Patient Preferences and Willingness to Pay for Cervical Cancer Prevention in Zambia: Protocol for a Multi-Cohort Discrete Choice Experiment

Background Although most countries in southern Africa have cervical cancer screening programs, these programs generally fail to reach a significant majority of women because they are often implemented as pilot or research projects, and this limits their scope and ability to scale up screening. Some countries have planned larger-scale programs, but these have either never been implemented or have not been successfully scaled up. Most of the global burden of cervical cancer is experienced in countries with limited resources, and mortality from cervical cancer is the most common cause of cancer-related deaths among women in Sub-Saharan Africa. Objective The purpose of this study is to learn about preferences for cervical cancer screening in Zambia, to identify barriers and facilitators for screening uptake, and to evaluate willingness to pay for screening services to support the scaling up of cervical cancer screening programs. Methods We will conduct a discrete choice experiment by interviewing women and men and asking them to choose among constructed scenarios with varying combinations of attributes relevant to cervical cancer screening. To inform the discrete choice experiment, we will conduct focus groups and interviews about general knowledge and attitudes about cervical screening, perception about the availability of screening, stigma associated with cancer and HIV, and payment for health care services. For the discrete choice experiment, we will have a maximum design of 120 choice sets divided into 15 sets of 8 tasks each with a sample size of 320-400 respondents. We will use a hierarchical Bayesian estimation procedure to assess attributes at the following two levels: group and individual levels. Results The model will generate preferences for attributes to assess the most important features and allow for the assessment of differences among cohorts. We will conduct policy simulations reflecting potential changes in the attributes of the screening facilities and calculate the projected changes in preference for choosing to undergo cervical cancer screening. The findings from the discrete choice experiment will be supplemented with interviews, focus groups, and patient surveys to ensure a comprehensive and context-based interpretation of the results. Conclusions Because willingness to pay for cervical cancer screening has not been previously assessed, this will be a unique and important contribution to the literature. This study will take into account the high HIV prevalence in Sub-Saharan Africa and prevailing gender attitudes to identify an optimal package of interventions to reduce cervical cancer incidence. This simulation of women’s decisions (and men’s support) to undergo screening will lay the foundation for understanding the stated preferences and willingness to pay to help design future screening programs. Registered Report Identifier RR1-10.2196/10429


DESCRIPTION (provided by applicant):
Although several cervical cancer screening programs and demonstrations have taken place in southern Africa, only limited evaluations in the real-world setting have assessed program effectiveness, cost, and barriers/facilitators. Furthermore, even though numerous projects have been initiated, only a few successful programs are in operation today. Lessons learned from successful programs have not been synthesized and disseminated to foster scale-up of cost-effective implementation strategies. Given the substantial prevalence of human immunodeficiency virus (HIV) in southern Africa, which significantly increases the risk for cervical cancer, there is an urgent need to scale up prevention and screening services. The specific aims of the proposed research to address the gaps in the evidence base are as follows: Aim 1: Perform systematic process evaluation of the successful Cervical Cancer Prevention Program in Zambia (CCPPZ) to identify lessons for scaling up services in other sub-Saharan countries. Aim 2: Undertake comprehensive assessment of stakeholder perspectives on current program operations to identify barriers and facilitators and innovative financing arrangements to ensure sustainability. Aim 3: Develop a novel microsimulation model to assess cost and effectiveness of interventions and strategies for scaling up cervical cancer prevention and screening at the population level under real-world conditions that include budget and capacity constraints. Successful implementation of the project aims will provide evidence-based implementation guidelines on the optimal selection of prevention and screening interventions to reduce incidence of and mortality from cervical cancer. We will model the impact of behavior change (for example, sexual behavior affects rate of HIV and human papillomavirus [HPV] infections), prevention with HPV vaccination, and screening with visual inspection techniques and the new rapid HPV test; all scenarios will be evaluated under a variety of budget and capacity constraints. This comprehensive approach will allow policymakers to view the changes in cost and outcomes when interventions focusing on both HIV and cervical cancer are implemented rather than when a single-disease-focused approach is used. The process evaluation of CCPPZ and stakeholder assessment will provide best practices, key lessons, review of innovative financing options, and synthesis of barriers and facilitators to guide large-scale program implementation. To ensure generalizability of the findings to other sub-Saharan African nations, we will actively engage health professionals from African countries, and the findings will be disseminated and debated in two symposiums specifically convened for this purpose.
PUBLIC HEALTH RELEVANCE: Sub-Saharan Africa experiences an enormous burden from cervical cancer, but lessons learned from successful programs have not been synthesized and disseminated to 1 R01 CA200845-01A1 3 DIRH SUBRAMANIAN, S foster scale-up of cost-effective implementation strategies. To address this gap, we will perform a process evaluation of the successful prevention program in Zambia, undertake a comprehensive assessment of stakeholder perspectives and funding options, and develop an innovative model to assess cost and effectiveness under real-world conditions. This study will provide evidence-based implementation guidelines on the optimal selection of prevention and screening interventions that can be scaled up in sub-Saharan Africa to reduce mortality from cervical cancer.

