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CTRI Number  CTRI/2022/09/045927 [Registered on: 27/09/2022] Trial Registered Prospectively
Last Modified On: 26/09/2022
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Other (Specify) [implementation]  
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Improving access to cancer care in India 
Scientific Title of Study   Access Cancer Care India 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr R Swaminathan 
Designation  Associate Director 
Affiliation  Cancer Institute WIA 
Address  Cancer Institute WIA, Sardar patel road, Adyar, Chennai
Cancer Institute WIA, Sardar patel road, Adyar, Chennai
Chennai
TAMIL NADU
600036
India 
Phone  914422209150  
Fax  04424912085  
Email  r.swaminathan@cancerinstitutewia.org  
 
Details of Contact Person
Scientific Query
 
Name  Dr R Swaminathan 
Designation  Associate Director 
Affiliation  Cancer Institute WIA 
Address  Cancer Institute WIA, Sardar patel road, Adyar, Chennai
Cancer Institute WIA, Sardar patel road, Adyar, Chennai

TAMIL NADU
600036
India 
Phone  914422209150  
Fax  04424912085  
Email  r.swaminathan@cancerinstitutewia.org  
 
Details of Contact Person
Public Query
 
Name  Dr R Swaminathan 
Designation  Associate Director 
Affiliation  Cancer Institute WIA 
Address  Cancer Institute WIA, Sardar patel road, Adyar, Chennai
Cancer Institute WIA, Sardar patel road, Adyar, Chennai

TAMIL NADU
600036
India 
Phone  914422209150  
Fax  04424912085  
Email  r.swaminathan@cancerinstitutewia.org  
 
Source of Monetary or Material Support  
International Agency for Research on Cancer – WHO 
 
Primary Sponsor  
Name  International Agency for Research on Cancer 
Address  150 cours Albert Thomas 69008 
Type of Sponsor  Research institution 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr R Swaminathan  Cancer Institute WIA  Cancer Institute WIA, Dr Krishnamurthy campus, Baghvan Adhinath Jain Complex, Room No: 47, Department of Epidemiology, Biostatistics and Cancer Registry No 38, Sardar patel road, Adyar Chennai 600 036
Chennai
TAMIL NADU 
04422209150
04424912085
r.swaminathan@cancerinstitutewia.org 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee,Cancer Institute (WIA)  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Healthy Human Volunteers  cancer prevention and control 
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Nil  As this is a randomized parallel group trial, each intervention/study arm should be presented separately by clicking on the ADD NEW button for each. Under details please mention the dose, frequency route of administration and total duration of such intervention. No drug is used as Intervention as this is an Implementation research study for a validated early detection for cancer ( Secondary Prevention) This involves the following: Work Package 1 Creating and engaging stake holders team representatives of the target population ( rural and urban men and women) Health Professionals ( Medical & Para medical) Local Body Personnal Work Package 2 Assessing the contextual factors that create barriers for the population to access early detection and treatment services Work package 3 Assessment of capacity of the local health systems catering to cancer early detection and treatment pathway The Intervention strategy will be designed from the inputs gathered from (Work packages 1-3) using PRISM model (practical robust implementation and sustainability) and (RE-AIM) framework. The implementation of intervention will be carried out in one randomly selected block, For Controls Existing standard of acre for early detection and treatment of care Duration: 18 Months This is an implementation research study in public health setting involving the existing cancer screening early detection practices. There is only one intervention group in the study, the intervention strategy will be apart of WP-4 only after completing WP 1-3 and taking the inputs. There is no DRUG uses as part of intervention hence the dose frequency and route of administration does not apply  
Comparator Agent  Nil  Nil 
 
Inclusion Criteria  
Age From  30.00 Year(s)
Age To  59.00 Year(s)
Gender  Both 
Details  All adults in the screening interval of 30-59 years of age in the chosen intervention / control villages will be included in the study.
Subjects with previous history of cancer will be excluded  
 
ExclusionCriteria 
Details  NA 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
A cancer early detection and treatment service delivery model tailored to the local context to scale up coverage for the rural Indian men and women and improve their participation to the entire downstream care continuum.  Baseline Measurement (Start Month-19)
Time Period–6 months
Intervention Strategies(Start Month-24)
Time Period–18 months 
 
