Quantifying the non-medical costs patients incur to access hepatitis C treatment in Southern Vietnam

Quantifying the non-medical costs patients incur to access hepatitis C treatment in Southern Vietnam | Research Square Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Quantifying the non-medical costs patients incur to access hepatitis C treatment in Southern Vietnam Huyen Anh Nguyen, Le Manh Hung, Barnaby Flower, Jennifer Ilo Van Nuil, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9031795/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Background Hepatitis C virus (HCV) infection is a global public health concern, with an estimated 58 million people affected worldwide. Direct-acting antivirals (DAA) have revolutionized hepatitis C treatment. However, the cost of DAA treatment in many low- and middle-income countries remains a potential barrier to treatment access. Our study aimed to assess the non-medical costs associated with patients accessing DAA treatment in Vietnam and investigate potential disparities. Methods We conducted a patient-level micro-costing analysis based on 102 hepatitis C participants recruited from 2020 until 2021 at the Hospital for Tropical Diseases in Ho Chi Minh City (HCMC), Vietnam. We collected data on the direct non-medical costs and productivity costs incurred by the patients and their informal caregivers. Direct medical costs (such as the drug costs) were not included. The costs were considered from the patient/household perspective. Outputs were stratified based by the location of residence (within HCMC or not). Results We estimated that the mean total cost incurred by an outpatient for accessing a standard 12-week DAA treatment would be US$73.90 (US$24.63 per clinic visit). This cost was lower for those who lived in HCMC (US$33.49) and higher for those needing to travel from another southern province (US$107.01). The disparity between these two groups became greater when participants travelled with an informal caregiver. Productivity cost estimates varied significantly depending on the calculation method used and participant subgroup investigated, ranging between US$4.35–29.88 per visit. Conclusions Although modest compared with the total cost of DAA therapy, non-medical costs constitute a substantial share of household income for many patients, particularly those residing outside Ho Chi Minh City. Decentralising hepatitis C services could reduce travel and productivity losses, enhance affordability, and improve the equity and efficiency of treatment scale-up in Vietnam. Cost analyses Productivity cost Inequity Hepatitis C Direct-Acting Antivirals Figures Figure 1 Figure 2 Background Hepatitis C remains one of the leading causes of liver disease worldwide ( 1 ). In response, the World Health Organization (WHO) has set a global goal to eliminate viral hepatitis as a public health threat by 2030, as part of its Global Health Sector Strategy on Viral Hepatitis ( 2 ). This strategy has outlined specific targets, such as reducing the number of new hepatitis C infections and deaths from liver cancer by 2025. Increasing access to direct-acting antiviral (DAA) treatments plays a crucial role in achieving these targets. Understanding the costs of hepatitis C treatment is vital for reaching these goals. Cost data support economic evaluations, such as cost-effectiveness analyses, which are important in informing health policy. However, there is limited cost data for hepatitis C in low- and middle-income countries (LMICs) ( 3 , 4 ) – even though two-thirds of hepatitis C cases occur in LMICs ( 5 ). These data gap pose a challenge for conducting economic evaluations and informing policies relevant to these countries. A 2016 systematic review ( 4 ) found that all 36 included studies were conducted in high-income countries. It is challenging to generalize findings from high-income countries to LMICs due to “ differences between settings, diseases, and health care systems ” ( 6 ). Similarly, a systematic review in 2017 ( 3 ) revealed that over half of the cost-effectiveness analyses of DAA treatment for hepatitis C (51%) were conducted in the USA, and the remaining studies focused on upper-middle income or high-income countries, such as Canada, South Africa, Spain, Switzerland, and the UK. Consequently, there is currently limited understanding of the cost of hepatitis C treatment in LMICs settings and a need for additional data. A particularly notable data gap relates to the costs outpatients incur to access hepatitis C treatment in LMIC settings, which is vital for understanding the full cost of DAA treatment. Additionally, little is known about how the patients’ costs may vary, particularly for patients living further away from treatment facilities. This issue is particularly relevant in countries like Vietnam, where