In 2009, the WHO estimated that 370 000 children were newly infected with HIV globally, with the majority dying before the second year of life [1,2]. More than 90% of these children acquire the infection during pregnancy, birth, or breastfeeding – the vast majority of which are preventable with antiretroviral prophylaxis . The situation is particularly acute in Nigeria, a country with limited resources and a high burden of HIV disease among pregnant women . Although estimates vary, between 4 and 12% of pregnant women are infected with HIV in Nigeria [3–5]. Data further suggest that mother-to-child transmission (MTCT) rates approach 30–45% without intervention in Nigeria, and the Federal Ministry of Health estimates that between 67 000 and 125 000 children are infected through MTCT each year [6,7]. Most recently, 240 000 children were reported to be living with HIV in Nigeria in 2009, among the highest numbers reported in the world [6,8].
Prevention of mother-to-child transmission (PMTCT) of HIV is, therefore, a key public health priority and a limited PMTCT program was introduced in Nigeria in 2002–2003 at tertiary centers, with plans to scale up services to other antenatal clinics [3,4]. Initial PMTCT guidelines advocated a single-dose of nevirapine (sd-NVP) for the mother during labor and for the newborn infant. Subsequently, current recommendations in Nigeria call for the addition of short-course combination antiretroviral prophylaxis [zidovudine (ZDV) and lamivudine (3TC) from 34 weeks gestation to 7 days postpartum], consistent with prior WHO guidelines [3,4,9]. Although potentially convenient and relatively cheap, these regimens have limitations. sd-NVP remains the least effective of all antiretroviral prophylaxis strategies for reducing HIV transmission and has the potential for selecting for nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations [1,3,10]. Short-course dual ART prophylaxis is more effective than sd-NVP, but offers little health benefit for the mother and is less effective at preventing transmission than a HAART regimen with three drugs .
Given these shortcomings, the WHO put forth revised PMTCT guidelines in 2009 based on the accumulation of new evidence . As one option for antiretroviral prophylaxis, the new recommendations suggest that all HIV-infected pregnant women (regardless of CD4 cell count) be started on a highly active three-drug ART regimen as early as 14 weeks of gestation, continuing through the end of breastfeeding . This regimen offers maternal health benefits through viral suppression and has the potential to reduce transmission to 1–2% [10,12]. Although the new WHO regimen for PMTCT has the potential to substantially reduce MTCT of HIV, it is likely to be more costly than a strategy that utilizes short-course combination ART prophylaxis or sd-NVP. In 2008, it was estimated that only 10% of all pregnant HIV-infected women received any ART prophylaxis to reduce MTCT in Nigeria [1,5]. Among those who received ART prophylaxis, the majority continue to receive short-course regimens, including sd-NVP . As the national PMTCT program in Nigeria is scaled up to reach more pregnant women, we sought to conduct a cost-effectiveness analysis to guide policy decisions on PMTCT regimen selection at different levels of program coverage.
We sought to determine whether the new WHO recommendations represent a cost-effective policy option for reducing the risk of MTCT of HIV compared to a strategy that employs short-course ART prophylaxis. The analysis was conducted from a health-system perspective, with the target population consisting of HIV-infected pregnant women in Nigeria. Target audiences include the Ministry of Health and public-sector healthcare payers. We used a decision-tree model to calculate the costs and effects (including downstream costs and effects extending to the duration of an HIV-infected child's life-expectancy) associated with delivery of 1 year of PMTCT services in Nigeria. Model development and analysis were performed using TreeAge Software.
A decision-analysis model was constructed (Supplemental Digital Content 1, http://links.lww.com/QAD/A128) to compare two strategies for PMTCT of HIV in Nigeria at different levels of PMTCT program coverage: intervention – long-course triple ART for the mother with infant ART prophylaxis, as advocated as one of the recommended options (i.e., option ‘B’) in recent WHO guidelines ; and minimal standard of care (MSOC) – current practice at most facilities in Nigeria for PMTCT involving short-course ART regimens .
