ABSTRACT
Afghanistan has experienced persistently high wasting levels. To improve treatment accessibility and reduce costs, a simplified treatment protocol (STP) with a fixed daily dose of two sachets of ready‐to‐use therapeutic food (RUTF) for severe wasting was introduced. This study evaluated the effectiveness on recovery of a fixed RUTF dosage versus the standard weight‐based dosage among children aged 6−59 months across 10 provinces in Afghanistan, five implementing the STP and five implementing the standard protocol. Per‐protocol and intention‐to‐treat (ITT) analysis were conducted on secondary data, with generalised linear mixed‐effects models and time‐dependent weighted Cox proportional hazards models assessing the association between dosing strategy and outcomes. Using a mixed‐methods design, primary quantitative and qualitative data were also collected from caregivers and program stakeholders to contextualize and explain these findings, including treatment satisfaction, barriers to access, and perceived costs. In the ITT 3265 children were included and 2912 children in the per‐protocol analysis. In the ITT analysis, recovery was similar between STP (85.6%) and standard protocol (86.4%). For STP, adjusted models indicated a 5.8‐day longer length of stay (LOS) (95% CI: 1.34, 12.93), and a lower MUAC gain velocity (−0.56 mm/week, 95%CI: −1.01, −0.11) compared to the standard protocol. Caregivers faced higher costs and an average of one additional visit under the STP due to the longer LOS. The fixed dosage for treating severe wasting in Afghan children yielded similar results to the standard dosage in terms of recovery and total weight gain. Adopting this reduced dosing strategy as standard should be weighed carefully against the potential for prolonged LOS, cost‐effectiveness, additional financial burden and access constraints experienced by caregivers.
Keywords: Afghanistan, effectiveness, fixed dosage, management of wasting, ready‐to‐use therapeutic food (RUTF), severe acute malnutrition, simplified protocol
Summary
Treating uncomplicated severe acute malnutrition in children 6‐59 months using a fixed ready‐to‐use therapeutic food (RUTF) dosage achieves recovery outcomes comparable to those of the standard protocol, though with slightly longer treatment durations.
Given the recent funding constraints and the increasing needs for prioritization, the reduced dosage strategy may offer a viable and scalable option to expand treatment coverage without compromising recovery.
Policymakers and implementers must weigh potential increases in indirect costs and caregiver burden resulting from longer treatment time before large‐scale adoption.
1. Introduction
Despite efforts to increase treatment coverage for severe acute malnutrition (SAM), only 40% of children with SAM were estimated to have received adequate treatment in 2020 in Afghanistan (OCHA 2022). Key barriers to scale‐up included frequent stock‐outs of ready‐to‐use therapeutic food (RUTF), limited integration of treatment services into the Basic Package of Health Services, and insufficient screening due to financial constraints (Bahwere et al. 2024).
Wasting remains one of the most pressing public health challenges globally and in Afghanistan. It is associated with an increased mortality rate of 73–187 per 1000 children/year (Collins et al. 2006) and long‐term adverse effects on growth, development, and overall health (Mwene‐Batu et al. 2020; Lelijveld et al. 2016). According to the 2022 Afghanistan National Nutrition Survey, 10.3% of children < 5 years had global acute malnutrition (GAM) and 1.5% had SAM (Afghanistan National Nutrition cluster 2022), translating to approximately 880,000 wasted children (IPC 2023). Malnutrition in Afghanistan is primarily driven by food insecurity, with over 55% of the population facing crisis or emergency levels—among the highest globally (OCHA 2022).
Since 2006, simplified treatment protocols (STPs), including adjusted RUTF dosage, have been tested and implemented globally to improve cost‐effectiveness and scalability of SAM treatment. Various dosing strategies and their impact on treatment outcomes have been assessed including fixed dosage (Maru et al. 2024), time‐based reduction of RUTF dose (Kangas et al. 2019), and reduction based on improved weight and MUAC status (Cazes et al. 2023; Daures et al. 2025). While evidence on adjusted RUTF dosages has demonstrated effectiveness, many questions remain including comparative effectiveness and cost‐effectiveness, particularly in conflict‐affected and fragile contexts like Afghanistan.
To contribute to global evidence on use of STP to optimize supplies and increase SAM treatment coverage, UNICEF obtained the approval of the Afghanistan Ministry of Public Health (MOPH) to implement the STP in November 2019. The STP introduced a fixed RUTF dosage of 2 sachets per day, replacing weight‐based dosing, and was piloted across five provinces from November 2019 until April 2023 (Ministry of Public Health 2018). One previous non‐inferiority study in Afghanistan assessed a non‐weight‐based RUTF dosage but had important methodological limitations. Further research was recommended to confirm non‐inferiority, treatment coverage, and cost‐effectiveness (Bahwere et al. 2024). The WHO guidelines on wasting recommends to reduce RUTF dosage from 150 to 185 kcal/kg/day to 100–130 kcal/kg/day when the child no longer is severely wasted. Although the guideline highlights the need for additional research comparing different protocol options, specifically regarding reducing RUTF quantities while maintaining treatment efficacy (World Health Organization 2023). Sachdev and Kurpad argue that the recommended RUTF dosage for SAM children can even further reduce to 105–120 kcal/kg/day (Sachdev and Kurpad 2024).
Our study aimed to assess both the overall and comparative effectiveness of the fixed dosage for the treatment of uncomplicated severe wasting in Afghanistan. Findings are intended to contribute to global evidence on fixed dosage strategies for SAM treatment and ultimately inform global technical decisions regarding recognition of STP as part of global guidelines.