Secondary Outcome  
Outcome  TimePoints 
•Following the key principles of implementation research, evaluate feasibility, effectiveness, cost-effectiveness and scalability of interventions of proven efficacy after contextualizing them to the local situation.
• Delivery of a new service model of the early detection multi-cancer intervention to address the socioeconomic and contextual factors
• A toolkit (open on-line) to integrate barriers and facilitators to strengthen the ‘building blocks’ of health systems relevant to secondary prevention of cancers derived from this programme along normative WHO framework: (i) service delivery, (ii) health
workforce, (iii) health information systems, (iv) ensuring quality (v) financing, and (vi) leadership/governance to ensure international relevance and utility 
from recruitment till 18 years 
 
Target Sample Size   Total Sample Size="100000"
Sample Size from India="100000" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   15/10/2022 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="4"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Yet Recruiting 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   Will be decided later, none yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  
Background
Of the 1.3 billion population of India more than 70% live in the rural areas. Cancer has a catastrophic impact on the rural men and women of India, the vast majority of whom are socio-economically disadvantaged with one fourth live below national poverty line. Studies have shown that among the rural population in India expenditure on cancer treatment is among the highest for any disease due to the advanced presentation. The cost for treating advanced and metastatic disease are much higher than early stage disease. Treatment is financed mostly through borrowings, sale of assets and contributions from friends and relatives.

Hypothesis
A strong and responsive cancer health system is necessary to ensure that the screen positive (in presence of a screening programme) and/or symptomatic individuals have access to prompt diagnosis and those detected with cancer have access to appropriate treatment. Rural population in India are socio-economically disadvantaged and vulnerable to huge inequity in cancer care.3 Our hypothesis is that improving their participation to the cancer early detection pathway through careful investigation into the implementation barriers at the levels of individuals, providers and systems to design strategies and policies that are evidence and context-specific based, will lead to better outcomes.

Objectives
General Objective
To design and evaluate a new multi-level strategy, integrated, and contextualised to the local health system, to improve access to the early detection and care continuum for oral, breast and cervical cancers among rural population in India.
Specific Objectives
1) To determine the current health services for early detection of oral, breast and cervical cancer among rural population in India
2) To determine barriers for access to early detection and treatment services for oral, breast and cervical cancer among rural population in India
3) To develop a capacity development response for early detection and treatment of oral, breast and cervical cancer among rural population in India
4) To design and cost an intervention strategy to improve participation of early detection of oral, breast and cervical cancer among rural population in India
5) To implement and evaluate a pilot intervention strategy to improve participation of early detection of oral, breast and cervical cancer among rural population in India
6) To assess readiness and capactiy to sustain and scale up interventions

Research Plan, Methodology and Data
Study settings
We propose to conduct our implementation research study in three (3) different states in India, targeting the rural population in each state. The states were selected not only because of the differences in their population characteristics, but also in their burden of common cancers and variations in the structure and organisation of the health system.
Kerala
The southernmost state of the Indian peninsula with the second lowest poverty index in the country. Here, the health services are much better organized compared to the rest of the country. The state achieved the highest SDG performance score of 70.19 The Thiruvananthapuram PBCR of Kerala reported the second highest (next to Delhi) incidence of cancer in males and females in the Indian mainland (the north-east regional registries have much higher rates) and the lowest incidence of cervical cancer in the country. The state has many features similar to a high resourced setting. However, the selected Palghat district has more disadvantaged rural population and vulnerable populations.
Tamil Nadu
It is also a state in Southern India ranking 10th by the poverty index. The state has well organized health system and ranks high on the SDG performance score (Score 67; rank 4th). Tamil Nadu has the longest running cancer screening programme in India with many components of an organised programme in place. The cancer burden is high with high incidence or oral, breast and cervical cancers. The selected site in the state (Viluppuram district) has predominantly rural population, the population coverage of the state-run screening programme is low and novel initiatives by the Cancer Institute (WIA) are in progress.
Rajasthan
It is northern Indian state that has a large area covered by desert with lot of impoverished rural communities. The state ranks 14th in the poverty index and has one of the lowest SDG performance score in the country. There is no PBCR in the state. The nearest PBCR in Wardha records very high oral and cervical cancer incidence. The Udaipur district of Rajasthan is the home to one of the most impoverished populations in the country. The complex geographic terrain is an additional challenge for the population to access screening and diagnostic services.

