Drugs for cardiovascular disease in India: perspectives of pharmaceutical executives and government officials on access and development-a qualitative analysis

Background: India shoulders the greatest global burden of cardiovascular diseases (CVDs), which are the leading cause of mortality worldwide. Drugs are the bedrock of treatment and prevention of CVD. India’s pharmaceutical industry is the third largest, by volume, globally, but access to CVD drugs in India is poor. There is a lack of qualitative data from government and pharmaceutical sectors regarding CVD drug development and access in India. Methods: By purposive sampling, we recruited either Indian government officials, or pharmaceutical company executives. We conducted a stakeholder analysis via semi-structured, face-to-face interviews in India. Topic guides allow for the exploration of key issues across multiple interviews, along with affording the interviewer the flexibility to examine matters arising from the discussions themselves. After transcription, interviews underwent inductive thematic analysis. Results: Ten participants were interviewed (Government Officials: n = 5, and Pharmaceutical Executives: n= 5). Two themes emerged: i) ‘Policy-derived Factors’; ii) ‘Patient- derived Factors’ with three findings. First, both government and pharmaceutical participants felt that the focus of Indian pharma is shifting to more complex, high-quality generics and to new drug development, but production of generic drugs rather than new molecular entities will remain a major activity. Second, current trial regulations in India may restrict India’s potential role in the future development of CVD drugs. Third, it is likely that the Indian government will tighten its intellectual property regime in future, with potentially far-reaching implications on CVD drug development and access. Conclusions: Our stakeholder analysis provides some support for present patent regulations, whilst suggesting areas for further research in order to inform future policy decisions regarding CVD drug development and availability. Whilst interviewees suggested government policy plays an important role in shaping the industry, a significant force for change was ascribed to patient-derived factors. This suggests a potential role for Indian initiatives that market the unique advantages of its patient population for drug research in influencing national and multinational pharmaceutical companies to undertake CVD drug development in India, rather than simply IP policy-directed factors

Strategies for Stakeholder Engagement and Uptake of New Intervention: Experience From State-Wide Implementation of mHealth Technology for NCD Care in Tripura, India.

BACKGROUND: Appropriate strategies and key stakeholder engagement are the keys to successful implementation of new health care interventions. OBJECTIVES: The study sought to articulate the key strategies used for scaling up a research-based intervention, mPower Heart electronic Clinical Decision Support System (e-CDSS), for state-wide implementation at health facilities in Tripura. METHODS: Multiple strategies were used for statewide implementation of mPower Heart e-CDSS at noncommunicable diseases clinics across the government health facilities in Tripura: formation of a technical coordination-cum-support unit, change management, enabling environment, adapting the intervention with user focus, and strengthening the Health Information System. RESULTS: The effective delivery of a new health system intervention requires engagement at multiple levels including political leadership, health administrators, and health professionals, which can be achieved by forming a technical coordination-cum-support unit. It is important to specify the role and responsibilities of existing manpower and provide a structured training program. Enabling environment at health facilities (providing essential equipment, space and time, etc.) is also crucial. Successful implementation also requires that patients, health care providers, the health system, and leadership recognize the immediate and long-term benefits of the new intervention and have a buy-in in the intervention. With constant encouragement and nudge from administrative authorities and by using multiple strategies, 40 government health facilities adopted the mPower Heart e-CDSS. From its launch in May 2017 until November 20, 2018, a total of 100,810 eligible individuals were screened and enrolled, with 35,884 treated for hypertension, 9,698 for diabetes, and 5,527 for both hypertension and diabetes. CONCLUSIONS: Multiple strategies, based on implementation principles, are required for successful scaling up of research-based interventions

Development of a Smartphone-Enabled Hypertension and Diabetes Mellitus Management Package to Facilitate Evidence-Based Care Delivery in Primary Healthcare Facilities in India: The mPower Heart Project.

