A Randomized Control Trial of an Antimicrobial Stewardship Program for Veterinary Service Providers and Farming Communities in Nepal

Last registered on April 30, 2025

Pre-Trial

Trial Information

General Information

Title
A Randomized Control Trial of an Antimicrobial Stewardship Program for Veterinary Service Providers and Farming Communities in Nepal
RCT ID
AEARCTR-0015884
Initial registration date
April 25, 2025

Initial registration date is when the trial was registered.

It corresponds to when the registration was submitted to the Registry to be reviewed for publication.

First published
April 30, 2025, 9:28 AM EDT

First published corresponds to when the trial was first made public on the Registry after being reviewed.

Locations

There is information in this trial unavailable to the public. Use the button below to request access.

Request Information

Primary Investigator

Affiliation
Henry Ford Health

Other Primary Investigator(s)

PI Affiliation
Henry Ford Health
PI Affiliation
Henry Ford Health
PI Affiliation
GTA Foundation
PI Affiliation
GTA Foundation

Additional Trial Information

Status
On going
Start date
2025-01-01
End date
2026-12-31
Secondary IDs
Prior work
This trial does not extend or rely on any prior RCTs.
Abstract
Recognized as a threat to the achievement of the Sustainable Development Goals (SDGs), the Quadripartite organizations developed the One Health Priority Research Agenda for antimicrobial resistance (AMR).(1) The Research Agenda emphasizes that addressing the interlinked and multi-faceted challenges posed by AMR necessitates a One Health approach. One Health is defined as "a collaborative, multisectoral, and transdisciplinary approach—working at the local, regional, national, and global levels—with the goal of achieving optimal health outcomes recognizing the interconnection between people, animals, plants, and their shared environment”.(2)

The ongoing intensification of the livestock industry to meet growing demands for nutrition has been largely successful in low- and middle-income countries (LMICs).(3) This is facilitated by the routine use of antimicrobials to treat, control, and prevent animal diseases and to increase the productivity of animals. While there is lack of reliable data on antimicrobial use (AMU) in agriculture in LMICs, some recent studies suggest that ~73% of all antimicrobials sold globally are used in food-producing animals.(4) Such over-use and misuse of antibiotics in animals contributes to the emergence and spread of AMR.

For the current project, we will utilize a One Health approach and address AMR in the animal health sector and supplement our ongoing efforts surrounding human health and AMR in Nepal, over the last decade.(5-11) A recent study conducted in Nepal identified a total of 96 trade name registered antimicrobials available for use in animals, comprising 35 different genera of antibiotics, belonging to 10 different classes.(12) While Nepal has a legal ban on the use of antimicrobials as growth promoters, sales of drugs without prescriptions from veterinarians are common practice for prophylactic and therapeutic purposes among paraprofessionals and agrovets.(13, 14) Moreover, a recent study reported that the volume of veterinary antibiotic sales increased over 50% from 2008 to 2012.(15, 16) Such misuse of antimicrobial agents in the livestock sector is one of the main drivers for farm-to-fork transmission and the continued spread of AMR, especially in LMICs where there are poor biosecurity measures in place, looser regulations on veterinary drugs, and frequent human-animal contact. Therefore, there is an urgent need to improve the awareness and understanding of AMR and institute established antimicrobial stewardship (AMS) principles in the animal health sector (veterinary service providers and community members) to optimize the use of antimicrobial agents. For the purposes of this study, veterinary service providers will include veterinarians, veterinary paraprofessionals, animal health technicians, and agrovets. Community members will include dairy and/or poultry farmers and farm workers in traditional smallholder and commercial farming settings. In Nepal, traditional farmers typically own 1-5 dairy animals and 10-50 poultry, while commercial dairy farms raise ~10-150 cows/buffaloes and commercial poultry farms have more than 500 chickens. The primary objectives of the proposed 2-year project include:

