This manuscript adheres to the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement: extension to cRCT [17].
2.1. Study design and setting
The proposed trial is a community-based, 12-month, open label, two-arm cRCT with an equal allocation of clusters (geographical wards) between intervention and control arms in a semi-urban area of Pokhara Metropolitan city (former Lekhnath municipality, administratively divided in to 15 wards). It is one of the two areas where the Cervical Cancer Screening and Prevention (CCSP) pilot program was first initiated in Nepal. The total population of Lekhnath municipality is 59,498 with the total number of households being 14,958 as per the 2011 census [18]. Each ward will be considered as one cluster. Although the study area is composed of 15 clusters, only 14 will be selected for the cluster randomization (one cluster that is comparatively different from others in socio-demography and health service availability is excluded). Allocation of the clusters into intervention and control arms is described below. The study area is limited to health services comprising one recently upgraded 25-bedded hospital from a primary health care center, three health posts, and six urban health care centers. According to the District Public Health Office, Kaski in 2018, there were 123 FCHVs in the municipality.
2.2. Participants
The populations targeted in our study area are women aged 30–60 years (the age range recommended for VIA screening in Nepal), listed in the Community-Based Intervention for Non-communicable diseases study for hypertension (COBIN-H) [7, 16]. We will invite all the selected women participants for a baseline survey. During the baseline survey, prevalence, knowledge, attitude and screening practice on cervical cancer will be obtained and eligible women will be invited to participate in the trial. The flow of trial participants is shown in Fig. 1, which includes the number of participants eligible, surveyed, excluded, recruited, randomized, and analyzed for the primary outcome. The SPIRIT checklist for this trial is provided as an Additional file 1.
2.3. Recruitment
A sampling framework was adopted from the COBIN-H trial that has taken a population framework of all eligible participants from the voter list prepared by the Election Commission in 2017 [16]. As of 31st December 2018, all the women of age group 30–60 years were included in the study. Trained women public health professionals (Data Enumerators) will carry out a baseline survey. The data enumerators will receive four days of intensive training before data collection. The survey tool is adapted from a joint survey report of Family Health Division of Nepal’s Ministry of Health and United Nations Population Fund (UNFPA) [8, 19–21]. It includes questions on survey information, consent, socio-demographic information, questions related to sexual and reproductive health, health-seeking behaviour, knowledge, attitude and cervical cancer screening practice, sign and symptoms. The questionnaire was modified as per the Nepalese settings, translated to the Nepali language and back to English to ensure content validity. Baseline data will be used for possible confounder adjustment and stratification by effect modifiers. Once the questionnaire has been completed, eligible participants will be identified and asked about their willingness to participate in the cRCT. The required number of participants will be randomly selected from those willing to participate in the cRCT: FCHVs will visit each household, meet the selected participant, and obtain consent to participate in the trial.
2.4. Randomization
Clusters will be randomly assigned to intervention and control areas using a 1:1 allocation ratio. Randomization will be done before the participants are recruited. Research teams responsible for identifying potential participants, obtaining consent and recruiting trial participants will be blinded to the participants’ allocation status. The following steps will be taken to avoid selection bias during random allocation: (a) clusters will be randomized only after the baseline survey; (b) clusters will not be withdrawn from or added to the study; and (c) a statistician from abroad who is not familiar to the study will randomize the clusters.
2.5. Inclusion and exclusion criteria
Women aged 30–60 years who are listed in COBIN-H and who indicated they planned to reside in a cluster in the study area for at least the next 12 months are eligible for inclusion in the baseline survey and for the invitation to participate in the study. Women who are severely ill, pregnant, less than six weeks after delivery, who are already diagnosed with cervical pre-cancer and cancer, with a history of total hysterectomy as well as those, who decline to participate in the study or unable to complete the interview, will be excluded from the study.
2.6. Outcomes
2.6.1. Primary and secondary outcomes
The primary outcome of the study is percentage change in cervical cancer screening uptake from baseline to follow up in the intervention group compared to the control group in a 12-month home-based health education intervention. The baseline survey will be conducted before the cluster randomization and a follow-up survey of similar method will be conducted after 12-month intervention. The response of each participant for cervical cancer screening in the baseline survey and the follow-up survey will be compared to evaluate the percentage. In addition, FCHV will provide a referral slip to the participants in the intervention group (keeping a copy of the referral slip to submit to the field supervisor) during the home-visit, which they take with them and submit to the health facility for VIA screening. The referral slip contains study code, name, age, address, and signature of both FCHV and the participant. FCHV will inform the participants about the health facility where the services are freely available. The key health personnel providing the VIA screening services are oriented about the study. Furthermore, confidentiality about the participants’ information will be maintained throughout the intervention. The field supervisor will collect the referral slip to confirm that the participants have received VIA screening and results from all the health facilities of the intervention ward as a reference to the participants’ response.
