BMJ Open · Achutha Menon Centre for Health Science Studies D'Esposito, Fabrizio; University of...

For peer review only

Cluster randomised feasibility trial to improve the Control of

Hypertension In Rural India (CHIRI): a study protocol

Journal: BMJ Open

Manuscript ID bmjopen-2016-012404

Article Type: Protocol

Date Submitted by the Author: 23-Apr-2016

Complete List of Authors: Riddell, Michaela; Monash University, Department of Medicine, School of Clinical Sciences Joshi, Rohina; University of Sydney, The George Institute for Global Health Oldenburg, Brian; University of Melbourne School of Population and Global Health Chow, Clara; University of Sydney, The George Institute for Global Health; Children\'s Hospital at Westmead, Department of Cardiology Thankappan, K; Sree Chitra Tirunal Institute for Medical Science and

Technology, Achutha Menon Centre for Health Science Studies Mahal, Ajay; Monash University, School of Public Health and Preventative Medicine; University of Melbourne School of Population and Global Health, Nossal Institute for Global Health THOMAS, NIHAL; CHRISTIAN MEDICAL COLLEGE, Department of Endocrinology, Diabetes & Metabolism Srikanth, Velandai; Monash University, School of Clinical Sciences at Monash Health Evans, Roger; Monash University, Cardiovascular Disease Program, Biosciences Discovery Institute and Department of Physiology Kalyanram, Kartik; Rishi Valley Rural Health Centre

Kartik, Kamakshi; Rishi Valley Rural Health Centre Maulik, Pallab; The George Institute for Global Health; University of Oxford, George Institute for Global Health Arabshahi, Simin; Monash University, Department of Medicine, School of Clinical Sciences at Monash Health Varma, R; Sree Chitra Tirunal Institute for Medical Science and Technology, Achutha Menon Centre for Health Science Studies Gugilla, Rama; The George Institute for Global Health Suresh, Oduru; Monash University, Department of Medicine, School of Clinical Sciences; Rishi Valley Rural Health Centre Mini, GK; Sree Chitra Tirunal Institute for Medical Science and Technology, Achutha Menon Centre for Health Science Studies

D'Esposito, Fabrizio; University of Melbourne School of Population and Global Health, Centre for Health Equity Sathish, Thirunavukkarasu; University of Melbourne School of Population and Global Health, Centre for Health Equity Mohammed, Alim; The George institute for Global Health, India Thrift, Amanda; Monash University, School of Clinical Sciences at Monash Health

<b>Primary Subject Heading</b>:

Global health

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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Secondary Subject Heading: Cardiovascular medicine

Keywords: Hypertension < CARDIOLOGY, prevalence, clinical trial, EDUCATION & TRAINING (see Medical Education & Training), India, self-management

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Cluster randomised feasibility trial to improve the Control of Hypertension In Rural India

(CHIRI): a study protocol

Michaela A Riddell1, Rohina Joshi

2 , Brian Oldenburg

3, Clara Chow

2,4, KR Thankappan

5, Ajay

Mahal6,7

, Nihal Thomas8, Velandai K Srikanth

1, Roger G. Evans

9, Kartik Kalyanram

10,

Kamakshi Kartik10

, Pallab K Maulik11,12

, Simin Arabshahi1, RP Varma

5, Rama K Guggilla

11,

Oduru Suresh2,10

, GK Mini5, Fabrizio D’Esposito

3, Thirunavukkarasu Sathish

3, Mohammed

Alim11

, Amanda G Thrift1*

1 School of Clinical Sciences at Monash Health, Monash University, Melbourne Australia

2 The George Institute for Global Health, University of Sydney, Australia

3Melbourne School of Population and Global Health, University of Melbourne, Australia

4 Department of Cardiology, Westmead Hospital, Sydney, Australia

5 Achutha Menon Centre for Health Science Studies, Sree Chitra Tirunal Institute for Medical

Sciences and Technology, Trivandrum, Kerala, India

6 School of Public Health and Preventative Medicine, Monash University, Melbourne

Australia

7Nossal Institute for Global Health, Melbourne School of Population and Global Health,

University of Melbourne, Australia

8 Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore,

Tamil Nadu, India

9 Cardiovascular Disease Program, Biosciences Discovery Institute and Department of

Physiology, Monash University, Melbourne, Australia

10 Rishi Valley Rural Health Centre, Chittoor District, Andhra Pradesh, India

11George Institute for Global Health, Hyderabad, Telangana, India

12George Institute for Global Health - Oxford University, Oxford, UK

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*Corresponding author:

Professor Amanda Thrift, Principal Investigator, School of Clinical Sciences at Monash Health,

Epidemiology and Prevention Unit, Level 5, Block E Monash Medical Centre, Monash

University, Melbourne AUSTRALIA

Email: [email protected]

Tel: +613-8572-2656

Keywords : Hypertension, prevalence, clinical trial, education, India, self-management

Word Count : 6,267 (includes acknowledgements and trial registration)

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ABSTRACT:

Introduction:

Hypertension is emerging in rural populations of India, with about 25% of adults having

hypertension and less than one fifth of those having their blood pressure under control.

Barriers to diagnosis and treatment of hypertension may differ according to the stage of

epidemiological transition of the region. We aim to estimate the prevalence, awareness,

treatment and control of hypertension; and evaluate the feasibility of a community based

intervention to improve control of hypertension.

Methods and analysis:

This study, conducted in three diverse rural regions in India, includes four main activities: (1)

Approximately 14,500 participants are assessed for risk factors, quality of life,

socioeconomic position, and barriers to changes in alcohol and tobacco behaviour; (2) focus

group discussions with individuals with hypertension and in-depth interviews with health

care providers, to identify barriers to control of hypertension; (3) a medicines-availability

survey to determine the availability, affordability and accessibility of medicines; and (4) an

intervention, comprising peer group based education and support for individuals with

hypertension, for self-management of blood pressure. Communities are randomly allocated

to receive the intervention, provided by village level Accredited Social Health Activists

(ASHAs). Changes in knowledge of hypertension and risk factors, and clinical and

anthropometric measures, are assessed. Evaluation of the intervention by participants

provides insight into perceptions of education and support of self-management delivered by

the ASHAs.

Ethics and Dissemination:

Approval for the overall study was obtained from the Health Ministry’s Screening

Committee, Ministry of Health and Family Welfare (Government of India), governing

institutional review boards at each site, and Monash University. In addition to publication in

peer-reviewed articles, results will be shared with federal, state and local government

health officers, local health care providers and communities.

Trial Registration:

The feasibility trial is registered with the Clinical Trials Registry - India (CTRI)

CTRI/2016/02/006678 (25/02/2016).

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INTRODUCTION

Hypertension is the leading contributor to the global burden of disease and mortality.[1] In

2000, approximately 120 million Indians had high blood pressure and this figure is expected

to increase to about 215 million by 2025.[2] According to a recent systematic review of

hypertension in India overall prevalence of hypertension was estimated to be nearly 30%,

with a significant difference in the overall pooled prevalence between urban (33.8% (95%

Confidence Interval (CI): 29.7, 37.8), and rural (27.6% (95%CI: 23.2, 32.0) populations

nationally. This disparity was particularly marked in West India (pooled prevalence urban

(35.8% (95% CI 35.2, 36.5), and rural (18.1% (95%CI: 16.9, 19.2)).[3] When limited to South

India the pooled estimates, using random effect analysis, for the prevalence of hypertension

in rural and urban populations were not significantly different (urban: 31.5% (95%CI, 23.6,

39.5) vs rural: 28.3% (95%CI, 21.4, 35.1), p = 0.62).[3]

Approximately one quarter of the people with a diagnosis of hypertension are receiving

treatment and, of this population, only approximately 30% has their blood pressure (BP)

within the therapeutic target [4 5] (systolic BP (SBP) <140 mmHg and diastolic BP (DBP) <90

mmHg).[6]

There are many different barriers to the diagnosis and treatment of hypertension in both

urban and rural regions. These barriers likely comprise proximate determinants [7] and

operate at both the individual and systems level.[8] For example, awareness (diagnosis) of

hypertension at the individual level may be influenced by distance to, and utilisation of,

health services, physical inactivity and social factors.[9] System level factors, which may

influence awareness of hypertension, include the knowledge of risk factors by health care

workers, availability of equipment for measuring blood pressure, and quality, availability

and expertise of health care providers. Treatment of hypertension is influenced by age,

distance to health care [10] and socioeconomic position (SEP).[11 12] At the system level,

treatment may be influenced by knowledge and implementation of current treatment

initiation guidelines and availability of medicines.[13] Control of hypertension is likely

influenced individually by adherence to medication, SEP, health literacy and understanding

of chronic disease and risk factors for chronic disease such as physical activity and tobacco

use.[10-12 14] Within health systems, control of hypertension may be influenced by

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understanding of treatment guidelines, availability of medication, and capacity to monitor

and follow up patients.[13]

There is also some emerging evidence that system and individual level barriers may vary

according to the stage of epidemiological, demographic and economic transition of different

populations.[7 15] For example, as the disease patterns in the population change rapidly,

training of the health workforce may not be adequately up-to-date and basic diagnostic

tools (such as BP machines) may be lacking. In regions where the demographic and

economic transition is more advanced, there is a greater prevalence of hypertension and

thus a greater awareness of hypertension-related factors such as obesity and physical

inactivity.[16] In disadvantaged and poverty-stricken communities, where the population

has not yet been exposed to economic development, the epidemiological transition is still in

its early stages.

Disadvantaged communities still comprise the largest proportion of the population in

resource poor countries, but little is known about the awareness of hypertension or of the

individual and system level barriers to its diagnosis and treatment in these settings. An

improved understanding of the awareness of hypertension in such disparate settings and

the barriers to prevention, diagnosis and treatment will provide the critical knowledge base

needed to overcome these barriers. The aims of this research are, within three diverse rural

regions, to (i) estimate the prevalence, awareness, treatment and control of hypertension;

(ii) use these baseline data to develop strategies to better manage hypertension in rural

communities in India; and (iii) evaluate the feasibility of a community-based intervention to

improve self-management and control of hypertension.

The research protocol described herein comprises two phases in each of the three settings,

with phase 1 having three parts:

Phase 1: Baseline assessment

a. A baseline cross-sectional study to obtain information about the prevalence,

awareness, treatment and control of hypertension.

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b. Qualitative studies, comprising focus group discussions among individuals with

hypertension and in-depth interviews with health care providers, to identify individual

and system level barriers to control of hypertension.

c. A medicines-availability survey to determine the availability, affordability and

accessibility of medicines used for treatment of hypertension, type 2 diabetes mellitus

and secondary prevention of cardiovascular diseases.

Phase 2: A feasibility study of an intervention to improve control of hypertension, developed

based on the findings of the cross-sectional survey and qualitative studies. The intervention

has two basic components: a) peer group based education and support for individuals with

hypertension for self-management of blood pressure; and b) health services and workforce

strengthening.

HYPOTHESES

We hypothesise that:

1. Knowledge/awareness of the presence of hypertension and about risk factors associated

with hypertension is greater in the late transition region than in the early transition

region.

2. Prior BP measurement is less common in the early transition region (Rishi Valley) than in

the late (Trivandrum) and medium transition region (West Godavari).

3. In those previously identified as having hypertension, costs of treatment are the greatest

barrier to ongoing management of hypertension in all settings.

4. Poor management of hypertension is more common in women, people living below the

poverty line, and in those who did not finish high school.

5. High salt intake is a major risk factor for hypertension in both men and women in the

late transition region, but its effect is limited to men in the early transition setting.

6. A community based peer group education and self-management programme conducted

by ASHA is feasible.

METHODS AND ANALYSIS

Setting

The study is being conducted in three diverse rural regions in Southern India, each of which

is at a different stage of economic and demographic transition: Trivandrum in Kerala, the

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West Godavari District in Northern Andhra Pradesh (AP) and the Rishi Valley region in

Southern AP (see Supplementary Figure 1).

Trivandrum, Kerala (late transition): Kerala is the most advanced state in demographic and

epidemiological transition in India.[17] Life expectancy is 76.4 years[18] and literacy is

93.9%.[19] Approximately half of the population in the state resides in non-urban areas.[20]

Changes in cultivation patterns from food crops to more profitable cash crops and large

scale international migration has rendered Kerala both a wealthier and a less agrarian state

than the rest of India.[18 21]

West Godavari, AP (medium transition): The Western Godavari study region comprises 897

villages. Life expectancy in Andhra Pradesh in 2001-6 was 62.8 years for men and 65 years

for females.[22] In 2011 approximately 75% of the population in West Godavari was literate,

and the majority of the residents (79.5%) lived in rural areas.[23]

Rishi Valley, AP (early transition): This rural site is located in the Kurabalakota Mandal, which

contains seven villages, in the Chittoor District near the South Western border of AP.

Approximately 38,000 residents in Kurabalakota Mandal reside in 221 hamlets

(habitations/sub-villages). Hamlets are the smallest administrative geographic units in this

region. The population of this Mandal are largely subsistence farmers and are economically

disadvantaged with an average monthly household income well below the global standard

for poverty. Approximately half the population in this region is estimated to have no formal

schooling.[24]

Study design/sampling frame

Wards/villages/hamlets of a larger mandal (also known as taluk), were identified as the

primary sampling unit (PSU). At each study site these PSUs were then randomly selected for

inclusion in the cross-sectional survey (Phase 1 of the study, Figure 1) using computer-

generated random numbers. For Trivandrum the PSU is wards, for West Godavari the PSU is

villages and for the Rishi Valley site the PSU is hamlets (habitations) (see supplementary

Figure 2A, 2B and 2C for site specific sampling frames).

1a: Baseline cross-sectional survey

A cross-sectional survey was initially conducted to quantify the burden and awareness of

hypertension and examine how the barriers to diagnosis and management differ between

settings. Recruitment for this study commenced in January 2014 and was completed in

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December 2015. Approximately 14,500 adults living in the study areas have been selected to

provide data for the baseline survey. The role of gender, socioeconomic deprivation, and

education on the diagnosis and management of hypertension in each of the three rural

areas is being explored. The data have been used to design the intervention component of

the study.

Recruitment to cross-sectional survey

Population censuses (specifically completed for this study or existing polling booth registers)

at each site were used to randomly select potential participants. In Trivandrum and West

Godavari sampling was stratified by age and sex using this approach. However, due to

structural factors related to distance between hamlets and demography, this was not

feasible in the Rishi Valley region. Residents of the PSU over the age of 18 years were

eligible for recruitment to the cross-sectional survey.

Trivandrum: Among the 14 districts in Kerala, Trivandrum district was selected based on its

proximity to the collaborating institute (Sree Chitra Tirunal Institute for Medical Sciences

and Technology). Chirayinkizhu taluk was selected randomly from the four taluks in

Trivandrum district. Of the 22 Panchayats (local administrative body in rural areas) within

Chirayinkizhu taluk, ten were randomly selected. From each of the selected Panchayats one

ward (the smallest geographic unit of a Panchayat) was randomly selected. In each ward,

using the polling booth list, the total number of individuals was divided into 12 age and sex

groups (18-24, 25-34, 35-44, 45-54, 55-64 and 65+). From each group 30 individuals were

randomly selected to get a total sample of 360 in each ward. Thus 3600 participants were

selected in the Trivandrum district to participate in the cross-sectional survey. Additional

sampling was conducted (40 from each age and sex band) to replace those participants who

had migrated, died or refused to participate.

West Godavari: A sampling frame was developed by mapping all 17 Primary Health Centres

(PHCs) within a 50 km radius around the town of Bhimavaram. We excluded those PHCs

participating in other studies conducted by the George Institute and randomly selected 10

of the remaining PHCs. All the villages serviced by each PHC were included in the list.

Villages with fewer than 3000 residents were excluded. One village was then randomly

selected from each PHC, resulting in inclusion of 10 villages. Mapping all the selected

villages enabled generation of an age and sex population list with house addresses.

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Population lists from the mapping were used to randomly select 4500 individuals over the

age of 18 years from each participating village. Additional sampling was conducted to

replace those participants who had migrated, died or refused to participate. Sampling was

stratified by 12 groups defined by age (18-24, 25-34, 35-44, 45-54, 55-64, 65+) and sex with

the goal of including comparable numbers of individuals from each group.