More specifically, the intervention parameters were based on clinical information wherein all HIV-positive pregnant women (regardless of CD4 cell count) receive a three-drug regimen [ZDV/3TC/efavirenz (EFV)] starting as early as 14 weeks of gestation and continuing until all infant exposure to breast milk has ended, as is being considered for PMTCT in Nigeria; additionally, infants receive daily NVP until 6 weeks of life . The duration of antiretroviral therapy within the intervention arm of the model was dependent on the mother seeking early or late antenatal care (ANC) and was divided into either long-course triple ART extending from 14 weeks gestation until after breastfeeding, and short-course triple ART consisting of treatment with three drugs starting after 24 weeks of gestation until after breastfeeding. The receipt of infant prophylaxis (i.e., 6 weeks of NVP) was dependent on the mother receiving peripartum healthcare within the model. The MSOC arm consisted of a short-course dual ART (ZDV/3TC) regimen starting at 34 weeks of gestation and continuing to 7 days postpartum, combined with a sd-NVP during labor; additionally, the infant receives sd-NVP at birth [3,4,7,9].
Key model parameters
Base-case values for all costs and key model parameters are shown in Table 1 [1–6,10,12–26], along with sources and ranges for sensitivity analysis.
Epidemiologic and prevention of mother-to-child transmission parameters
Our model incorporated elements of ANC and PMTCT coverage. For purposes of comparison, we evaluated cost-effectiveness at three different levels of PMTCT program coverage for infected women: current PMTCT coverage (reaching 10% of all HIV-infected women); current level of ANC coverage (reaching 58% of HIV-infected women; base-case) ; and full PMTCT coverage (100% of HIV-infected women). Duration, efficacy, and receipt of ART prophylaxis were dependent on presentation for PMTCT/antenatal care for both arms in our model (Table 1; Supplemental Digital Content 1, http://links.lww.com/QAD/A128). Currently, PMTCT care is available only in a limited number of tertiary centers in Nigeria, but is being expanded to all antenatal clinics. For the base-case, we assumed that PMTCT care will be delivered to all HIV-positive women accessing ANC clinics and/or hospitals for delivery. The current ANC rate in Nigeria is 58%; among those receiving ANC, we estimated 75% present early in pregnancy (before end of second trimester) with the remainder presenting for late ANC [1,5,12,13]. In both arms, women (and infants) not receiving ANC were eligible for sd-NVP prophylaxis if they presented to a healthcare facility for delivery (Supplemental Digital Content 1, http://links.lww.com/QAD/A128); we estimated that 50% of pregnant women deliver in healthcare facilities and access postpartum care [3,12,13]. Breastfeeding rates are low in Nigeria, and we assumed 6 weeks of breastfeeding when calculating PMTCT cost and efficacy parameters . Efficacy of various ART regimens for PMTCT was based on studies from the African region and was assumed to be valid for Nigeria (Table 1). The model assumes all pregnant women receive voluntary counseling and testing of HIV as part of the PMTCT program in both arms.
The primary outcomes were the expected costs, pediatric HIV cases, and disability-adjusted life years (DALYs) accrued for the intervention and MSOC. Cost-effectiveness was represented using incremental cost-effectiveness ratios (ICERs), expressed as US$ dollars/DALY-averted and US$ dollars/HIV case-averted comparing the intervention to MSOC. DALY calculations were based on the disability accrued from infant HIV or AIDS and premature AIDS death . Nigerian life-expectancy at birth without HIV is 49.0 years . Without ART, infant life-expectancy with HIV was estimated to be 12 months [16–18]; life-expectancy with ART was estimated at 10 years, extrapolated from recent data of early infant antiretroviral initiation in Africa . Based on natural history of pediatric HIV, we used AIDS disability weights for HIV-infected children in their final 9 months of life [17,28]. We assumed that 25% of HIV-infected children receive ART, based on current Nigerian ART coverage . DALY calculations incorporated age-weighting and a 3% annual discounting rate to adjust future costs and effects [29,30]. Maternal health benefits accrued from taking ART during pregnancy were not considered as part of the model and did not contribute to averted DALYs for either arm.
PMTCT program costs for MSOC and intervention in our model included ANC, antiretroviral, and voluntary counseling/testing (VCT) from presentation through 6 weeks postpartum and were derived from the literature as well as from budget data provided by the President's Emergency Plan for AIDS Relief (PEPFAR) program in Nigeria through the Institute for Human Virology (IHV-N) [7,8,19,31]. Unit costs are shown in Table 1. Because the proposed intervention involves providing a fully active HIV treatment regimen, we included associated HIV care costs (i.e., diagnostic monitoring, provider costs) as part of the intervention PMTCT program costs for the duration a woman received ANC. For both arms, costs associated with one day of hospitalization were included for women presenting to the hospital for labor and delivery. Lowest internationally available market antiretroviral costs were used for the base-case [11,19]. An additional 10% of the PMTCT program costs were added to cover estimated capital costs.