Methodology
The objectives of the study will be delivered through six (6) sequential but integrated work packages(WP).

WP 1. Creating & engaging a stakeholder’s team
(Lead: RTI) Start date: M1; End date: M48
Cancer screening programmes are complex interventions involving different target groups, health professionals, civil society and policy makers. Implementing new interventions requires reorganizing health services to be more accessible as well as the roles of many health professionals, including re-allocating resources within the public health sector. Such complex cascade of effects and interests needs a careful analysis of how stakeholders from micro-, meso, and macro- levels can be affected by interventions and how they can affect the interventions. Moreover, involving representatives of the target population (rural men and women) as stakeholders and participants in the implementation of the tailored early detection strategies will allow us to consider context specific challenges.
We will create a team of stakeholders through an iterative stakeholder mapping and formally engage them during planning, implementation and evaluation process. As the first step we will identify a list of stakeholders, classifying them according to how they can be affected by actions and how they can affect the actions. In the next step, the stakeholders can incorporate in the list with other macro (policy makers, programme coordinators, Superintendents of district hospital and oncology centres, patients) and meso (service providers, civil society, special interest groups, CHWs) stakeholders that may not have been initially considered.
Competent stakeholders at micro (community) level will be selected by the key stakeholders from the meso level who act as ‘gate-keepers’. The micro level stakeholders will be encouraged to bring additional stakeholders specially from the rural community as needed in the ‘snowball sampling’ process.
The stakeholders will be consulted in workshops, virtual meetings and informal group discussions. Power relations in group interaction will be addressed carefully in settings where some participants have prior experience in engaging in academic policy and practice discussions and others not. A tool for stakeholder engagement will be developed to collect, collate and analyze the inputs from the stakeholders in planning, implementing and evaluating the intervention strategies.

WP 2. Assessing the contextual factors that create barriers for the population to access early detection and treatment services
(Lead: RTI) Start date: M1; End date: M12
This WP focuses to understand the context-specific barriers and challenges for rural men and women to access the cancer early detection care continuum we will conduct a mixed-methodology study. In this WP we will examine the entire pathway of early detection – community mobilization, access to screening and diagnostic services, navigating the systems. We will assess the contextual factors at individual, provider and systems levels using the Rapid Assessment and Response Evaluation (RARE) methodology, which is a rapid ethnographic assessment to elicit beliefs and perceptions around health prevention and treatment. We will use the following components of the RARE technique to study the knowledge, attitude, perceptions and beliefs of the target population: a) Key informant interview; b) Focus group discussions (FGDs) and c) Client questionnaire survey.
At each study site (Palghat in Kerala, Viluppuram in Tamil Nadu and Udaipur in Rajasthan) we will identify a rural block where the pilot intervention will be implemented (discussed later). The contextual factors and barrier assessment study will be implemented in the pilot blocks.
Sample Size Calculation
WP2 involves a population survey. A multistage cluster sampling design will be followed to identify the participants to the surveys with the villages being the primary sampling units (PSU) and the households being the secondary sampling units (SSU). We expect 50% of the participants to have knowledge and understanding about the common symptoms of cancers and assume a 10% precision with 96% confidence. The survey will require to be conducted in total 28 villages in the block and in each village approximately 15 households will be visited to interview men and women in the target age.25 The number of participants required for the hospital-based survey in WP 2 has been empirically decided. The protocol to be designed in WP 4 may require sample size estimation depending on the interventions selected to be piloted and evaluated.