DAA treatment is primarily provided in major hospitals in big cities. Understanding these costs is crucial for designing strategies to improve outpatients' access to DAA in resource-limited settings. This study therefore aimed to quantify the costs incurred by patients to access DAA based treatment for hepatitis C at the Hospital for Tropical Diseases in Ho Chi Minh City (HCMC), Vietnam. It also investigated how these costs are influenced by the distance to treatment facilities. This is important for the evaluation of new strategies to improve outpatients' access to DAA treatment in resource-limited settings, supporting efforts to achieve the WHO’s 2030 elimination targets. Methods Study location, population and timeline A patient-level micro-costing study was performed to investigate the costs participants incur when accessing hepatitis C treatment. We recruited 102 adult participants who were living with chronic hepatitis C, but without cirrhosis, and accessing treatment at the outpatient clinic of the Hospital for Tropical Diseases in HCMC, Vietnam, between 1/8/2020 and 31/8/2021. The Hospital for Tropical Diseases is the biggest government hospital specialising in infectious diseases in Southern Vietnam, with a capacity of around 650 beds ( 7 ). It is also designated for viral hepatitis patients, receiving more than 18,000 patients with viral hepatitis annually ( 7 ). During the study period, it was the only facility in Southern Vietnam providing DAA therapy. Participants were those participating in the VIETNARMS trial, a randomized controlled trial of DAA treatment strategies for hepatitis C in Vietnam ( 8 ). Convenience sampling was employed, following the sequence of patients enrolling into the trial. Cost questionnaire Participants were interviewed following a costing questionnaire (see Additional file 1), administered by a trained research assistant. The questionnaire, based on the ingredient-costing approach, identified all the cost inputs associated with hepatitis C treatment access. The questions reflected the activities of those visiting the hospital’s outpatient department from their homes. The questionnaire was piloted with 30 participants from a different hepatitis C treatment trial at the Hospital for Tropical Diseases between 2019–2020 ( 9 ). Feedback from the pilot study was used to refine and clarify the questions (the pilot data were not included in the main study analyses). The finalized questionnaire consisted of nine different sections, enabling the quantification of the incurred direct non-medical cost, and productivity costs. Outputs and statistical analyses Based on the data collected with the questionnaire, two cost categories were analysed: direct non-medical costs and productivity costs (also known as indirect costs). These are summarized in Table 1 . The costs were considered from the patient/household perspective. Table 1 The variables and indicators used to estimate the participants' cost of accessing hepatitis C treatment. Outcome Variable Indicator Direct non-medical costs The costs related to the consumption of non-medical resources (such as transportation to the health facility, food expenses and accommodation). Travel Distance from their home to the health facility (km) Method of transportation from home to facility Cost of travel (including costs incurred by informal caregivers) Food Cost of food expenses (including costs incurred by informal caregivers) Other costs Cost of accommodation (including costs incurred by informal caregivers) and any other costs incurred Productivity costs (indirect costs) Represents the value of productivity losses that result from illness, treatment, or premature death. Participant time Time spent travelling Time waiting to see the doctors or nurse Time spent having health exam Informal caregivers time Time spent travelling Time spent at the facility The cost results were reported focusing on two main categories: participants who did not travel with an informal caregiver and those who did. This was further stratified by whether the participants lived in HCMC or travelled from another southern province (i.e. lived outside of HCMC). The data were summarised using basic descriptive statistics including mean, standard deviation, and frequency. The costs were presented in US $ 2021 prices, using the 2021 exchange rate (US $ 1 = VND23,159) ( 10 ). The estimates of the direct non-medical costs were based on the responses to the questionnaire. In contrast, productivity costs were estimated by assigning a monetary value to the reported productivity losses of the participants and their informal caregivers. Given the lack of consensus on optimal methodology for such calculations ( 11 , 12 ), we used a range of approaches, as outlined in Table 2 . These methods accounted for both paid and