Total health system costs included both the PMTCT program costs and downstream costs for caring for children who become infected with HIV through MTCT. Little data was available on lifetime healthcare costs for HIV-infected infants in Nigeria, particularly when considering provisions for ART and extended life-expectancy. To determine these costs, we multiplied yearly unit costs for HIV care (provider visits, drugs, diagnostics) by life-expectancy estimates described above with and without ART. We assumed that base costs for diagnostics and provider visits for infants are similar to those of adults in the outpatient setting. Drug costs were based on recommended pediatric regimens and doses in Nigeria (ZDV/3TC/NVP). We assumed that starting ART reduced hospitalizations and associated costs for HIV-infected infants . To account for potentially increased costs with immunosuppression, we assumed an average of 7 days of hospitalization per year for HIV-infected infants not on ART. As for DALY calculations, we assumed 25% of infected children would receive ART in the base-case model. Recognizing the challenges of estimating these lifetime health costs, sensitivity analysis was performed across a wide range of costs, using low and high estimates of unit costs and life-expectancies.
Future costs were discounted 3% per year. All costs were converted to 2010 US dollars. A probabilistic sensitivity analysis (PSA) was performed using Monte-Carlo simulation methods to further explore uncertainty in all parameter estimates. Ranges and applied distributions are shown in Table 1. Triangular distributions were applied for parameters with an established base-case (high and low estimates) derived from clinical studies; uniform distributions were applied for parameters with greater uncertainty regarding the base-case, but established ranges; and log-normal distributions were applied to HIV life-expectancy parameters to account for a nonnormal skewed distribution around the base-case. Results of the PSA were represented in a cost-effectiveness acceptability curve.
At the current coverage of PMTCT services (10% of HIV-infected mothers), expected mother-to-child HIV transmission rates were 24.3% with MSOC and 23.7% with the intervention. If PMTCT were scaled up to current ANC coverage levels (reaching 58% of HIV-infected mothers; base-case for this analysis), HIV transmission in Nigeria would be reduced to 16.1% with the MSOC and reduced further to 12.8% with the intervention (Table 2). Importantly, however, if PMTCT services were scaled up to reach all HIV-infected women, transmission would be reduced to just 9% with MSOC and 3% with the intervention.
At current low level of coverage of PMTCT services, the intervention is expected to avert 0.16 DALYs per pregnancy compared to MSOC. Alternatively, if PMTCT services are scaled up to the level of ANC coverage (base-case), the intervention is expected to avert 0.96 DALYs per pregnancy compared to MSOC and if these are scaled up to reach all HIV-infected women, the intervention would lead to 1.65 DALY-averted per pregnancy.
Overall, with an estimated 240 000 annual pregnancies among HIV-positive women in Nigeria , the intervention would be expected to avert 1440 infant HIV cases and lead to a total of 38 400 DALY-averted, compared to the MSOC, if both were implemented at current PMTCT coverage levels. These net effects are increased if PMTCT programs are implemented at the level of ANC coverage (7680 HIV cases-averted and 230 400 DALY-averted) or if scaled up to reach all HIV-infected women (14 400 HIV cases-averted and 396 00 DALY-averted). If future effects are not discounted, in the base-case the effect size increases to 503 040 DALY-averted (2.10 DALY-averted/pregnancy). Conversely, without age-weighting, the incremental benefit in the base-case is slightly reduced to 194 160 DALY-averted (0.81 DALY-averted/pregnancy).
In the base-case scenario, the incremental PMTCT program cost was $160 per pregnancy comparing the intervention to MSOC (PMTCT program cost of $204/pregnancy with intervention vs. $44/pregnancy with MSOC, Table 2). The incremental PMTCT program cost comparing intervention to MSOC was $30 per pregnancy if implemented at current PMTCT coverage levels and $274 per pregnancy if implemented to cover all HIV-infected women (Table 2). In the base-case, the incremental total health system cost (including lifetime treatment costs for HIV-infected infants) comparing intervention to MSOC was $108 per pregnancy (total health system cost of $401/pregnancy for intervention compared to $293/pregnancy for MSOC, Table 2). The incremental total health system cost was $21 per pregnancy if implemented at current PMTCT coverage levels and increases to $184 per pregnancy if implemented at full coverage for all HIV-infected women.