2. Methods
2.1. Study Design
This study employed a retrospective cohort design supplemented by primary data collection for triangulation, including qualitative methods (focus group discussions [FGDs], key informant interviews [KIIs]) and a quantitative household survey. KII interviewees and FGDs were purposively sampled and household sample size was determined based on single‐group proportion with one‐stage simple random sampling with a final sample of 308 participants. The retrospective cohort component utilized secondary treatment data of children enrolled in SAM treatment services from 1 January to 31 December 2022. This period captured a full year of treatment prior to the suspension of the STP protocol in April 2023 and was selected to avoid the impacts of COVID‐19 and the 2021 service disruptions following the government transition. Qualitative data served a specific explanatory purpose: where quantitative results were unexpected or counter‐intuitive, qualitative findings helped explain the mechanisms behind them, consistent with a convergent mixed‐methods approach (Creswell and Clark 2007).
Children aged 6–59 months were enrolled in treatment if diagnosed with SAM (mid‐upper arm circumference (MUAC) < 11.5 cm, weight for height Z‐score (WHZ) < −3, and/or bilateral edema as per the national protocol) (Ministry of Public Health 2018). However, health facilities most likely used MUAC as the predominant admission criteria as highlighted by Bahwere et al. (2024). Children in the STP group received two RUTF sachets/day (1000 kcal/day), while children in the standard group received weight‐based RUTF dosing according to the national protocol. Actual consumption was not monitored but empty sachets were returned with the next visit. Both study groups had weekly follow‐up visits, received routine medication, and caretakers received regular nutrition counseling.
2.2. Selection of Provinces and Health Facilities
The STP was implemented in five provinces (Parwan, Kapisa, Daikundi, Nangarhar, and Kunar). Five other provinces (Bamyan, Kabul, Laghman, Logar, Noristan), where the standard protocol was used, were selected as the comparison group by the MoPH and UNICEF based on demographic comparability. Two health facilities in each STP province were purposively selected based on overall accessibility for routine monitoring and data collection, rurality, and health facility type. Comparison facilities were selected to match on health facility type, catchment area, population size, and number of admissions comparable to the health facilities implementing the STP.
2.3. Outcomes
The primary outcome measures included recovery defined as the proportion of children discharged as recovered (WHZ > −2 and MUAC > 125 mm and without bilateral edema), and length of stay in the treatment defined as days between admission and discharge with a maximum of 90 days as per the national protocol. Secondary outcomes included absolute weight gain and weight gain velocity (g/kg/day), absolute MUAC gain and MUAC gain velocity (mm/week) as well as operational aspects including household perception of STP.
2.4. Sample Size
Power calculations were conducted based on the population size available in the treatment database during 2022, assuming a 1:1 ratio of STP to standard children to determine the minimum detectable difference in recovery between dosing strategies. Allowing for a 15% reduction due to potential data quality issues, the effective sample size was estimated at 2524 children (1262 per group). Given that more children were enrolled for treatment in the standard arm, they were randomly selected from the total cohort. This provided 80% power to detect a minimum difference of 7.9 percentage points in recovery rates between the two groups at a 95% confidence level.
2.5. Data Collection, Entry, and Management
Only data from children treated between 1 January and 31 December 2022 was collected and used for this study. For the STP group, individual‐level data were originally collected prospectively as part of the pilot implementation and study. Clinical information was recorded in real time on patient cards during routine service delivery and subsequently entered into Excel line lists for monitoring and study purposes. For the present secondary analysis, we obtained these existing STP line list registers.
For the standard protocol group, data were derived from historical facility records. Although clinical information had been recorded prospectively on patient cards during routine care, no pre‐existing analytical line list was available. Study teams therefore retrospectively abstracted data from patient cards and entered them into an Excel line list structured to mirror the STP dataset, ensuring comparability across groups.
All line lists were imported into R for data management, cleaning, and statistical analysis. Data quality checks and cleaning were conducted on completeness, inconsistencies, and discrepancies for the correct range of age at admission (aged 6−59 months), and feasible ranges of: MUAC at admission and follow‐up (≥ 70 and ≤ 140 mm), weight at admission and follow‐up (≥ 3 and ≤ 30 kg), height at admission (≥ 40 and ≤ 140 cm), and Shamsi calendar in which dates were recorded. Observations were excluded if they had extreme values, missing admission and discharge dates, LOS > 120 days, or missing anthropometric data at admission.
2.6. Statistical Analyses
Children with an LOS ≤ 90 days were included in the analysis per national treatment guidelines while sensitivity analyses were conducted among children with LOS ≤ 120 days. (Supporting Information S1: Tables 1–3, and Supporting Information S1: Figure 1). Differences between the means or medians were tested using t‐tests or the Mann–Whitney U test, respectively, for continuous variables, and chi‐square tests for categorical variables. To control for differences between the two groups, we used propensity‐score weighting methods. Factors associated with both dosing strategies or recovery were selected as predictor variables, including age, sex, health facility type, province, MUAC at admission, WHZ score at admission, and month of admission. Propensity scores were applied through inverse probability of treatment weighting (IPTW) by computing weights inversely proportional to a child's probability of STP exposure, with children in the STP group receiving a weight of 1 and the standard group receiving a weight of propensity score/(1‐propensity score). We assessed covariate balance through standardized bias plots before and after weighting. We calculated standardized bias estimates as the difference in the proportions or means between the two groups divided by the standard deviation in the STP group, using a range of −0.1 and 0.1 to indicate whether adequate covariate balance was achieved (Austin and Stuart 2015; Chesnaye et al. 2022).