1. Conduct a mixed-methods study to assess knowledge and perceptions among veterinary service providers and community members to identify antibiotic dispensing and use practices and key factors which contribute to inappropriate use of antibiotics in livestock and pathogen resistance. The mixed methods will include qualitative interviews, focus groups and surveys with veterinarian service providers, community members, and district and national policy makers. The qualitative data will provide socioeconomic contextual information to support understanding of emergent issues and factors associated with antibiotic dispensing/use patterns. The surveys will provide more generalizable data to assess types of antibiotics dispensed/used for livestock, factors associated with antibiotic dispensing/use, farm hygiene/sanitation and infection prevention and control (IPC) practices, and knowledge and perceptions of antimicrobial resistance and impact on animal and human health. These data will help establish a baseline for a longitudinal outcome evaluation of the intervention (Aims 2 & 3). During this assessment phase, we will also expand our existing AMR Scientific Advisory Board (SAB) and establish a Community Advisory Board (CAB) in order to promote broader engagement in the program and local involvement in program development, implementation, and evaluation. Experts from Nepal Veterinary Association, Nepal Paraveterinary Association, and Nepal Animal Health service technician's association will be included as members of SAB. The CAB will include leaders and members of Nepal Poultry Farmers Association, Nepal Dairy Association, Nepal Egg Producers Association, and District Milk Producers Cooperative Association.

2. Utilize data to develop/adapt AMR education, training, and stewardship to support appropriate antibiotic dispensing and use among veterinary service providers and community members, and promote behavior change and decrease AMR in Nepal. The study team in collaboration with the SAB and CAB will develop context- and country-specific education modules to support One Health stewardship goals. These modules will be implemented with local stakeholders including veterinary service providers, and a comprehensive social mobilization and communication strategy will be developed for community members.

3. Implement a randomized control trial of the veterinarian service provider and community interventions. Districts will be randomized to receive or not receive the interventions. Longitudinal evaluation data will include the above-mentioned baseline surveys (Aim 1) and 6-month post-intervention surveys. The survey will provide data on the impact of the educational modules and communication strategy.

4. Conduct a process evaluation based on the Consolidated Framework for Implementation Research.(17) This approach will provide data at multiple levels (policy, programmatic, health system, and community) which can inform further dissemination of the intervention by the Nepal Ministry of Agriculture and Livestock Development (MoALD) and Nepal Agricultural Research Council (NARC).

5. Engage with policy makers, program managers, veterinary service providers and community members through scientific and community advisory boards (SAB/CABs) and a post-project dissemination workshop. This engagement is designed to support data interpretation, intervention adaptation/development, and future implementation of the interventions at a national level.

Assessment (Aim 1)
Hypothesis 1: Farmers and farm workers reporting greater awareness/knowledge of AMU and AMR are more likely to exhibit animal healthcare seeking behavior which support One Health stewardship goals.
Hypothesis 2: Veterinary service providers reporting greater knowledge of recommended antibiotic prescribing/dispensing guidelines and policies are less likely to prescribe/dispense unjustified use of antibiotics.

Outcome Evaluation (Aim 3)
Hypothesis 1: Farmers and farm workers exposed to the communication strategy, compared to those not exposed, will have increased awareness of appropriate usage of antibiotics and AMR.
Hypothesis 2: Farmers and farm workers exposed to the communication strategy, compared to those not exposed, will have increased intent to visit veterinarians and exhibit animal healthcare seeking behavior which supports AMR stewardship.
Hypothesis 3: Agrovets exposed to the educational intervention will be more likely to require prescriptions before selling antibiotics.
Hypothesis 4: Veterinarians and paraprofessionals exposed to the educational intervention, compared to those not exposed, will be more aware of justified antibiotic use in agriculture which can result in decrease in AMR and risks to human health.

The proposed project is a collaboration between Henry Ford Health Global Health Initiative (HFH-GHI) and Division of Infectious Disease, the Nepal Ministry of Agriculture and Livestock Development (MoALD), and Nepal Agricultural Research Council (NARC), and a local non-profit, GTA Foundation. NARC is a governmental agency that falls within MoALD, has regional offices, and works closely with the provincial and local government to develop/enhance the dissemination of agricultural research. HFH and GTA have partnered on multiple projects related to infectious disease over the past seven years.