Rishi Valley region: Hamlets were randomly selected in accordance with the sampling

strategy using computer-generated random numbers (generated at Monash University). A

study centre was set up in a communal area of the hamlet convenient for all the residents.

All residents above the age of 18 years were invited to participate in the cross-sectional

survey. Research officers ensured that all residents were informed of the presence of the

study team in the habitation by house to house notification and encouragement to attend.

Data collection/measurement

The instruments and measurements chosen for this project are based on recommendations

from the World Health Organization (WHO) STEPwise approach to disease surveillance

(WHO STEPS) [25] and other validated tools for quality of life, socioeconomic position (SEP),

and barriers to changes in alcohol and tobacco behaviour as listed in Supplementary Table 1.

The list of measures comprise (1) basic demographic information including age, income,

gender, marital status, religion, number of children, and type of work undertaken; (2)

lifestyle-related factors such as physical activity, tobacco use, and alcohol consumption,

dietary factors, including cooking practices and use of salt, stress, and overcrowding; (3)

knowledge about hypertension and its risk factors, awareness of hypertensive status, and

reports of the timing and outcome of prior blood pressure measurements; and (4) further

details about use of medications (both allopathic and AYUSH or other traditional therapies),

barriers to treatment including access, cost, adoption of lifestyle factors and compliance

with medication use (see Supplementary Table 1 for full list of variables). Questionnaires

were developed in English and then translated into the site-specific language (Telugu (AP),

Malayalam (Kerala)) and back translated to detect and correct errors.

Standardised clinical measurements are collected as follows; arterial BP and heart rate are

measured after the participant has sat quietly for at least 15 minutes. BP is measured at

least three times at three minute intervals using the appropriate cuff size and a Digital

Automatic Blood Pressure Monitor (DABPM- OMRON HEM-907, OMRON Healthcare

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Company, Kyoto, Japan) according to the WHO STEPs protocol, modified only by using the

right arm for all measurements.[25] Measurement continues until two consecutive readings

differ by <10 mmHg systolic and <6 mmHg diastolic, with a maximum of five measurements.

The mean of the last two consecutive measurements are used to define hypertensive status.

Height is measured to the nearest 0.1 cm using a portable stadiometer (213, Seca, Hamburg,

Germany). Weight is measured to the nearest 0.1 kg using a portable digital weighing scale

(9000SV3R, Salter, Kent, UK). Waist and hip circumference is measured using a spring-

loaded tension tape (Gulick M-22C, Patterson Medical, Illinois, United States) in a private

setting. In accordance with the WHO STEPS protocol [25] waist circumference is measured

at the midpoint between the lowest rib and upper point of the iliac crest and at the end of

normal expiration and hip circumference is measured at the maximum protrusion of the

buttocks.

Data collectors are trained in collection of anthropometric measures, in accordance with the

WHO STEPS protocol,[25] for at least 5 days, to ensure consistency of data collection

between sites. Further training is undertaken to ensure that administration of the

questionnaire is also consistent across all sites. Training is conducted by the project

manager and site supervisors.

Definitions: Participants whose measured mean systolic BP (SBP) is ≥140 mmHg and/or

mean diastolic BP (DBP) is ≥ 90 mmHg or who are taking medication for lowering blood

pressure are defined as hypertensive.[6] Waist circumference is deemed high when >80 cm

in women and >90 cm in men. A body mass index (BMI) ≥ 23 kg/m2 is defined as obese

according to current guidelines for Asian Indians.[26]

Outcomes

Socio-demographic and economic characteristics of each population are determined,

including gender, SEP, education, income and expenditure. Information on utilisation of

health care, physical activity, tobacco use and consumption of alcohol are also collected.

Primary outcomes for Phase 1a of the study are prevalence, awareness, treatment, control,

knowledge of hypertension and associated risk factors. We compare knowledge of

hypertension, previous measurement of BP and barriers to treatment and management

(such as cost, education and SEP) of hypertension across study sites. Good (BP<140/90

mmHg) or poor (SBP≥140 mmHg or DBP≥90 mmHg) control of hypertension is assessed in

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relation to lifestyle factors (physical activity, use of tobacco and consumption of alcohol),

dietary factors (including salt intake) and health care utilisation. Attitudes to healthy

behaviour change are also assessed.

Qualitative studies to identify barriers (Phase 1b)

To further investigate barriers to diagnosis, treatment and control of hypertension, focus

group discussions with people having hypertension are used to explore peoples’ experiences

with health care systems and their perceptions and beliefs about hypertension in

accordance with predetermined and shared exploratory questions. Up to four focus groups

involving up to 10 people with hypertension in each focus group, identified in the cross-

sectional survey as being aware of their hypertension status, are conducted at each site

(refer Supplementary Figure 2A, 2B, and 2C). Focus groups are voice recorded and a second

research officer takes notes throughout the session. The recordings are translated and

transcribed into English and checked for accuracy with the research notes. Data analysis is

carried out using the process described by Green and colleagues.[27] We use a socio-

ecological approach to the identification of themes, which considers the complex interplay

between individual, social, and systemic factors.[28-30]

In-depth interviews are carried out with health care providers at each site to explore

management of hypertension, and perceptions of the health care system in relation to

screening and management of hypertension and other chronic conditions.

Medicine pricing and availability: (Phase 1c)

To investigate the availability and price of medicines for hypertension and other related

non-communicable diseases (e.g. cardiovascular diseases [CVD], type 2 diabetes) a cross-

sectional survey of price and availability of essential medicines is undertaken. Included in

this survey are public (hospitals, clinics and health facilities), private (licensed retail

pharmacies and licensed drug stores) and ‘other’ sector medicine outlets (facilities selling

medicines at subsidised prices to all patients) located in the sampling frames of the CHIRI

study sites in AP and Kerala (refer Supplementary Figure 2A, 2B, and 2C). The medicines

selected for review are those used for treatment of hypertension, secondary prevention of

CVD, and treatment of type 2 diabetes mellitus and that are listed in the WHO Model List of

Essential Medicines,[31] National List of Essential Medicines of India,[32] Essential

Medicines List of the Government of (unified) Andhra Pradesh and the Rational Drug List

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2012-13 of Kerala Medical Services Corporation Ltd.[33] The study methods have been

developed based on the WHO/HAI (Health Action International) methodology for measuring

medicine prices, availability, affordability and price components.[34] The survey is being

conducted across 20 public, 16 private and 2 ‘other’ sector pharmacies in the three regions.

Phase 2: Feasibility of a community based programme for management of hypertension

facilitated by Accredited Social Health Activists (ASHA)

Phase 2 of the study is a feasibility trial which incorporates random allocation of

approximately 20% of the PSUs to the intervention and 40% of the PSUs to the control

condition (Figure 1). Specifically for the Trivandrum region two of 10 wards are allocated to

the intervention and four of 10 wards are allocated to the control condition. For the West

Godavari region two of 10 villages are allocated to the intervention and four of 10 villages

are allocated to the control condition. For the Rishi Valley region one of six hamlets is

allocated to the intervention and two of six hamlets to the control condition.

Allocation of only a subset of the initial PSUs was necessary due to budgetary and

programme timeline constraints. Random allocation of the PSUs to intervention or non-

intervention conditions is undertaken by a principal investigator at each site (Figure 1). As

this is a feasibility study, the sample size for those receiving the intervention is not powered

to determine effectiveness. However, changes in individual measurements over time are

assessed. The intervention addresses those factors identified during the qualitative and

cross-sectional studies which contribute to control of hypertension in these settings and

includes both management and control strategies aimed at the individual, health service

delivery and policy levels.

Blinding

As this is a behavioural intervention programme, the people delivering the intervention

cannot be blinded to the intervention group. However, participants in the control regions

remain unaware of the intervention programme, and outcome assessors are blinded to the

intervention allocation of participants.

Recruitment and eligibility

Community members from the randomly selected PSUs, who are identified as hypertensive

in the cross-sectional study, are invited to participate in the intervention and control arms in

accordance with eligibility criteria given below (also see Figure 2). Recruitment commenced

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in January 2016, and the intervention is expected to be completed in June 2016. Participants

are approached at their homes after identification, and recruited and consented during this

visit. For the intervention sites, the list of consented participants is provided to the

Accredited Social Health Activists (ASHAs) from those villages.

Eligible participants are those who:

1. Indicate they are aware of being hypertensive in the cross-sectional survey.

2. Are identified as having an average SBP of ≥140 mmHg and/or DBP ≥90 mmHg at the

cross-sectional survey, subsequently attend their primary health care provider and are

then formally clinically diagnosed with hypertension. Verification occurs by sourcing the

medical record, contacting the health care provider or by confirmation of use of

medication(s) for hypertension (as observed);

3. Have an average BP of ≥140 mmHg SBP and/or ≥90 mmHg DBP during the cross-

sectional survey and then, at the time of recruitment to the intervention (or control),

have their blood pressure remeasured, and are found to still have an average BP of ≥140

mmHg SBP and/or ≥90 mmHg DBP.

4. Are taking medication(s) for hypertension (including diuretics, ACE inhibitors,

angiotensin II antagonists, β-blockers, Ca++

channel blockers or renin inhibitors.)

Intervention components

The intervention arm incorporates a community based self-management and education

support group, led by ASHAs, every 2 weeks for 3 months (i.e. six meetings). ASHAs are

female lay health workers, residing in each village, most of whom have completed

secondary schooling. Their work accountability primarily lies within the purview of the

Village Health Sanitation and Nutrition Committee (VHSNC) which is a committee formed at

the revenue village level and acts as a sub-committee of Gram Panchayat. They are

compensated for their time in specific situations (attending training and meetings) and

given incentives under various national health programmes, predominantly for maternal

and child health.

Content for the intervention components was driven by preliminary analysis of the cross-

sectional data which reflected poor knowledge of hypertension. Furthermore principles of

the Chronic Disease Self-Management Program (CDSMP) as described by Lorig,[35] and

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found to significantly contribute to improved self-management, were incorporated into the

programme content.[36] Content includes strategies to increase knowledge and

understanding of the disease, promote healthy behaviour change and clinical interaction

through goal setting. At each group meeting participants are weighed, have their blood

pressure measured and receive self-management and lifestyle education (Figure 3) from

locally sourced “expert” advisers. These advisers may include, but will not be limited to,

clinicians from the primary health centre servicing the region, pharmacists, and nutritional

advisors.

ASHA Training

For the intervention, ASHAs in each location are trained to deliver the self-management

sessions of the intervention and to collect data regarding the implementation of the

intervention. At the beginning of the first training session the knowledge of ASHAs regarding

hypertension and other non-communicable diseases (NCDs) and their skills in measuring BP

and recording weight are assessed. The 5-day training regimen includes education about

NCDs that is based on, and complimentary to, the existing ASHA training Module for NCDs

(Module # 8),[37] measurement and recording of BP and weight, and maintaining records of

each meeting (attendance, measurements, meeting content, record problems or issues

faced by participants). Additionally, ASHAs are trained to deliver the educational material

regarding hypertension and self-management using pictorial flip-chart resources developed

for the intervention. ASHAs are also trained to initiate and support self-management of

hypertension by the participants through goal-setting. Incentives for ASHA are based on

remuneration under the schedule for Village Health Sanitation and Nutrition Committee

Activities [38] as well as Village Health and Nutrition Days.[39] In the two regions in Andhra

Pradesh the ASHAs are incentivised to promote attendance by as many participant and

support members as possible, via payment of 200 Indian rupees per meeting if more than

75% of enrolled participants attend. Thus, those that do not attend one meeting will be

followed up by an ASHA and encouraged to attend the next meeting. In the Kerala site the

ASHAs are paid according to remuneration under the schedule for Village Health Sanitation

and Nutrition Committee Activities [38] as well as Village Health and Nutrition Days,[39] and

were not paid extra when more than 75% of participants attended.

Self-management education and group-based support

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Each community group comprises up to 20 individuals with hypertension. The community-

based support group is supported and promoted by the Panchayat at each site. The

Sarpanch (the elected head of village) provides a letter of support and encouragement for

the intervention activities. This letter is enclosed with the letter of invitation to participate

in the intervention. The facilitator of the group, either the appointed village ASHA

(Trivandrum, West Godavari and Rishi Valley regions) or a person with equivalent

qualifications employed for the project (West Godavari region), is assisted by a member of

the research team at each meeting. The facilitator of the group organises and schedules

meetings, collects data during the meeting, and submits these data to the research team.

Each of the six meetings lasts approximately 90 minutes, and consists of various topics

related to hypertension (see Table 1). Next of kin or additional support persons are

encouraged to accompany and support the person with hypertension at each group meeting.

Table 1: Meeting schedule and details of meeting content

Meeting

Number

Topic Detailed information provided

1 Introduction Education session: what is hypertension?, risk factors,

chronic nature of disease “know your numbers”, etc to be

carried out by a local health care provider

2 Self-management

education

Risk factors and modifiable activities to improve control/

management. Importance of medication adherence

3 Physical activity Incorporating physical activity into your day, including

group physical activity

4 Nutrition and Diet Importance of salt reduction (including recipes)/ alcohol

reduction/ dietary assistance/ increased fruit and vegetable

consumption (it is especially important for women to be

given strategies to save some vegetables and meat for

themselves)

5 Practical Self-

management

Practical ways to improve your control / management

(medication diary/ reminder system, etc). A pharmacist may

attend and provide information about drug availability

6 Next steps/

continuation

plans

Review, changes made, ongoing difficulties, ongoing group

activities

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Because of the nature of the intervention, a community-based peer support group with self-

management education, no data safety monitoring committee is required.

The community-based groups are used to educate group members about hypertension as

well as implement and enhance strategies for self-management of hypertension and related

NCDs (Table 1 and Figure 3). Resources developed specifically for the intervention are

primarily pictorial to ensure consistency of information at each site and to account for

disparities in educational levels across the three sites.[24]

Health systems activities/interaction

This feasibility study incorporates interaction and active involvement with providers from

the structured health systems. Involvement of the health providers (at primary, community

and sub-health centre levels) may strengthen and complement the group-based

intervention as well as enhance follow-up interactions with the health system (including

clinical and pharmaceutical services). The facilities of health care providers serving the

communities, selected for the baseline study, are assessed to identify how equipment and

staffing could be supported to improve diagnosis, treatment and ongoing management of

hypertension.

Analysis of the costs of the intervention

Costs of the intervention will be assessed in terms of programme costs such as ASHA

incentives and meeting set-up costs. Cost of developing resources including development

time and production of resources will inform this analysis

Outcomes of the Intervention

Participants attending the group meetings are revisited approximately 6 - 8 weeks after the

last meeting to complete final data collection. In these participants, and in those in the

control arm, we re-measure BP and anthropometry and re-asses health care utilisation,

attitudes to behaviour change and activities related to self-management of hypertension

(see Supplementary Table 1). Changes in continuous and categorical variables are assessed

relative to their values determined at the time of the cross-sectional survey. These include

SBP, DBP, waist and hip circumference, and weight. Medication initiation and any dosage

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changes (observed and documented) are recorded. Medication adherence to BP lowering

medication is assessed in accordance with the Hill-Bone Compliance Adherence survey.[40]

This survey is used to assess use of prescribed medication over the prior 2-week period.[40]

Knowledge about hypertension and associated risk factors relating to hypertension is

reassessed, along with physical activity over the 2 weeks prior to final administration of the

questionnaire. Barriers to attending the meetings are assessed, as are engagement and

utilisation of health services during the period of the intervention.

Perceptions by participants of the level of support obtained from the ASHA [41 42] is

assessed in the final survey using a three scale response (not at all/some of the time/all of

the time). Usefulness of advice and self-management assistance received by the participant

is assessed using a seven-point Likert scale (a little useful to extremely useful).

Encouragement and support received, as perceived by the participant, resulting from

various group meeting activities is assessed using a four-point response (no support, a little,

moderate, a lot of support).

After each meeting ASHAs complete a meeting report to aid the assessment of fidelity of the

meeting structure and content to the protocol (Supplementary Table 2). This report includes

details of the meetings such as the number of enrolled participants and community

members attending the meeting, and major activities undertaken during the meeting.

Additional activities by the ASHA to extend the healthy behaviour messages, such as

tobacco cessation and physical activity, as well as behaviours specific to the management of

hypertension from the meeting to the wider community by the ASHAs is also measured

categorically (Yes/No). This measure captures support/interactions of ASHAs with meeting

participants outside the meeting and their discussions of the meeting content with other

members of the community and/or with community leaders or health service members.