The per‐protocol analysis excluded children who did not complete treatment: those who exited the study as transfers to other facilities, defaulters lost to follow‐up, or those who died. For the binary outcome, we used time‐dependent weighted Cox proportional hazards models to evaluate the association between dosing strategy and recovery while accounting for censoring due to defaulting, referrals, or missing an outcome in the ITT cohort (Zhang et al. 2018; Bellera et al. 2010). The hazard ratio (HR) and 95% confidence intervals (CIs) were estimated for recovery at discharge by comparing the two groups, adjusting for individual characteristics (age, sex, season, health facility type, and MUAC and WHZ at admission).
For continuous outcomes we used generalized linear mixed effects models for ITT and per‐protocol analysis with fixed effects for age, sex, season of admission, WHZ at admission, and MUAC at admission, and random intercepts at the health facility level. We used weighted linear generalized estimating equations (GEE) models to predict weight and MUAC trajectories adjusted for baseline characteristics. All analyses used clustered robust standard errors to adjust for repeated measures within health facilities. Artificial intelligence tools (ChatGPT 4o [OpenAI 2023]) were used to assist in developing portions of the R code used for data analysis and for copy editing. All analyses were performed in R 4.4.0 (R Core Team 2023).
2.7. Primary Data
Primary data collection occurred from November 10–30, 2024, following delays due to administrative approvals. This included a quantitative household survey of 308 caregivers whose children received STP services, as well as 20 FGDs (four per province, two per health facility, one each for STP and standard protocol caregivers), and 29 KIIs with stakeholders such as UNICEF, MOPH, nutrition nurses, health facility in‐charges, and humanitarian agency representatives. Additional, 10 KIIs had been conducted earlier in February 2024. Household survey data underwent continuous quality checks, reviewed locally daily and every other day at Kabul level for completeness and accuracy. Qualitative data from FGDs and KIIs were audio‐recorded, translated, transcribed, and analyzed manually using thematic analysis to identify recurring themes and address research objectives.
2.8. Ethics Statement
This study was conducted according to the guidelines laid down in the Declaration of Helsinki. The research protocol and supporting documents were submitted to the Ministry of Public Health Institutional Review Board (IRB) committee on December 13, 2023 and was approved by the MOPH's Ethical Review Board on the 27th of January 2024 under IRB Code no: A‐1‐24‐436 as well as the Afghanistan National Public Health Institute. Verbal informed consent was obtained from all participants which was witnessed and formally recorded.
3. Results
3.1. Population Characteristics
A total of 2406 children in the STP arm and 859 children in the standard arm were included in the ITT analysis whereas 2912 children (2179 STP and 733 in the standard arm) were included in the per‐protocol analysis (Figure 1). Differences were observed between the two groups for age, facility type, provinces, season during enrollment, and MUAC and WHZ‐score (Tables 1). Differences were no longer observed with IPT weights, balancing baseline characteristics between the two groups, except for the treatment region. In both treatment arms, the weighted sample had more girls than boys and more children aged 6−23 months than 24−59 months.
Figure 1.
Flow diagram of participant enrollment, exclusions, and analysis population for intention‐to‐treat and per‐protocol analyses.
Table 1.
Baseline characteristics of children at admission in the reduced dosing strategy and standard treatment protocols, comparing unweighted and IPTW‐weighted distributions.
| Unweighted | Weighteda | |||||
|---|---|---|---|---|---|---|
| Simplified (n = 2406) | Standard (n = 859) | Simplified (n = 3243) | Standard (n = 3231) | |||
| Variable | n (%) | n (%) | p‐value | n (%) | n (%) | p‐value |
| Child characteristics | ||||||
| Sex | ||||||
| Female | 1479 (61.5) | 522 (60.8) | 0.747 | 1958 (60.4) | 1926 (59.6) | 0.757 |
| Male | 927 (38.5) | 337 (39.2) | 1285 (39.6) | 1304 (40.4) | ||
| Age group | ||||||
| 6–23 months | 2091 (86.9) | 674 (78.5) | < 0.001 | 2778 (85.7) | 2763 (85.5) | 0.935 |
| 24–59 months | 315 (13.1) | 185 (21.5) | 465 (14.3) | 467 (14.5) | ||
| Age in months (mean, SD) | 13.88 (8.47) | 16.59 (11.15) | < 0.001 | 14.45 (8.84) | 14.48 (9.12) | 0.931 |
| Health facility type | ||||||
| Basic health center | 588 (24.4) | 183 (21.3) | < 0.001 | 775 (23.9) | 782 (24.2) | 0.791 |
| Comprehensive health center (CHC/CHC+) | 1695 (70.4) | 346 (40.3) | 2039 (62.9) | 1982 (61.3) | ||
| District hospital | 59 (2.5) | 268 (31.2) | 285 (8.8) | 325 (10.0) | ||
| Provincial hospital | 64 (2.7) | 62 (7.2) | 145 (4.5) | 143 (4.4) | ||
| Region | ||||||
| Central | 604 (25.1) | 263 (30.6) | < 0.001 | 756 (23.3) | 549 (17.0) | < 0.001 |
| Central highlands | 123 (5.1) | 21 (2.4) | 429 (13.2) | 24 (0.8) | ||
| East | 1679 (69.8) | 575 (66.9) | 2058 (63.5) | 2658 (82.3) | ||
| Season | ||||||
| Winter | 850 (35.3) | 292 (34.0) | 0.067 | 1115 (34.4) | 1159 (35.9) | 0.809 |
| Spring | 461 (19.2) | 150 (17.5) | 605 (18.6) | 609 (18.8) | ||
| Summer | 617 (25.6) | 260 (30.3) | 913 (28.2) | 910 (28.2) | ||
| Fall | 478 (19.9) | 157 (18.3) | 610 (18.8) | 553 (17.1) | ||
| Admission anthropometrics | ||||||
| MUAC, mean ± SD | 111.04 ± 5.63 | 112.41 ± 6.47 | < 0.001 | 111.19 ± 5.97 | 111.28 ± 5.17 | 0.733 |
| MUAC < 115 mm | 2255 (93.7) | 686 (79.9) | < 0.001 | 2949 (90.9) | 2918 (90.3) | 0.718 |
| 115 mm ≤ MUAC < 125 mm | 132 (5.5) | 130 (15.1) | 256 (7.9) | 260 (8.0) | ||
| MUAC ≥ 125 mm | 19 (0.8) | 43 (5.0) | 39 (1.2) | 53 (1.6) | ||
| WHZ, mean ± SD | −2.11 ± 1.19 | −2.64 ± 1.38 | < 0.001 | −2.23 ± 1.20 | −2.24 ± 1.55 | 0.960 |
| WHZ < −3 | 557 (23.2) | 363 (42.3) | < 0.001 | 927 (28.6) | 943 (29.2) | 0.957 |
| −3 ≤ WHZ < −2 | 709 (29.5) | 260 (30.3) | 961 (29.6) | 948 (29.3) | ||
| WHZ ≥ −2 | 1140 (47.4) | 236 (27.5) | 1355 (41.8) | 1340 (41.5) | ||
Weighted values reflect inverse probability of treatment weights (IPTW) derived from a logistic regression model including age, sex, season of admission, admission WHZ, admission MUAC, and health facility type, with clustering at the health facility level. The analysis includes children in the intention‐to‐treat sample with a length of stay ≤ 90 days. p‐values reflect univariate comparisons: chi‐square tests were used for categorical variables and t‐tests for continuous variables, after applying weights.
