Investigating feasibility of 2021 WHO protocol for cervical cancer screening in underscreened populations: PREvention and SCReening Innovation Project Toward Elimination of Cervical Cancer (PRESCRIP-TEC) | BMC Public Health

Primary and secondary goals

The main goal of PRESCRIP-TEC is to judge the modifications in protection and uptake of main screening by means of hrHPV self-testing, and adherence to follow-up and remedy suggestions after screening, ensuing from an enhanced screening program launched in Bangladesh, India, Uganda and the Slovak Republic, and in comparison with the present screening program in every of the international locations. Secondary goals embrace analyzing the boundaries and facilitators associated to the uptake of hrHPV self-sampling (client-related and well being system-related components), performing a validation examine of an AI determination assist system (AI-DSS) for VIA, and conducting a model-based financial analysis of the potential cost-effectiveness of the improved screening program for every of the international locations.

Study setting

The mission might be carried out in 4 international locations: three LMICs (Bangladesh, India and Uganda) and one HIC (Slovak Republic) [15]. These international locations have been chosen as a result of of variations regarding excessive cervical cancer incidence and/or low uptake of screening, totally different implementation settings and hard-to-reach areas and susceptible inhabitants teams. In addition, these international locations have been early adopters of screening and remedy strategies in the previous. The data relating to the demographic and cervical cancer profiles of the international locations is summarized in Table 1. In every nation, examine areas and susceptible populations had been chosen primarily based on context evaluation.

Participants

The enhanced screening program will goal girls in age teams outlined in accordance with the prevailing screening coverage of the international locations. In Bangladesh, the screening intervention will goal girls aged 30-60, dwelling in a number of distant areas. In the northern half of Bangladesh, 4 districts (Kurigram, Gaibandha, Bogura and Sirajganj) had been chosen for the examine and one district (Sathkhira) was chosen in the southern half of the nation. In India, girls aged 35-63 might be focused in rural and city areas, together with city slum and hilly areas, in Udupi, Sikkim, Kolkata, Bangalore and Mumbai. In addition, HIV optimistic girls, intercourse employees and different susceptible teams might be approached in Bangalore by collaborating establishments. In the Slovak Republic, the goal teams are girls aged 19-64 from Roma communities in 16 districts throughout Prešov, Banská Bystrica and Košice areas in the japanese half of the nation and girls aged 19-64 working in 15 automotive factories throughout all areas. In Uganda, girls aged 30-49 dwelling in rural areas in the Kakumiro district might be focused.

Eligible girls who might be supplied the hrHPV self-test in the goal age group and areas are outlined as follows:

• They are non-pregnant girls eligible for participation in the screening program in accordance with the nationwide screening coverage;

• Prior to the examine, they haven’t been screened inside the interval outlined by the nationwide screening coverage.

To take part in the analysis element (main and secondary analysis goals), the next standards might be utilized to girls eligible for the hrHPV self-test as described above, in addition to different respondents, together with husbands, family determination makers and different stakeholders:

• They perceive details about the examine and present knowledgeable consent for participation in the examine;

• They have the verbal expertise to reply to questions and/or have interaction in an interview.

Intervention

Prior to the introduction of the screening program, data campaigns might be carried out to succeed in the target market. These will embrace, amongst others, speaking by means of radio, social media, telephone messaging, theater, flyers, posters and different awareness-raising actions. The marketing campaign codecs might be chosen primarily based on the nation context. We intention to succeed in over 100,000 males and girls per nation by means of on-line and offline communication channels.

The mission goals to offer screening companies for 6000-8000 eligible girls in every nation. The mission will apply a community-based strategy, in which eligible girls might be visited in their houses and/or mobilized by means of outreach efforts and might be supplied a self-test for hrHPV screening. Depending on the ladies’s preferences and the group circumstances, the self-test might be taken at their houses or on the close by clinics with the likelihood of help by a healthcare employee.

The screening methods carried out in the international locations as half of PRESCRIP-TEC are introduced in Figs. 1, 2, 3. In Bangladesh, India and Slovak Republic, in case of a optimistic hrHPV end result, the ladies might be invited for the follow-up examination in a display, triage and deal with strategy. This follow-up examination will contain VIA, aided by AI-DSS, in Bangladesh and India, whereas in Slovak Republic this examination will contain the use of Pap smear (with out AI-DSS). This distinction is because of present screening insurance policies in the collaborating international locations, upon which PRESCRIP-TEC builds. In Uganda, the screen-and-treat strategy might be used, in which all girls recognized as hrHPV-positive might be handled in accordance with the nationwide guideline. Hereby, AI-DSS might be used in visible evaluation of girls for eligibility for thermal ablation remedy. Alternatively, relying on availability, cryotherapy could also be used. The scientific efficiency of the AI-DSS for VIA might be evaluated in this examine as a secondary goal.