Members of the research team also complete a report after each meeting to provide further

information about the meeting activities and detail the shared experiences or difficulties of

the participants in managing their hypertension or achieving their goals (Supplementary

Table 2). These reports are used to assess the fidelity of the implementation of the

intervention to the protocol.

System outcomes of the programme are obtained via surveys of ASHAs at the end of the

intervention (and compared to surveys conducted at the commencement of the

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intervention) to assess changes in knowledge of ASHAs (Supplementary Table 2). We also

assess the integration or engagement of health providers in the programme by assessing

their participation during the intervention. Furthermore, participants provide information

about other providers of assistance and information/advice (health care team and

family/friends/community) and assess meeting activities (goal setting, attendance, problem

solving) for delivering self-management support. The overall response rate (people with

hypertension in the cross-sectional survey, number consented to participate in meetings) is

calculated and participants who discontinue the programme are asked to complete a

programme evaluation form and to undertake final measurements at the end of the

intervention.

Data Management

All assessments and data forms are checked on the day of completion. Any forms with

missing data or inconsistencies are returned to the Health Worker for completion. Data are

coded and entered as the study progresses. Edit checks are performed and data verified as

necessary.

All forms are designed in TELEform Elite version 10.5®. Completed questionnaires are

electronically scanned into a computer using a Tagged Image File Format (TIFF). These data

are then transferred to Monash University and uploaded into a Microsoft Access database

using TELEform. The database contains no identifying information and is housed on a secure

server at Monash University. All principal investigators will have access to the de-identified

final data.

Data Analysis

Analysis will be based on intention to treat. For individual outcomes proportions will be

compared using Chi-squared (χ2) test

and continuous measures will be compared using

Student’s unpaired t-test. Univariable analysis will also be undertaken using logistic and

linear regression. Multivariable analyses will be adjusted for age, sex and study site.

Considering the unequal distribution of age and sex in the participating population,

appropriate sampling weights will be applied to all data analyses.

Knowledge/awareness of the presence of hypertension and about risk factors will be

calculated using the known (and measured) prevalence of hypertension in each population.

Between-group differences in knowledge, previous measurement of hypertension, and

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barriers to treatment and their change over time will be compared using χ2. Logistic

regression (appropriate for the binary outcome variable of presence/absence of BP≥140/90

mmHg) will be used to study the factors associated with control of hypertension. Those

factors identified as either potentially significant (p < 0.20) or biologically relevant will then

be introduced into multivariable regression analyses in a backward stepwise fashion to

construct a predictive model for good management of hypertension. This technique enables

the assessment of both categorical variables (e.g. gender) as well as continuous variables

(e.g. age). The scales of the continuous covariates will be checked for suitability using

fractional polynomial plots. Collinearity between variables will be evaluated using partial

correlations. In addition, routine diagnostic tests (Hosmer-Lemeshow test) will be used to

validate the fitted model. We will test efficacy of the intervention by analysis of covariance.

This allows us to adjust for baseline differences between groups.

Ethics and Dissemination


Committee, Ministry of Health & Family Welfare, Government of India (No.

58/4/Indo_CHR/2013/NCD-II) and Monash University Human Research Ethics Committee

(MUHREC number 2013001327). Each site obtained ethics approval from individual

governing institutional review boards (IRBs) for site specific aspects of the study. The site in

Trivandrum obtained approval from Sree Chitra Tirunal Institute for Medical Sciences and

Technology Institutional Ethics Committee (IEC Regn No. ECR/189/Inst/KL/2013). The West

Godavari site obtained approval from the Centre for Chronic Disease Control, New Delhi (IEC:

IRB00006330). The Rishi Valley site obtained approval from the IRBs of the Rishi Valley

Education Centre and Christian Medical Centre, Vellore (IRB Min No. 8313). Prior to

inclusion in the survey, Sarpanches are approached to obtain approval for the study team to

seek participation from the residents of the village in the study.

All participants are provided a written participant information sheet and informed consent

form in the local language. The study research staff at each site is responsible for obtaining

informed consent. For those participants who are illiterate, the participant information

sheet is read out to them. All participants sign (thumb print for those who are illiterate) the

informed consent form.

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Each consenting participant is assigned a study identification number. To maintain

confidentiality all questionnaires, and other study documents, include only this

identification number, with no identifying information present.

Feedback from study phases 1b and 1c will be consolidated after the intervention and

disseminated to public health systems to inform health provision services. Based on

medicines availability (Phase 1c) and qualitative feedback from focus groups and in depth

interviews (Phase 1b) a treatment algorithm/guideline which is consistent with the Indian

Hypertension management guidelines [6] will be developed. In order to strengthen the

integration of community-based and delivered education programmes for self-management

of health into the local primary health care system, we will disseminate the following

information to benefit local health services through:

1. sharing of information gained from the cross-sectional survey;

2. developing resources for use by health system staff for assessing and treating

hypertension;

3. providing details to health centres about the resources and training they require to

support such an intervention.

We will also disseminate the following information to improve availability of pharmaceutical

preparations:

1. informing pharmacies about medicine availability and possibilities for providing

medications to suit communities enrolled in the intervention;

2. discussing options for enhancing or improving medication adherence (by addressing

availability, dosing and packaging options).

Results will be shared with the Ministry of Health & Welfare and officials of the National

Health Mission and relevant local health care providers and communities at each of the sites.

Further dissemination of the results to research, clinical and health communities will be

pursued via international peer-reviewed journal articles and conference presentations. The

Global Alliance of Chronic Diseases (GACD) will also be informed of the findings of the study.

DISCUSSION

Comprehensive assessment of the barriers to control of hypertension across three diverse

settings will provide important information about the diversity of barriers to care across

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settings. Development of an intervention programme, based on the individual and system

barriers identified and tailored to the specific needs of each area included in the study, may

provide a solution to address the current deficiencies in managing hypertension across rural

regions. We will also be able to determine the feasibility of using ASHAs to deliver a

community group based self-management programme for management of hypertension.

Because ASHAs are employed in most rural regions, the programme is more likely to be

scalable across rural India, if government can be encouraged to fund ASHAs to manage non-

communicable diseases or to identify a new cadre of village health workers to work in the

area of non-communicable disease. This information will also contribute to disease

prevention at a global level as the lessons learned could be suitably adapted across other

similar settings.

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AUTHOR’S CONTRIBUTIONS

MAR wrote the first draft of the manuscript. AGT is the Principal Investigator, and conceived

the study. All authors provided input into the study design, provided intellectual input to the

manuscript, and approved the final version of the manuscript.

FUNDING STATEMENT

This work was funded by The National Health and Medical Research Council (NHMRC) under

the Global Alliance for Chronic Disease (GACD) programme (grant number GNT1040030),

with additional funds provided from Monash University (via the principal investigator). AGT

was supported by a fellowship from the NHMRC (GNT1042600). PKM is a Wellcome

Trust/Department of Biotechnology Intermediate Career Fellow. RJ was supported by a

fellowship from the National Heart Foundation (GNT100484). The funders had no role in the

design or conduct of the study, and no role in the decision to submit the protocol for

publication.

DECLARATIONS OF INTEREST

Michaela A Riddell has nothing to disclose

Rohina Joshi reports grants from National Health & Medical Research Council, during the

conduct of the study

Brian Oldenburg has nothing to disclose

Clara Chow reports grants from National Health & Medical Research Council, during the


KR Thankappan has nothing to disclose.

Ajay Mahal reports grants from National Health & Medical Research Council, during the


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Nihal Thomas reports grants from National Health & Medical Research Council, during the


Velandai K Srikanth reports grants from National Health & Medical Research Council, during

the conduct of the study

Roger G. Evans reports receiving grant funding from the Australian National Health and

Medical Research Council

Kartik Kalyanram has nothing to disclose

Kamakshi Kartik has nothing to disclose

Pallab K Maulik reports receiving an Intermediate Career Fellowship from the Wellcome

Trust/DBT India Alliance, during the conduct of the study

Simin Arabshahi reports grants from National Health and Medical Research Council, during

the conduct of the study

RP Varma has nothing to disclose

Rama K Guggilla has nothing to disclose

Oduru Suresh has nothing to disclose

GK Mini has nothing to disclose

Fabrizio D’Esposito has nothing to disclose

Thirunavukkarasu Sathish has nothing to disclose

Mohammed Alim has nothing to disclose

Amanda G Thrift reports grants from National Health and Medical Research Council

(GNT1040030 and GNT1042600), grants from Monash University, during the conduct of the

study

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37 Ministry of Health and Family Welfare. Secondary Reading Material for ASHA. Role in Prevention

and Control of Non Communicable Diseases (NCDs). Book No. 8, 2009. Available at

http://mohfw.nic.in/showfile.php?lid=656. Accessed April 2016.

38 National Rural Health Mission. Community Processes Guidelines - 2013. New Delhi, 2013.

Available at http://nrhm.gov.in/images/pdf/communitisation/asha/Orders-

Guidelines/Guidelines_for_Community_Processes_2014_English.pdf. Accessed April 2016.

39 National Rural Health Mission. Guidelines for Village Health Sanitation and Nutrition Committee

Part B. In: Gupta A, ed. Guidelines for Community Processes. New Delhi: Ministry of Health

and Family Welfare, 2013:29. Available at

http://nrhm.gov.in/images/pdf/communitisation/vhsnc/order-

guidelines/Guidelines_for_Community_Processes_2014%20English.pdf. Accessed April 2016.

40 Kim MT, Hill MN, Bone LR, et al. Development and testing of the Hill-Bone Compliance to High

Blood Pressure Therapy Scale. Prog Cardiovasc Nurs 2000;15(3):90-6.

41 Glasgow RE, Whitesides H, Nelson CC, et al. Use of the Patient Assessment of Chronic Illness Care

(PACIC) with diabetic patients: relationship to patient characteristics, receipt of care, and

self-management. Diabetes Care 2005;28(11):2655-61. doi: 10.2337/diacare.28.11.2655

42 McCormack LA, Williams-Piehota PA, Bann CM, et al. Development and validation of an

instrument to measure resources and support for chronic illness self-management: a model

using diabetes. Diabetes Educ 2008;34(4):707-18. doi: 10.1177/0145721708321021

34/4/707 [pii]

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27

Figure Legends:

Figure 1: CHIRI Study Design outlines the approach taken to select and survey the

populations. Primary Sampling Unit (PSU)

Figure 2: Recruitment flow chart for intervention study. Residents of the Primary sampling

unit who participated in the baseline cross sectional survey are eligible to be recruited into

the feasibility trial (intervention and control arms) based on the criteria and recruitment

flow chart depicted here. BP – blood Pressure, HCP – Health Care Provider, HTN –

Hypertension, SYS – systolic, DIA- diastolic, WHO – World Health Organization

Figure 3: Feasibility trial intervention components and proposed outcomes

ASHA –Accredited Social Health Activist, HCP -Health Care Provider, PHC -Primary Health

Centre, BMI -Body Mass Index

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Cross sectional surveyPhase 1

Estimated number of Hypertensives

identified

InterventionPhase 2

3600

1080

Larger control40% of PSU with hypertension

Smaller Intervention

20% of PSU with hypertension

Trivandrum

Estimated 30%

prevalence

4500

900




West Godavari

6500

650




RishiValley

Estimated 20%

prevalence

Estimated 10%

prevalence

Random selection of PSU

Random assignment of PSU

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Identify all potential participants from survey answers

Aware of hypertension

APPROACH TO RECRUIT INTO INTERVENTION

Taking known antihypertensive medications


Average BP reading during cross sectional survey ≥140 sys or ≥90 dia last two readings which are not more than 10/6 mmHg apart or if 5 readings taken and not consistent (ie > 10/6 mmHg aprt) take average of all five readings and

determine if BP ≥140 sys or ≥90 dia

Visited HCP after cross sectional survey and obtained a confirmed diagnosis of hypertension (according to

participant)

Visited HCP but not on HTN medication

Re‐assess BPusing WHO steps criteria as per cross sectional survey to measure BP,

use last 2 readings to average BP

BP RESULTAverage last two BP readings ≥140 sys

and ≥ 90 dia


BP RESULTAverage last two BP readings

<140 sys and < 90 dia

Request permission to contact HCP for confirmation of diagnosis

Permission not given or diagnosis not confirmed NOT ELIGIBLE

Diagnosis of Hypertension confirmed by HCPAPPROACH TO RECRUIT INTO INTERVENTION

DIAGNOSIS CONFIRMED by observing medication for HTN as a result of HCP visit and diagnosis


Did not visit HCP or get confirmed diagnosis of hypertension

Re assess BPusing WHO steps criteria as per cross sectional survey to

measure BP

BP RESULTAverage last two BP

readings ≥140 sys or ≥90 dia


BP RESULTAverage last two BP readings

<140 sys and < 90 dia

NOT ELIGIBLE

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RESEARCH OFFICER

Support and supervision :1. Source and organise “expert” speakers for each meeting 2. Assist ASHA with data collection3. Collect Health systems data and information

ASHA

Resource Manual ‐ information about hypertension to be used by the ASHA to provide ongoing information to the community

(supplemental to ASHA NCD training module #8)

1. Organise location for biweekly meeting2. Ensure and advocate (register) participants to attend the group meeting3. Collect weekly data from group meeting BP measure, participant progress4. Assist with goal setting

5 days training ‐measurement collection and ‐ group meeting facilitation and organisation

PARTICIPANTS

Group bi‐ weekly meetings facilitated and organised by ASHARegular BP /weight monitoring (at meeting)Goal setting for adopting lifestyle changesSupport from other group members/sharing stories and difficulties

Self management education and information organised by research teamPractical assistance with goal setting related to physical activity, nutrition, medication adherence

Intervention components OUTCOMES

KEY PROGRAM OUTCOMESDemonstrated feasibility

trained ASHAIncorporation into health system/

engagement with local HCPs and PHC

Group meetings‐ regular‐ >70% participation‐ ongoing?‐ Supported by Panchayat

Program costsASHA paymentscommunity payments“expert” payments

KEY INDIVIDUAL OUTCOMESReduction in BP measurement,Reduction in anthropometric

measures (BMI, waist /hip circum)

Improved knowledge of hypertension risk factors.

Improved medication adherenceImproved mental health and

quality of lifeImproved linkages/access/

engagement to clinical care team

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Supplementary material

Cluster randomised feasibility trial to improve the Control of Hypertension In Rural India (CHIRI): a study protocol

Michaela A Riddell1, Rohina Joshi2 , Brian Oldenburg3, Clara Chow2,4, KR Thankappan5, Ajay

Mahal6,7, Nihal Thomas8, Velandai K Srikanth1, Roger G. Evans9, Kartik Kalyanram10, Kamakshi

Kartik10, Pallab K Maulik11,12, Simin Arabshahi1, RP Varma5, Rama K Guggilla11, Oduru Suresh2,10, GK

Mini5, Fabrizio D’Esposito3, Thirunavukkarasu Sathish3, Mohammed Alim11, Amanda G Thrift1*



3 Melbourne School of Population and Global Health, University of Melbourne, Australia




6 School of Public Health and Preventative Medicine, Monash University, Melbourne Australia

7Nossal Institute for Global Health, Melbourne School of Population and Global Health, University

of Melbourne, Australia

8 Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, Tamil

Nadu, India

9 Cardiovascular Disease Program, Biosciences Discovery Institute and Department of Physiology,

Monash University, Melbourne, Australia

10 Rishi Valley Rural Health Centre, Chittoor, Andhra Pradesh, India

11George Institute for Global Health, Hyderabad Telangana, India

12George Institute for Global Health ‐ Oxford University, Oxford, UK

1

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Trivandrum

Rishi Valley

West Godavari

Supplementary Figure 1. Location of each site.