The objectives and approach of this proposal meet the Interests of the Merck Investigator Studies Program (MISP) request for proposals for studies evaluating a CDC One Health approach to stewardship. Specifically, the study will identify barriers which contribute to imprudent use of antibiotics in agriculture and utilize a randomized control trial to evaluate interventions to improve knowledge, attitude and practices related to antibiotic use in agriculture in Nepal. The resulting evidence-based AMS program could be scaled up in Nepal and adapted and implemented elsewhere in South Asia and other LMICs.
External Link(s)

Registration Citation

Citation
Bajracharya, Deepak et al. 2025. "A Randomized Control Trial of an Antimicrobial Stewardship Program for Veterinary Service Providers and Farming Communities in Nepal." AEA RCT Registry. April 30. https://doi.org/10.1257/rct.15884-1.0
Sponsors & Partners

Sponsors

Partner

Experimental Details

Interventions

Intervention(s)
The adaptation/development of veterinary service providers training and the community intervention will utilize multiple sources of information and data. For the community intervention with farmers and farm workers, we will utilize a literature review of community interventions to increase uptake of veterinarian services and animal healthcare seeking behavior. We will focus on evidence-based interventions and those implemented in LMICs and the South/Southeast Asian region.

Assessment Data: Both the qualitative and survey assessment data will be used to develop and/or adapt both the veterinarian healthcare provider’ training and the communication strategy for community interventions. The assessment data will help to identify specific barriers and facilitators to use of animal health services within the study sites and also respondents’ preferred approaches (e.g., face-to-face, group meetings, social media) to receiving information.

SAB and CABs: Both the SAB and CABs will play an important role in the development/adaptation of the training and intervention. The assessment data will be organized and presented to the members of the SAB and CABs for comments, discussion, and suggested translation into locally salient programs.

Community Training of Trainers (TOT): TOT approaches have been evaluated and shown to increase local capacity and program sustainability within health settings including in relation to delivery of AMS programs. In this proposal, the community TOT will be implemented by our research team members and local experts (e.g., animal health workers) within the intervention districts. The protocol will include skills and knowledge related to outreach and communication, knowledge about appropriate AMU in agriculture, importance of prescriptions from authorized personnel, animal/farm hygiene and IPC, vaccination programs, and specific details on logistics and program delivery within the intervention community contexts. TOT participants will be engaged at multiple levels including didactic learning of basic knowledge and awareness necessary to the program, seeing delivery of the program modeled by the research team members, and opportunity to practice delivery of the program and receive constructive feedback from their peers and the project investigators.
Intervention Start Date
2025-11-30
Intervention End Date
2026-06-30

Primary Outcomes

Primary Outcomes (end points)
Outcome and Independent Variables.

Veterinary Service Providers. The primary outcome variable will be adherence to antibiotic prescription guidelines. Additional variables will include: 1) knowledge and awareness of appropriate use of antimicrobials; 2) perceptions of disease risk and antimicrobial stewardship strategies; 3) perceptions of veterinarian role and influence on farmers’ behavior surrounding antimicrobials; 4) perception of need for change and their role in implementation of AMS strategies within their settings. [see Table 3]

Community members. The primary outcome variable will be intention to utilize veterinary service providers for animal healthcare. Additional variables will include: 1) knowledge and awareness about veterinary services and vaccination programs; 2) perceptions of practicing good animal / farm hygiene and IPC; 3) perceptions of risk of administering wrong products, over- and/or under-dosing and barriers for obtaining prescriptions from authorized personnel; 4) awareness and knowledge on AMR, effects on animal and human health, withdrawal period; 5) perception of implementing AMS strategies at farm-level. [see Table 3]

Assessment Hypotheses
Hypothesis 1: Farmers and farm workers reporting greater awareness/knowledge of AMU and AMR are more likely to exhibit animal healthcare seeking behavior which support One Health stewardship goals.
Hypothesis 2: Veterinary service providers reporting greater knowledge of recommended antibiotic prescribing/dispensing practices and policies are less likely to prescribe/dispense unjustified use of antibiotics.