The assessment will involve the following tasks at each study site:

a) Questionnaire survey will be conducted among the men and women aged 30-65 years to understand their knowledge and understanding of common symptoms of cancer, health seeking behaviour, their choices related to screening and diagnostic services, myths and beliefs, access to the health facilities, perceptions of staff attitude expenses on treatment etc. The survey will be conducted in the intervention block identified in each target state. To get adequate samples, 28 villages in each block and 15 households in each village will be surveyed.
b) FGDs involving rural men and women will be held at each site, each group size not exceeding 8 persons. The focus groups will be 30-65 year old males only, 30-65 year old females only and males and females (30-65 years of age) combined. The FGDs will explore barriers to accessing screening and early detection services and factors that might affect uptake of a referral. We will also explore views on potential solutions/interventions. The participants for the FGDs will be identified from the different villages by the local community leaders and/or the CHWs who are members of the stakeholder’s team
c) FGDs with CHWs (one FGD at each site, each group size not to exceed 6-8 participants) and frontline healthcare providers (two FGDs at each site, each group size not to exceed 6-8 participants) such as local general practitioners, nurses and physicians from the health sub- centers, primary health centers and district hospitals. The participants will be identified through the local stakeholder’s team. We will document their knowledge and understanding of common symptoms of cancer, the screening guidelines, referral practices, the advice they generally give and the compliance to such advice. We will learn from the CHWs about their current roles and responsibilities, working patterns, challenges they perceive to provide home based screening services, training needs, capacity to navigate patients etc.
d) Key informant interviews will be held with the head of the panchayat (rural administrative body), chief medical officer of the district, coordinator of cancer screening programme of the state and the Directors/Superintendent of the local tertiary care facilities. Through these interviews we will document the status of implementation of the cancer screening programme, the barriers for the rural men and women to participate, the future plans for improvement, the challenges of modifying the existing system to introduce new concepts like CHW driven early detection at home or using a navigational service etc. We will also document current practices of symptomatic men and women to receive early detection services including treatment of cancer and the common barriers they may face in accessing the services.
e) Questionnaire survey will be administered to breast, cervical and oral cancer patients in the tertiary care centers that receive referrals from the district. We will conduct these surveys at the leading tertiary care center(s) that are the primary referral centers for the cancer patients detected in the rural blocks to be included in the pilot intervention. At each of the three study sites we will select 100 patients (number empirically decided), registered at the oncology hospital(s) with a confirmed diagnosis of oral, breast or cervical cancer, for the interviews. The cases should be resident of the district or surrounding rural areas and the consecutive consenting patients will be selected at the hospital. Using a structured questionnaire, we will document their journey from disease onset to the final diagnosis. This will allow us to estimate the access (or systems) and diagnostic delays as well as the possible reasons for such delays.

WP 3. Assessment of capacity of the local health systems catering to cancer early detection and treatment pathway
(Lead: IARC) Start date: M1; End date: M12
The capacity assessment will be performed in the three target districts (Palghat, Kanyakumari and Udaipur). We will use the rapid capacity assessment tools and methodology developed by the United Nations Development Fund (UNDP) as these are tailored to assess programmes run by the ministry of health and participatory in nature. In short, we will perform the capacity assessment according to the following steps:20
ï‚· Engage the relevant stakeholders and plan the capacity assessment jointly.
ï‚· List the scope of the capacities to be assessed across the building blocks of health system (e.g. Governance, leadership and programme management, service delivery and available technologies).
ï‚· Review and capture existing documentary evidence of current capacity from previous assessments, strategy documents and audit reports.
ï‚· Collect data and information using a landscape survey questionnaire. This will be supported by the key informant interviews and focus group discussions involving the clinic managers, nursing supervisors, hospital superintendents, CHWs, nurses, physicians, specialists (surgeons, gynecologists and ENT specialists) and oncologists.
ï‚· Perform site visits to selected service delivery points and use a site assessment form to document the findings.
ï‚· Review and confirm findings with the stakeholders; compare the desired capacities against existing capacities to determine the level of effort required to bridge the gap between them.
 Formulate a capacity development response and share it with our stakeholders’ team for final feedback.

WP 4. Designing and costing a multi-level intervention strategy to improve participation of the rural populations to early detection care continuum
(Lead: KCL) Start date: M12; End date: M18
We will use the Practical, Robust Implementation and Sustainability Model (PRISM)21 to design a sustainable and contextualized multi-level intervention strategy and evaluate this using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. The model considers how the external environment, intervention design, implementation infrastructure and adopting organization (with special emphasis on the health care providers) and its patients influence programme implementation and success. Further, we will conduct an ingredients-based costing of the intervention strategy that will inform district-level budget planning.