CRITIQUE 1
Significance: 1 Investigator(s): 1 Innovation: 2 Approach: 2 Environment: 1 Overall Impact: This is a revised application that proposes to use a mixed methods approach to conduct extensive process evaluation of a successful cervical cancer prevention program in Zambia, obtain stakeholder perspectives on current operations, and ultimately develop a microsimulation model to assess cost and effectiveness of interventions and strategies for scaling up cervical cancer prevention and screening programs. The proposed study is highly significant in that it will provide evidence-based implementation guidelines on the optimal selection of prevention and screening interventions to reduce incidence of and mortality from cervical cancer in sub -Saharan African countries. It addresses a critical public health problem of risk for cervical cancer in southern Africa partly due to the prevalence of HIV infection. The proposed approach can have a substantial impact on policy makers deciding upon adoption or revision of a cervical cancer control program. Weaknesses include little detail about day to day operations and communication among various partners and limited discussion about how information gathered about other countries will be used; no mention on whether or not this information may inform modification or tailoring of the microsimulation model to better inform scale up efforts.

Significance: Strengths
If the aims of the study are accomplished, the resulting model and products will allow policymakers to view the changes in cost and outcomes when interventions focusing on both HIV and cervical cancer are implemented. The process evaluation of CCPPZ and stakeholder assessment will provide best practices, key lessons, review of innovative financing options, and synthesis of barriers and facilitators to guide large-scale program implementation.

Weaknesses
There is limited information about how data obtained from stakeholders from other countries would be used to inform or further adapt the model to be more relevant for scale up in other countries.

Investigator(s): Strengths
The investigators are highly qualified with many years of relevant and successful research. Dr. Subamanian has extensive experience with large scale screening programs including those in low resources setting. The involvement of Dr. Sankaranarayanan from WHO IARC who directs the Screening and Early Detection Group is a strength of this proposal. He has extensive experience directing large randomized screening trials including the assessment of VIA in low resource settings. The investigators address concerns raised in the prior critique about roles of key personnel and these are appropriate. The team is well rounded, incudes individuals with expertise in areas relevant for the proposed study including process evaluation, community engagement, qualitative data analysis, and statistical techniques for analysis of quantitative data including mathematical modeling.

Weaknesses
None noted.

Innovation: Strengths
Project is highly innovative in that it will be the first to use dynamic microsimulation to assess the process of acquiring HIV and HPV infections and the subsequent pathway to cervical cancer. The model then can be used to assess the value of programs that integrate prevention and screening options for HIV and HPV. The model will use data gathered through the first two aims and incorporate data from realworld implementation efforts to include parameters affecting scale up (such as access, quality, adherence, willingness to pay) Weaknesses Methods used for process evaluation are not particularly innovative but seem appropriate.