At current pregnancy rates, the net total health system costs in Nigeria with the intervention are, thus, estimated to be $25 920 000 more than that of MSOC ($96 240 000 vs. $70 320 000; Table 2) per year in the base-case. Importantly, however, the net costs for both the intervention and MSOC are expected to decline if PMTCT coverage were expanded to 100% of HIV-infected women, due to lower MTC HIV transmission rates with subsequent cost-savings ($94 320 000 and $50 160 000 for the intervention and MSOC, respectively; Table 2). Maintaining PMTCT coverage at current low levels would be the most costly option when all health-system costs are considered ($98 400 000 and $93 360 000 for intervention and MSOC, respectively).
Using base-case parameters and total health system costs, we estimate the intervention would be associated with an ICER of $113 per DALY-averted and $3203 per HIV case-averted, compared to the current MSOC. Without 3% annual discounting, the ICER would be only $52 per DALY-averted. Without age-weighting, the ICER would be $133/DALY-averted. In all scenarios, the intervention would be considered highly cost-effective using a WHO-recommended willingness-to-pay (WTP) threshold of per-capita Nigerian GDP per DALY-averted [US$ 1191, (2010) ] .
One-way sensitivity analyses were performed on all model parameters. Figure 1 highlights results for those variables found to have the most effect on the base-case (i.e., 58% PMTCT coverage level) ICER. The ICER was most sensitive to the lifetime healthcare costs for a child who acquires HIV through maternal transmission (base-case value: $495 without ART, $4674 with ART). When lifetime healthcare costs for an HIV-infected child are hypothetically reduced to $0, the ICER rises from a base-case of $113/DALY-averted to $153/DALY-averted. On the other hand, if lifetime healthcare costs for an infected child increase beyond approximately $17 000, the intervention becomes cost-saving compared to MSOC. Additionally, the intervention would be cost-saving if the estimated efficacy of the MSOC is reduced and transmission rates rise above 20% (base-case: 8%). We note, however, that it is unlikely that MTCT rates would rise this high with MSOC (i.e., >20%) based on published efficacy of this regimen [10,13]. However, it should be noted that MTCT rates for MSOC are likely to cross this threshold when incompletely implemented at low PMTCT/ANC coverage (i.e., 24.3% transmission at 10% PMTCT coverage; Table 1).
Increasing PMTCT coverage to 100% of HIV-positive pregnant women increases both the incremental costs and incremental benefits for the intervention (Table 2), but has minimal impact on the overall ICER (Fig. 1). Implementing the intervention at full PMTCT coverage (100% of all HIV-infected pregnant women) could reduce HIV transmission rates to only 3%, averting 51 120 cases of HIV each year compared to maintaining MSOC at the current level of PMTCT.
Three-way sensitivity analyses were performed on MSOC efficacy, intervention efficacy, and lifetime costs for HIV-infected children to further explore interactions of model parameters (Supplemental Digital Content 2, http://links.lww.com/QAD/A128). At a WTP threshold of per-capita Nigerian GDP, the intervention is the preferred option at essentially all points, except in the scenario when low intervention efficacy (transmission >∼3.5%) is coupled with high MSOC efficacy (<∼5%) and lifetime HIV care costs are set at $0. Alternatively, if a lower WTP threshold for low-income settings is considered ($50/DALY-averted [35,36]), the ICER for the intervention exceeds this threshold as intervention efficacy is lowered and lifetime HIV care costs for infected children are reduced (Supplemental Digital Content 2, http://links.lww.com/QAD/A128).
Our initial analysis compared intervention to MSOC when both are implemented at the same PMTCT coverage levels (i.e., 10, 58, 100%). We conducted a two-way sensitivity analysis to evaluate cost-effectiveness of intervention vs. the MSOC when coverage levels for each arm were varied independently. At a WTP threshold of per-capita Nigerian GDP, we find that it is preferable to implement MSOC at higher coverage levels compared to implementing the intervention at lower coverage levels (Supplemental Digital Content 3, http://links.lww.com/QAD/A128). However, we find that when the intervention is implemented at a level greater than approximately 75% coverage, it is the preferred option regardless of coverage level for MSOC (i.e., intervention is preferred even if MSOC is implemented at higher coverage levels).