2

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Kerala State

14 districts

Trivandrum District

Medicines survey

Chirayinkizhu Taluk (Sampling Frame)

Random Sampling (1 of 4 Taluks)

360 individuals from each of 10 wards = 3600

individuals (Sample)

Cross-sectional study

2 Wards (Intervention)

4 Wards (Control)

Hypertensive individuals from cross-sectional study

Random allocation of

wards

Feasibility study

FGDs and IDIs

Selected based on access to coordinating

institute

10 Panchayats

Random Sampling 10 of 22

Panchayats

Random Sampling 1 ward from each of 10 Panchayats

10 wards (one from each Panchayat)

Age/Sex stratified random sampling

Supplementary Figure 2: Sampling frames for individual study sites: A. Chirayinkizhu Taluk, Trivandrum District, Kerala B. West Godavari District, Andhra Pradesh, and C. Rishi Valley Region, Chittoor District, Andhra Pradesh. FGD – Focus Group Discussion, IDI – In Depth Interview

A.

3

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B. Andhra Pradesh State

All 3 Revenue Divisions

11 Mandals

Medicines survey

10 Villages (Sampling Frame)

Random Allocation

450 individuals each from 10 villages = 4,500



4 villages (Control)


Random Allocation

Feasibility study

FGDs & IDIs

3 Villages

West Godavari District

2 villages (Intervention)

76 Villages (Study Population)

Villages located within a 50 km radius of Bhimavaram town

Age- and sex-stratified sampling

4

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C. Andhra Pradesh State

Madanapalle Revenue

Kurabalakota Mandal

Medicines survey

221 Hamlets (Sampling Frame)

Random Sampling of Hamlets

Stratified by Hamlet size (45 small, 44

medium, 44 large), 6 excluded (5 no

inhabitants, 1 RV school habitation)

133 Hamlets, 6246 individuals (Sample)


2 Hamlet cluster (Control)


Random allocation

Feasibility study

FGDs

IDIs

7 Hamlets

Chittoor District

1 Hamlet cluster (Intervention)


5

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Supplementary Table 1: Data collection, study phase and tools

Component Measurement tools/Questions Phase 1

Survey

Phase 2

Survey

Demographic Measures Population measures[1,2]

Age, Sex, Marital status, Age oldest child Literacy (read/write), Highest Education, Average Household Income Source of household income (amount), Household earners Occupation, Ration Card (if yes what type), Household Expenditure Number of people and adults in household Health care insurance (type and who pays) Household structure (walls/floor/roof) Access to drinking water Toilet facility Use of washing after toilet

Clinical InformationFamily History

Close relative: history of heart attack before 60yr, history of stroke before 60yr, history of diabetes (any age), history of high BP (any age)

Co‐morbidities/ Risk Factors [1]

Ever had heart attack, coronary bypass, angioplasty/stent Ever told by HCW: heart problems. Diabetes, chronic Kidney disease, high fats: if yes;

about how long ago (years/months)

Anthropometric [1]

Blood Pressure, Weight, Height, Waist and Hip Circumference

Treatment/ Awareness history [1]

Ever told Hypertension Ever had BP checked: if yes;

was it in last 12 months, who checked Blood Pressure

Ever had prescription for Blood Pressure medication; if yes;

where did you get it,

do you take it as directed

Behavioural Knowledge barriers

Which actions prevent Hypertension

What have you done in last 12mth

Physical Activity[ 1]

Physical activity as per WHO STEPS (including work and leisure related) Hours of Sleep Barriers to physical activity

Diet [1, 3‐5] Person who prepares food Add salt during cooking, if yes how many teaspoons What type of salt and whether iodised Add salt before eating

Daily salt intake

Added sugar to food and drink before consuming

Days/week fruit intake

Typical servings of fruit/ typical day Days/week vegetable intake

Typical servings of vegetables/ typical day No. of meals/week with fried vegetables, meat/poultry, fish, nuts or legumes Number of times/week consuming dairy products, deep fried/fast foods Type of oil used to prepare meals Number of days eating eggs, chicken, fish, other seafood, mutton, beef, pork, rice(idly dosa, puttu etc), pulses (dhal kidney beans etc) other cereals (chapathi, puris, roti, chickpeas etc)

Barriers to eating fruit/vegetables

6

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Smoking [1, 6]

Ever smoked (100 cigarettes or 100 times smokeless) Age initiated Current smoking(smokeless) _ amount/day Frequency of tobacco use (smoking/smokeless) Time since quitting Passive exposure Barriers to quitting tobacco use

Alcohol [1]

Ever consumed alcoholic beverage Use and frequency past 30 days Drinking habit (now and previous 12 months) Use in past 12months Frequency of one standard drink over past 12 months Quantity /day (average) Quit due to health reason Age drinking initiated CAGE substance abuse screening tool [7] Barriers to quitting alcohol [8]

Medication

Do you take medication for BP as directed? Taking any medications? Taking any AYUSH or traditional medications? How often do you forget to take all medications Name/dose of medication (Coded), Medication taken as directed by health care worker, medication confirmed by research team

Hill Bone Compliance to therapy for high blood pressure [40]

Quality of Life General Assessment Chronic Burden [9]

Support[10] Bothered by problems[11]

How helpful to talk with about personal problem

How helpful to talk to about borrowing money

Bothered by problems

Mediators and Moderators Hypertension Knowledge[12] Hypertension beliefs

How does it affect health Likelihood of other disease if hypertension is controlled Which diseases prevented if hypertension is controlled High blood pressure when working/worried Lie down when having high blood pressure Medication too costly Doctor too far to see about high blood pressure

Cost Effective Analysis Health care utilisation

Medical treatment/advice as outpatient last 3 months: if yes;

Number of times in 1 and 3 months

Where and from whom, how did you pay

Medical use over last 12 months similar? If no, is it more or less? Admission as inpatient over last 12 months: if yes;

What type of facility, length of stay, how did you pay?

Last routine check‐up

If longer than 5 years – why? Ease or difficulty to see a doctor Transportation mode to health centre Length of time to get to health centre

Focus Group Discussions Explore current situation/beliefs of population

In depth Interviews Explore current situation/beliefs & attitudes of health personnel

Medicine availability surveyExplore current availability of prescribed medication for hypertension as per WHO essential list

WHO STEPS (World health Organisation STEPwise approach to disease surveillance;

7

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Supplementary Table 2: Data collection and tools for process evaluation

Process Evaluation Pre‐

Intervention During

Intervention Post

Intervention

ASHA pre training knowledgeIntervention process evaluation (training)

ASHA post training knowledge & evaluation Intervention process evaluation (training)

Intervention Fidelity

Meeting attendance

Blood pressure monitoring

Medication adherence

Intervention Fidelity & ProcessGoal setting list

Participant Action plans completed ASHA Meeting report Research member meeting report Participant Intervention Evaluation (including ‐ Attendance, reasons for missed meetings

Support from family/friends/community

Relationship with clinician/HCP

Perceived support from ASHA [41 42])

People with hypertension who did not participate

Factors enhancing ability to attend

Knowledge about hypertension

Perceptions of the community to extended role ofASHAs

ASHA post intervention knowledge Intervention process evaluation (training and retained knowledge)

ASHA, Accredited Social health Activist; HCP, health care provider

8

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REFERENCES 1. World Health Organization. The WHO STEPwise approach to chronic disease risk factor

surveillance. Secondary The WHO STEPwise approach to chronic disease risk factorsurveillance 2004. http://www.who.int/chp/steps/riskfactor/en/index.html.

2. International Institute for Population Sciences (IIPS), Ministry of Health and Family Welfare(MOHFW). India ‐ National Family Health Survey 1998‐1999 (NFHS‐2). 2013. Available athttp://microdata.worldbank.org/index.php/catalog/1405. Accessed April 2016.

3. Kennedy G, Ballard T, Dop MC. Guidelines for measuring household and individual dietarydiversity. Food and Agricultural Organization of the United Nations, Rome, Italy, 2013:60.Available at http://www.fao.org/3/a‐i1983e.pdf. Accessed April 2016.

4. Brantsæter AL, Haugen M, Alexander J, et al. Validity of a new food frequencyquestionnaire for pregnant women in the Norwegian Mother and Child Cohort Study(MoBa). Matern Child Nutr 2008;4(1):28‐43.

5. Morris Hicks J. The 4Leaf Survey. 4Leaf Global, 2015. Available athttps://4leafprogramdotcom.files.wordpress.com/2015/10/4leaf‐pdf‐survey‐103015.pdf.Accessed April 2016.

6. International Tobacco Control Policy Evaluation Project. ITC Survey‐ 4‐Country W9Replensihment Web US online survey code 4C9‐Pw‐US. 2015. Available athttp://www.itcproject.org/files/ITC_4C9_US_Replenishment_SNQ_web_EN.pdf. AccessedApril 2016.

7. Ewing JA. Detecting alcoholism. The CAGE questionnaire. JAMA 1984;252(14):1905‐7.8. Girish N, Kavita R, Gururaj G, et al. Alcohol use and implications for public health: patterns

of use in four communities. Indian J Community Med 2010;35(2):238‐44.9. Gebreab SY, Diez‐Roux AV, Hickson DA, et al. The contribution of stress to the social

patterning of clinical and subclinical CVD risk factors in african americans: The JacksonHeart Study. Soc Sci Med 2012;75(9):1697‐707.

10. Seidman E, Allen L, Aber JL, et al. Development and validation of adolescent‐perceivedmicrosystem scales: social support, daily hassles, and involvement. Am J CommunityPsychol 1995;23(3):355‐88.

11. Spitzer RL, Kroenke K, Williams JB, et al. A brief measure for assessing generalized anxietydisorder: the GAD‐7. Arch Intern Med 2006;166(10):1092‐7.

12. Oliveria SA, Chen RS, McCarthy BD, et al. Hypertension knowledge, awareness, and

attitudes in a hypertensive population. J Gen Intern Med 2005;20(3):219‐25.

9

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1

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*

Section/item ItemNo

Description

Administrative information

Title 1 Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym

Trial registration 2a Trial identifier and registry name. If not yet registered, name of intended registry

2b All items from the World Health Organization Trial Registration Data Set

Protocol version 3 Date and version identifier

Funding 4 Sources and types of financial, material, and other support

Roles and responsibilities

5a Names, affiliations, and roles of protocol contributors

5b Name and contact information for the trial sponsor

5c Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities

5d Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint adjudication committee, data management team, and other individuals or groups overseeing the trial, if applicable (see Item 21a for data monitoring committee)

Introduction

Background and rationale

6a Description of research question and justification for undertaking the trial, including summary of relevant studies (published and unpublished) examining benefits and harms for each intervention

6b Explanation for choice of comparators

Objectives 7 Specific objectives or hypotheses

Trial design 8 Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group), allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory)

Page 1

Page 3

Identified on Master protocol Version 9, 2 March 2016

Page 22Page 1 and 22

Not applicable

Page 22

Not applicable

Pages 4-6

Pages 12-13

Page 6

Pages 6-12

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2

Methods: Participants, interventions, and outcomes

Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be collected. Reference to where list of study sites can be obtained

Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and individuals who will perform the interventions (eg, surgeons, psychotherapists)

Interventions 11a Interventions for each group with sufficient detail to allow replication, including how and when they will be administered

11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease)

11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests)

11d Relevant concomitant care and interventions that are permitted or prohibited during the trial

Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended

Participant timeline

13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for participants. A schematic diagram is highly recommended (see Figure)

Sample size 14 Estimated number of participants needed to achieve study objectives and how it was determined, including clinical and statistical assumptions supporting any sample size calculations

Recruitment 15 Strategies for achieving adequate participant enrolment to reach target sample size

Methods: Assignment of interventions (for controlled trials)

Allocation:

Sequence generation

16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions

Page 7

Pages 8, 9, and 13 and Figure 2

Page 13

Not applicable

Pages 14 and 17

Not applicable

Pages 16 and 17

Page 13 and Figure 3

Page 12

Page 12

Pages 7, 9 and Figure 1

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3

Allocation concealment mechanism

16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned

Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to interventions

Blinding (masking)

17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how

17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s allocated intervention during the trial

Methods: Data collection, management, and analysis

Data collection methods

18a Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known. Reference to where data collection forms can be found, if not in the protocol

18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols

Data management

19 Plans for data entry, coding, security, and storage, including any related processes to promote data quality (eg, double data entry; range checks for data values). Reference to where details of data management procedures can be found, if not in the protocol

Statistical methods

20a Statistical methods for analysing primary and secondary outcomes. Reference to where other details of the statistical analysis plan can be found, if not in the protocol

20b Methods for any additional analyses (eg, subgroup and adjusted analyses)

20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation)

Methods: Monitoring

Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed


Page 12.

Page 12/13

Not applicable

Page 14

Page 18 and Supplementary Table 1

Page 18

Page 14

Pages 18 and 19

Page 19

Page 19

Page 16

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4

21b Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial

Harms 22 Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct

Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent from investigators and the sponsor

Ethics and dissemination

Research ethics approval

24 Plans for seeking research ethics committee/institutional review board (REC/IRB) approval

Protocol amendments

25 Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes, analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals, regulators)

Consent or assent 26a Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and how (see Item 32)

26b Additional consent provisions for collection and use of participant data and biological specimens in ancillary studies, if applicable

Confidentiality 27 How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial

Declaration of interests

28 Financial and other competing interests for principal investigators for the overall trial and each study site

Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators

Ancillary and post-trial care

30 Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial participation

Dissemination policy

31a Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals, the public, and other relevant groups (eg, via publication, reporting in results databases, or other data sharing arrangements), including any publication restrictions

31b Authorship eligibility guidelines and any intended use of professional writers

31c Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code

Not applicable

Not applicable

Not applicable

Page 19

Not applicable

Page 19

Not applicable

Page 19 and 20

Pages 22 and 23

Page 18

Not applicable

Pages 19 and 20

Page 20

Not applicable

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Appendices

Informed consent materials

32 Model consent form and other related documentation given to participants and authorised surrogates

Biological specimens

33 Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in the current trial and for future use in ancillary studies, if applicable

*It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013Explanation & Elaboration for important clarification on the items. Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons “Attribution-NonCommercial-NoDerivs 3.0 Unported” license.

In protocol document

Not applicable

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Cluster randomised feasibility trial to improve the Control of

Hypertension In Rural India (CHIRI): a study protocol

Journal: BMJ Open

Manuscript ID bmjopen-2016-012404.R1

Article Type: Protocol

Date Submitted by the Author: 02-Aug-2016

Complete List of Authors: Riddell, Michaela; Monash University, Department of Medicine, School of Clinical Sciences Joshi, Rohina; University of Sydney, The George Institute for Global Health Oldenburg, Brian; University of Melbourne School of Population and Global Health Chow, Clara; University of Sydney, The George Institute for Global Health; Children\'s Hospital at Westmead, Department of Cardiology Thankappan, K; Sree Chitra Tirunal Institute for Medical Science and

Technology, Achutha Menon Centre for Health Science Studies Mahal, Ajay; Monash University, School of Public Health and Preventative Medicine; University of Melbourne School of Population and Global Health, Nossal Institute for Global Health THOMAS, NIHAL; CHRISTIAN MEDICAL COLLEGE, Department of Endocrinology, Diabetes & Metabolism Srikanth, Velandai; Monash University, School of Clinical Sciences at Monash Health Evans, Roger; Monash University, Cardiovascular Disease Program, Biosciences Discovery Institute and Department of Physiology Kalyanram, Kartik; Rishi Valley Rural Health Centre

Kartik, Kamakshi; Rishi Valley Rural Health Centre Maulik, Pallab; The George Institute for Global Health; University of Oxford, George Institute for Global Health Arabshahi, Simin; Monash University, Department of Medicine, School of Clinical Sciences at Monash Health Varma, R; Sree Chitra Tirunal Institute for Medical Science and Technology, Achutha Menon Centre for Health Science Studies Gugilla, Rama; The George Institute for Global Health Suresh, Oduru; Monash University, Department of Medicine, School of Clinical Sciences; Rishi Valley Rural Health Centre Mini, GK; Sree Chitra Tirunal Institute for Medical Science and Technology, Achutha Menon Centre for Health Science Studies

D'Esposito, Fabrizio; University of Melbourne School of Population and Global Health, Centre for Health Equity Sathish, Thirunavukkarasu; University of Melbourne School of Population and Global Health, Centre for Health Equity Mohammed, Alim; The George institute for Global Health, India Thrift, Amanda; Monash University, School of Clinical Sciences at Monash Health

<b>Primary Subject Heading</b>:

Global health


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Secondary Subject Heading: Cardiovascular medicine

Keywords: Hypertension < CARDIOLOGY, prevalence, clinical trial, EDUCATION & TRAINING (see Medical Education & Training), India, self-management

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Cluster randomised feasibility trial to improve the Control of Hypertension In Rural India

(CHIRI): a study protocol

Michaela A Riddell1, Rohina Joshi

2 , Brian Oldenburg

3, Clara Chow

2,4, KR Thankappan

5, Ajay

Mahal6,7

, Nihal Thomas8, Velandai K Srikanth

1, Roger G. Evans

9, Kartik Kalyanram

10,

Kamakshi Kartik10

, Pallab K Maulik11,12

, Simin Arabshahi1, RP Varma

5, Rama K Guggilla

11,

Oduru Suresh2,10

, GK Mini5, Fabrizio D’Esposito

3, Thirunavukkarasu Sathish

3, Mohammed

Alim11

, Amanda G Thrift1*



3Melbourne School of Population and Global Health, University of Melbourne, Australia




6 School of Public Health and Preventative Medicine, Monash University, Melbourne

Australia

7Nossal Institute for Global Health, Melbourne School of Population and Global Health,

University of Melbourne, Australia

8 Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore,

Tamil Nadu, India

9 Cardiovascular Disease Program, Biosciences Discovery Institute and Department of

Physiology, Monash University, Melbourne, Australia

10 Rishi Valley Rural Health Centre, Chittoor District, Andhra Pradesh, India

11George Institute for Global Health, Hyderabad, Telangana, India

12George Institute for Global Health - Oxford University, Oxford, UK

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*Corresponding author:

Professor Amanda Thrift, Principal Investigator, School of Clinical Sciences at Monash Health,

Epidemiology and Prevention Unit, Level 5, Block E Monash Medical Centre, Monash

University, Melbourne AUSTRALIA

Email: [email protected]

Tel: +613-8572-2656

Keywords : Hypertension, prevalence, clinical trial, education, India, self-management

Word Count : 7,093

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ABSTRACT:

Introduction:

Hypertension is emerging in rural populations of India. Barriers to diagnosis and treatment

of hypertension may differ regionally according to economic development. Our main

objectives are to estimate the prevalence, awareness, treatment and control of

hypertension in three diverse regions of rural India; identify barriers to diagnosis and

treatment in each setting and evaluate the feasibility of a community based intervention to

improve control of hypertension.