Approach: Strengths
Uses a mixed methods evaluation protocol based on Re-AIM. Carries framework throughout; ties expected themes to be identified in the first two aims to framework. In response to reviewers comments, provide detailed description of procedures involved in the process evaluation (Aim 1) including both the qualitative and quantitative analyses; the approach is reasonable and will likely lead to data that will inform Aim 3 (the microsimulation model).
Provides description of key measures and data sources for the process evaluation.
Describes inputs for microsimulation model according to Re-AIM framework.

Weaknesses
Little discussion about how the information obtained from the program database analysis (of cervical cancer screening programs in sub-Saharan Africa) and the face to face meetings with officials from other countries will be used to inform the microsimulation model or to modify it for use in other settings.

Environment: Strengths
Strong environment; research conducted at multiple sites with good coordination. UNC personnel based in Zambia will provide academic and research support and the Global Women's Health Fund-Zambia will provide administrative support and staff for data collection. Therefore, activities correspond with where expertise lies. Includes collaborations with the African Centre of Excellence for Women's Cancer Control (AfCoE), which coordinates the Cervical Cancer Prevention Program in Zambia and is codirected by Dr. Parham Includes collaboration with the Mother and Child Health (MCDMCH), which oversees the clinics from which patients will be recruited for focus group and the discrete choice experiment.

Weaknesses
None noted.

Resubmission:
Highly responsive to reviewer comments; adequately addressed issues related to details and roles of key investigators; clarified the link between HIV and HPV and underscored the innovative features of the proposed project related to that link; added detail about the process evaluation and the Discrete Choice Experiment; included description about future situation analyses using the model; added organizational chart to illustrate the relationships between collaborators.

Budget and Period of Support:
Recommend as Requested

CRITIQUE 2
Significance: 1 Investigator(s): 2 Innovation: 3 Approach: 3 Environment: 1 Overall Impact: This implementation research application seeks to learn lessons from a successful cervical cancer prevention program in Zambia, and use that information alongside local perceptions to develop a simulation model that will aid in planning and assessing scale up of such programs in other similar settings. The proposal is clear, and the methodological approach sound. The study aims take a logical approach from collecting the necessary information on key variables that would then be used in the model, followed by a test of the model. The investigator team is strong and has a proven track record of previous work in this area and context. This application seeks to learn lessons from the implementation of a successful cervical cancer prevention program in Zambia. If successful, it would yield very pertinent information on implementation and scaling up of such programs in other such settings. The modeling approach proposed in Aim 3 is a significant component that if successfully developed would be an important tool that can be used for simulating scale up of such programs in other settings.

Weaknesses
None noted.

Investigator(s): Strengths
The PI has a track record of relevant research experience and the proposed application seems to fit in well with the PIs area of expertise There is a strong team of investigators with pertinent experience in cancer epidemiology and prevention, as well as modeling Weaknesses None noted.

Innovation: Strengths
The proposed microsimulation modeling approach is a novel idea and will yield a useful tool for modeling scale up of such programs in a variety of different settings.

Weaknesses
None noted.

Approach: Strengths
The project is built on a strong approach that first aims to collect information on implementation (Aim 1), and stakeholder perspectives (Aim 2), then use this information to develop a model that can be used to simulate different scenarios that may arise in the scale up of a cervical cancer prevention program.

Weaknesses
None noted.