The findings of the WP2, WP3 and WP4 will be synthesized and triangulated to feed the ‘intervention’ domain of the PRISM and will be presented to the stakeholders’ team workshop. In collaboration with the stakeholders we will identify the intervention elements that are ‘best fit’ from the perspectives of the organization and populations/patients to be targeted. The interventions may be different to suit the local context in the three target districts and will be selected from a ‘menu’ of options. The ‘menu’ will incorporate CHW-driven home based early detection and navigation approach proved to be very effective in a randomized trial in Bangladesh and our own community-based study, provided the stakeholders conceive this as useful.22,23

Other interventions may be switching VIA-based cervical cancer screening to HPV detection -based screening, shifting from systematic CBE screening to ‘early diagnosis’ approach, training of frontline health providers (CHWs, nurses, clinicians at primary and secondary levels) in detecting the ‘warning’ symptoms of common cancers, performing appropriate clinical examination and referring suspected cases for further investigations. Develop a setting-appropriate referral guideline from primary care to secondary care and finally to oncology centers utilizing the online portal developed by the National Cancer Grid (https://ncgeducation.in) for training, navigating the men and women who are screen-positive and/or have ‘warning’ symptoms through diagnostic and treatment pathway are likely to be included in the ‘menu’. Navigation strategy may be selected from various options e.g. navigation by CHWs or a designated nurse at the clinics, telephone helplines run by the cancer survivors. Thus, the intervention package will include strategies considered by the stakeholders as locally adaptable, and feasible. Once the interventions are identified, the WP will develop the protocol and other toolkits that will be necessary for piloting and evaluating the interventions.

This WP will include a costing toolkit that allows for district-level ingredients-based costing of the intervention strategy. The toolkit will be modeled after the Global HEARTS costing tool developed by RTI International and provided to WHO and its partners to assess the district-level costs of delivering the Global HEARTS protocol in multiple countries. Costs include human resources and requisite training, equipment and supplies, the depreciated value of structures and vehicles, and a cost estimate of the contribution of other health system components. Costs will be collected during the rollout of the pilot phase of intervention and then the cost expansion path will be estimated based on the scale-up scenario described in WP6. Indicators of affordability at the district and state levels will be provided based on the variables that determine health budgets for the relevant jurisdictions. These variables may include catchment population, disease burden in the population, number of health facilities, level of infrastructure at health facilities, and human resource capacity.

WP5. Pilot implementation and evaluation of intervention strategies
(Lead: KCL) Start date: M19; End date: M44
The implementation of the intervention strategies developed in cooperation with the stakeholders will be nested into the existing public health services in each selected district (Palghat, Kanyakumari and Udaipur). In each district we will choose one rural block (population size ranges between 250,000 to 500,000) for piloting the interventions. We will select a ‘control’ block that matches the population of the intervention block and is at a sufficient distance to avoid ‘contamination’. The population of the control block will only receive the local ‘standard of care’ in cancer early detection. There will be a baseline run-in period (over six months, starting at month 19) of data capture in both intervention and control blocks before intervention with data capture (without any intervention) continuing in the control block for total two years till month 42. The intervention strategies will be rolled out in the intervention block starting at month 24 and ending after 18 months at month 42. This will allow us to understand any secular trends in both blocks (i.e. initial 6 months data will show if things were already changing on the ground). Data collected from initiation of interventions will show whether any baseline secular trends have changed in the intervention block compared to the control block (before and after design). In addition, the costing protocol will be developed and tested during pilot implementation of the intervention strategies and adapted as needed to the existing public health infrastructure and local costs prevailing in each of the selected districts in the three States. The adaptation will produce a custom costing tool for on-going use in each district that will support local officials for budgeting purposes. We will define and measure certain output indicators (direct products of activities and will include types, levels and targets of services to be delivered) and SMART outcome indicators (specific changes in participants’ behavior, health providers knowledge and skills, access and participation to cancer early detection and treatment) in the intervention blocks. Similar indicators measured in the control blocks and the pre-intervention period will allow us to correlate between the interventions and their impact.