Methods and analysis:

This study includes four main activities: (1) assessment of risk factors, quality of life,

socioeconomic position, and barriers to changes in lifestyle behaviours in approximately

14,500 participants; (2) focus group discussions with individuals with hypertension and in-

depth interviews with health care providers, to identify barriers to control of hypertension;

(3) use of a medicines-availability survey to determine the availability, affordability and

accessibility of medicines; and (4) trial of an intervention provided by Accredited Social

Health Activists, comprising group based education and support for individuals with

hypertension to self-manage blood pressure. Wards/villages/hamlets of a larger Mandal are

identified as the primary sampling unit (PSU). PSUs are then randomly selected for inclusion

in the cross-sectional survey, with further randomisation to intervention or control. Changes

in knowledge of hypertension and risk factors, and clinical and anthropometric measures,

are assessed. Evaluation of the intervention by participants provides insight into perceptions

of education and support of self-management delivered by the ASHAs.

Ethics and Dissemination:


Committee, Ministry of Health and Family Welfare (India), institutional review boards at

each site, and Monash University. In addition to publication in peer-reviewed articles,

results will be shared with federal, state and local government health officers, local health

care providers and communities.

Trial Registration:

The feasibility trial is registered with the Clinical Trials Registry - India (CTRI)

CTRI/2016/02/006678 (25/02/2016).

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Strengths and limitations of this study

• The study is being conducted in three economically and developmentally diverse

rural populations in Southern India, potentially enabling generalisability to many

other regions within India.

• Data collection is standardised and consistent across the three settings.

• Validated tools allow for comparison with other studies conducted in India and

similar settings in low to middle income countries.

• Inclusion of a cross-sectional survey, a survey of availability of medicines, and

qualitative interviews with doctors and patients will allow triangulation of potential

barriers to diagnosis, treatment and control of hypertension.

• The training programme delivered to non-physician health workers has not been

formally tested, thereby potentially limiting the efficacy of the intervention

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INTRODUCTION

Hypertension is the leading contributor to the global burden of disease and mortality.[1] In

2000, approximately 120 million Indians had high blood pressure and this figure is expected

to increase to about 215 million by 2025.[2] According to a recent systematic review of

hypertension in India overall prevalence of hypertension was estimated to be nearly 30%,

with a significant difference in the overall pooled prevalence between urban (33.8% (95%

Confidence Interval (CI): 29.7, 37.8), and rural (27.6% (95%CI: 23.2, 32.0) populations

nationally. This disparity was particularly marked in West India (pooled prevalence urban

(35.8% (95% CI 35.2, 36.5), and rural (18.1% (95%CI: 16.9, 19.2)).[3] With the rapid

urbanisation of India, lifestyle changes, known to be associated with increased risk of

hypertension, become more common. These lifestyle changes may be driving the

convergence of the prevalence of hypertension between urban and rural India.[4] Such

convergence is observed in the pooled estimates, using random effect analysis, for South

India where there were no detectable differences in the prevalence of hypertension

between rural and urban populations (urban: 31.5% (95%CI, 23.6, 39.5) vs rural: 28.3%

(95%CI, 21.4, 35.1), p = 0.62).[3]

Recent observations indicate that only approximately one quarter of the people with a

diagnosis of hypertension in rural Kerala receive treatment and, of this population, only

approximately 30% has their blood pressure (BP) within the therapeutic target [5, 6]

(systolic BP (SBP) <140 mmHg and diastolic BP (DBP) <90 mmHg).[7]

There are many different barriers to the diagnosis and treatment of hypertension in both

urban and rural regions. These barriers likely comprise proximate determinants [8] and

operate at both the individual and systems level.[9] For example, awareness (diagnosis) of

hypertension at the individual level may be influenced by distance to, and utilisation of,

health services, physical inactivity and social factors.[10] System level factors, which may

influence awareness of hypertension, include the knowledge of risk factors by health care

workers, availability of equipment for measuring blood pressure, and quality, availability

and expertise of health care providers. Treatment of hypertension is influenced by age,

distance to health care [11] and socioeconomic position (SEP).[12, 13] At the system level,

treatment may be influenced by knowledge and implementation of current treatment

initiation guidelines and availability of medicines.[14] Control of hypertension is likely

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influenced individually by adherence to medication, SEP, health literacy and understanding

of chronic disease and risk factors for chronic disease such as physical activity and tobacco

use.[11-13, 15] Within health systems, control of hypertension may be influenced by

understanding of treatment guidelines, availability of medication, and capacity to monitor

and follow up patients.[14]

There is also some emerging evidence that system and individual level barriers may vary

according to the stage of epidemiological, demographic and economic transition of different

populations.[8, 16] For example, as the disease patterns in the population change rapidly,

training of the health workforce may not be adequately up-to-date and basic diagnostic

tools (such as BP machines) may also be lacking. In regions where the demographic and

economic transition is more advanced, there is a greater prevalence of hypertension and

thus a greater awareness of hypertension-related factors such as obesity and physical

inactivity.[17] In disadvantaged and poverty-stricken communities, where the population

has not yet been exposed to economic development, the epidemiological transition is still at

an earlier stage.

Disadvantaged communities still comprise the largest proportion of the population in

resource poor countries, but little is known about the awareness of hypertension or of the

individual and system level barriers to its diagnosis and treatment in these settings. An

improved understanding of the awareness of hypertension in such disparate settings and

the barriers to prevention, diagnosis and treatment will provide the critical knowledge base

needed to overcome these barriers. The aims of this research are, within three diverse rural

regions, to (i) estimate the prevalence, awareness, treatment and control of hypertension;

(ii) use these baseline data to develop strategies to better manage hypertension in rural

communities in India; and (iii) evaluate the feasibility of a community-based intervention to

improve self-management and control of hypertension.

The research protocol described herein comprises two phases in each of the three settings,

with phase 1 having three parts:

Phase 1: Baseline assessment

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a. A baseline cross-sectional study to obtain information about the prevalence,

awareness, treatment and control of hypertension.

b. Qualitative studies, comprising focus group discussions among individuals with

hypertension and in-depth interviews with health care providers, to identify individual

and system level barriers to control of hypertension.

c. A medicines-availability survey to determine the availability, affordability and

accessibility of medicines used for treatment of hypertension, type 2 diabetes mellitus

and secondary prevention of cardiovascular diseases.

Phase 2: A feasibility study of an intervention to improve control of hypertension, developed

based on the findings of the cross-sectional survey and qualitative studies. The intervention

has two basic components: a) peer group based education and support for individuals with

hypertension for self-management of blood pressure; and b) health services and workforce

strengthening.

Setting

The study is being conducted in three diverse rural regions in Southern India, each of which

is at a different stage of economic and demographic transition: Trivandrum in Kerala, the

West Godavari District in Northern Andhra Pradesh (AP) and the Rishi Valley region in

Southern AP (see Supplementary Figure 1).

Trivandrum, Kerala (late transition): Kerala is the most advanced state in demographic and

epidemiological transition in India.[18] Life expectancy is 76.4 years[19] and literacy is

93.9%.[20] Approximately half of the population in the state resides in non-urban areas.[21]

Changes in cultivation patterns from food crops to more profitable cash crops and large

scale international migration has rendered Kerala both a wealthier and a less agrarian state

than the rest of India.[19, 22]

West Godavari, AP (medium transition): The Western Godavari study region comprises 897

villages. Life expectancy in Andhra Pradesh in 2001-6 was 62.8 years for men and 65 years

for females.[23] In 2011 approximately 75% of the population in West Godavari was literate,

and the majority of the residents (79.5%) lived in rural areas.[24]

Rishi Valley, AP (early transition): This rural site is located in the Kurabalakota Mandal, which

contains six villages, in the Chittoor District near the South Western border of AP.

Approximately 38,000 residents in Kurabalakota Mandal reside in 221 hamlets

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(habitations/sub-villages). Hamlets are the smallest administrative geographic units in this

region. The population of this Mandal are largely subsistence farmers and are economically

disadvantaged with an average monthly household income well below the global standard

for poverty. Approximately half the population in this region is estimated to have no formal

schooling.[25]

HYPOTHESES

We hypothesise that:

1. Knowledge/awareness of the presence of hypertension and about risk factors associated

with hypertension is greater in the late transition region than in the early transition

region.

2. Prior BP measurement is less common in the early transition region (Rishi Valley) than in

the late (Trivandrum) and medium transition region (West Godavari).

3. In those previously identified as having hypertension, costs of treatment are the greatest

barrier to ongoing management of hypertension in all settings.

4. Poor management of hypertension is more common in women, people living below the

poverty line, and in those who did not finish high school.

5. High salt intake is a major risk factor for hypertension in both men and women in the

late transition region, but its effect is limited to men in the early transition setting.

6. A community based peer group education and self-management programme conducted

by ASHAs is feasible.

METHODS AND ANALYSIS

Study design/sampling frame

Wards/villages/hamlets of a larger mandal (also known as taluk), were identified as the

primary sampling unit (PSU). At each study site these PSUs were then randomly selected for

inclusion in the cross-sectional survey (Phase 1 of the study, Figure 1) using computer-

generated random numbers. For Trivandrum the PSU is wards, for West Godavari the PSU is

villages and for the Rishi Valley site the PSU is hamlets (habitations) (see Supplementary

Figure 2A, 2B and 2C for site specific sampling frames).

1a: Baseline cross-sectional survey

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A cross-sectional survey was initially conducted to quantify the burden and awareness of

hypertension and examine how the barriers to diagnosis and management differ between

settings. Recruitment for this study commenced in January 2014 and was completed in

December 2015. Approximately 14,500 adults living in the study areas have been selected to

provide data for the baseline survey. The role of gender, socioeconomic deprivation, and

education on the diagnosis and management of hypertension in each of the three rural

areas is being explored. The data have been used to design the intervention component of

the study.

Recruitment to cross-sectional survey

Population censuses (specifically completed for this study or existing polling booth registers)

at each site were used to randomly select potential participants. In Trivandrum and West

Godavari sampling was stratified by age and sex using this approach. However, due to

structural factors related to distance between hamlets and demography, this was not

feasible in the Rishi Valley region. Residents of the PSU aged at least 18 years were eligible

for recruitment to the cross-sectional survey.

Trivandrum: Among the 14 districts in Kerala, Trivandrum district was selected based on its

proximity to the collaborating institute (Sree Chitra Tirunal Institute for Medical Sciences

and Technology). Chirayinkizhu taluk was selected randomly from the four taluks in

Trivandrum district. Of the 22 Panchayats (local administrative body in rural areas) within

Chirayinkizhu taluk, ten were randomly selected. From each of the selected Panchayats one

ward (the smallest geographic unit of a Panchayat) was randomly selected. In each ward,

using the polling booth list, the total number of individuals was divided into 12 age and sex

groups (18-24, 25-34, 35-44, 45-54, 55-64 and 65+). From each group 30 individuals were

randomly selected to get a total sample of 360 in each ward. Thus 3600 participants were

selected in the Trivandrum district to participate in the cross-sectional survey. Additional

sampling was conducted (10 from each age and sex band) to replace those participants who

had migrated, died or refused to participate.

West Godavari: A sampling frame was developed by mapping all 17 Primary Health Centres

(PHCs) within a 50 km radius around the town of Bhimavaram. We excluded those PHCs

participating in other studies conducted by the George Institute and randomly selected 10

of the remaining PHCs. All the villages serviced by each PHC were included in the list.

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Villages with fewer than 3000 residents were excluded. One village was then randomly

selected from each PHC, resulting in inclusion of 10 villages. Mapping all the selected

villages enabled generation of an age and sex population list with house addresses.

Population lists from the mapping were used to randomly select 4500 individuals over the

age of 18 years from each participating village. Additional sampling was conducted to

replace those participants who had migrated, died or refused to participate. Sampling was

stratified by 12 groups defined by age (18-24, 25-34, 35-44, 45-54, 55-64, 65+) and sex with

the goal of including comparable numbers of individuals from each group.

Rishi Valley region: The study population comprised the six villages of the Kurabalakota

Mandal in the Chittoor District, Southern AP. These villages comprised 221 hamlets or small

habitations. Hamlets were stratified by population size (small, medium and large) and then

139 were randomly selected in accordance with the sampling strategy using computer-

generated random numbers (generated at Monash University). This was to ensure sampling

of approximately equal numbers of hamlets from each size stratification. Six hamlets were

excluded due to migration of population. We also excluded the hamlet in which the Rishi

Valley Rural Education Centre was located because the population was largely transient,

comprising teachers and students who reside in the hamlet only during school time. A study

centre was set up in a communal area of the hamlet convenient for all the residents. All

residents aged at least 18 years were invited to participate in the cross-sectional survey.

Research officers ensured that all residents were informed of the presence of the study

team in the habitation by house-to-house notification and encouragement to attend.

Data collection/measurement

The instruments and measurements chosen for this project are based on recommendations

from the World Health Organization (WHO) STEPwise approach to disease surveillance

(WHO STEPS) [26] and other validated tools for quality of life, socioeconomic position (SEP),

and barriers to changes in alcohol and tobacco behaviour as listed in Supplementary Table 1.

The list of measures comprise (1) basic demographic information including age, income,

gender, marital status, religion, number of children, and type of work undertaken; (2)

lifestyle-related factors such as physical activity, tobacco use, and alcohol consumption,

dietary factors, including cooking practices and use of salt, stress, and overcrowding; (3)

knowledge about hypertension and its risk factors, awareness of hypertensive status, and

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reports of the timing and outcome of prior blood pressure measurements; and (4) further

details about use of medications (both allopathic and AYUSH or other traditional therapies),

barriers to treatment including access, cost, adoption of lifestyle factors and compliance

with medication use (see Supplementary Table 1 for full list of variables). Questionnaires

were developed in English and then translated into the site-specific language (Telugu (AP),

Malayalam (Kerala)) and back translated to detect and correct errors.

Standardised clinical measurements are collected as follows; arterial BP and heart rate are

measured after the participant has sat quietly for at least 15 minutes. BP is measured at

least three times at three minute intervals using the appropriate cuff size and a Digital

Automatic Blood Pressure Monitor (DABPM- OMRON HEM-907, OMRON Healthcare

Company, Kyoto, Japan) according to the WHO STEPs protocol, modified only by using the

right arm for all measurements.[26] Measurement continues until two consecutive readings

differ by <10 mmHg systolic and <6 mmHg diastolic, with a maximum of five measurements.