Environment: Strengths
RTI is well positioned to provide a supportive environment for the study. The availability of adequate IT support by the institution will be important for the success of this study. UNC and GWHF-Z have had presence in Zambia (infrastructure and personnel) that will be key to providing an enabling environment for this study Weaknesses None noted. Overall Impact: The application proposes to develop evidence based implementation guidelines on the optimal selection of cervical cancer prevention and screening interventions, through performing a process evaluation on integrating HIV and cervical cancer prevention programs in Zambia, to reduce incidence of and mortality from cervical cancer in sub Saharan countries. If the project is successful, it will fill in the knowledge gap on cost effectiveness of the integrated programs in Zambia, which may inform policy makers in Zambia and other countries in sub Saharan Africa. The investigators are from various backgrounds, living in both the US and Zambia, and have lots of experiences in the proposed topics. The application proposes to develop a microsimulation model to assess cost and effectiveness of interventions under real world conditions, which is new to both research and policy makers in the sub Saharan Africa. The application will use mixed methods approach to process studies on costs and effectiveness (Aim 1), barriers or facilitators (Aim 2) of the program in Zambia, which will generate needed evidence for constructing the microsimulation model (Aim 3). To address the concerns raised in previous reviews, the application provides more details on data, analysis, modeling, and protecting human subjects. However, it still lacks sufficient details on developing innovative financing arrangements (user fee) to ensure sustainability. It is not clear whether the cost components include patient side costs. For data collected from the Discrete Choice Experiments, there is little discussion on voluntary participation and possible self-selection bias, and how that may affect the statistical results and developing microsimulation model. Overall, the application is likely to have medium impact.

Significance: Strengths
If the project is successful, It will fill in the knowledge gap on cost-effectiveness of scaled up cervical cancer screening integrated with HIV interventions in Zambia, which may inform other countries in the sub-Saharan Africa. It will develop a micro-simulation model that enables other countries to assess the feasibility (based on budget constraints) of integrating and scaling up cervical cancer screening into HIV interventions. It will have important impact on public health by address preventing cervical cancer.

Weaknesses
None noted.

Investigator(s): Strengths
The team is multidisciplinary with investigators from various backgrounds who have been working on the related topics.
Some key investigators in the US are now working in Zambia and leading cervical cancer prevention program in the country. The PI has long-time collaborative experiences with some investigators.

Weaknesses
Some Co-Investigators and local agencies (AfCoE and MCDMCH) will not be paid for their participation in the project, which raises concerns on how their timing and quality contributions will be guaranteed.

Innovation: Strengths
The application proposes assessing costs and effectiveness of integrating HIV and cervical cancer prevention in Zambia, which is not known in the region. The application will develop a microsimulation model to assess cost and effectiveness of interventions under real-world conditions that include budget and capacity constraints.

Weaknesses
None noted.

Approach: Strengths
The proposal uses mixed methods to conduct process evaluation and undertake comprehensive assessment of stakeholder perspectives on current program operations to identify barriers and facilitators. The research will collect the data at various levels from stakeholders and also use the best available data to produce parameters for developing microsimulation model. Discrete choice experiments will be used to investigate patients/partners' preference over the screening programs. The application takes other African countries into consideration when developing microsimulation models.

Weaknesses
The completion of Aim 3 will depend on the success of Aim1 and Aim 2: Aims 1 and 2 will provide data on implementation indicators that will be incorporated in the model to be developed in Aim 3. There are no discussions regarding the risks of processing Aims 1 and 2 and how that would affect processing Aim 3. The application proposes user-fee to sustain the scale-up of screening by assessing willingness to pay from patient-side. There is no sufficient information on (1) how to measure and analyze willingness to pay, (2) how to integrate the assessment of willingness into microsimulation, and (3) how to measure the tradeoff between user fees and patient compliance with screening. It is not clear whether the activity-based costs include patient-side costs such as transportation costs.
1 R01 CA200845-01A1 9 DIRH SUBRAMANIAN, S For data collected from the Discrete Choice Experiments, there is little discussion on selfselection issue as a result of voluntary participation, and how self-selection may affect the statistical results and developing microsimulation model? Other concerns include: (1) microsimulation model will not be finalized and disseminated in the 2017 annual meetings; (2) references and text are not consistent.

Environment: Strengths
RTI and UNC have appropriate sources and facilities for the proposed project. UNC has a team in Zambia who will lead the local projects.

Weaknesses
None noted.