unpaid work, and were in line with the human capital approach [12]. Table 2 Approaches employed for valuing productivity losses Approach Value of a lost day Sources Calculation a Valued based on the GDP per capita GDP per capita per day US $ 14.21 a Based on the 2020 per capita GDP reported by the World Bank (US $ 3,694 per year) ( 33 ) Productivity losses of all the participants and caregivers were valued at US $ 14.21 a per day Valued based on the minimum wage Those from HCMC: Minimum wage per day US $ 8.81 a Based on the monthly minimum wage values set by government regulation in 2021 for different locations reported by Vietnam’s General Statistics Office in 2021 ( 34 ). These were on average; From HCMC: US $ 191 From outside HCMC b : US $ 167 Productivity losses of participants and caregivers from HCMC were valued at US $ 8.81 a per day on average Those from outside HCMC: Minimum wage per day US $ 7.81 a Productivity losses of participants and caregivers from outside HCMC were valued at US $ 7.81 a per day on average Valued based on the mean wage of the job category reported c Participants: Mean wage per day US $ 9.68 a Based on the mean monthly wage values for different job categories reported by Vietnam’s General Statistics Office in 2021( 34 ); Paid work: US $ 285 Unpaid work: US $ 186 d Productivity losses of participants and caregivers were valued depending on their reported replacement activities. Caregivers: Mean wage per day US $ 9.53 a Valued based on the mean wage of participants’ home province Those from HCMC: Mean wage per day US $ 16.82 a Based on the mean monthly wage values for different living areas reported by Vietnam’s General Statistics Office in 2021( 34 ); From HCMC: US $ 364 From outside HCMC: US $ 292 (on average) b Productivity losses of participants and caregivers from HCMC were valued at US $ 16.82 a per day on average Those from outside HCMC: Mean wage per day US $ 13.47 a Productivity losses of participants and caregivers from outside HCMC were valued at US $ 13.47 a per day on average GDP: Gross Domestic Product, HCMC: Ho Chi Minh City. The costs were presented in US$2021 prices ( 10 ). a The costs were adjusted to daily values assuming that people in Vietnam work five days per week, following the Vietnam Labour Code 2019 (i.e. 260 work days per year – corresponding to an mean of 21.6 work days a month). b Based on the mean of all provinces in Southern Vietnam excluding HCMC. c The participants were assigned to lost paid or unpaid work based on the replacement activity they reported (the activity they would do if they were not visiting the hospital). c The value for unpaid work was based on the values reported for domestic hired labourers and farming. Results A total of 102 participants were recruited into this costing study (Table 3 ). The majority of the participants were male, middle-aged, and married. Most of the participants (93%) were covered by the government’s health insurance programme. Only 25% of them had formal paid employment. The proportion that lived in HCMC compared to those that travelled from another southern province (from outside HCMC) was relatively balanced (45% vs 55% respectively). Approximately 39% of the participants who visited the hospital were accompanied by an informal caregiver; those from outside HCMC were more likely to be accompanied by an informal caregiver (70% versus 30%). Most caregivers (78%) were family members (e.g. child, spouse) but sometimes the caregiver was a friend. We observed that 22% of the participants had a co-infection: 15% were co-infected with human immunodeficiency virus (HIV) and 6% were co-infected with hepatitis B virus (HBV) and one participant was co-infected with both. Table 3 Demographic characteristics of the study participants Characteristic Number (N) Percentage (%) Total sample 102 100 Sex Male 60 59% Female 42 41% Age 20–39 years old 19 19% 40–59 years old 56 55% ≥ 60 years old 27 26% Marital status Married 78 76% Single 12 12% Separate/Divorce/Widow 12 12% Participant’s residence From HCMC 46 45% From outside HCMC 56 55% Health insurance status Has health insurance 95 93% Do not have health insurance 7 7% Co-infections HIV 15 15% HBV 6 6% HIV and HBV 1 1% Has children Children 56 55% No children 46 45% Job status Formal employment 26 25% Informal work 76 75% Replacement activity a Paid job 24 24% Unpaid work 78 76% Travel method Bus 53 44% Own motorbike 45 52% Other 4 4% Accompanied by an informal caregiver Yes 40 39% No 62 61% Participants with caregivers From HCMC 12 30% From outside HCMC 28 70% Caregivers’ relationship to participant Family member 31 78% Friend 9 22% Mean Min Max Household size 4 1 10 Monthly household income (US $ ) 678.18 43.18 4317.98 From HCMC 916.89 86.36 4317.98 From outside HCMC 500.43 43.18 2158.99 Monthly income of paid