3.2. Discharge Outcomes
Recovery was similar between the two groups (STP recovery: 85.6% vs. standard recovery: 86.4%, p = 0.644) in the weighted analysis (Table 2). Similarly, in the per‐protocol analysis, recovery (95.9% STP vs. 95.7% standard) and non‐response (4.1% STP vs. 4.3% standard) were similar between the STP and standard groups (p = 0.872). However, there were some differences in treatment outcomes between the two groups. More children were classified as non‐response in the standard group compared to the STP group (5.5% vs. 1.9%); however, more children were transferred to either the same level of care in other facilities or to inpatient treatment in the STP group compared to the standard group (6.1% vs. 1.5%). Four deaths (0.2%) were documented in the STP group while no deaths were recorded in the standard arm indicating a slight difference. However, given the extremely low absolute mortality and small event counts, the finding likely reflects chance variation rather than a clinically meaningful difference.
Table 2.
Nutritional status at discharge and treatment outcomes in the simplified and standard treatment protocols, with univariate comparisons using unweighted and IPTW‐weighted data.
| Unweighted | Weighteda | |||||
|---|---|---|---|---|---|---|
| Simplified (n = 2406) | Standard (n = 859) | Simplified (n = 3243) | Standard (n = 3231) | |||
| n (%) | n (%) | p‐value | n (%) | n (%) | p‐value | |
| Discharge anthropometrics | ||||||
| MUAC, mean ± SD | 125.58 ± 6.28 | 125.12 ± 7.09 | 0.076 | 125.59 ± 6.69 | 126.50 ± 5.93 | 0.707 |
| MUAC < 115 mm | 129 (5.4) | 79 (9.2) | < 0.001 | 189 (5.8) | 206 (6.4) | |
| 115 mm ≤ MUAC < 125 mm | 87 (3.6) | 131 (15.3) | 208 (6.4) | 230 (7.1) | ||
| MUAC ≥ 125 mm | 2190 (91.0) | 649 (75.6) | 2846 (87.8) | 2795 (86.5) | ||
| WHZ, mean ± SD | 0.54 ± 1.75 | −0.34 ± 1.90 | < 0.001 | 0.35 ± 1.78 | 0.20 ± 2.03 | 0.966 |
| WHZ < −3 | 77 (3.2) | 51 (5.9) | < 0.001 | 110 (3.4) | 112 (3.5) | |
| −3 ≤ WHZ < −2 | 65 (2.7) | 64 (7.5) | 140 (4.3) | 132 (4.1) | ||
| WHZ ≥ −2 | 2264 (94.1) | 744 (86.6) | 2993 (92.3) | 2986 (92.4) | ||
| Discharge outcomes | ||||||
| Recovered | 2139 (88.9) | 655 (76.3) | < 0.001 | 2777 (85.6) | 2791 (86.4) | < 0.001 |
| Death | 4 (0.2) | 0 (0.0) | 7 (0.2) | 0 (0.0) | ||
| Defaulted | 118 (4.9) | 95 (11.1) | 201 (6.2) | 214 (6.6) | ||
| Non‐response | 36 (1.5) | 78 (9.1) | 61 (1.9) | 178 (5.5) | ||
| Transfer | 109 (4.5) | 31 (3.6) | 198 (6.1) | 48 (1.5) | ||
| Discharge outcome for intention to treat | ||||||
| Recovered | 2139 (88.9) | 655 (76.3) | < 0.001 | 2777 (85.6) | 2791 (86.4) | 0.644 |
| Non‐recovered | 267 (11.1) | 204 (23.7) | 466 (14.4) | 440 (13.6) | ||
| Discharge outcome for per protocol (no deaths) | ||||||
| Recovered | 2139 (98.3) | 655 (89.4) | < 0.001 | 2781 (95.9) | 2752 (95.7) | 0.872 |
| Non‐response | 36 (1.7) | 78 (10.6) | 119 (4.1) | 123 (4.3) | ||
| Time in treatment and other treatment measures | ||||||
| Length of stay (days), mean ± SD | 59.83 ± 17.12 | 53.30 ± 23.21 | < 0.001 | 60.24 ± 17.63 | 54.52 ± 21.81 | < 0.001 |
| Among recovered | 62.37 ± 13.79 | 59.21 ± 18.47 | < 0.001 | 63.28 ± 14.17 | 58.06 ± 18.92 | < 0.001 |
| Total RUTF, mean ± SD(sachets) | 84.43 ± 24.65 | 145.47 ± 64.08 | < 0.001 | 86.12 ± 26.07 | 141.32 ± 54.93 | < 0.001 |
| Among recovered | 86.54 ± 21.64 | 161.13 ± 54.70 | < 0.001 | 88.61 ± 23.18 | 149.45 ± 48.03 | < 0.001 |
| Total MUAC gain (mm), mean ± SD | 14.71 ± 5.68 | 12.75 ± 7.27 | < 0.001 | 14.59 ± 6.19 | 15.25 ± 6.76 | 0.047 |
| Among recovered | 15.61 ± 4.41 | 15.28 ± 5.85 | 0.124 | 15.77 ± 4.72 | 16.87 ± 5.35 | < 0.001 |
| Average MUAC gain per week (mm/week), mean ± SD | 1.70 ± 0.61 | 1.84 ± 1.22 | < 0.001 | 1.67 ± 0.65 | 2.22 ± 1.35 | < 0.001 |