BACKGROUND: The high burden of undetected and undertreated hypertension and diabetes mellitus is a major health challenge worldwide. The mPower Heart Project aimed to develop and test a feasible and scalable intervention for hypertension and diabetes mellitus by task-sharing with the use of a mobile phone-based clinical decision support system at Community Health Centers in Himachal Pradesh, India. METHODS AND RESULTS: The development of the intervention and mobile phone-based clinical decision support system was carried out using mixed methods in five Community Health Centers. The intervention was subsequently evaluated using pre-post evaluation design. During intervention, a nurse care coordinator screened, examined, and entered patient parameters into mobile phone-based clinical decision support system to generate a prescription, which was vetted by a physician. The change in systolic blood pressure, diastolic blood pressure, and fasting plasma glucose (FPG) over 18 months of intervention was quantified using generalized estimating equations models. During intervention, 6797 participants were enrolled. Six thousand sixteen participants had hypertension (mean systolic blood pressure: 146.1 mm Hg, 95% CI: 145.7, 146.5; diastolic blood pressure: 89.52 mm Hg, 95% CI: 89.33, 89.72), of which 3152 (52%) subjects were newly detected. Similarly, 1516 participants had diabetes mellitus (mean FPG: 177.9 mg/dL, 95% CI: 175.8, 180.0), of which 450 (30%) subjects were newly detected. The changes in systolic blood pressure, diastolic blood pressure, and FPG observed at 18 months of follow-up were -14.6 mm Hg (95% CI: -15.3, -13.8), -7.6 mm Hg (CI: -8.0, -7.2), and -50.0 mg/dL (95% CI: -54.6, -45.5), respectively, and were statistically significant even after adjusting for age, sex, and Community Health Center. CONCLUSIONS: A nurse-facilitated, mobile phone-based clinical decision support system-enabled intervention in primary care was associated with improvements in blood pressure and blood glucose control and has the potential to scale-up in resource poor settings. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01794052. Clinical Trial Registry-India: CTRI/2013/02/003412

Improving access to medicines via the Health Impact Fund in India: a stakeholder analysis.

BACKGROUND: In India, 50-65% of the population face difficulties in accessing medicines. The Health Impact Fund (HIF) is a novel proposal whereby pharmaceutical companies would be paid based on the measured global health impact of their drugs. We conducted a key stakeholder analysis to explore access to medicines in India, acceptability of the HIF and potential barriers and facilitators at policy level. OBJECTIVES: To conduct a stakeholder analysis of the HIF in India: to determine key stakeholder views regarding access to medicines in India; to evaluate acceptability of the HIF; and to assess potential barriers and facilitators to the HIF as a policy. METHODS: In New Delhi, we conducted semi-structured interviews. There was purposive recruitment of participants with snowball sampling. Transcribed data were analysed using stakeholder analysis frameworks and directed content analysis. RESULTS: Participation rate was 29% (14/49). 14 semi-structured interviews were conducted among stakeholders in New Delhi. All participants highlighted access to medicines as a problem in India. There were mixed views about the HIF in terms of relevance and scaleability. Stakeholders felt it should focus on diseases with limited or no market and potentially incorporate direct investment in research. CONCLUSIONS: First, access to medicines is perceived to be a major problem in India by all stakeholders, but affordability is just one factor. Second, stakeholders despite considerable support for the idea of the HIF, there are major concerns about scaleability, generalisability and impact on access to medicines. Third, the HIF and other novel drug-related health policies can afford to be more radical, e.g. working outside the existing intellectual property rights regime, targeting generic as well as branded drugs, or extending to research and development. Further innovations in access to medicines must involve country-specific key stakeholders in order to increase the likelihood of their success

Park availability and major depression in individuals with chronic conditions: Is there an association in urban India?