workers (US $ ) 346.09 43.18 1079.49 From HCMC 353.59 215.90 1079.49 From outside HCMC 329.25 43.18 647.70 a Replacement activity : Activities participants do if they do not spend time visiting the hospital. HCMC: Ho Chi Minh Cit. The time participants and their informal caregivers spent visiting the hospital is summarised in Table 4 . The primary travel method to the hospital was a motorbike for participants who were from HCMC and a bus if they were from outside HCMC (Table 3 ). The mean travel time for participants living in HCMC and outside HCMC was approximately one hour and five hours, respectively. Including travel, the mean total time spent on a visit was 4 hours for participants living in HCMC, and 9 hours for those outside of HCMC (Table 4 ). The total time reported by the informal caregivers was similar, with values generally consistent with those reported by the participants themselves. Any small difference was likely due to caregivers travelling separately and from different locations to the participants. Table 4 Time (hours) spent visiting the hospital by the participants Visit time (hours) Participants from HCMC Participants from outside HCMC Mean Min-Max Mean Min-Max Participants Travel time 0.94 0.17-5.00 4.77 1.00–10.00 Waiting time 0.39 0.15-2.00 1.80 0.10–6.50 Examination time 2.63 1.00–4.00 2.39 1.00-3.50 Total time 3.95 2.00–9.00 8.97 2.50–16.50 Informal caregivers Travel time 0.85 0.25-2.00 4.54 0.50–10.00 Waiting time 2.58 2.00–4.00 3.32 2.00–7.00 Total time 3.44 2.00-5.50 7.86 3.00–13.00 HCMC: Ho Chi Minh City. Participants and their informal caregivers' direct non-medical costs included the costs related to travel, food, and any other non-medical costs (e.g. parking fees) (Table 5 ). The mean total direct non-medical cost was US $ 8.16 per visit. These costs were notably higher for the participants who lived outside HCMC and for participants who travelled with an informal caregiver (Table 5 ). The participants who lived in HCMC and did not travel with a caregiver incurred direct non-medical costs of US $ 2.48 while those who lived outside of HCMC spent three times more (US $ 8.13). This gap between the two living areas increased if the outpatient travelled with a caregiver (US $ 2.76 vs US $ 17.40). For participants who lived outside HCMC, the travel cost was the main contributor to their direct non-medical costs (representing 80% of the total). In contrast, the travel costs for participants living in HCMC were relatively small, equivalent to their mean food cost. In some cases (as seen in the travel costs of participants with caregivers from HCMC), the travel cost was negligible because they could use their motorbikes to travel a short distance to the hospital. Table 5 The direct non-medical costs incurred by participants and informal caregivers (per visit) Participants from HCMC Participants from outside HCMC All participants Mean Min-Max Mean Min-Max Mean Min-Max Participants without caregivers Travel cost 1.20 0.00-34.54 6.67 0.00-18.14 3.67 0.00-34.54 Food cost 1.26 0.00-3.45 1.45 0.00-6.48 1.35 0.00-6.48 Other costs a 0.01 0.00-0.43 0.02 0.00-0.43 0.01 0.00-0.43 Total direct non-medical costs 2.48 0.00-35.84 8.13 1.30-19.65 5.03 0.00-44.48 Participants with caregivers Travel cost 0.00 0.00-0.02 13.96 0.00-43.18 9.78 0.00-43.18 Food cost 2.36 0.00-8.64 3.29 0.00-12.52 3.01 0.00-12.52 Other costs a 0.40 0.00-4.32 0.15 0.00-3.02 0.22 0.00-4.32 Total direct non-medical costs 2.76 0.00-8.64 17.40 0.43–44.48 13.01 0.00-44.48 All participants Travel cost 0.89 0.00-34.54 10.31 0.00-43.18 6.06 0.00-43.18 Food cost 1.55 0.00-8.64 2.37 0.00-12.52 2.00 0.00-12.52 Other costs a 0.11 0.00-4.32 0.08 0.00-3.02 0.10 0.00-4.32 Total direct non-medical costs 2.55 0.00-35.84 12.77 0.43–44.48 8.16 0.00-44.48 HCMC: Ho Chi Minh City a Other cost includes parking fees (if they used their own vehicle) and any other non-medical costs incurred during the visit to the hospital. The standard deviations for the corresponding values are presented in Additional file 2. The mean productivity costs per visit ranged between US $ 4.35–29.88 (Fig. 1 ), based on estimated mean hours lost per visit (summarized in Additional file 3). The corresponding estimated productivity costs varied depending on the valuation method used (Table 2 ). The highest productivity cost per visit occurred when using the mean wage based on living areas. Meanwhile, the lowest value occurred when valuing time based on the minimum wage. The results when valuing lost time based on the GDP per capita and the mean wage based on job categories were relatively similar. The productivity cost of participants who travelled from another southern province was higher than those from HCMC, despite the income of those from outside HCMC being lower (Table 2 and Table 3 ). When participants were