| Among recovered | 1.78 ± 0.46 | 2.03 ± 1.20 | < 0.001 | 1.79 ± 0.48 | 2.33 ± 1.31 | < 0.001 |
| Total weight gain (kg), mean ± SD | 1.68 ± 0.91 | 1.43 ± 0.89 | < 0.001 | 1.64 ± 0.89 | 1.49 ± 0.86 | < 0.001 |
| Among recovered | 1.79 ± 0.84 | 1.71 ± 0.77 | 0.020 | 1.79 ± 0.81 | 1.61 ± 0.78 | < 0.001 |
| Average weight gain velocity (g/kg/day), mean ± SD | 3.78 ± 1.92 | 3.99 ± 2.96 | 0.024 | 3.67 ± 1.96 | 4.14 ± 2.97 | < 0.001 |
| Among recovered | 4.00 ± 1.52 | 4.30 ± 2.76 | 0.001 | 3.95 ± 1.52 | 4.29 ± 2.73 | 0.008 |
Abbreviations: MUAC: mid‐upper arm circumference, RUTF: ready to use therapeutic food; WHZ; weight for height Z‐score.
Weighted values reflect inverse probability of treatment weights (IPTW) derived from a logistic regression model adjusting for age, sex, season of admission, admission WHZ score, admission MUAC, and health facility type, with clustering at the health facility level. All p‐values reflect univariate comparisons: chi‐square tests were used for categorical variables and t‐tests for continuous variables, after applying weights. The sample includes children in the intention‐to‐treat cohort with a length of stay ≤ 90 days.
In the ITT analysis, differences in discharge outcomes were no longer observed between the two groups. In the weighted time‐dependent Cox model, there was no evidence of a difference in recovery between the two dosing strategies. (HR: 0.85, 95% CI: 0.59, 1.23) (Figure 2; Supporting Information S1: Figures 2 and 3).
Figure 2.
Forest plot of hazard ratios for time to recovery from a time‐dependent Cox model, inverse probability of treatment–weighted (IPTW) and adjusted for age, sex, season, health facility type, and MUAC and WHZ at admission. Adm = Admission, MUAC = Mid‐Upper Arm Circumference.
3.3. Length of Stay
In IPTW univariate analysis, the mean LOS was longer in the STP group than the standard group, both overall (STP: 60.24 days, standard: 54.52 days) and among those who recovered (STP: 63.28 days, standard: 58.06 days) (p < 0.001). The mean total number of RUTF sachets distributed was lower in the STP group compared to the standard group, both overall (STP: 86.12 doses, standard: 141.32 doses) and among those who recovered (STP: 88.61 doses, standard: 149.45 doses) (p < 0.001). In the adjusted model, the mean difference in LOS was 5.80 (95% CI: −1.34, 12.93) days higher in the STP group (Table 3).
Table 3.
Unweighted and weighted adjusted mean differences from generalized estimating equation (GEE) models comparing reduced dosing strategy vs standard treatment protocols in length of stay, total MUAC gain, velocity of MUAC gain, total weight gain, and velocity of weight gain.
| Unweighted | Weighteda | |||
|---|---|---|---|---|
| Outcomes | Mean difference (95% CI) | p‐value | Mean difference (95% CI) | p‐value |
| Length of stay (days) | 6.89 (−0.18, 13.96) | 0.056 | 5.80 (−1.34, 12.93) | 0.111 |
| Total MUAC gained (mm) | 0.12 (−2.23, 2.48) | 0.919 | −0.73 (−2.61, 1.15) | 0.445 |
| Total weight gained (kg) | 0.14 (−0.11, 0.38) | 0.269 | 0.15 (−0.06, 0.36) | 0.170 |
| Velocity of MUAC gain (mm/week) | −0.44 (−0.84, −0.03) | 0.033 | −0.56 (−1.01, −0.11) | 0.015 |
| Velocity of weight gain (g/kg/day) | −0.63 (−1.30, 0.04) | 0.067 | −0.49 (−1.07, 0.09) | 0.098 |
Abbreviation: MUAC: mid‐upper arm circumference.
Inverse probability of treatment‐weighted (IPTW) and adjusted for age, sex, season of admission, admission WHZ score, admission MUAC, and health facility type with clustering at the health facility level. p‐values are based on Wald tests from the GEE models. The analysis includes children in the intention‐to‐treat cohort with a length of stay ≤ 90 days.