Primary Outcomes (explanation)

Secondary Outcomes

Secondary Outcomes (end points)
Secondary Outcomes (explanation)

Experimental Design

Experimental Design
Study Design Overview. The proposed study combines qualitative and quantitative methodologies and utilizes an implementation science approach. The study is divided into five phases which correspond to the specific objectives (see Section 2.1).

Phase 1: A multi-level mixed-methods assessment to understand knowledge, attitude, and practices regarding AMU and prescription practices in agriculture, and establish a baseline for a longitudinal outcome evaluation of the intervention in selected districts. The qualitative data will provide socioeconomic contextual information to support understanding of emergent issues and factors associated with antibiotic dispensing/use patterns. The surveys will provide more generalizable data to assess types of antibiotics dispensed/used for livestock, factors associated with antibiotic dispensing/use, farm hygiene/sanitation and IPC practices, animal healthcare seeking behavior, and knowledge and perceptions of AMR and impact on animal and human health. Participants will include farmers/farm workers in traditional smallholder and commercial farming settings, veterinarians, agrovets, and district and national policy makers. Veterinary service providers in study districts will be recruited through members of the SAB representing the Nepal Veterinary Association, Nepal Paraveterinary Association, Nepal Animal Health service technician's association, and Veterinary Practioner's Association of Nepal. Community members (farmers and farm workers) is study districts will be recruited through members of the CAB representing Nepal Poultry Farmers Association, Nepal Dairy Association, Nepal Egg Producers Association, District Milk Producers Cooperative Association. The assessment will use the Consolidated Framework for Implementation Research (CFIR) model and include key informant interviews, focus group discussions, and surveys with veterinary service providers and community members.
Phase 2: Adaptation/development of AMR education, training, and stewardship to support appropriate antibiotic dispensing and use among veterinary service providers and a communication strategy for farmers/farm workers to promote behavior change to address the spread of AMR in Nepal. The adaptation process will include analysis and review of the assessment data, and local engagement through a scientific advisory board (SAB) and community advisory boards (CABs).
Phase 3: A randomized control trial (RCT) will be used to evaluate intervention outcomes. Districts will be randomized to receive or not receive the interventions. The longitudinal outcome evaluation will include two data collection points: baseline (the assessment survey from phase 1 will serve as the baseline) and 6-month post intervention. A mixed methods process evaluation will be conducted for veterinarians, paraprofessionals, agrovets, and farmers.
Phase 4: Conduct a process evaluation based on the Consolidated Framework for Implementation Research.(17) This approach will provide data at multiple levels (policy, programmatic, health system, and community) which can inform further dissemination of the intervention by the Nepal Ministry of Agriculture and Livestock Development (MoALD) and Nepal Agricultural Research Council (NARC).
Phase 5: After completion of the evaluation, a program review and dissemination workshop will be undertaken. This phase will also include convening the SAB/CABs to review the evaluation data and suggest modifications to the interventions to improve delivery and content. This information will then be presented at a larger dissemination workshop including policy, programmatic, administrative, health system, and community leaders to determine action steps to expand the interventions into other districts in Nepal.
Experimental Design Details
Not available
Randomization Method
For our program, we anticipate selecting and randomizing sites as follows: 1) Characterize the pilot districts by province, population size and density (urban/rural), and demographic (e.g., ethnicities) and economic indicators. 2) After stratification, two rural and two urban districts will be randomly selected. 3) In each pair, one district will be randomized to intervention and the other to control.
Randomization will be conducted prior to collection of the baseline data (Phase 1, Assessment). We will stratify districts by characteristics (e.g., rural/urban, province, population characteristics). Once stratified, we will randomly select 2 urban and 2 rural districts. We will then randomly select 1 urban and 1 rural district as the intervention arm and 1 urban and 1 rural as control.
The farmers and farm workers in traditional smallholder and commercial farming settings will be randomly selected from municipality/ward offices and animal healthcare clinics. Lists of potential participants will be put into a SPSS file and the software randomization process will be used to select participants by district.
Randomization Unit
Intervention: District
Survey Participation: Individual (within intervention/control district)
Was the treatment clustered?
Yes