accompanied by a caregiver, the productivity cost was approximately doubled (39% of the sample had an informal caregiver travel with them). A standard 12-week DAA treatment course for a hepatitis C patient (without cirrhosis and no co-infections) typically requires three visits to the outpatient clinic. Based on this, we estimated that on average, the total cost incurred by an outpatient for accessing a standard 12-week treatment was US $ 73.90. The mean total cost for participants from HCMC was estimated at US $ 33.49, while for those travelling from outside HCMC, the cost significantly increased to US $ 107.01 (Fig. 2 ). Within each group, participants travelling with a caregiver incurred costs nearly twice as high as those who travelled alone. The estimated total cost was sensitive to the approach used to value the productivity losses (See Additional file 4). However, the substantial cost disparity between participants living in HCMC vs outside of HCMC remained across different valuation approaches. Discussion We estimated that the mean total cost incurred by an outpatient for accessing a standard 12-week treatment with DAA would be US $ 73.90 in southern Vietnam. This cost was lower for patients who lived in HCMC (US $ 33.49) compared to those who travelled from another southern province (US $ 107.01). The disparity was more pronounced for participants travelling with an informal caregiver. Meanwhile, the income data revealed a contrasting picture, with the mean monthly wage being higher for those living in HCMC (US $ 364) than those living outside of HCMC (US $ 292) (Table 2 ). This notable cost associated with accessing hepatitis C treatment could therefore act as a barrier, potentially limiting treatment uptake. These costs are important to consider when evaluating any alternative Hepatitis C treatment strategies in future studies ( 8 ). Direct non-medical costs On average, an outpatient would incur US $ 24.48 in direct non-medical costs to access a standard 12-week DAA treatment. The costs were notably higher for those living outside HCMC (US $ 38.30) compared to those within HCMC (US $ 7.65). Travel costs contributed the most to the direct non-medical costs, accounting for up to 80% for participants living outside HCMC, followed by costs related to food. Accommodation costs had only a minor contribution to these direct non-medical costs. This is likely because hepatitis C participants travelled back and forth within the same day. Even participants who needed to travel a long distance would likely take the night bus to save time and money compared to renting accommodation. Another study in Vietnam quantifying the costs of tuberculosis treatment also found that transportation and food were the main components of the direct non-medical costs ( 13 ). Productivity costs The primary components of productivity losses were travel, waiting, and examination times. Travel times averaged one hour for participants in HCMC and five hours for those outside HCMC. Overcrowding at national public hospitals, such as the Hospital for Tropical Diseases in Vietnam, contribute to long waiting time. Despite the setting of this study, specifically a clinical trial where participants did not need to register and wait, many still arrived early. The mean waiting time for the sampled participants was around 1.16 hours, consistent with another study reporting a mean of 1.15 hours (among nearly 8,000 participants) in a similar national public hospital setting in HCMC ( 14 ). In our sample of participants (who typically went to the hospital and came home within a day), 39% were accompanied by an informal caregiver. Most caregivers were family members (78%) – such as spouses or their sons/daughters. A higher proportion of participants travelling from outside HCMC were accompanied by than those living at HCMC (Table 3 ). Caregiver-related costs added to the economic burden, particularly for participants from outside HCMC. Data on the costs incurred by informal caregivers are still limited in LMIC settings ( 15 , 16 ). For example, a systematic review investigating the inclusion of caregiver cost studies in costs-of-illness studies identified only two studies (2/51) from Thailand, with the remaining (49/51) being from European settings and the United States ( 15 ). Our findings further underscore the importance of addressing this gap in future research and the need to capture caregiver-related costs. There are multiple methods used to value lost productivity within productivity cost calculations ( 17 , 18 ), and the choice of method can have a notable impact on the outcome. For example, in a health economic modelling study on hepatitis C in Pakistan, the cost of productivity life year lost was US $ 603.91 when using median income to value productivity losses compared to US $ 