WP6. Assessment of settings readiness and capacity to sustain and scale up interventions
(Lead: IARC) Start date: M37; End date: M46
We will use the validated Intervention Scalability Assessment Tool (ISAT), which is designed to assist practitioners, policy makers, programme managers and researchers to determine the scalability of a discrete health programme or intervention.24 The tool consists of three sections and each section has multiple domains:
ï‚· Part A: consists of 5 domains: 1) the problem; 2) the intervention; 3) strategic and political context; 4) evidence of effectiveness; and 5) intervention costs and benefits.
ï‚· Part B: consists of 5 domains: 1) fidelity and adaptation; 2) reach and acceptability; 3) delivery setting and workforce; 4) implementation infrastructure; and 5) sustainability.
ï‚· Part C: summarizes all the information gathered to facilitate the process of making a recommendation on scalability.

We will synthesize information (based on the data collected from the pilot, other WPs as well as from local practice-based information) including thematic analysis interviews at three sites (n=20) related to the different domains and present them to the stakeholder, based on which the stakeholders will respond. The responses will generate scores that will be put in a matrix, which will allow us to understand the scalability of different interventions. Based on the results of the assessments of strengths, weaknesses, opportunities and threats (SWOT) of the proposed model of intervention in light of sustainability and scalability will be listed for each study site as well as visual representation of scores across each domain

Data management and study monitoring
No patient identifiable data will be housed in UK but under custodianship of local PIs. All other data for purposes of health systems and economic analysis will be under custodianship of Co-PIs Sullivan and Basu with designated DMP in compliance with local data management policy(s) (http://www.kcl.ac.uk/library/researchsupport/research-data- management/index.aspx), and data security and sharing policy.

Data at the study sites will be recorded on paper questionnaires; CRFs and laboratory report forms and subsequently entered into the data capture tools by a data entry clerk or laboratory staff. Study de-identified data will be collected and managed using REDCap electronic data capture tools (https://projectredcap.org/) hosted and stored at IARC and will be shared with KCL through a data transfer agreement. REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies.

We will use a set of comprehensive input measures, milestones and outcome measures and develop and implement a dedicated information system to monitor the trials at each site. Milestones will reflect the accomplishment of various activities in a timely fashion and will be monitored. Site visits by the study monitor from IARC will be arranged at study initiation and once every six months.

Good clinical practices and Good Laboratory Practices will be implemented. Standardised questionnaires and Standard Operating Procedures (SOP) will be developed for each of the procedures to collect data and adherence to it will be monitored on a regular basis. Data entry and management SOPs will also be used. The data manager at IARC will routinely conduct pre- defined quality control checks on the data and raise queries for resolution by the study team. Only fully anonymised data will be received, stored and handled at IARC. Data will be stored in a central secure server localized at IT department of IARC. Data will be archived in IARC to allow retrieval for any scientific or regulatory external audits. No patient identifiable data will be housed in UK but under custodianship of local PIs. All other data for purposes of health systems and economic analysis will be under custodianship of Co-PIs Sullivan and Basu with designated DMP in compliance with local data management policy(s) (http://www.kcl.ac.uk/library/researchsupport/research-data- management/index.aspx), and data security and sharing policy.