Results of a PSA using Monte-Carlo simulation methods are represented in a cost-effectiveness acceptability curve in Fig. 2. The mean ICER was $160/DALY-averted (median $127/DALY-averted) with a 95% confidence interval (CI) from $−42/DALY-averted (i.e., intervention is cost-saving) to $542/DALY-averted. The mean incremental cost was $125 (95% CI $ −59 to $333) between the intervention and MSOC [mean intervention cost $485/person (95% CI $222–$978); mean MSOC cost $359/person (95% CI $118–$994)]. The mean DALYs averted with the intervention compared to MSOC was 1.11 (95% CI 0.18–2.79). At a WTP threshold of GDP per capita in Nigeria ($1191), there is an 99.7% chance that the intervention would be cost-effective; if the WTP threshold were lowered to $50/DALY-averted, there is a 21% chance that the intervention would still be cost-effective.
With a growing HIV epidemic, reducing MTCT is an important issue for the Nigerian healthcare system. Our economic evaluation indicates that one of the key new WHO recommendations for a long-course highly active ART regimen with three drugs for HIV-infected pregnant women is a highly cost-effective intervention in Nigeria, compared to current practice using short-course antiretroviral prophylaxis. This WHO-recommended regimen would be associated with an ICER of US$113 per DALY-averted. This value compares favorably to a WHO-recommended WTP threshold of per-capita annual GDP of US$ 1191 in Nigeria.
Without any intervention, MTCT rates may be as high as 40% in Nigeria. Despite this fact, PMTCT services are currently available to only a small fraction of HIV-infected pregnant women. Using even a MSOC with short-course antiretroviral prophylaxis, transmission could be reduced to 16% if PMTCT services were scaled up from current levels to at least the level of ANC coverage, averting almost 20 000 cases of infant HIV. Importantly, however, we show that HIV transmission could be further reduced to only 3% if PMTCT services were extended to all HIV-infected women using the WHO's new recommendations (option ‘B’) for long-course maternal triple ART and infant prophylaxis (intervention). Such an intervention would avert more than 50 000 cases of infant HIV each year compared to maintaining PMTCT coverage at its current levels. Despite challenges, scale-up of PMTCT coverage beyond its current level is likely feasible. Thus far, there have been modest but demonstrable increases in PMTCT services. Less than a decade ago, there were only six centers at tertiary care facilities providing PMTCT services in the country, reaching less than 1% of HIV-infected pregnant women [5,37]. Since then, with increasing funding from government and outside sources, including PEPFAR, greater than 450 PMTCT service outlets now exist, reaching up to 10% of pregnant HIV-positive women [5,8]. Continued political commitment toward scaling up antenatal and PMTCT services will be critical to ensure sustained progress toward reaching a greater number of HIV-infected women.
PMTCT of HIV is particularly important for the Nigerian healthcare system because of the high costs for delivering HIV care. Children infected through maternal transmission are expected to incur substantial lifetime healthcare costs, and these costs are likely to rise even further as life-expectancy is extended with antiretroviral therapy. From a health-system perspective, we found that the new WHO recommendations for PMTCT are actually a potentially cost-saving intervention if the lifetime health costs for an HIV-infected infant increase beyond $17 000, or if MTCT rates exceed 20% using the currently recommended short-course regimens.
Although the WHO recommendations for PMTCT are likely highly cost-effective, affordability remains a concern that could preclude a change in PMTCT strategies. Total healthcare expenditure by the government in Nigeria is limited and annual per-capita spending remains at less than $50 . Currently, the government contributes less than 20% of total spending on HIV/AIDS services, with the majority of funding coming from outside sources . In 2008, PEPFAR allocated US$450 million dollars for HIV/AIDS services in Nigeria, and the Global Fund disbursed an additional US$95 million [8,37]. During a 2010 PEPFAR country audit, however, it was found that only US$5.8 million was directed at PMTCT services . At current pregnancy rates, the total PMTCT program cost (if delivered at the level of ANC coverage) is expected to be approximately $48 million per year using the new WHO recommendations and $10.5 million per year using current short-course dual ART regimens. Achieving adequate coverage with either PMTCT program would, thus, represent a significant healthcare expenditure. We note, however, that despite the cost of the PMTCT programs, the net health-system costs would be expected to decline due to cost-savings from reduced cases of infant HIV as PMTCT services are scaled up. In fact, we estimate that maintaining PMTCT coverage at current low levels (∼10%) using only MSOC is among the most expensive options and will cost the Nigerian health system almost $93 000 000 each year. This amount is roughly equivalent to the cost of offering the full intervention (i.e., new WHO recommendations) for 100% of HIV-positive pregnant women.