1,443.63, when using GDP per capita ( 17 ). To account for this, we used a range of different wage sources to value a lost day ranging from US $ 7.81 to US $ 16.82 (Table 2 ). These findings emphasize the critical need for transparency in reporting the methodology used for productivity cost calculations and for carefully considering the potential impact of different valuation approaches on study outcomes. Geographic inequity In line with Vietnam‘s National Health Insurance policy, DAA are classified as an expensive drug and predominantly provided in centralized locations at major hospitals in big cities, such as Hanoi and HCMC. We found that participants from outside HCMC had a lower mean income but incurred higher costs to access treatment (Table 2 and Fig. 2 ). This is particularly relevant as the income gap between people living in urban versus rural areas in Vietnam has been found to be increasing ( 19 ). More generally, distance and transportation have also been proven to be negative factors in health access, particularly for chronic diseases ( 20 ). A study in Vietnam that analysed the factors linked to health status and health service utilization proved that lack of transportation and higher travel costs are associated with barriers to healthcare access ( 21 ). Studies in other LMICs (such as China ( 22 ), Thailand ( 23 ), and Nepal ( 24 )) have found similar results. Policy implications These data are critical input for informing future cost-effectiveness analysis of hepatitis C treatment interventions in Vietnam. Furthermore, these results highlight the geographic disparities in hepatitis C treatment access, underscoring the need for targeted actions to reduce inequalities. Addressing these disparities aligns with the United Nations Sustainable Development Goals ( 25 ) and the achievement of WHO targets for the elimination of Hepatitis C as a public health problem by 2030 ( 26 , 27 ). Decentralizing hepatitis C treatment to primary healthcare facilities could reduce geographic inequities. The use of primary healthcare has been shown to improve service coverage and healthcare outcomes, which is in line with the notions of “healthcare for all” ( 28 , 29 ). Decentralization could enhance the equality, quality, and allocation efficiency in healthcare services ( 30 , 31 ). However, building trust in the quality of primary healthcare also needs to be strengthened to prevent self-referral to an upper-level hospital, which could exacerbate inequities, as wealthier individuals are more likely to pay for higher-quality treatment. In parallel with improving the quality of healthcare services, capacity management should also be strengthened. Limitations The initial plan was to obtain a sample size of 200 based on the general recommendations of Johnston et al . ( 32 ), with participants recruited from both the HTD in HCMC and the National Hospital for Tropical Diseases in Hanoi (two of the three hospitals providing DAA-based treatment for hepatitis C in Vietnam at the time). However, our final sample was limited to 102 participants from the HTD due to data availability and COVID-19 restrictions. Despite this constraint, the sample remains adequate within the context of cost-of-illness studies. If the coefficient of variation (standard deviation divided by the mean) ranges from 0.25 to 1, a sample size of 102 provides a 95% confidence interval with a precision of approximately ± 5–20% of the mean. In our study, the estimated coefficient of variation was approximately 1, leading to a precision of ± 20% of the mean. Increasing the sample size to 200 would only have improved the precision to approximately ± 15%. Another limitation is that, while HTD is a key site for DAA-based treatment in Vietnam, the cost estimates may not be fully representative of the entire country. However, our finding of regional cost disparities based on patients' locations is likely robust due to the centralized nature of DAA treatment in Vietnam. Additionally, the data collected in this study reflect only participants’ first treatment visit. Productivity losses from subsequent visits may be lower. Furthermore, this study focused solely on the costs associated with patient access to DAA-based treatments, excluding direct medical costs. Finally, 15% of our sample was co-infected with HIV and 6% with HBV. Patients with co-infections may incur different costs, such as requiring more treatment visits. However, due to the small number of co-infected participants, we were unable to analyse their specific cost patterns, highlighting an area for further research Conclusion These results highlight that outpatients can incur a notable cost for accessing Hepatitis C treatment, potentially generating a barrier to increasing treatment coverage in such settings. Centralising treatment at major