3.4. Weight and MUAC Trajectories
In the IPTW univariate analysis, the overall absolute MUAC gain was slightly lower in the STP group (−0.73 mm p = 0.445). However, differences were observed among those who recovered, with 15.77 mm gained in the STP group versus 16.87 mm gained in the standard group. MUAC gain velocity was greater overall and among those who recovered in the non‐STP group. The STP group had a MUAC gain velocity of 0.56 mm/week less than the standard group (p = 0.015) (Table 3). In contrast, absolute weight gain was higher among the STP group (1.64 kg overall, 1.79 kg among recovered) compared to the standard group (1.49 kg overall, 1.61 kg among recovered). There were no mean differences between the two groups for weight gain velocity (Table 3). The weight trajectory was similar across the two groups through the third visit, after which the STP group showed a higher weight gain velocity compared to the standard group. The MUAC trajectory exhibited a similar pattern across both groups although velocity was lower among STP throughout treatment (Supporting Information S1: Figure 4).
3.5. Treatment Costs and Caregiver Perspectives
Household survey, FGD, and KII data contextualize and explain the quantitative outcomes presented above. The household survey included 308 caregivers (62% reporting female children) (Supporting Information S1: Table 4). Most caregivers (56%) self‐referred to treatment programs (Supporting Information S1: Table 5). Consistent with the similar recovery rates observed in both treatment arms (ITT: 85.6% STP vs. 86.4% standard protocol), therapeutic food adherence was high (92%), and caregivers predominantly reported high satisfaction with treatment quality and clarity of information provided.
Reflecting the longer length of stay in the STP arm (mean 60.24 vs. 54.52 days), caregivers completed more treatment visits, driving higher per‐child expenditure. Cost analysis suggested expenses were higher under the fixed dosage protocol (2114 AFN per child) compared to the standard protocol (1879 AFN), linked to the extended treatment duration (one additional visit on average) for children receiving a smaller number of sachets. Transportation and medical fees were common and significant expenses, with caregivers of non‐cured children reporting notably higher costs (median 1150 vs. 400 AFN for cured children, p = 0.003). Caregivers consistently described financial challenges, distance, security issues, childcare, climate‐related difficulties, and cultural barriers (e.g., the requirement for male accompaniment). Major cost categories included medication, transportation, food, accommodation, and lost income. Most caregivers perceived these costs as burdensome, with only 2.6%–3.4% considering them manageable.
The expenses…were covered by the family, including paying for the car rental, buying biscuits, water, and other things for the child on the way. The family's accessibility under the STP program was difficult compared to standard protocol because the number of RUTF was less under the STP, so the mothers would not like to come to the clinic many times.
Nutrition Nurse, Narang CHC – Kunar
I couldn't afford the prescription or the taxi ride, and I still owe money to the drug store. I've been struggling to make ends meet.
Parwan FGD
Consistent with the longer mean length of stay under STP in adjusted analyses (5.80 days, 95% CI: −1.34, 12.93), frontline staff reported perceptions of higher relapse rates and longer treatment durations under the reduced dosage strategy, which they attributed to the fixed RUTF dosage. In contrast, program administrators highlighted the benefits of STP in terms of cost savings and streamlined logistics.
In the STP program, less time is spent [by employees] because the patients are checked based on MUAC, and height and weight are not included… fewer supplies are needed, and costs are also reduced.
KI from NahriShahi BHC ‐ Nangarhar
4. Discussion
This study contributes to the growing body of evidence on the treatment of uncomplicated severe wasting among children aged 6−59 months using a fixed dosage. Recovery was similar between both study arms and exceeded the Sphere standard for recovery (75%) (Sphere Project 2011). No deaths were observed in the standard group whereas 4 deaths were observed in the STP arm. No meaningful difference in the hazard of recovery was observed in either analysis. Our findings align with prior research conducted by UNICEF in Afghanistan, which observed non‐inferiority of the STP group compared to standard group for recovery (93.3% vs. 90.2%) although groups in their analysis were enrolled in treatment sequentially and the control group was only from one province, limiting its generalizability (Bahwere et al. 2024). A fixed dosage of 2 sachets of RUTF in Ethiopia yielded similar results; recovery was non‐inferior to the weight‐based protocol (Maru et al. 2024). A non‐inferiority trial in Burkina Faso showed that a reduction of RUTF dosage after the 3rd week of treatment to discharge did not negatively impact recovery (Kangas et al. 2019), similar to the results of a systematic review (Likoswe et al. 2023).
We observed an adjusted mean difference in LOS of 5.8 days between the two groups, consistent with the prior study in Afghanistan reporting a difference of 7 days (Bahwere et al. 2024). Similar results were found in Burkina Faso, where the LOS was 6.9 days longer in the reduced dosage arm (Kangas et al. 2019). Despite the longer LOS, the STP group required significantly fewer RUTF sachets (86.1 vs. 141.3). In DRC, the OptiMA study applied a reduced RUTF dosage which decreased when weight and MUAC increased, and reported a median of 78 sachets in the reduced arm versus 147 sachets in the standard arm, although the LOS was a uniform 77 days across both arms (Cazes et al. 2023). Given the range of dosing strategies of the studies, comparison should be interpreted with caution. From the caregiver perspective, the longer treatment duration translated directly into a higher number of facility visits, amplifying transportation, medication, and indirect costs. This burden was particularly acute for households whose children had not yet recovered and who remained in treatment the longest.