In Bangladesh, India and Uganda, direct remedy throughout the identical follow-up go to might be offered if lesions are recognized as eligible. Otherwise, girls might be referred for remedy in accordance with the prevailing nationwide pointers.

Subsequent prognosis and remedy are exterior the scope of analysis in this mission. In case of unfavourable hrHPV take a look at, girls might be suggested to comply with the nationwide pointers relating to screening intervals for their subsequent screening take a look at.

Outcomes

The fundamental outcomes linked to the first goal of PRESCRIP-TEC are described in Table 2.

Logic mannequin

To characterize the analysis parts of PRESCRIP-TEC, we tailored the Implementation Research Logic Model [18], check with the Additional file 1. The determinants are divided into client-related components, tailored from [19], and well being system components, tailored from [20]. The determinants are linked to the intervention and the implementation methods, which result in outcomes by means of the hypothesized mechanisms.

Study design

PRESCRIP-TEC is an implementation examine, in which a multi-method strategy might be utilized to judge the improved screening program in 4 international locations. For the first goal, the design of the examine might be described as a pre-post quasi-experimental examine with non-equivalent management teams [21]. Control areas have been chosen in every collaborating nation to match the designated intervention areas on the provision of screening companies supplied and the goal inhabitants traits.

The pre-post comparability to measure the primary outcomes might be carried out utilizing the difference-in-differences examine design. In this strategy, the protection, uptake and adherence to follow-up might be in contrast between intervention areas and management areas in every nation at baseline (previous to the implementation of the screening intervention) and end-line (after the total implementation) by means of retrospective surveys. Additional outcomes of the follow-up take a look at and the proportion of girls receiving direct remedy after the examination might be analyzed as nicely. Baseline knowledge in the intervention and management areas might be collected retrospectively concurrently the endline survey. Where potential, the baseline knowledge might be validated utilizing different sources, akin to historic knowledge and knowledge collected as half of the secondary goals.

Sample dimension

Analysis of knowledge might be carried out on the cluster stage, which might be recognized for every nation (clinic, village or district). Sample sizes for various numbers of potential clusters had been estimated utilizing an strategy for energy calculation for group-randomized trials with a number of assumptions [22].

Uptake was used as the primary final result for pattern dimension concerns. The absolute enhance in uptake was assumed at 20%. Based on the uptake of cervical cancer screening, the intraclass correlation coefficient was assumed to be 0.02. This additionally ranged between 0.01 and 0.05, relying on the kind of cluster. The variance discount was conservatively assumed to be 1. Type I error (alpha) was set at 5% and sort II error (beta) was set at 80%. Based on these assumptions, we anticipate the pattern sizes for the pre-post comparability to range between 375 and 1500. These closing pattern sizes are topic to identification of the quantity and sort of clusters in every nation.

Statistical evaluation

To decide if the intervention resulted in important modifications in uptake, protection and adherence to follow-up in the intervention areas in comparison with management areas, multivariable regression evaluation might be carried out.

Secondary goals

Client-related components

For the needs of this examine, we categorize potential components influencing the first outcomes of uptake, protection and adherence to follow-up into client-related components and well being system-related components. Client-related components might be grouped into contextual, particular person or group influences, in addition to cancer-specific features of screening (Table 3, tailored from [19]).

In order to realize perception into group cervical cancer consciousness, as nicely the acceptability, accessibility and adherence to the improved screening protocol, a blended strategies strategy might be utilized and varied contributors might be enrolled for the examine. First, on the group stage, males, girls and family determination makers might be approached in order to measure baseline group cervical cancer consciousness previous to the intervention. The African Woman Awareness of CANcer (AWACAN) software might be used in order to measure consciousness of cervical cancer in baseline and endline family surveys. The AWACAN software has been developed in order to measure breast and cervical cancer consciousness and has proven to be dependable and legitimate for use in Sub-Saharan Africa [23]. The questionnaire is a combination of open, closed and multiple-choice questions and consists of questions on socio-demographic determinants. As PRESCRIP-TEC focuses on cervical cancer, solely the questions specializing in cervical cancer consciousness had been derived from the AWACAN software. The AWACAN software incorporates 41 questions particular to cervical cancer on threat components, signs, lay beliefs, confidence in appraisal, help-seeking behaviors, and 12 questions on boundaries to searching for well being care for breast and cervical cancer.

After implementation of the intervention, the AWACAN and the Healthcare Systems Trust Framework, [24] might be administered amongst girls in intervention areas and management areas. In addition, amongst girls who accepted the hrHPV self-test a questionnaire of girls’s experiences with the take a look at might be administered. The Health Care Systems Trust Framework was developed in India and supplies validated questionnaires with 23 objects scored on a Likert scale. Each merchandise is an element of one of the 5 domains (perceived high quality of companies, efficient communication, transparency in relations, reliability and technical competence) and has a weight resulting in an total belief rating. The questionnaire used to review the acceptability of the hrHPV self-test incorporates 13 questions associated to the self-sampling process, in addition to information of hrHPV and cervical cancer [25].