Green space exposure has been positively correlated with better mental-health indicators in several high income countries, but has not been examined in low- and middle-income countries undergoing rapid urbanization. Building on a study of mental health in adults with a pre-existing chronic condition, we examined the association between park availability and major depression among 1208 adults surveyed in Delhi, India. Major depression was measured using the Mini International Neuropsychiatric Interview. The ArcGIS platform was used to quantify park availability indexed as (i) park distance from households, (ii) area of the nearest park; and within one km buffer area around households - the (iii) number and (iv) total area of all parks. Mixed-effects logistic regression models adjusted for socio-demographic characteristics indicated that relative to residents exposed to the largest nearest park areas (tertile 3), the odds [95% confidence interval] of major depression was 3.1 [1.4-7.0] times higher among residents exposed to the smallest nearest park areas (tertile 1) and 2.1 [0.9-4.8] times higher in residents with mid-level exposure (tertile 2). There was no statistically significant association between other park variables tested and major depression. We hypothesized that physical activity in the form of walking, perceived stress levels and satisfaction with the neighborhood environment may have mediating effects on the association between nearest park area and major depression. We found no significant mediation effects for any of our hypothesized variables. In conclusion, our results provide preliminary and novel evidence from India that availability of large parks in the immediate neighborhood positively impacts mental well-being of individuals with pre-existing chronic conditions, at the opportune time when India is embarking on the development of sustainable cities that aim to promote health through smart urban design - one of the key elements of which is the inclusion of urban green spaces

Physicochemical equivalence of generic antihypertensive medicines (EQUIMEDS): protocol for a quality of medicines assessment.

BACKGROUND: Prevention and optimal management of hypertension in the general population is paramount to the achievement of the World Heart Federation (WHF) goal of reducing premature cardiovascular disease (CVD) mortality by 25% by the year 2025 and widespread access to good quality antihypertensive medicines is a critical component for achieving the goal. Despite research and evidence relating to other medicines such as antimalarials and antibiotics, there is very little known about the quality of generic antihypertensive medicines in low-income and middle-income countries. The aim of this study was to determine the physicochemical equivalence (percentage of active pharmaceutical ingredient, API) of generic antihypertensive medicines available in the retail market of a developing country. METHODS: An observational design will be adopted, which includes literature search, landscape assessment, collection and analysis of medicine samples. To determine physicochemical equivalence, a multistage sampling process will be used, including (1) identification of the 2 most commonly prescribed classes of antihypertensive medicines prescribed in Nigeria; (2) identification of a random sample of 10 generics from within each of the 2 most commonly prescribed classes; (3) a geographical representative sampling process to identify a random sample of 24 retail outlets in Nigeria; (4) representative sample purchasing, processing to assess the quality of medicines, storage and transport; and (5) assessment of the physical and chemical equivalence of the collected samples compared to the API in the relevant class. In total, 20 samples from each of 24 pharmacies will be tested (total of 480 samples). DISCUSSION: Availability of and access to quality antihypertensive medicines globally is therefore a vital strategy needed to achieve the WHF 25×25 targets. However, there is currently a scarcity of knowledge about the quality of antihypertensive medicines available in developing countries. Such information is important for enforcing and for ensuring the quality of antihypertensive medicines

Rationale and protocol for estimating the economic value of a multicomponent quality improvement strategy for diabetes care in South Asia

Background: Economic dimensions of implementing quality improvement for diabetes care are understudied worldwide. We describe the economic evaluation protocol within a randomised controlled trial that tested a multi-component quality improvement (QI) strategy for individuals with poorly-controlled type 2 diabetes in South Asia. Methods/Design: This economic evaluation of the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) randomised trial involved 1146 people with poorly-controlled type 2 diabetes receiving care at 10 diverse diabetes clinics across India and Pakistan. The economic evaluation comprises both a within-trial cost-effectiveness analysis (mean 2.5 years follow up) and a microsimulation model-based cost-utility analysis (life-time horizon). Effectiveness measures include multiple risk factor control (achieving HbA1c \u3c 7% and blood pressure \u3c 130/80 mmHg and/or LDL-cholesterol\u3c 100 mg/dl), and patient reported outcomes including quality adjusted life years (QALYs) measured by EQ-5D-3 L, hospitalizations, and diabetes related complications at the trial end. Cost measures include direct medical and non-medical costs relevant to outpatient care (consultation fee, medicines, laboratory tests, supplies, food, and escort/accompanying person costs, transport) and inpatient care (hospitalization, transport, and accompanying person costs) of the intervention compared to usual diabetes care. Patient, healthcare system, and societal perspectives will be applied for costing. Both cost and health effects will be discounted at 3% per year for within trial cost-effectiveness analysis over 2.5 years and decision modelling analysis over a lifetime horizon. Outcomes will be reported as the incremental cost-effectiveness ratios (ICER) to achieve multiple risk factor control, avoid diabetes-related complications, or QALYs gained against varying levels of willingness to pay threshold values. Sensitivity analyses will be performed to assess uncertainties around ICER estimates by varying costs (95% CIs) across public vs. private settings and using conservative estimates of effect size (95% CIs) for multiple risk factor control. Costs will be reported in US$ 2018. Discussion: We hypothesize that the additional upfront costs of delivering the intervention will be counterbalanced by improvements in clinical outcomes and patient-reported outcomes, thereby rendering this multi-component QI intervention cost-effective in resource constrained South Asian settings

Association between poor oral health and diabetes among Indian adult population: potential for integration with NCDs.