hospitals can create geographic inequities in the patients’ incurred cost: we estimated that on average the total cost incurred by an outpatient for accessing a standard 12-week DAA treatment was lower for those who lived in HCMC (US $ 33.49) and higher for those who needed to travel from another Southern province (US $ 107.01). The disparity between these two groups became more pronounced when participants travelled with an informal caregiver. Addressing this geographic inequity requires targeted actions, such as considering more decentralised treatment. These results also highlight the importance of accounting for uncertainties in productivity cost calculations. Clear and transparent reporting of the methodology used is crucial to ensure the robustness and comparability of study outcomes. Declarations Conflict of interests: None Acknowledgements: SEARCH investigators (Alphabetical order): Azim Ansari, Eleanor Barnes,  Graham S. Cooke, Bich Dang Thi, Thuan Dang Trong, Khoa Dao Bach, Jeremy N. Day, Barnaby Flower, Leanne McCabe, Richard M. Hoglund, Evelyne Kestelyn, Cherry Kingsley, Hung Le Manh, Chau Le Ngoc, Phuong Le Thanh, Thao Le Thi, Chau N. V. Vinh, Tran Nguyen Bao, An Nguyen Chau, Tuyen Nguyen Kim, Phuong Nguyen Ngoc, Dung Nguyen Thanh, Sarah Pett, Thach Pham Ngoc, Motiur Rahman, David Smith, Joel Tarning, Guy E. Thwaites, Hugo C Turner, Rogier Van Doorn, Jennifer Van Nuil, Quang Vo Minh, Thu Vo Thi, Hang Vu Kim, Huong Vu Thu, A. Sarah Walker Ethics: These data were collected within the VIETNARMS trial. The research was conducted in accordance with the principles of the Declaration of Helsinki and applicable local and international ethical guidelines. Ethical approval for the trial, including this data collection, was obtained from the local hospital ethics committees at the Hospital for Tropical Diseases and the National Hospital of Tropical Disease; the Ministry of Health, Viet Nam; Imperial College London, UK; and the University of Oxford, UK (ref. 110-0319/35CN). This trial is registered with ISRCTN (61522291) on 4 October 2019 . Consent to Participate : Written informed consent was obtained from all participants prior to their inclusion in the study. Funding: The study was funded by the Wellcome Trust [award number 206296/Z/17/Z]. Preparatory work was supported by an award from the UK MRC [award number MR-P025064-1]. HCT acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/X020258/1), funded by the UK Medical Research Council (MRC). This UK funded award is carried out in the frame of the Global Health EDCTP3 Joint Undertaking. ASW was supported by core support to the MRC Clinical Trials Unit at UCL (MC_UU_00004/03). GC and ASW are NIHR Senior Investigators. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. Funders have no roles in study design, collection, analysis, and decision to publish or preparation of the manuscript. For the purpose of open access, the author has applied a ‘Creative Commons Attribution’ (CC BY) licence to any Author Accepted Manuscript version arising from this submission. Data availability: Primary analyses were conducted using summary statistics, which are fully reported in the manuscript and/or supplementary materials. Researchers interested in further details may contact the corresponding author for additional information. References Yang J, Qi J-L, Wang X-X, Li X-H, Jin R, Liu B-Y, et al. 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Supplementary Files Additionalfile1Outpatientvisitcostingquestionnaire.docx Additional file 1 (docx): Outpatient visit costing questionnaire Additionalfile2Thedirectnonmedicalcostsincurredbyparticipantsandinformalcaregiverspervisitwithstandarddeviation.docx Additional file 2 (docx): The direct non-medical costs incurred by participants and informal caregivers (per visit) - with standard deviation Additionalfile3Averagetotalproductivitylostpervisit.docx Additional file 3 (docx): Average total productivity lost per visit Additionalfile4Thetotalcostsincurredbyparticipantsaccessingstandard12weektreatmentwithDAAstratifiedbyproductivitycostmethod.docx Additional file 4 (docx): The total costs incurred by participants accessing standard 12 week treatment with DAA, stratified by productivity cost method Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 22 Apr, 2026 Reviews received at journal 22 Apr, 2026 Reviews received at journal 29 Mar, 2026 Reviews received at journal 27 Mar, 2026 Reviewers agreed at journal 08 Mar, 2026 Reviewers agreed at journal 05 Mar, 2026 Reviewers agreed at journal 05 Mar, 2026 Reviewers invited by journal 05 Mar, 2026 Editor assigned by journal 05 Mar, 2026 Submission checks completed at journal 05 Mar, 2026 First submitted to journal 04 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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