Study Impact and Dissemination Plan
Expected Impact
Deliver a new model for cancer early detection for India
ï‚· We will have co-created, through co-development framework, a cancer early detection and treatment service delivery model tailored to the local context to scale up coverage for the rural Indian men and women and improve their participation to the entire downstream care continuum.
Create a new framework/model for implementation research for early detection
ï‚· Following the key principles of implementation research we will evaluate feasibility, effectiveness, cost-effectiveness and scalability of interventions of proven efficacy after contextualizing them to the local situation.
ï‚· We will use some tools used in other health research contexts (e.g. UNDP capacity assessment or ISAT tools) in implementation research to find the best solutions to improve cancer early detection for vulnerable populations in India. The same framework/model will be made available to greater scientific community for future use.
Deliver a new service model of the early detection multi-cancer intervention to address the socioeconomic and contextual factors
ï‚· We will deliver a service delivery model customized and contextualized to our partners local needs in the three different sites.
ï‚· Our nested studies approach will provide other State and Federal policymakers with the evidence to scale up the intervention at national and international levels.
ï‚· Involving the policy-makers in each step of planning, implementation and evaluation will ensure their buy-in of the interventions that we identify as feasible, effective & cost-effective.
Create a suite of indicators and issues for national and international utilisation
 Toolkit (open on-line) to integrate barriers and facilitators to strengthen the ‘building blocks’ of health systems relevant to secondary prevention of cancers derived from this programme along normative WHO framework: (i) service delivery, (ii) health workforce, (iii) health information systems, (iv) ensuring quality (v) financing, and (vi) leadership/governance to ensure international relevance and utility.
Align with the priorities in national/regional cancer control programme across India
ï‚· Government of India strongly supported cervical cancer elimination agenda at WHO Executive Board meeting (January 2020) and is keen to improve the entire screening programme. The Prime Minister himself is a champion of NCD prevention. The Ministry of Health will be receptive to evidence/suggestions on improving reach and impact of the program.
ï‚· Active participation of the local policymakers, advisors and program managers will ensure buy in of the successful interventions.
New pathway to embed this intervention into local, regional and/or global health policy and practice.
 The co-developed interventions will be a new strategy to improve access for vulnerable populations. A generic template for integration will be created and dissemination through partners (see above) to aid other countries. We will ensure to meet broader stakeholders’ needs to adopt such interventions at national scale through the NCG and internationally though dissemination partners, including WHO and UICC
Budget Impact assessment data and generic template
ï‚· Health economic data captured will be used to ensure the programme is economically viable and sustainable. We will create a costing tool that can serve as a template for conducting such studies for context specific implementation assessments in other contexts.

Exploitation and dissemination
Building on the long term collaboration between Institute of Cancer Policy KCL (Sullivan) and the team at IDSI network (https://idsihealth.org/), specifically the India hub, this implementation science project will be a core part of IDSI ongoing cancer economic and systems that is fully funded by the Bill & Melinda Gates Foundation. This will ensure independent economic and systems analysis that is closely linked to policy-making both in India and across other LMIC settings. Along with our open access dissemination partners – eCancer (https://ecancer.org/en/) – we will have major on-line dissemination platforms for India and face-to face and webinar programmes hosted by IDSI-eCancer with the major partners in the ACCI consortium.

Given the increasing cancer incidence in LMICs, especially India, there is need to establish frugal delivery systems on the back of a centralized knowledge architecture. There is also an acute need to improve medical outcomes given 5 year survival rates for all cancer in India are 50-60% lower than the USA.

ACCI is expected to build a robust knowledge system, however, these will have to be accompanied by delivery platforms where the knowledge so established is tried out with a degree of consistency in an iterative manner. Such delivery systems built on a distributed hierarchy or care will also need to be financially sustainable. ACCI (KCL lead) will work with social entrepreneurship partners (Karkinos: Venkataramanan Ramachandran) to achieve this through a periodic multi-stakeholder engagement between policy makers in government, regulators, public health professions and members of civil society in the form of workshops, seminars, communication as well as advocacy at the highest levels, which will help in keeping the attention of key stakeholders. We will also seek patient involvement and guidance until completion of the programme and dissemination of results. We will explore wider methods of communication to patients, carers and the community at large by publicising this programme extensively through multiple avenues involving social media, interactive forums, IAPG, and wide distribution of resources developed during the programme, thereby ensuring greater involvement of patients and public.

According to KCL and IARC’s ‘open science’ policy, we will create ‘open access’ to research tools and findings to ensure that key stakeholders or any other interested constituencies are able to access, use and benefit from the work. By making the protocol, data tools and publications openly accessible through our websites, we will ensure greater visibility and impact of the research.

Research Team and Project Governance
Study Team and Research Environment
Our programme brings together outstanding international institutions, researchers, public health programme leaders and advocates for cancer patients. The major partners in this bid –King’s College London (KCL), International Agency for Research on Cancer (IARC, WHO), RTI International, National Cancer Grid of India, Cochin Cancer Research Centre, Cancer Institute (W.I.A), American Indian Institute of Medical Sciences, GBH Memorial Cancer Hospital and Kingston, Canada have a long standing and deep partnerships across research, capacity and capability building and service delivery.