The secondary outcomes of the study is change in the level of knowledge and awareness among women on cervical cancer screening and prevention. The response of each participants for knowledge and awareness on cervical cancer screening in the baseline survey and the follow-up survey will be compared to evaluate the change.
2.7. Sample size calculation
The sample size for the baseline survey is calculated based on the method suggested by the WHO STEPWISE Approach [22]: for our study, we calculate 884 participants with 20% non-response. A systematic random sampling method will be performed as a sampling technique. For the power calculation, we took reference from a quasi-experimental study from Nigeria that reported an effect size of 5% between intervention and control group during a 13 weeks period [23]. We expect an effect size of 10% increase in our study with a one-year follow-up where FCHVs are mobilized to conduct home visit counselling once every three months and the intervention takes place in an ongoing community-based program for non-communicable diseases from 2014 [16]. Assuming, 20% loss to follow-up and ICC of 0.01 and seven clusters per arm will provide 90% power resulting to 49 women per cluster. The total sample size needed for the intervention study is 690 that will be recruited from the 884 participants (baseline survey), which is enough to obtain 90% power.
2.8. Interventions
After randomization, the FCHVs in intervention wards will receive training coordinated by the research team in collaboration and close supervision of the local health authority. The training manual is designed under the guidance of experts in cervical cancer and public health from the national and international organizations. The training manual is based on, Training of community health workers, WHO, 2017 training manual [24] and Cervical Cancer Screening and Prevention (CCSP) A Reference Manual 2015 [25]. The FCHVs will receive a 3-day training package highlighting: (a) an introduction to NCDs and cervical cancer, (b) Cervical cancer causes and risk factors, (c) Cervical cancer screening and service availability, (d) Providing health education and counseling women (30–60 years), and (e) recording, reporting and follow-up. An overview of program content is presented in Table 1. Educational sessions are guided by the use of the Health Belief Model [26], and training materials will be reviewed and validated by experts and major stakeholders. The developed training materials will be pretested with the FCHVs from a nearby area not included in the study. In addition, the FCHVs will also receive health education materials (pamphlets), referral cards and a recording register during the training session.
At the end of the training, FCHVs will assign the number of households that have to be visited based on the baseline survey. Consequently, FCHVs will visit each household, meet the selected participant, and ask for informed consent to participate in the trial. Participants in the intervention clusters will receive a 12-month, home-based, health education package administered by FCHVs in a household setting. On average, one FCHV will meet 18 participants three times a year. FCHV will complete the three visits to provide health education even if the participants have already received VIA screening.
During the visit, FCHVs will deliver the health education intervention, to encourage and empower women for cervical cancer screening uptake available free of cost at their local health facility. They will also conduct two reinforcement visits every four months from the first visit (three home visits in a year).
Health workers, conducting cervical cancer screening at the local health facility in the intervention group will receive orientation about the study to make sure that the women attending the health facility receive screening. They will ensure that the equipment is functional and reagents are available, record information, provide psychosocial counselling to the case positives and refer for further confirmation and treatment. The recorded information at the health facility will be tallied using the referral slip to confirm women's participation for cervical cancer screening. Information confidentiality will be maintained.
A field supervisor will routinely visit each FCHV in order to maintain motivation and collection of records from the health facilities. The supervisor also provides ad-hoc help to the FCHVs when needed during the intervention period. We will also use a supervision checklist to track and update the knowledge and skill levels of FCHVs as well as to ensure fidelity to the study protocol.
In the control clusters, participants will receive ‘usual care.’ The usual care means the current health education and promotion practices for cervical cancer screening at the community level provided by the government health system. They will not receive further contact, information, or educational materials from FCHVs until the 12-month assessment.