The mean of the last two consecutive measurements are used to define hypertensive status.

Height is measured to the nearest 0.1 cm using a portable stadiometer (213, Seca, Hamburg,

Germany). Weight is measured to the nearest 0.1 kg using a portable digital weighing scale

(9000SV3R, Salter, Kent, UK). Waist and hip circumference is measured using a spring-

loaded tension tape (Gulick M-22C, Patterson Medical, Illinois, United States) in a private

setting. In accordance with the WHO STEPS protocol [26] waist circumference is measured

at the midpoint between the lowest rib and upper point of the iliac crest and at the end of

normal expiration and hip circumference is measured at the maximum protrusion of the

buttocks.

To ensure standardisation, data collectors are trained in collection of anthropometric and

blood pressure measurements in accordance with the WHO STEPS protocol.[26]. This

training, conducted by the project manager for at least 5 days, is to ensure consistency of

data collection between sites. Training is provided in a similar manner to ensure that

questionnaire administration is also consistent across all sites. A study-specific training

manual containing step-by-step procedures for all data collection (anthropometric and

survey administration) is provided to each data collector. Data collection at each site is

further monitored by site supervisors. Follow-up training by the project manager and/or site

supervisor is also undertaken at each site approximately one month after commencement

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of data collection to ensure that data collection methods are implemented according to the

protocol.

Definitions: Participants whose measured mean systolic BP (SBP) is ≥140 mmHg and/or

mean diastolic BP (DBP) is ≥ 90 mmHg or who are taking medication for lowering blood

pressure are defined as hypertensive.[7] Waist circumference is deemed high when >80 cm

in women and >90 cm in men. A body mass index (BMI) ≥25 to 29.99 kg/m2 is defined as

overweight and BMI ≥30 kg/m2 as obese according to the revised BMI classification.[27]

Outcomes

Socio-demographic and economic characteristics of each population are determined,

including gender, SEP, education, income and expenditure. Information on utilisation of

health care, physical activity, tobacco use and consumption of alcohol are also collected.

Primary outcomes for Phase 1a of the study are prevalence, awareness, treatment, control,

knowledge of hypertension and associated risk factors. We compare knowledge of

hypertension, previous measurement of BP and barriers to treatment and management

(such as cost, education and SEP) of hypertension across study sites. Good (BP<140/90

mmHg) or poor (SBP≥140 mmHg or DBP≥90 mmHg) control of hypertension is assessed in

relation to lifestyle factors (physical activity, use of tobacco and consumption of alcohol),

dietary factors (including salt intake) and health care utilisation. Attitudes to healthy

behaviour change are also assessed.

Qualitative studies to identify barriers (Phase 1b)

To further investigate barriers to diagnosis, treatment and control of hypertension, focus

group discussions with people having hypertension are used to explore peoples’ experiences

with health care systems and their perceptions and beliefs about hypertension in

accordance with predetermined and shared exploratory questions (see Supplementary

Table 2 for the interview guide). Up to four focus groups involving up to 10 people with

hypertension in each focus group, identified in the cross-sectional survey as being aware of

their hypertension status, are conducted at each site (refer Supplementary Figure 2A, 2B,

and 2C). Focus groups are voice recorded and a second research officer takes notes

throughout the session. The recordings are translated and transcribed into English and

checked for accuracy with the research notes. Data analysis is carried out using the process

described by Green and colleagues.[28] We use a socio-ecological approach to the

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identification of themes, which considers the complex interplay between individual, social,

and systemic factors.[29-31]

In-depth interviews are carried out with health care providers (doctors, staff nurses,

ANMs/ASHAs) at each site to explore management of hypertension, and perceptions of the

health care system in relation to screening and management of hypertension and other

chronic conditions (see Supplementary Tables 3 and 4 for the interview guides).

Medicine pricing and availability: (Phase 1c)

To investigate the availability and price of medicines for hypertension and other related

non-communicable diseases (e.g. cardiovascular diseases [CVD], type 2 diabetes) a cross-

sectional survey of price and availability of essential medicines is undertaken. Included in

this survey are public (hospitals, clinics and health facilities), private (licensed retail

pharmacies and licensed drug stores) and ‘other’ sector medicine outlets (facilities selling

medicines at subsidised prices to all patients) located in the sampling frames of the CHIRI

study sites in AP and Kerala (refer Supplementary Figure 2A, 2B, and 2C). The medicines

selected for review are those used for treatment of hypertension, secondary prevention of

CVD, and treatment of type 2 diabetes mellitus and that are listed in the WHO Model List of

Essential Medicines,[32] National List of Essential Medicines of India,[33] Essential

Medicines List of the Government of (unified) Andhra Pradesh and the Rational Drug List

2012-13 of Kerala Medical Services Corporation Ltd.[34] The study methods have been

developed based on the WHO/HAI (Health Action International) methodology for measuring

medicine prices, availability, affordability and price components.[35] The survey is being

conducted across 20 public, 16 private and two ‘other’ sector pharmacies in the three

regions.

Phase 2: Feasibility of a community based programme for management of hypertension

facilitated by Accredited Social Health Activists (ASHA)

Phase 2 of the study is a feasibility trial which incorporates random allocation of

approximately 20% of the PSUs to the intervention and 40% of the PSUs to the control

condition (Figure 1). Specifically for the Trivandrum region two of 10 wards are allocated to

the intervention and four of 10 wards are allocated to the control condition. For the West

Godavari region two of 10 villages are allocated to the intervention and four of 10 villages

are allocated to the control condition. For the Rishi Valley region hamlets in one of six

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villages are allocated to the intervention and hamlets in two of six villages to the control

condition.

Allocation of only a subset of the initial PSUs was necessary due to budgetary and

programme timeline constraints. Random allocation of the PSUs to intervention or non-

intervention conditions is undertaken by the principal investigator (Figure 1). As this is a

feasibility study, the sample size for those receiving the intervention is not powered to

determine effectiveness. However, changes in individual measurements over time are

assessed. The intervention addresses those factors identified during the qualitative and

cross-sectional studies which contribute to control of hypertension in these settings and

includes both management and control strategies aimed at the individual, health service

delivery and policy levels.

Blinding

As this is a behavioural intervention programme, the people delivering the intervention

cannot be blinded to the intervention group. However, participants in the control regions

remain unaware of the intervention programme, and outcome assessors are blinded to the

intervention allocation of participants.

Recruitment and eligibility

Community members from the randomly selected PSUs, who are identified as hypertensive

in the cross-sectional study, are invited to participate in the intervention and control arms in

accordance with eligibility criteria given below (also see Figure 2). Recruitment commenced

in January 2016, and the intervention is expected to be completed in June 2016. Participants

are approached at their homes after identification, and recruited and consented during this

visit. For the intervention sites, the list of consented participants is provided to the

Accredited Social Health Activists (ASHAs) from those villages.

Eligible participants are those who:

1. Indicate they are aware of being hypertensive in the cross-sectional survey.

2. Are identified as having an average SBP of ≥140 mmHg and/or DBP ≥90 mmHg at the

cross-sectional survey, subsequently attend their primary health care provider and are

then formally clinically diagnosed with hypertension. Verification occurs by sourcing the

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medical record, contacting the health care provider or by confirmation of use of

medication(s) for hypertension (as observed);

3. Have an average BP of ≥140 mmHg SBP and/or ≥90 mmHg DBP during the cross-

sectional survey and then, at the time of recruitment to the intervention (or control),

have their blood pressure remeasured, and are found to still have an average BP of ≥140

mmHg SBP and/or ≥90 mmHg DBP.

4. Are taking medication(s) for hypertension (including diuretics, ACE inhibitors,

angiotensin II antagonists, β-blockers, Ca++

channel blockers or renin inhibitors.)

Intervention components

The intervention arm incorporates a community based self-management and education

support group, led by ASHAs, every 2 weeks for 3 months (i.e. six meetings). ASHAs are

female lay health workers, residing in each village, most of whom have completed

secondary schooling. Their work accountability primarily lies within the purview of the

Village Health Sanitation and Nutrition Committee (VHSNC) which is a committee formed at

the revenue village level and acts as a sub-committee of Gram Panchayat. They are

compensated for their time in specific situations (attending training and meetings) and

given incentives under various national health programmes, predominantly for maternal

and child health.

Content for the intervention components was driven by preliminary analysis of the cross-

sectional data which reflected poor knowledge of hypertension. Furthermore, principles of

the Chronic Disease Self-Management Program (CDSMP) as described by Lorig,[36] and

found to significantly contribute to improved self-management, were incorporated into the

programme content.[37] Content includes strategies to increase knowledge and

understanding of the disease, promote healthy behaviour change and clinical interaction

through goal setting. At each group meeting participants are weighed, have their blood

pressure measured and receive self-management and lifestyle education (Figure 3) from

locally sourced “expert” advisers. These advisers may include, but are not limited to,

clinicians from the primary health centre servicing the region, pharmacists, and nutritional

advisors.

ASHA Training

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For the intervention, ASHAs in each location are trained to deliver the self-management

sessions of the intervention and to collect data regarding the implementation of the

intervention. Training of ASHAs is standardised and undertaken by the site supervisors at

each site in accordance with the study specific ASHA training manual to ensure consistency

of training between sites. Training of ASHAs was first piloted at the Rishi Valley site using

four volunteer ASHAs not involved in the implementation of the intervention. Pilot training

was conducted by the Project Manager and included each site supervisor utilising “train the

trainer” principles.[38] Materials and resources for training ASHAs, as well as standardised

resources and education material for delivering the intervention were initially developed in

English. ASHAs involved in the pilot training provided important feedback that enabled us to

refine the educational resources for ASHAs and participants. Once these resources were

finalised, they were translated/back translated into site specific language (Telugu and

Malayalam).

At the beginning of the first training session the knowledge of ASHAs regarding

hypertension and other non-communicable diseases (NCDs) and their skills in measuring BP

and recording weight are assessed. The 5-day training regimen includes education about

NCDs that is based on, and complimentary to, the existing ASHA training Module for NCDs

(Module # 8),[39] measurement and recording of BP and weight, and maintaining records of

each meeting (attendance, measurements, meeting content, record problems or issues

faced by participants). Additionally, ASHAs are trained to deliver the educational material

regarding hypertension and self-management using pictorial flip-chart resources developed

for the intervention. ASHAs are also trained to initiate and support self-management of

hypertension by the participants through goal-setting. Incentives for ASHA are based on

remuneration under the schedule for Village Health Sanitation and Nutrition Committee

Activities [40] as well as Village Health and Nutrition Days.[41] In the two regions in Andhra

Pradesh the ASHAs are incentivised to promote attendance by as many participant and

support members as possible, via payment of 200 Indian rupees per meeting if more than

75% of enrolled participants attend. Thus, those that do not attend one meeting will be

followed up by an ASHA and encouraged to attend the next meeting. In the Kerala site the

ASHAs are paid according to remuneration under the schedule for Village Health Sanitation

and Nutrition Committee Activities [40] as well as Village Health and Nutrition Days,[41] and

were not paid extra when more than 75% of participants attended.

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Self-management education and group-based support

Each community group comprises up to 20 individuals with hypertension. The community-

based support group is supported and promoted by the Panchayat at each site. The

Sarpanch (the elected head of village) provides a letter of support and encouragement for

the intervention activities. This letter is enclosed with the letter of invitation to participate

in the intervention. The facilitator of the group, either the appointed village ASHA

(Trivandrum, West Godavari and Rishi Valley regions) or a person with equivalent

qualifications employed for the project (West Godavari region), is assisted by a member of

the research team at each meeting. The facilitator of the group organises and schedules

meetings, collects data during the meeting, and submits these data to the research team.

Each of the six meetings lasts approximately 90 minutes, and consists of various topics

related to hypertension (see Table 1). Next of kin or additional support persons are

encouraged to accompany and support the person with hypertension at each group meeting.

Table 1: Meeting schedule and details of meeting content

Meeting

Number

Topic Detailed information provided

1 Introduction Education session: what is hypertension?, risk factors,

chronic nature of disease, “know your numbers”, etc to be

carried out by a local health care provider

2 Self-management

education

Risk factors and modifiable activities to improve

control/management. Importance of medication adherence

3 Physical activity Incorporating physical activity into your day, including

group physical activity

4 Nutrition and Diet Importance of salt reduction (including recipes), alcohol

reduction, dietary assistance, increased fruit and vegetable

consumption (it is especially important for women to be

given strategies to save some vegetables and meat for

themselves)

5 Practical Self-

management

Practical ways to improve your control/management

(medication diary/ reminder system, etc). A pharmacist may

attend and provide information about drug availability

6 Next steps/

continuation

Review, changes made, ongoing difficulties, ongoing group

activities

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plans

Because of the nature of the intervention, a community-based peer support group with self-

management education, no data safety monitoring committee is required.

The community-based groups are used to educate group members about hypertension as

well as implement and enhance strategies for self-management of hypertension and related

NCDs (Table 1 and Figure 3). Resources developed specifically for the intervention are

primarily pictorial to ensure consistency of information at each site and to account for

disparities in educational levels across the three sites.[25]

Health systems activities/interaction

This feasibility study incorporates interaction and active involvement with providers from

the structured health systems. Involvement of the health providers (at primary, community

and sub-health centre levels) may strengthen and complement the group-based

intervention as well as enhance follow-up interactions with the health system (including

clinical and pharmaceutical services). The facilities of health care providers serving the

communities, selected for the baseline study, are assessed to identify how equipment and

staffing could be supported to improve diagnosis, treatment and ongoing management of

hypertension.

Analysis of the costs of the intervention

Costs of the intervention will be assessed in terms of programme costs such as ASHA

incentives and meeting set-up costs. Cost of developing resources including development

time and production of resources will inform this analysis

Control group

At the time of the initial data collection, all participants with elevated BP (SBP ≥140mmHg

and/or DBP ≥90mmHg) in the control sampling units are informed that their BP is elevated

and are advised to visit their local health provider for further investigation. Additionally,

these participants are provided basic nutritional advice such as reducing dietary salt,

reducing use of palm oil, increasing intake of fruits and vegetables, increasing physical

activity, and reducing use of tobacco and alcohol. Participants who were previously aware of

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their hypertensive status are advised to revisit their doctor for review of their medication

and to take their medication as told by their doctor. No further care or advice is provided

during the intervention period.

At the end of the intervention period the participants with hypertension in the control

sampling units are revisited for outcome measures, as outlined below. At this time these

participants receive further advice and recommendations regarding their hypertension

status. Furthermore, they are provided with pictorially-based educational material about

hypertension and how to manage the disease.

Outcomes of the Intervention

Participants attending the group meetings are revisited approximately 6 to 8 weeks after

the last meeting to complete final data collection. In these participants, and in those in the

control arm, we re-measure BP and anthropometry and re-asses health care utilisation,

attitudes to behaviour change and activities related to self-management of hypertension

(see Supplementary Table 1). Changes in continuous and categorical variables are assessed

relative to their values determined at the time of the cross-sectional survey. These include

SBP, DBP, waist and hip circumference, and weight. Medication initiation and any dosage

changes (observed and documented) are recorded. Medication adherence to BP lowering

medication is assessed in accordance with the Hill-Bone Compliance Adherence Survey.[42]

This survey is used to assess use of prescribed medication over the prior 2-week period.[42]

Knowledge about hypertension and associated risk factors relating to hypertension is

reassessed, along with physical activity over the 2 weeks prior to final administration of the

questionnaire. Barriers to attending the meetings are assessed, as are engagement and

utilisation of health services during the period of the intervention.

Perceptions by participants of the level of support obtained from the ASHA [43, 44] are

assessed in the final survey using a three scale response (not at all/some of the time/all of

the time). Usefulness of advice and self-management assistance received by the participant

is assessed using a seven-point Likert scale (a little useful to extremely useful).

Encouragement and support received, as perceived by the participant, resulting from

various group meeting activities is assessed using a four-point response (no support, a little,

moderate, a lot of support).

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After each meeting ASHAs complete a meeting report to aid the assessment of fidelity of the

meeting structure and content to the protocol (Supplementary Table 5). This report includes

details of the meetings such as the number of enrolled participants and community

members attending the meeting, and major activities undertaken during the meeting.