Prior to administration of the devices, nation groups accustomed to the goal inhabitants will fastidiously evaluation the devices and focus group discussions or particular person interviews might be organized in order to contextualize the devices to make sure compatibility with the goal inhabitants. In addition, all devices might be translated into languages of the goal populations.

Thereafter, a qualitative follow-up examine utilizing in-depth interviews (IDI) and/or focus group discussions (FGD) with eligible girls and family decision-makers might be carried out to realize perception into their perceptions of hrHPV self-tests and boundaries and facilitators for screening participation. Women might be approached 2-3 weeks after acceptance of hrHPV self-test for an interview or FGD. We intention to conduct 30-40 IDIs and/or FGDs till saturation of themes is achieved. We anticipate to succeed in saturation by this quantity of contributors. Thematic content material evaluation might be used to research the transcripts of IDIs/FGDs.

Health system components

The well being system components related for cervical cancer screening participation are introduced in Table 4 throughout the “constructing blocks” of the WHO Health Systems Framework (tailored from [20]). The well being system components might be measured by means of surveys throughout the full operation of the improved screening program, ongoing assessments throughout facility visits, and in-depth interviews and/or FGDs with key stakeholders. All amenities in the goal areas of the intervention, together with cellular items, well being posts, well being facilities or hospitals, might be concerned.

The Facility Based Survey instrument, included in the WHO Cervical Cancer Prevention Toolkit (26), might be used for the survey and ongoing evaluation of healthcare amenities in this examine goal. This survey instrument relies on the Service Availability and Readiness Assessment software and is tailor-made for cervical cancer screening and prevention.

Semi-structured interviews might be carried out among the many varied key stakeholders on the matters of the progress of implementation, potential moderating components, and the boundaries and facilitators of implementation of the screening protocol. Furthermore, views of healthcare employees could also be studied through FGDs. Topic guides for the interviews and focus teams might be developed with the Conceptual Framework for Implementation Fidelity [26] and the Consolidated Framework for Implementation Research [27] serving as frameworks. Follow-up FGDs might be carried out on the finish of the mission among the many identical contributors to debate the boundaries and facilitators of implementation, and to mirror on the implementation.

AI-DSS

An picture processing algorithm, developed on the Manipal Academy of Higher Education in India [28], might be evaluated by means of a validation examine in Bangladesh, India and Uganda. This algorithm capabilities as an Android-based software. The inter-observer variability of the algorithm might be assessed amongst healthcare employees and gynecological specialists. The mannequin efficiency might be evaluated primarily based on calibration, discrimination, scientific usefulness and error evaluation standards [29].

Before the sphere implementation of AI-DSS, the diagnostic accuracy of healthcare employees, specialists and the AI-DSS might be assessed in a dry run utilizing a database of VIA footage. Next, the AI system might be used as a “second opinion” for the healthcare employees performing VIA. In case of disagreement between the healthcare employee and the AI-DSS, an knowledgeable will present a second opinion and scientific steering. Finally, if the AI system is discovered to show excessive convergence both with each the healthcare employees and the specialists in the mission, or with the specialists solely (with want for additional coaching for healthcare employees), the examine will look at choices for job shifting utilizing the AI-DSS.

Economic analysis

To produce related and actionable data for the decision-making context in every collaborating nation, a model-based financial analysis of the screening protocol might be carried out, incorporating a spread of knowledge sources, together with the protection, uptake and adherence to follow-up outcomes, and secondary knowledge. This analysis will embrace country-specific cost-effectiveness analyses and funds impression analyses of the screening protocol. The analysis will evaluate the screening protocol state of affairs to a “business-as-usual” state of affairs of the prevailing screening coverage in every nation. The financial evaluation goals to tell a enterprise case of implementing the WHO suggestions in LMICs, specializing in the potential affordability of the screening protocol. Special consideration might be given to evaluation of eventualities for introduction of hrHPV testing in the context of tools and take a look at prices, as affordability is a serious bottleneck for introduction of the brand new WHO protocol in many international locations.

Data administration and monitoring

Data assortment will happen in Slovakia, Uganda, Bangladesh, and India beneath accountability of native companions in the PRESCRIP-TEC analysis consortium. Digital knowledge, each uncooked and processed/analyzed knowledge, in addition to the codebooks with metadata, documentation of steps taken or choices made, scripts and software program used for evaluation, might be saved at servers in the international locations the place the info is collected. Data might be pseudonymized earlier than it may be shared to a devoted server at University Medical Center Groningen.

Risks

Due to the COVID-19 pandemic, delays in the mission might probably come up in consequence of care provision disruptions or COVID-related measures in the chosen international locations. We anticipate that the mission is not going to expertise important delays as soon as the screening program is launched by the nation groups.

Safety

Since PRESCRIP-TEC goals to outline situations to scale-up already confirmed screening methods, no particular security dangers are anticipated past these recognized in the WHO suggestions [10].