The slower anthropometric recovery observed in the STP group may not compromise clinical outcomes, but it may contribute to greater indirect costs and burdens on households. This was clearly reflected in qualitative data from FGDs and KIIs. Caregivers reported increased expenses, time demands, and logistical challenges due to longer treatment durations, compounded by transportation costs, climate‐related barriers, and gender‐based restrictions (e.g., male accompaniment requirements).
However, our own cost analysis of eight facilities in this study accounting for RUTF, medication, transportation, training, supervision and monitoring, and household costs (transportation, medication fees, food during clinic visits, accommodation, and lost income) indicated the average cost per child treated was higher in the STP arm compared to the standard arm ($168.90 vs. $132.42), and the cost per child cured was similarly higher ($174.12 vs. $153.60). The elevated cost per child in the STP arm was largely attributable to higher supervision and monitoring costs (median $15,784 vs. $8,728 per facility), which likely reflect additional support required during early implementation of the protocol rather than intrinsic inefficiencies of the fixed dosing approach. When non‐RUTF costs were standardized to median values across facilities ‐ reflecting that RUTF consumption is the primary cost driver affected by the protocol ‐ the cost differential narrowed considerably ($151.47 per child for STP vs. $165.16 for the standard arm). Household costs were nearly equivalent between groups ($21.14 STP vs. $20.06 standard), driven primarily by one additional clinic visit under STP. In Ethiopia, where a fixed dosage of 2 sachets was provided, savings on RUTF of $13.79 per recovered child were observed (Maru et al. 2024). An economic evaluation in Burkina Faso concluded that a reduced dosage has a cost saving of US$15.43 per child treated, although there was no difference in the LOS (median 56 days) (N'Diaye et al. 2021). The principal saving was induced by lower RUTF costs, with RUTF accounting for 56.2% and 47.0% of the overall costs in the standard protocol versus the fixed dosage arms. The OptiMA study observed no difference in treatment costs in the two arms of $123 in reduced dosage vs $127 in standard arm (Resch et al. 2025). These findings underscore the economic efficiency of the fixed dosage protocol, at least in the short‐term. Qualitative accounts from caregivers align with this picture: while most reported treatment‐related costs as burdensome, high satisfaction with care quality and treatment process suggests that the STP's efficiency gains do not come at the expense of caregiver acceptability.
Among recovered children, total weight gain was higher in the STP group, though weight gain velocity was lower, aligning with results from the OptiMA study, where children in the standard arm had a slightly higher weight gain velocity compared to those in the reduced dosage arm (4.6 g/kg/day vs. 4.0 g/kg/day) p = 0.062 (Cazes et al. 2023). The MANGO trial reported no differences in weight gain velocity between treatment arms, with a median velocity of 3.4 g/kg/day across both groups (Kangas et al. 2019). Slower weight gain velocity in the STP group is expected, as the lower RUTF dosage provides fewer calories per day, resulting in more gradual catch‐up growth that may accelerate in later stages of treatment. The longer LOS in the STP group suggests that children may have experienced delayed catch‐up growth over the extended treatment period but ultimately gained more weight because of the additional week of treatment.
Children in the standard group experienced greater MUAC gain and higher MUAC gain velocity than those in the STP group. Similar findings were reported in the Democratic Republic of Congo, where children in the reduced dosage arm had lower MUAC velocity (2.14 vs. 2.36 mm/w) (Ntaongo Alendi et al. 2025). However, the OptiMA study observed no difference in MUAC gain velocity between the two arms, indicating that the impact of reduced dosage protocols on MUAC velocity may vary based on context, implementation factors, and baseline nutritional status (Cazes et al. 2023).
While frontline providers expressed concern about higher relapse risk and delayed recovery under the reduced dosing strategy, health administrators emphasized the operational benefits, such as reduced supply requirements and simplified clinical procedures. This divergence highlights a tension in simplified treatment approaches: balancing clinical equivalence and system‐level cost savings with the lived realities of caregivers, who often absorb the cost of extended care and reduced supplies. These findings suggest the need to situate nutrition protocol decisions within a broader framework that considers maternal and household impacts. While simplified protocols offer critical advantages in contexts of constrained resources, they may inadvertently place added strain on caregivers, particularly women, whose time, labor, and caregiving responsibilities are often unrecognized in purely clinical evaluations (Mchenga et al. 2025; Njuguna et al. 2020). Programmatic adaptations, such as decentralizing services, providing transport support, or combining nutrition care with integrated maternal–child health visits, could help mitigate these burdens.
A strength of this study includes its robust methodological approach, utilizing a large sample size and IPTW weighting to ensure baseline comparability between groups despite non‐random assignment. The integration of primary qualitative data from caregivers and health workers provides critical context that enhances the interpretation of clinical findings and draws attention to barriers often overlooked in clinical trials.
Limitations include the variability in data recording practices, particularly for missed visits and discharge dates. To address this, we applied cut‐off thresholds to determine when to use the last recorded visit date in place of the discharge date. While these inconsistencies may introduce some bias, we found no evidence of systematic differences between study arms. Secondly, RUTF intake and household diet were not measured. Finally, the study was not designed to examine longer‐term outcomes such as relapse. This is an important area for future research to provide a more comprehensive understanding of the long‐term effects of fixed dosage protocols.
5. Conclusion
Our study demonstrated that a reduced dosing strategy using a fixed RUTF dosage can achieve recovery outcomes similar to those of the standard protocol, offering significant cost savings in RUTF. Given the reduced funding landscape and consequently recurring RUTF shortages in Afghanistan, this strategy may offer a viable and scalable alternative for expanding treatment coverage without compromising recovery. However, these benefits must be weighed against potential increases in indirect costs and caregiver burden due to longer treatment durations. Policymakers considering a reduced dosing strategy should adopt a comprehensive view of cost‐effectiveness that includes household economic burden, risk, and broader socio‐cultural and logistical factors impacting treatment adherence. Future research should further explore these dimensions to fully understand the long‐term health and socio‐economic implications of simplified treatment strategies.