Our study had several limitations. First, estimating lifetime costs for an HIV-infected child is challenging. Country-specific pediatric HIV cost information is sparse, and long-term survival data with antiretroviral therapy are not yet available. Nevertheless, we utilized published estimates when available and used a broad range for sensitivity analysis. Second, our model did not include the maternal health benefits from starting on a highly active triple ART regimen. However, consideration of these benefits would likely only result in the new WHO recommendations being even more cost-effective. Third, our model focused on ‘option B’ of recent WHO recommendations for PMTCT, as this is the strategy being proposed in Nigeria . Our results may not be applicable to other settings that choose to implement alternative WHO recommendations (i.e., ‘option A’) . Additionally, we did not include healthcare costs of HIV-negative children in our model, which were assumed to be similar between the two arms of our analysis. Healthcare cost differences for HIV-infected and uninfected children may contribute toward the ultimate cost-effectiveness of any PMTCT intervention, including both the MSOC and the intervention. Nevertheless, we did consider a very wide range of lifetime care costs during sensitivity analysis, which likely captured the true cost difference between infected and uninfected children. Of note, we found that the intervention was still considered highly cost-effective even when lifetime cost for HIV-infected child were set to $0 (ICER $153/DALY-averted). Finally, we assumed a high uptake of VCT and PMTCT interventions among Nigerian women. However, social and behavioral issues, including fear of stigma, represent potential barriers to PMTCT service delivery . Further research is needed to define strategies to increase acceptability and adoption of VCT and PMTCT.
On the other hand, our study has several important strengths. Our model incorporated elements of access to ANC, allowing a more realistic representation of PMTCT cost-effectiveness. We also explored cost-effectiveness of PMTCT strategies at multiple levels of coverage for pregnant women to provide insight that can guide plans to scale up services. Additionally, to our knowledge, this study is the first to formally evaluate the cost-effectiveness of PMTCT services in Nigeria. Importantly, we explore the cost-effectiveness of highly relevant and newly released WHO recommendations compared to the more predominant practice of using short-course ART prophylaxis, allowing better planning for PMTCT expansion. With receipt of substantial international funding for HIV/AIDS care in Nigeria, this economic evaluation will allow informed decisions on allocation of limited resources.
A prophylactic regimen of three antiretroviral drugs initiated early in pregnancy and extended through the end of breastfeeding (coupled with infant ART prophylaxis) for PMTCT of HIV is a highly cost-effective intervention compared to short-course regimens in Nigeria. The degree of cost-effectiveness (i.e., ICER) is most sensitive to the lifetime cost of caring for infants infected with HIV through maternal transmission, and the efficacy of prophylactic antiretroviral drug regimens. Despite potential variability in these parameters, PSA suggests an almost 100% chance that the new WHO recommendations of maternal HAART and infant prophylaxis are the preferred option for PMTCT at a WTP threshold of Nigerian per-capita GDP per-DALY-averted. As the Nigerian government begins to expand its PMTCT program, consideration should be given to implementing the new WHO recommendations in place of simpler short-course regimens.
The authors would like to thank Dr Amita Gupta for her editorial support and guidance, and Chuck Shih for support with TreeAge software. M.S. received support through an institutionally administered NIH KL2 Award (KL2RR025006). M.S. had primary responsibility for the conception and execution of the study and study methods, model development and implementation, determination of model parameters, and led manuscript preparation. B.J. assisted with methods for costing and model development, provided support for using TreeAge software, and assisted in manuscript preparation. A.A. provided country-specific expertise in HIV and PMTCT care, assisted with determining country-specific costs for HIV care, and assisted in manuscript editing. D.W. provided expertise in the concepts and conduct of economic evaluations, provided support for model development, costing, and sensitivity analysis, and assisted in manuscript preparation.
The authors have no conflicts of interest related to this study, its findings, or this manuscript.
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