to increase access to quality treatment.
If the iCCM trained-drug seller model were more costly and more effective, the decision on financing it or not would depend on the government’s willingness-to-pay (WTP), as there is no threshold to suggest how much extra money is reasonable to pay per additional case appropriately treated.
If the iCCM trained-drug seller model was less costly but less effective, it is not likely to be considered worthwhile using public funds unless the difference in effectiveness is minimal. In case the iCCM trained-drug seller model was dominated, this would suggest that the intervention should not be supported.
Sensitivity analysis
One-way sensitivity analyses were conducted by varying the values of individual parameters and assumptions in the decision models to observe the effect on the ICER. The parameters assessed included the probability of seeking care from an iCCM trained-drug seller or CHW, drug seller or CHW utilization of mRDTs and respiratory rate timers, malaria, and pneumonia positivity rate.
Scenario analysis was performed for iCCM costs (50% increase or decrease), iCCM effectiveness (50% increase or decrease), and varying prevalence of malaria, pneumonia, and diarrhea, to assess their impact on the ICER.
Probabilistic sensitivity analysis was performed to assess the sensitivity of the ICER to simultaneous variation in the relevant model input parameters by defining probability distributions to selected parameters rather than point estimates [34]. Beta distributions were used for all branch probabilities, except the prevalence of malaria, pneumonia, and diarrhea that were assumed point estimates. Cost parameters were entered in the analysis as point estimates since there was insufficient data to derive their distribution [30]. Simultaneous selection of values from these parameter distributions and point estimates, followed by calculation of ICERs, was performed 10,000 times in Amua modeling software [17] to propagate uncertainty in the ICERs. Uncertainty surrounding the ICERs was summarized by plotting a cost-effectiveness acceptability curve (CEAC), which shows the probability that the use of iCCM delivery models to treat malaria, pneumonia, and diarrhea is cost-effective for different levels of a health policymaker’s hypothetical willingness-to-pay (WTP) for an appropriately treated child under-five.