Additional activities by the ASHA to extend the healthy behaviour messages, such as

tobacco cessation and physical activity, as well as behaviours specific to the management of

hypertension from the meeting to the wider community by the ASHAs is also measured

categorically (Yes/No). This measure captures support/interactions of ASHAs with meeting

participants outside the meeting and their discussions of the meeting content with other

members of the community and/or with community leaders or health service members.

Members of the research team also complete a report after each meeting to provide further

information about the meeting activities and detail the shared experiences or difficulties of

the participants in managing their hypertension or achieving their goals (Supplementary

Table 5). These reports are used to assess the fidelity of the implementation of the

intervention to the protocol.

System outcomes of the programme are obtained via surveys of ASHAs at the end of the

intervention (and compared to surveys conducted at the commencement of the

intervention) to assess changes in knowledge of ASHAs (Supplementary Table 5). We also

assess the integration or engagement of health providers in the programme by assessing

their participation during the intervention. Furthermore, participants provide information

about other providers of assistance and information/advice (health care team and

family/friends/community) and assess meeting activities (goal setting, attendance, problem

solving) for delivering self-management support. The overall response rate (people with

hypertension in the cross-sectional survey, number consented to participate in meetings) is

calculated and participants who discontinue the programme are asked to complete a

programme evaluation form and to undertake final measurements at the end of the

intervention.

Data Management

All assessments and data forms are checked on the day of completion. Any forms with

missing data or inconsistencies are returned to the Health Worker for completion. Data are

coded and entered as the study progresses. Edit checks are performed and data verified as

necessary.

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All forms are designed in TELEform Elite version 10.5®. Completed questionnaires are

electronically scanned into a computer using a Tagged Image File Format (TIFF). These data

are then transferred to Monash University and uploaded into a Microsoft Access database

using TELEform. The database contains no identifying information and is housed on a secure

server at Monash University. All principal investigators will have access to the de-identified

final data.

Data Analysis

Analysis will be based on intention to treat. For individual outcomes proportions will be

compared using Chi-squared (χ2) test

and continuous measures will be compared using

Student’s unpaired t-test. Univariable analysis will also be undertaken using logistic and

linear regression. Multivariable analyses will be adjusted for age, sex and study site.

Considering the unequal distribution of age and sex in the participating population,

appropriate sampling weights will be applied to all data analyses.

Knowledge/awareness of the presence of hypertension and about risk factors will be

calculated using the known (and measured) prevalence of hypertension in each population.

Between-group differences in knowledge, previous measurement of hypertension, and

barriers to treatment and their change over time will be compared using χ2. Logistic

regression (appropriate for the binary outcome variable of presence/absence of BP≥140/90

mmHg) will be used to study the factors associated with control of hypertension. Those

factors identified as either potentially significant (p < 0.20) or biologically relevant will then

be introduced into multivariable regression analyses in a backward stepwise fashion to

construct a predictive model for good management of hypertension. This technique enables

the assessment of both categorical variables (e.g. gender) as well as continuous variables

(e.g. age). The scales of the continuous covariates will be checked for suitability using

fractional polynomial plots. Collinearity between variables will be evaluated using partial

correlations. In addition, routine diagnostic tests (Hosmer-Lemeshow test) will be used to

validate the fitted model. We will test efficacy of the intervention by analysis of covariance.

This allows us to adjust for baseline differences between groups.

Trial registration

We applied for registration of the feasibility trial with the Clinical Trials Registry of India

(CTRI) on the 28th of September 2015, approximately 2 months before the first patient was

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enrolled. Our registration number (CTRI/2016/02/006678) was obtained from the CTRI on

25th

of February 2016, without any changes to the study design outlined in our original

application. Such delays are very common in India and so it is usual practice to commence

recruiting patients before the final registration number is received.

Ethics and Dissemination


Committee, Ministry of Health & Family Welfare, Government of India (No.

58/4/Indo_CHR/2013/NCD-II) and Monash University Human Research Ethics Committee

(MUHREC number 2013001327). Each site obtained ethics approval from individual

governing institutional review boards (IRBs) for site specific aspects of the study. The site in

Trivandrum obtained approval from Sree Chitra Tirunal Institute for Medical Sciences and

Technology Institutional Ethics Committee (IEC Regn No. ECR/189/Inst/KL/2013). The West

Godavari site obtained approval from the Centre for Chronic Disease Control, New Delhi (IEC:

IRB00006330). The Rishi Valley site obtained approval from the IRBs of the Rishi Valley

Education Centre and Christian Medical Centre, Vellore (IRB Min No. 8313). Prior to

inclusion in the survey, Sarpanches are approached to obtain approval for the study team to

seek participation from the residents of the village in the study.

All participants are provided a written participant information sheet and informed consent

form in the local language. The study research staff at each site is responsible for obtaining

informed consent. For those participants who are illiterate, the participant information

sheet is read out to them. All participants sign (thumb print for those who are illiterate) the

informed consent form.

Each consenting participant is assigned a study identification number. To maintain

confidentiality all questionnaires, and other study documents, include only this

identification number, with no identifying information present.

Feedback from study phases 1b and 1c will be consolidated after the intervention and

disseminated to public health systems to inform health provision services. Based on

medicines availability (Phase 1c) and qualitative feedback from focus groups and in depth

interviews (Phase 1b) a treatment algorithm/guideline which is consistent with the Indian

Hypertension Management Guidelines [7] will be developed. In order to strengthen the

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integration of community-based and delivered education programmes for self-management

of health into the local primary health care system, we will disseminate the following

information to benefit local health services through:

1. sharing of information gained from the cross-sectional survey;

2. developing resources for use by health system staff for assessing and treating

hypertension;

3. providing details to health centres about the resources and training they require to

support such an intervention.

We will also disseminate the following information to improve availability of pharmaceutical

preparations:

1. informing pharmacies about medicine availability and possibilities for providing

medications to suit communities enrolled in the intervention;

2. discussing options for enhancing or improving medication adherence (by addressing

availability, dosing and packaging options).

Results will be shared with the Ministry of Health & Welfare and officials of the National

Health Mission and relevant local health care providers and communities at each of the sites.

Further dissemination of the results to research, clinical and health communities will be

pursued via international peer-reviewed journal articles and conference presentations. The

Global Alliance of Chronic Diseases (GACD) will also be informed of the findings of the study.

DISCUSSION

Comprehensive assessment of the barriers to control of hypertension across three diverse

settings will provide important information about the diversity of barriers to care across

these settings and how these might most appropriately be addressed in the future.

Development of an intervention programme, based on the individual and system barriers

identified and tailored to the specific needs of each area included in the study, may provide

a solution to address the current deficiencies in managing hypertension across rural regions.

We will also be able to determine the feasibility of using ASHAs to deliver a community

group based self-management programme for management of hypertension. Task shifting

disease management and control from physicians to non-physician health workers is

increasingly being explored as a possible solution for populations with limited access to

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health care. In a systematic review of task shifting for non-communicable disease

management in low and middle income countries Joshi et al suggest that the use of non-

physician health workers may be effective and additionally be cost effective.[45] There are

mixed results for the effectiveness of community health workers (CHWs) in identification

and management of cardiovascular disease in various settings in India.[46, 47] Further trials

to assess the effectiveness of CHWs in the management of cardiovascular risk factors are

currently underway.[48, 49] Neither of these trials are testing the exclusive use of ASHAs in

specifically delivering hypertension self-management education and monitoring. However

these trials, along with ours, will provide valuable evidence which may encourage the

government to fund ASHAs to manage non-communicable diseases or to identify a new

cadre of village health workers to work in the area of non-communicable disease. Because

ASHAs are employed in most rural regions, the programme is more likely to be scalable

across rural India. This information will also contribute to disease prevention at a global

level as the lessons learned could be suitably adapted across other similar settings.

Strengths and limitations

A limitation to this study is that the training programme delivered to ASHAs has not been

formally tested. This may limit the efficacy of the intervention. However, after seeking input

from ASHAs involved in the pilot training, we were able to make important refinements to

both the ASHA training booklet and the educational resources for participants. We also

assessed the ASHAs skills in measuring anthropometry and BP, as well as their knowledge of

hypertension and NCDs before and after the formal training period as well as at the end of

the intervention. This will enable us to determine the competencies of the ASHAs.

There are also a number of strengths to this study. First, this is a large community based

study in three economically and developmentally diverse rural populations in Southern India,

with detailed data on demographics; lifestyle-related factors including physical activity,

tobacco use, and alcohol consumption; dietary factors, including cooking practices and use

of salt; stress; and overcrowding. Secondly, there is detailed knowledge about hypertension

and its risk factors, awareness of hypertensive status, and further details about use of

medications, barriers to treatment including access, cost, adoption of lifestyle factors and

compliance with medication use. Such a rich data set will enable detailed exploration of

associations between hypertension and economic and epidemiological transition.

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Furthermore, the additional qualitative studies, including the medicines availability survey,

in-depth interviews, and focus group discussions, will allow us to triangulate potential

barriers to diagnosis, treatment and control of hypertension. Data are collected using

validated and standardised tools which will allow comparisons with other studies in India

and other LMICs.

Finally, the feasibility study of employing ASHAs in community-based activities to prevent

and manage hypertension will add to the increasing body of evidence for utilising non-

physician health workers in the detection and management of NCDs, particularly in LMICs.

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AUTHOR’S CONTRIBUTIONS

MAR wrote the first draft of the manuscript. AGT is the Principal Investigator, and conceived

the study. All authors provided input into the study design, provided intellectual input to the

manuscript, and approved the final version of the manuscript.

FUNDING STATEMENT

This work was funded by The National Health and Medical Research Council (NHMRC) under

the Global Alliance for Chronic Disease (GACD) programme (grant number GNT1040030),

with additional funds provided from Monash University (via the principal investigator). AGT

was supported by a fellowship from the NHMRC (GNT1042600). PKM is a Wellcome

Trust/Department of Biotechnology Intermediate Career Fellow. RJ was supported by a

fellowship from the National Heart Foundation (GNT100484). The funders had no role in the

design or conduct of the study, and no role in the decision to submit the protocol for

publication.

DECLARATIONS OF INTEREST

Michaela A Riddell has nothing to disclose

Dr Rohina Joshi reports nothing to disclose

Brian Oldenburg has nothing to disclose

Clara Chow has nothing to disclose

KR Thankappan has nothing to disclose.

Ajay Mahal reports grants from National Health & Medical Research Council of Australia,

during the conduct of the study

Nihal Thomas reports grants from National Health & Medical Research Council of Australia,

during the conduct of the study

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Velandai K Srikanth reports nothing to disclose

Roger G. Evans reports receiving grant funding from the National Health and Medical

Research Council of Australia

Kartik Kalyanram has nothing to disclose

Kamakshi Kartik has nothing to disclose

Pallab K Maulik reports receiving an Intermediate Career Fellowship from the Wellcome

Trust/DBT India Alliance, during the conduct of the study

Simin Arabshahi reports grants from National Health and Medical Research Council of

Australia, during the conduct of the study

RP Varma has nothing to disclose

Rama K Guggilla has nothing to disclose

Oduru Suresh has nothing to disclose

GK Mini has nothing to disclose

Fabrizio D’Esposito has nothing to disclose

Thirunavukkarasu Sathish has nothing to disclose

Mohammed Alim has nothing to disclose

Amanda G Thrift reports grants from National Health and Medical Research Council of

Australia (GNT1040030 and GNT1042600), and grants from Monash University, during the


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Figure Legends:

Figure 1: CHIRI Study Design outlines the approach taken to select and survey the

populations. Primary Sampling Unit (PSU)

Figure 2: Recruitment flow chart for intervention study. Residents of the Primary sampling

unit who participated in the baseline cross sectional survey are eligible to be recruited into

the feasibility trial (intervention and control arms) based on the criteria and recruitment

flow chart depicted here. BP – blood Pressure, HCP – Health Care Provider, HTN –

Hypertension, SYS – systolic, DIA- diastolic, WHO – World Health Organization


ASHA –Accredited Social Health Activist, HCP -Health Care Provider, PHC -Primary Health

Centre, BMI -Body Mass Index

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Figure 1: CHIRI Study Design outlines the approach taken to select and survey the populations. Primary

Sampling Unit (PSU)

92x49mm (600 x 600 DPI)

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Figure 2: Recruitment flow chart for intervention study. Residents of the Primary sampling unit who participated in the baseline cross sectional survey are eligible to be recruited into the feasibility trial

(intervention and control arms) based on the criteria and recruitment flow chart depicted here. BP – blood Pressure, HCP – Health Care Provider, HTN – Hypertension, SYS – systolic, DIA- diastolic, WHO – World

Health Organization

105x66mm (600 x 600 DPI)

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ASHA –Accredited Social Health Activist, HCP -Health Care Provider, PHC -Primary Health Centre, BMI -Body

Mass Index

126x92mm (600 x 600 DPI)

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Supplementary material Cluster randomised feasibility trial to improve the Control of Hypertension In Rural India (CHIRI): a study protocol

Michaela A Riddell1, Rohina Joshi2 , Brian Oldenburg3, Clara Chow2,4, KR Thankappan5, Ajay

Mahal6,7, Nihal Thomas8, Velandai K Srikanth1, Roger G. Evans9, Kartik Kalyanram10, Kamakshi

Kartik10, Pallab K Maulik11,12, Simin Arabshahi1, RP Varma5, Rama K Guggilla11, Oduru Suresh2,10, GK

Mini5, Fabrizio D’Esposito3, Thirunavukkarasu Sathish3, Mohammed Alim11, Amanda G Thrift1*



3 Melbourne School of Population and Global Health, University of Melbourne, Australia




6 School of Public Health and Preventative Medicine, Monash University, Melbourne Australia

7Nossal Institute for Global Health, Melbourne School of Population and Global Health, University

of Melbourne, Australia

8 Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, Tamil

Nadu, India

9 Cardiovascular Disease Program, Biosciences Discovery Institute and Department of Physiology,

Monash University, Melbourne, Australia

10 Rishi Valley Rural Health Centre, Chittoor, Andhra Pradesh, India

11George Institute for Global Health, Hyderabad Telangana, India

12George Institute for Global Health ‐ Oxford University, Oxford, UK

1

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Trivandrum

Rishi Valley

West Godavari

Supplementary Figure 1. Location of each site.

2

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Kerala State

14 districts

Trivandrum District

Medicines survey

Chirayinkizhu Taluk (Sampling Frame)

Random Sampling (1 of 4 Taluks)

360 individuals from each of 10 wards = 3600



2 Wards (Intervention)

4 Wards (Control)


Random allocation of

wards

Feasibility study

FGDs and IDIs

Selected based on access to coordinating

institute

10 Panchayats

Random Sampling 10 of 22

Panchayats

Random Sampling 1 ward from each of 10 Panchayats

10 wards (one from each Panchayat)

Age/Sex stratified random sampling

Supplementary Figure 2: Sampling frames for individual study sites: A. Chirayinkizhu Taluk, Trivandrum District, Kerala B. West Godavari District, Andhra Pradesh, and C. Rishi Valley Region, Chittoor District, Andhra Pradesh. FGD – Focus Group Discussion, IDI – In Depth Interview

A.