BACKGROUND: Studies in high-income countries have reported associations between oral health and diabetes. There is however a lack of evidence on this association from low and middle-income countries, especially India. The current study aimed to assess the prevalence of common oral diseases and their association with diabetes. METHODS: This cross-sectional study was nested within the second Cardiometabolic Risk Reduction in South Asia Surveillance Study. A subset of study participants residing in Delhi were administered the World Health Organization's Oral Health Assessment Questionnaire and underwent oral examination for caries experience and periodontal health assessment using standard indices. Diabetes status was ascertained by fasting blood glucose, glycosylated hemoglobin values or self-reported medication use. Information was captured on co-variates of interest. The association between oral health and diabetes was investigated using Multivariable Zero-Inflated Poisson (ZIP) regression analysis. RESULTS: Out of 2045 participants, 47% were women and the mean age of study participants was 42.17 (12.8) years. The age-standardised prevalence (95% confidence interval) estimates were 78.9% (75.6-81.7) for dental caries, 35.9% (32.3-39.6) for periodontitis. Nearly 85% participants suffered from at least one oral disease. Compared to diabetes-free counterparts, participants with diabetes had more severe caries experience [Mean Count Ratio (MCR)?=?1.07 (1.03-1.12)] and attachment loss [MCR?=?1.10 (1.04-1.17)]. Also, the adjusted prevalence of periodontitis was significantly higher among participants with diabetes [42.3%(40.0-45.0)] compared to those without diabetes [31.3%(30.3-32.2)]. CONCLUSION: We found that eight out of ten participants in urban Delhi suffered from some form of oral disease and participants with diabetes had worse oral health. This highlights the need for public health strategies to integrate oral health within the existing Non-Communicable Disease control programs

Process evaluation protocol for a cluster randomised trial of a complex, nurse-led intervention to improve hypertension management in India.

INTRODUCTION: India has high prevalence of hypertension but low awareness, treatment and control rate. A cluster randomised trial entitled 'm-Power Heart Project' is being implemented to test the effectiveness of a nurse care coordinator (NCC) led complex intervention to address uncontrolled hypertension in the community health centres (CHCs). The trial's process evaluation will assess the fidelity and quality of implementation, clarify the causal mechanisms and identify the contextual factors associated with variation in the outcomes. The trial will use a theory-based mixed-methods process evaluation, guided by the Consolidated Framework for Implementation Research. METHODS AND ANALYSIS: The process evaluation will be conducted in the CHCs of Visakhapatnam (southern India). The key stakeholders involved in the intervention development and implementation will be included as participants. In-depth interviews will be conducted with intervention developers, doctors, NCCs and health department officials and focus groups with patients and their caregivers. NCC training will be evaluated using Kirkpatrick's model for training evaluation. Key process evaluation indicators (number of patients recruited and retained; concordance between the treatment plans generated by the electronic decision support system and treatment prescribed by the doctor and so on) will be assessed. Fidelity will be assessed using Borrelli et al's framework. Qualitative data will be analysed using the template analysis technique. Quantitative data will be summarised as medians (IQR), means (SD) and proportions as appropriate. Mixed-methods analysis will be conducted to assess if the variation in the mean reduction of systolic blood pressure between the intervention CHCs is influenced by patient satisfaction, training outcome, attitude of doctors, patients and NCCs about the intervention, process indicators etc. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the ethics committees at Public Health Foundation of India and Deakin University. Findings will be disseminated via peer-reviewed publications, national and international conference presentations. TRIAL REGISTRATION NUMBER: NCT03164317; Pre-results