Table 1
Session plan for FCHV training
Day | Session | Main Contents |
Day 1 | | |
| Introduction to Non-Communicable Diseases (NCD) | What is NCD and its situation in Nepal? What are the different types of NCDs? What are the risk factors for NCDs? How can we prevent NCDs? |
| Cervical Cancer Causes and symptoms | Have you ever heard of cancer? What is cancer? What is cervical cancer? What causes cervical cancer? What are the symptoms of cervical cancer? How does the community perceive cervical cancer? |
| Discussion | Questions / answers and doubt clearance |
| Evaluation | First day evaluation and FCHV selection |
Day 2 | | |
| Cervical Cancer Causes and symptoms | What causes cervical cancer? What are the symptoms of cervical cancer? What is the cause of cervical cancer? Human papilloma virus and it’s transmission Who are at risk of having cervical cancer? What are the symptoms of cervical cancer? |
| Cervical cancer screening and prevention | What to do to prevent cervical cancer? What are the different type of screening methods? Visual Inspection with Acetic acid (VIA) What is the recommended age group for VIA screening? Who does the VIA screening? Service delivery points and cost Role of FCHV to prevent cervical cancer Myths about VIA screening. |
| FCHV home visit | Planning for home-visit Number of visits and timing Rapport building Reason for the visit and the health education session Recording, reporting |
| Interactive learning | Flip chart topics FCHV posture, body language, preparedness, proactive towards the situation, voice Detailing the flip chart |
Day 3 | | |
| Recording register | Explain the content of the recording register How to prepare and fill the recording register? Name, age, location of the participants and FCHV Submission of completed register to the research officer |
| Pamphlet | Explain the content of the pamphlet How to stress the points in the pamphlet What to suggest to the participants who are not able to read the pamphlet? |
| Referral card | Explain the content of the referral card How to fill the referral card? Name, age, location and health facility address for referral Communication with the health facility |
| Scenario planning | Role play |
| Household selection and list preparation | Selection of the household for home-visit according to FCHVs working area. |
2.9. Minimization of contamination
The risk and level of contamination will be monitored at the levels of FCHVs and participants. FCHVs will be instructed not to share information about the study and not to provide any support to people from other clusters in the community, other than the ones who are assigned. The risk of contamination will also be minimized by the cluster design, whereby the intervention and control clusters will be geographically separated and the chance of intervention cluster participants regularly meeting control cluster participants will be negligible. All possible means of contamination between intervention and control participants will be collected during the follow-up survey and adjustments will be made for estimating the effect.
2.10. Intervention fidelity
The intervention is designed under the guidance of experts in cervical cancer and public health from the national and international organizations. The subject experts and major stakeholders reviewed and validated the training materials. The education session were delivered under the close supervision of the local level health authority and the research team, who will monitor the intervention. Data Safety and Monitoring Board (DSMB) along with a member from the Nepal Health Research Council will evaluate the progress of the trial, including periodic assessments of data quality and timeliness, participant recruitment, accrual and retention, participant risk versus benefit, performance of the trial site, and other factors that can affect study outcome. Each FCHV in the intervention cluster will be advised of the importance of following the intervention steps and content during the training session. The field supervisor will monitor FCHVs tasks. FCHVs will deliver the services guided by a register that keeps them reminded of stages of the intervention and will report every four months.
STATA version 15 software (StataCorp, College Station, TX, USA) will be used for quantitative analysis following the Consolidated Standards of Reporting Trials (CONSORT) guidelines for cluster-randomized trials. Flowcharts (Fig. 1) will include the number of participants seen at each stage of the trial, eligible, randomized, and analyzed for the primary outcome. In the initial analysis, we will compare baseline characteristics of enrolled participants in the study arms and follow-up status. We will use mixed-effect logistic regression to compare between the groups as the outcome; (the primary outcome would be the difference in the proportion of women who participate in the cervical cancer-screening program between intervention and control within one year). Comparison of the knowledge scores between baseline and follow-up, after one-year intervention will measure the knowledge level. Estimation will take into account the effect of potential confounders (age, ethnicity, education, parity, income, religion, location, etc.).
3. Interim Analyses And Stopping Rules
There is no plan for interim analysis, as we do not expect a situation that would lead us to stop the study. However, in the event of an extreme situation such as a natural disaster, a conflict, or duplication of similar interventions in our control area, we will temporarily stop the study to assess the implications on the study design.
4. Trial Management
We have a robust mechanism to ensure data quality. At first, the data enumerators will receive intensive training on the process of data collection. The principal investigator will monitor the data enumerators on a day-to-day basis. The Research Assistant assigned for data entry will inspect the data manually and enter the data in EpiData software file (EpiData Association, Odense, Denmark). Double entry for ten percent of the data will qualify potential errors in data entry quality. The Research Officer will crosscheck the data quality on the spot and in our field office for any incomplete, inconsistent, and invalid data. Any deviation in the data quality will require recollecting in the field.
5. Indemnities
The study carries minimal risk to the study participants, which is why we have no compensation or insurance plan for the participants. However, we will provide US$5 per home visit to FCHVs for transportation expenses.
6. Publication Plan
The results of the trial will be published in a peer-reviewed journal.