3

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B. Andhra Pradesh State

All 3 Revenue Divisions

11 Mandals

Medicines survey

10 Villages (Sampling Frame)

Random Allocation

450 individuals each from 10 villages = 4,500



4 villages (Control)


Random Allocation

Feasibility study

FGDs & IDIs

3 Villages

West Godavari District

2 villages (Intervention)


Villages located within a 50 km radius of Bhimavaram town

Age- and sex-stratified sampling

4

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C. Andhra Pradesh State

Madanapalle Revenue

Kurabalakota Mandal

Medicines survey

221 Hamlets (Sampling Frame), Stratified by Hamlet Size (small, medium, large)

Random Sampling of Hamlets

133 Hamlets (45 small, 44 medium, 44 large),

6246 individuals (Sample)


Randomised Hamlets from 2 Villages (Control)


Random allocation

Feasibility study

FGDs

IDIs

7 Hamlets

Chittoor District

Randomised Hamlets from 1 Village (Intervention)


6 excluded (5 no inhabitants, 1 Rishi

Valley School habitation)

5

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Supplementary Table 1: Data collection, study phase and tools

Component Measurement tools/Questions Phase 1

Survey

Phase 2

Survey

Demographic Measures Population measures[1]]

Age, Sex, Marital status, Age oldest child Literacy (read/write), Highest Education, Average Household Income Source of household income (amount), Household earners Occupation, Ration Card (if yes what type), Household Expenditure Number of people and adults in household Health care insurance (type and who pays) Household structure (walls/floor/roof) Access to drinking water Toilet facility Use of washing after toilet

Clinical InformationFamily History

Close relative: history of heart attack before 60yr, history of stroke before 60yr, history of diabetes (any age), history of high BP (any age)

Co‐morbidities/ Risk Factors [1]

Ever had heart attack, coronary bypass, angioplasty/stent

Ever told by HCW: heart problems. Diabetes, chronic Kidney disease, high fats: if yes;

about how long ago (years/months)

Anthropometric [1]

Blood Pressure, Weight, Height, Waist and Hip Circumference

Treatment/ Awareness history [1]

Ever told Hypertension Ever had BP checked: if yes;

was it in last 12 months, who checked Blood Pressure

Ever had prescription for Blood Pressure medication; if yes;

where did you get it,

do you take it as directed

Behavioural Knowledge barriers

Which actions prevent Hypertension

What have you done in last 12mth

Physical Activity[ 1]

Physical activity as per WHO STEPS (including work and leisure related) Hours of Sleep Barriers to physical activity

Diet [1, 3‐5] Person who prepares food Add salt during cooking, if yes how many teaspoons What type of salt and whether iodised

Add salt before eating

Daily salt intake

Added sugar to food and drink before consuming

Days/week fruit intake

Typical servings of fruit/ typical day Days/week vegetable intake

Typical servings of vegetables/ typical day No. of meals/week with fried vegetables, meat/poultry, fish, nuts or legumes Number of times/week consuming dairy products, deep fried/fast foods Type of oil used to prepare meals Number of days eating eggs, chicken, fish, other seafood, mutton, beef, pork, rice(idly dosa, puttu etc), pulses (dhal kidney beans etc) other cereals (chapathi, puris, roti, chickpeas etc)

Barriers to eating fruit/vegetables

6

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Smoking [1, 6]

Ever smoked (100 cigarettes or 100 times smokeless) Age initiated Current smoking(smokeless) _ amount/day Frequency of tobacco use (smoking/smokeless) Time since quitting Passive exposure Barriers to quitting tobacco use

Alcohol [1]

Ever consumed alcoholic beverage Use and frequency past 30 days Drinking habit (now and previous 12 months) Use in past 12months Frequency of one standard drink over past 12 months Quantity /day (average) Quit due to health reason Age drinking initiated CAGE substance abuse screening tool [7]

Barriers to quitting alcohol [8]

Medication

Do you take medication for BP as directed?

Taking any medications? Taking any AYUSH or traditional medications? How often do you forget to take all medications Name/dose of medication (Coded), Medication taken as directed by health care worker, medication confirmed by research team

Hill Bone Compliance to therapy for high blood pressure [9]

Quality of Life General Assessment Chronic Burden [10]

Support[11] Bothered by problems[12]

How helpful to talk with about personal problem

How helpful to talk to about borrowing money

Bothered by problems

Mediators and Moderators Hypertension Knowledge[13] Hypertension beliefs

How does it affect health Likelihood of other disease if hypertension is controlled Which diseases prevented if hypertension is controlled High blood pressure when working/worried Lie down when having high blood pressure Medication too costly Doctor too far to see about high blood pressure

Cost Effective Analysis Health care utilisation

Medical treatment/advice as outpatient last 3 months: if yes;

Number of times in 1 and 3 months

Where and from whom, how did you pay

Medical use over last 12 months similar? If no, is it more or less? Admission as inpatient over last 12 months: if yes;

What type of facility, length of stay, how did you pay?

Last routine check‐up

If longer than 5 years – why?

Ease or difficulty to see a doctor

Transportation mode to health centre Length of time to get to health centre

Focus Group Discussions Explore current situation/beliefs of population

In depth Interviews Explore current situation/beliefs & attitudes of health personnel

Medicine availability surveyExplore current availability of prescribed medication for hypertension as per WHO essential list

WHO STEPS (World health Organisation STEPwise approach to disease surveillance;

7

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Supplementary Table 2: Focus Group Question Guide for Participants with Hypertension

Question Number

Guide question

1 Where do you usually go if you are ill with any disease?

1a Why do you go where you go?

2 Where do you usually go for chronic diseases, especially cardiovascular diseases?

2a Why do you go where you go?

3 What do you mean by high blood pressure?

4 Who gets high blood pressure (and cardiovascular diseases)?

5 What do you think causes high blood pressure?

6 How do people know if they have high blood pressure?

7 How blood pressure is usually diagnosed

7a How was blood pressure diagnosed in you?

8 Could you tell me about the care you receive for your high blood pressure?

8a Where do you usually go to receive care for your high blood pressure?

8b Could you tell me your experiences of receiving care for your high blood pressure (time to go to

hospital, time spent at hospital, your interactions with doctors and other health care workers)?

8c Could you explain about the instructions that you receive from doctors and other health care

workers?

9 What do you mean by control of high blood pressure?

9a Could you tell me how blood pressure can be controlled?

9b What do you think are the reasons for not being able to control high blood pressure?

10 Could you tell me what prevents you from seeking care for your blood pressure?

11 Could you explain about costs involved in getting care for your high blood pressure?

12 Could you explain where do you get your blood pressure medications?

12a What would you do if you don’t get the same medications as prescribed by your doctor or other

health care worker?

13 Could you explain about how you take your blood pressure medications?

14 Why do you think you are not able to take medications regularly?

15 Is there anything else you want to tell about high blood pressure treatment and control?

16 Could you tell me something about ASHAs in your village?

17 What could ASHAs do to control your high blood pressure?

18 If any program is done through your primary health centre to control your high blood pressure, what do

you want it to be like?

19 Is there anything else you want to tell me?

8

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Supplementary Table 3: Interview guide for in‐depth interview with doctors from Primary Health Centres (PHCs)

Question Number

Guide question

1 Could you describe how you usually manage patients with hypertension?

2 Could you tell me in whom do you regularly check blood pressure?

2a What is the approximate percentage?

2b What are the reasons for not checking blood pressure?

3 Could you tell me about any guidelines that you follow for the diagnosis and management of hypertension?

3a If yes, what guidelines do you follow?

3b If no, what are the reasons?

4 What do you think about absolute risk approach for management of patients with cardiovascular disease?

4a Do you use absolute risk approach?

4b If not, could you tell me the reasons?

5 How do you think the health care system in which you are working now is equipped for the diagnosis and management of hypertension?

5a If yes, what are the reasons for inadequate diagnosis and treatment of hypertension?

5b If not, what can be done to improve it?

6 Do you feel you are sufficiently equipped to diagnose and manage individuals with hypertension?

7 Do you think you need anything more, such as training, to deal with individuals with high blood pressure?

8 Could you tell me how you manage hypertensive patients with complications?

9 Do you have any comments or suggestions for improving the diagnosis and management of individuals with hypertension?

10 Do you have any other thing to say?

Supplementary Table 4: Interview guide for in‐depth interview with staff nurse or ANM/ASHA

Question Number

Guide question

1 Could you describe me your typical "working” day and what is usually involves?

2 Could you tell me how you are involved in the management of chronic conditions?

3 Could you tell me about your involvement in identification and management of individuals with high blood pressure?

4 Could you tell me about any training that you have received for checking blood pressure and identification and management of individuals with high blood pressure?

5 How do you think the health care system in which you are working now is equipped for the identification and management of individuals with high blood pressure?

5a If yes, then what do you think are the reasons for inadequate diagnosis and control of high blood pressure?

5b If not, what do you think can be done to improve it?

6 Do you feel you are sufficiently equipped to manage individuals with high blood pressure?

7 Do you think you need anything more, such as training, to deal with individuals with high blood pressure?

8 How is your relationship with other healthcare providers in your PHC and sub‐centre?

9 Could you tell me how do you feel about completing all the tasks given to you in a working day?

10 What do you think about having another health care worker to work with you?

11 Could you tell me about your salary?

12 Do you have any other comments or suggestions about how we can improve the identification and management of individuals with high blood pressure?

13 Do you have any other thing to say?

9

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Supplementary Table 5: Timing and use of data collection tools for process evaluation

Process Evaluation Pre‐

Intervention During

Intervention Post

Intervention

ASHA pre training knowledgeIntervention process evaluation (training)

ASHA post training knowledge & evaluation Intervention process evaluation (training)

Intervention Fidelity

Meeting attendance

Blood pressure monitoring

Medication adherence

Intervention Fidelity & Process Goal setting list

Participant Action plans completed

ASHA Meeting report

Research member meeting report

Participant Intervention Evaluation (including ‐ Attendance, reasons for missed meetings

Support from family/friends/community

Relationship with clinician/HCP

Perceived support from ASHA [14,15]

People with hypertension who did not participate

Factors enhancing ability to attend

Knowledge about hypertension

Perceptions of the community to extended role of ASHAs

ASHA post intervention knowledge Intervention process evaluation (training and retained knowledge)

ASHA, Accredited Social health Activist; HCP, health care provider

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REFERENCES 1. World Health Organization. The WHO STEPwise approach to chronic disease risk factor

surveillance. Secondary The WHO STEPwise approach to chronic disease risk factor surveillance 2004. http://www.who.int/chp/steps/riskfactor/en/index.html.

2. International Institute for Population Sciences (IIPS), Ministry of Health and Family Welfare (MOHFW). India ‐ National Family Health Survey 1998‐1999 (NFHS‐2). 2013. Available at http://microdata.worldbank.org/index.php/catalog/1405. Accessed April 2016.

3. Kennedy G, Ballard T, Dop MC. Guidelines for measuring household and individual dietary diversity. Food and Agricultural Organization of the United Nations, Rome, Italy, 2013:60. Available at http://www.fao.org/3/a‐i1983e.pdf. Accessed April 2016.

4. Brantsæter AL, Haugen M, Alexander J, et al. Validity of a new food frequency questionnaire for pregnant women in the Norwegian Mother and Child Cohort Study (MoBa). Matern Child Nutr 2008;4(1):28‐43.

5. Morris Hicks J. The 4Leaf Survey. 4Leaf Global, 2015. Available at https://4leafprogramdotcom.files.wordpress.com/2015/10/4leaf‐pdf‐survey‐103015.pdf. Accessed April 2016.

6. International Tobacco Control Policy Evaluation Project. ITC Survey‐ 4‐Country W9 Replensihment Web US online survey code 4C9‐Pw‐US. 2015. Available at http://www.itcproject.org/files/ITC_4C9_US_Replenishment_SNQ_web_EN.pdf. Accessed April 2016.

7. Ewing JA. Detecting alcoholism. The CAGE questionnaire. JAMA 1984;252(14):1905‐7. 8. Girish N, Kavita R, Gururaj G, et al. Alcohol use and implications for public health: patterns

of use in four communities. Indian J Community Med 2010;35(2):238‐44. 9. Kim MT, Hill MN, Bone LR, et al. Development and testing of the Hill‐Bone Compliance to

High Blood Pressure Therapy Scale. Progress in cardiovascular nursing 2000;15(3):90‐6. 10. Gebreab SY, Diez‐Roux AV, Hickson DA, et al. The contribution of stress to the social

patterning of clinical and subclinical CVD risk factors in African Americans: The Jackson Heart Study. Soc Sci Med 2012;75(9):1697‐707.

11. Seidman E, Allen L, Aber JL, et al. Development and validation of adolescent‐perceived microsystem scales: social support, daily hassles, and involvement. Am J Community Psychol 1995;23(3):355‐88.

12. Spitzer RL, Kroenke K, Williams JB, et al. A brief measure for assessing generalized anxiety disorder: the GAD‐7. Arch Intern Med 2006;166(10):1092‐7.

13. Oliveria SA, Chen RS, McCarthy BD, et al. Hypertension knowledge, awareness, and

attitudes in a hypertensive population. J Gen Intern Med 2005;20(3):219‐25.

14. Glasgow RE, Whitesides H, Nelson CC, et al. Use of the Patient Assessment of Chronic Illness Care (PACIC) with diabetic patients: relationship to patient characteristics, receipt of care, and self‐management. Diabetes care 2005;28(11):2655‐61.

15. McCormack LA, Williams‐Piehota PA, Bann CM, et al. Development and validation of an instrument to measure resources and support for chronic illness self‐management: a model using diabetes. Diabetes Educ 2008;34(4):707‐18 doi: 10.1177/014572170832102134/4/707 [pii][published Online First: Epub Date]|.

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1

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*

Section/item ItemNo

Description

Administrative information

Title 1 Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym

Trial registration 2a Trial identifier and registry name. If not yet registered, name of intended registry

2b All items from the World Health Organization Trial Registration Data Set

Protocol version 3 Date and version identifier

Funding 4 Sources and types of financial, material, and other support

Roles and responsibilities

5a Names, affiliations, and roles of protocol contributors

5b Name and contact information for the trial sponsor

5c Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities

5d Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint adjudication committee, data management team, and other individuals or groups overseeing the trial, if applicable (see Item 21a for data monitoring committee)

Introduction

Background and rationale

6a Description of research question and justification for undertaking the trial, including summary of relevant studies (published and unpublished) examining benefits and harms for each intervention

6b Explanation for choice of comparators

Objectives 7 Specific objectives or hypotheses

Trial design 8 Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group), allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory)

Page 1

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Identified on Master protocol Version 9, 2 March 2016

Page 22Page 1 and 22

Not applicable

Page 22

Not applicable

Pages 4-6

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Page 6

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2

Methods: Participants, interventions, and outcomes

Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be collected. Reference to where list of study sites can be obtained

Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and individuals who will perform the interventions (eg, surgeons, psychotherapists)

Interventions 11a Interventions for each group with sufficient detail to allow replication, including how and when they will be administered

11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease)

11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests)

11d Relevant concomitant care and interventions that are permitted or prohibited during the trial

Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended

Participant timeline

13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for participants. A schematic diagram is highly recommended (see Figure)

Sample size 14 Estimated number of participants needed to achieve study objectives and how it was determined, including clinical and statistical assumptions supporting any sample size calculations

Recruitment 15 Strategies for achieving adequate participant enrolment to reach target sample size

Methods: Assignment of interventions (for controlled trials)

Allocation:

Sequence generation

16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions

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Allocation concealment mechanism

16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned

Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to interventions

Blinding (masking)

17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how

17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s allocated intervention during the trial

Methods: Data collection, management, and analysis

Data collection methods

18a Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known. Reference to where data collection forms can be found, if not in the protocol

18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols

Data management

19 Plans for data entry, coding, security, and storage, including any related processes to promote data quality (eg, double data entry; range checks for data values). Reference to where details of data management procedures can be found, if not in the protocol

Statistical methods

20a Statistical methods for analysing primary and secondary outcomes. Reference to where other details of the statistical analysis plan can be found, if not in the protocol

20b Methods for any additional analyses (eg, subgroup and adjusted analyses)

20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation)

Methods: Monitoring

Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed


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21b Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial

Harms 22 Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct

Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent from investigators and the sponsor

Ethics and dissemination

Research ethics approval

24 Plans for seeking research ethics committee/institutional review board (REC/IRB) approval

Protocol amendments

25 Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes, analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals, regulators)

Consent or assent 26a Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and how (see Item 32)

26b Additional consent provisions for collection and use of participant data and biological specimens in ancillary studies, if applicable

Confidentiality 27 How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial

Declaration of interests

28 Financial and other competing interests for principal investigators for the overall trial and each study site

Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators

Ancillary and post-trial care

30 Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial participation

Dissemination policy

31a Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals, the public, and other relevant groups (eg, via publication, reporting in results databases, or other data sharing arrangements), including any publication restrictions

31b Authorship eligibility guidelines and any intended use of professional writers

31c Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code

Not applicable

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Appendices

Informed consent materials

32 Model consent form and other related documentation given to participants and authorised surrogates

Biological specimens

33 Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in the current trial and for future use in ancillary studies, if applicable

*It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013Explanation & Elaboration for important clarification on the items. Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons “Attribution-NonCommercial-NoDerivs 3.0 Unported” license.

In protocol document

Not applicable

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