Author Contributions
I.B. and J.M. led on the funding acquisition. I.B., J.M., N.Q. contributed to the conceptualization and design. I.B., J.M., D.M., N.Q., S.M. developed the methodology. D.M., N.Q. contributed to the data collection. I.B., N.Q. and G.D. led the project administration. D.M. supervised the project in Afghanistan. J.M. and C.K. led the data analysis and created the graphs and figures. I.B., J.M. and C.K. wrote the initial manuscript whereas A.M., H.M., S.M., H.V., G.D., D.M., N.Q., A.Y. critically reviewed and edited the manuscript. All authors have read and approved the final manuscript.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Figure S1: Unweighted and weighted recovery adjusted odds ratio from intention‐to‐treat and per‐protocol analyses (among children with length of stay at or below 120 days).
Figure S2: Probability of recovery over time by treatment protocol.
Figure S3: Cumulative incidence of recovery by treatment protocol. This figure presents the cumulative incidence function (CIF) for recovery among children enrolled in outpatient treatment for severe acute malnutrition under two treatment protocols: standard protocol (yellow) and simplified protocol (blue). The figure reflects an unweighted analysis using individual‐level treatment data, with censoring applied for children who defaulted, were referred, or had missing discharge outcomes. Confidence intervals and median recovery time are displayed. The risk table shows the number of children remaining under observation at each time point.
Figure S4: Weight (a) and mid‐upper arm circumference (MUAC) (b) weighted trajectories according to treatment protocol. Inverse probability of treatment‐weighted (IPTW) and adjusted for age, sex, season of admission, admission WHZ score, admission MUAC, and health facility type with clustering at health facility level. Intention‐to‐treat outcome (LOS ≤ 90 days) used.
Table S1: Unweighted and weighted characteristics of children at admission in the simplified and standard treatment protocols (among children with length of stay at or below 120 days).
Table S2: Unweighted and weighted characteristics of nutritional status at admission and treatment outcomes in the simplified and standard treatment protocols (among children with length of stay at or below 120 days).
Table S3: Unweighted and weighted adjusted mean differences between simplified vs standard treatment protocols in the length of stay, total MUAC gain, and total weight gain (among children with a length of stay at or below 120 days).
Table S4: Key Characteristics of Caregivers and Children by Treatment Outcome (Based on Health Facility Database Records).
Acknowledgements
We are immensely grateful for the efforts of the IMC research team including Obaidullah Rafiqi and Mohammad Abobaker Yousofi. This study would not have been possible without the support of the Public Nutrition Directorate, of the Ministry of Public Health, particularly Dr. Sanga Muhai. Furthermore, the authors would like to express their appreciation to both UNICEF Afghanistan, Amirhossein Yarparvar, Shafiqullah Safi; Dr Bismillah Enayat and Dr Sayed Abdullah for their contributions towards the study, providing the secondary data, supporting data quality checks as well as liaising with the Afghanistan authorities. We also would like to express our gratitude to Hailu Wondim and Jalaa Abdalrahman from ACF for their support in administrative and contractual matters as well as reviews during critical times. In addition, we would like to thank all IMC operations staff in Afghanistan and headquarters who provided support for the successful completion of the study. Finally, our deepest appreciation goes to all the caretakers who have taken the time for the interviews, without them this research would not have been possible. This study was funded by UNICEF Afghanistan under the global framework with Action Against Hunger.
Majer, J. , Bollemeijer I., Zarghoon M. Q., et al. 2026. “Comparative Effectiveness of Fixed and Standard RUTF Dosing Protocols for Treatment of Uncomplicated Severe Acute Malnutrition in Afghanistan.” Maternal & Child Nutrition 22: e70201. 10.1111/mcn.70201.
Jennifer Majer and Iris Bollemeijer contributed equally to this work.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1: Unweighted and weighted recovery adjusted odds ratio from intention‐to‐treat and per‐protocol analyses (among children with length of stay at or below 120 days).
Figure S2: Probability of recovery over time by treatment protocol.
Figure S3: Cumulative incidence of recovery by treatment protocol. This figure presents the cumulative incidence function (CIF) for recovery among children enrolled in outpatient treatment for severe acute malnutrition under two treatment protocols: standard protocol (yellow) and simplified protocol (blue). The figure reflects an unweighted analysis using individual‐level treatment data, with censoring applied for children who defaulted, were referred, or had missing discharge outcomes. Confidence intervals and median recovery time are displayed. The risk table shows the number of children remaining under observation at each time point.
Figure S4: Weight (a) and mid‐upper arm circumference (MUAC) (b) weighted trajectories according to treatment protocol. Inverse probability of treatment‐weighted (IPTW) and adjusted for age, sex, season of admission, admission WHZ score, admission MUAC, and health facility type with clustering at health facility level. Intention‐to‐treat outcome (LOS ≤ 90 days) used.
Table S1: Unweighted and weighted characteristics of children at admission in the simplified and standard treatment protocols (among children with length of stay at or below 120 days).
Table S2: Unweighted and weighted characteristics of nutritional status at admission and treatment outcomes in the simplified and standard treatment protocols (among children with length of stay at or below 120 days).
Table S3: Unweighted and weighted adjusted mean differences between simplified vs standard treatment protocols in the length of stay, total MUAC gain, and total weight gain (among children with a length of stay at or below 120 days).
Table S4: Key Characteristics of Caregivers and Children by Treatment Outcome (Based on Health Facility Database Records).
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.