King’s College London has worked closely with the National Cancer Grid of India across a range of major programmes over the last seven years including high level Lancet Oncology commissions, supporting the development of research into cancer health economics and policy. King’s College London under the stewardship of Professor Purushotham, has partnered with the Tata Trusts in India over the last 3 years to develop a transformational cancer care programme to deliver high quality, accessible and affordable cancer care to a population of 70 million people across 6 states.

The focus of the research activities of Screening Group at IARC is early detection and primary prevention of common cancers through interventions that are relevant to LMICs. The group contributes scientific evidence to support development of resource-appropriate policies and engages substantially in developing training resources and educational programmes. IARC has successfully implemented major field studies on cancer early detection in the three target states in collaboration with the Indian partners. IARC will coordinate between the Indian sites because of their long history of collaboration with them and experience in successfully conducting trials in India.

RTI International has extensive experience of developing and promoting effective and cost-effective strategies that reduce the burden of cancer. RTI’s work includes determining cost-effectiveness of cancer prevention, screening, and treatment programs; conducting research to understand local contexts and how it can be used to inform the development of cancer programs; and implementing strategies to promote health literacy about cancer. RTI International India will lead the stakeholder engagement activity, and has considerable experience of involving patients, carers and lay members of the public in different research studies in defining the research question, designing the research, developing patient facing documents, monitoring and disseminating progress. The stakeholders will include, healthcare professionals, civil society representatives, policy makers, and patients.

We strongly feel that the inclusion of patient perspectives in our stakeholder team would be integral during the planning, implementation, and evaluation phases of the programme. Patients have multiple ongoing interactions with the health system over long periods of time and can provide rapid review and feedback to research team on comprehensibility, terminology used, and patient acceptability of aspects of study design, and also review draft patient information materials.

For the same, we will be engaging with the Indian Alliance of Patient Groups (IAPG). IAPG is a cross-disease alliance of 42 different patient groups, set up with the objective to support the cause of patients and highlighting their needs. It focuses on bringing patient voices to the centre of the conversation. IAPG is actively involved in the drafting of several policies (Rare Diseases, Dementia, and Noncommunicable Diseases) and is connected to policy makers and patient groups across the country.
Dr Ratna Devi of Indian Alliance of Patient Groups and Dr Julie Torode of UICC will represent the national and international civil society organizations. At each study site, we have already engaged with the key functionaries of the Ministry of Health and ensured their support. Dr R Sankaranarayanan, the current Chief Advisor to the Government of Kerala and Tamil Nadu on NCD and also a Senior Visiting Scientist at IARC will play a key role in coordinating with the Ministries of Health. Dr CS Pramesh, Director of Tata Memorial Hospital, Mumbai and Director of National Cancer Grid will lead the training components and bring in his expertise in standardizing education in oncology care in India.

Project Governance
The overall project coordination will be carried out through the Management Board, which will be chaired by Professor Purushotham and comprise of all principal Investigators. Management Board meetings will be e-convened monthly to review deliverables, progress, communications, policy engagement and trouble shoot issues. Junior faculty will join these meetings after senior leadership’s session. This is essential to build capacity into junior faculty to high level programme deliberations and management. The leads for the WP will set their own timetable and report directly to the Board. Face to face meetings of all PIs and key collaborators will take place once a year rotating between Indian centres. Stakeholder engagement will be multi-level and described in further details in WP1. Additional updates webinars will be regularly scheduled in to allow in depth regular engagement with study sites.

An International Monitoring Committee will be constituted drawing high level expertise outside the partners to this programme. Key SOP including risk registers, open publication of minutes, etc (see r4hc-mena.org for processes that will be put in place) will ensure full and transparent oversight and governance of programme faculty. The diverse healthcare landscape across India is deeply understood by major partners IARC, NCG and RTI and has been well mapped out for stakeholders through previous work. IARC will support NCG to create a distance learning and tele-mentoring program for continued capacity building of the frontline health providers participating in the project, which will enable learnings to be shared with wider National Cancer Grid of India.
 
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