Experiment Characteristics

Sample size: planned number of clusters
4 districts (1 urban/1 rural in intervention arm, 1 urban/1 rural in control) with 2 study classes (service providers and farmers) each arm.
Sample size: planned number of observations
2 assessments
Sample size (or number of clusters) by treatment arms
We anticipate an estimated sample size of (N=280) for veterinary service providers and (N=180) for farmers, in each arm. Estimated 920 participants through control and intervention phase, with 460 participants invited to participate for post-intervention.
Minimum detectable effect size for main outcomes (accounting for sample design and clustering)
Survey Development: To ensure that participants are representative of significant dimensions of the target populations, we will purposefully select respondents based on specific criteria. These criteria will depend on the population.(see below) As is standard practice with qualitative research, we will use ‘data saturation’ to finalize our sample size. Data saturation refers to the point at which no new information or themes are observed in the data. This will be done to ensure that we have maximized variability within our data and have sufficient data to identify patterns within and across assessment populations. Policy makers- National (MoALD and NARC) and district level government staff involved in veterinary health National:3-4 Individual Interviews (II) Urban District: 3-4 II Rural district: 3-4 II Total: 9-12 II Local service providers- Veterinarians, veterinary paraprofessionals, animal health technicians, agrovets Urban District: 2-3 II and 2 Focus Group Discussions (FGD) Rural District: 2-3 II and 2 FGD Total:4-6 II and 4 FGD Community leaders- Local community health volunteers and leaders of farmers’ associations; other local leaders to be identified through CAB Urban District: 2 FGD Rural District: 2 FGD Total: 4 FGD Pilot of the Survey Instrument: To ensure internal validity and reliability of the survey instruments, we will conduct both qualitative and quantitative pilots. The qualitative pilot will utilize ‘cognitive interviewing’ methods. The qualitative pilot will be conducted with a total of 35 veterinary service providers and 35 farmers. These cognitive interviews will be conducted in rural and urban wards and districts not included in the randomized control trial. A quantitative pilot will be conducted within the same two wards with a total of 35 veterinary service providers and 35 farmers. Through the quantitative pilot we will assess scale internal consistency (Cronbach’s alpha). Veterinary Service Provider/Community Survey Randomization will be conducted prior to collection of the baseline data (Phase 1, Assessment). We will stratify districts by characteristics (e.g., rural/urban, province, population characteristics). Once stratified, we will randomly select 2 urban and 2 rural districts. We will then randomly select 1 urban and 1 rural district as the intervention arm and 1 urban and 1 rural as control. We estimate (N=280) per arm (intervention and control) for veterinarian service providers and for farmers (N=180) in each arm. To address refusals and potential attrition between baseline and post-intervention, we will increase the initial sample by 20% (N=216/study arm). We will utilize 4 districts randomly assigned to the intervention arm (1 rural/1 urban) and the control arm (1 rural/1 urban). Among our two study classes (service providers and farmers), we anticipate an estimated sample size of (N=280) for veterinary service providers and (N=180) for farmers, in each arm.Mean differences among subgroups from the two study classes will be included during analysis among the following: veterinarians, veterinary paraprofessionals & animal health technicians, agrovets, and farmers. It is assumed the effect size will be small (0.2=small) and groups are normally distributed. We will apply the One-Way ANOVA (an extension of the Two Means T-test for more than two groups) for this step of the analysis. Any differences between groups at baseline and after the intervention among the four groups is assumed to be balanced.
IRB

Institutional Review Boards (IRBs)

IRB Name
IRB Approval Date
IRB Approval Number