A range of in-depth, significant projects carried out by our cohorts of Emerging Leaders
CARdiovascular Disease: Identification of Obstacles and facilitators to MAximize secondary Prevention Policy and Strategies
This study aims at identifying obstacles to and facilitators of the use of evidence-supported medications for the secondary prevention of CVD. The overarching goal is to create context-specific tools to allow the information of evidence briefs for policymakers with respect to the optimal use of evidence-supported medications for the secondary prevention of cardiovascular disease.
This goal will be accomplished by two complementary approaches:
Aspirin, statins, ACEIs, and beta-blockers have demonstrated efficacy in the reduction of mortality when used in the secondary prevention of CVD. The PURE study has shown that in countries of all income levels, the use of these medications for CVD secondary prevention is sub-optimal. In the PURE study, the rate of use of evidence-supported secondary preventative medications ranged from 40-66.5% in high-income countries to 3.3-9.7% in low-income countries. The implication of this finding is that despite the existence of relatively inexpensive and simple measures that have been proven to reduce the burden of CVD in this high-risk population, patient care is far from ideal, and consequently, potential reductions in CVD morbidity and mortality are not being achieved.
We urgently need to identify the reasons for this gap between evidence and practice.
The reasons for sub-optimal uptake of effective medications in secondary prevention are likely to be context-specific. The gradient in their use from high- to low-income countries observed in PURE supports this contention. Therefore, context-appropriate research is needed to understand the reasons behind sub-optimal use, and strategies that may be successful in increasing their uptake. For optimal utilization of these treatments, a complex series of conditions need to be met. These conditions begin at the health systems level, and involve governments, drug manufacturers and distributors, individual drug prescribers, drug dispensers, and consumers. Obstacles to drug uptake in secondary prevention may occur anywhere along this continuum. While individual obstacles have been previously studied, we believe that the urgency with which the gap between evidence and implementation needs to be bridged is of such magnitude that a paradigm shift in approach is necessary. A conventional approach to address barriers to secondary prevention might be to identify individual barriers using observational techniques, then to test possible interventions targeted at these barriers in clinical trials. This approach is costly, slow, and can only effect change piecemeal, one intervention at a time. We propose, instead, that a policy-driven approach to aligning the conditions required for secondary prevention might offer advantages in delivering an increase in medication uptake. Policy influences a large proportion of the population in a relatively short timeframe. There is an important need to generate the evidence to inform policymakers in a timely manner. However to date, there has not been comprehensive evaluation of obstacles and facilitators of medication use for secondary CVD prevention at multiple levels and in diverse financial and sociocultural settings. This evidence is a requisite step, however, before policy recommendations can be made, both globally and to individual governments. The World Heart Federation Emerging Leaders program offers a unique opportunity to leverage expertise and energy from researchers from around the world to be able to identify these obstacles and facilitators in a manner tailored to individual countries and settings.
Qualitative inquiries with policy makers, patients, practitioners, health system workers and other stakeholders in New Delhi, India and Hamilton, Canada. Ethical clearance for the Delhi part of the study has been obtained from Public Health Foundation of India (PHFI), New Delhi, India. In New Delhi the research is being coordinated by Public Health Foundation of India and in Canada it is being coordinated by Population Health Research Institute (PHRI). All necessary permissions (local health authorities, as applicable) were taken well in advance for smooth conduct of the study. Individual proposals have been submitted to Ethics committees in PHFI and PHRI for approval in New Delhi and Hamilton respectively. The study will be explained in detail to each participant and will be asked to give written informed consent and also will be provided with Participant Information Sheet. A systematic review will be undertaken in addition to the qualitative interviews and a conceptual framework shall be designed based on this research.
The team is also supported by 3 research assistants – Ms Malvika Saxena (PHFI) (MS), Ms Lavanya Nambiar (PHFI) (LN) and Ms Victoria Peck (PHRI) (VP).
To conduct a systematic review of the barriers and facilitators to drugs for secondary prevention (beta-blockers, statins, angiotensin receptor inhibitors and antiplatelet drugs) in patients with cardiovascular disease.
Step 1: Designing of the Search strategy
In consultation with a specialist librarian, our search included the following databases: Medline, EMbase, Cochrane Library, Psychinfo, Health Systems Evidence, Health Management Information Consortium (HMIC), Latin American and Caribbean Health Sciences Literature (LILACS), Africa-Wide Information, Google Scholar.
A protocol for this study has been published on the PROSPERO international prospective register of systematic reviews, with the record number PROSPERO 2015: CRD42015019079.
Step 2: Selection criteria
Inclusion criteria: We included studies that reported on the effects of local, national, regional or international health system level arrangements (including factors, interventions, policies, or programs) on drugs for secondary prevention of cardiovascular disease (CVD), particularly adherence. The following types of studies concerning adult populations were included:
We focused on studies which considered beta-blockers, statins, angiotensin receptor inhibitors and antiplatelet drugs. There were no language restrictions and studies until October 2015 were included.
Exclusion criteria: We excluded studies that were not concerned with CVD or secondary prevention.
Step 3: Study Selection
Initially two reviewers independently screened the search results by title and abstract for potential eligibility. Full texts of potentially suitable articles were obtained and were further screened for inclusion by the following reviewers: JPW and JRFN; AB and M; KCQ and VP; MS and LN. Disagreements in the screening of full texts were resolved by a third reviewer.
Step 4: Data Extraction
A data extraction form was developed in Microsoft Excel by discussions between group members. A validation exercise was conducted to ensure reproducibility of data extraction. Data were extracted from each study on study design, setting, health system domains investigated, study methods, and outcomes. Included studies were independently assessed for risk of bias by two reviewers using a framework previously used in similar systematic reviews. Data was extracted according to a “health system framework” (as described by Maimaris et al 2013), incorporating: (a) health systems delivery; (b) health systems governance; (c) health systems financing; (c) health systems inputs: physical, human, intellectual and social resources; (d) outcomes for secondary prevention drugs of CVD- drug adherence, drug uptake. Full texts of potentially suitable articles were obtained and were further screened for inclusion with extraction performed by the following reviewers: JPW and JRFN; AB and M; KCQ and VP; MS and L. In addition, we searched conference proceedings and reference lists of relevant research articles. We also consulted experts in health policy regarding access to medicines.
Step 5: Team members are currently in the process of writing the paper.
Step 1: Interview Guides
We conducted an interpretative phenomenological analysis using multiple descriptive case study to examine the barriers and facilitators to CVD medication adherence in two settings, Hamilton, Canada and Delhi, India. A case study was selected as the most appropriate qualitative research design because the phenomenon of interest, cardiovascular medication adherence, was bound by its context and the boundaries between the context and phenomenon were not easily differentiated.
Step 2: Sample size
The units of analyses were the stakeholder groups involved in the study; patients, physicians (cardiologists, family physicians, nurse practitioners, AYUSH practitioners), and non-physician healthcare workers (pharmacists, social workers, nurses, hospital administrators, policy makers). In-depth, semi-structured interviews were conducted to explore the perceptions of cardiovascular medication use in secondary prevention, and the factors that influenced medication uptake.
A purposeful sample (n=61) of 23 patients, 12 physician/nurse practitioners, 2 AYUSH physicians, 10 pharmacists, 3 nurses, 4 hospital administrators, 1 social worker, 2 NGOs and 4 policy makers partook in an in-depth face-to-face or phone interview in Hamilton, Canada (n=20) or Delhi, India (n=41).
The sample was a mix of public and private sector workers; experienced and fresher doctors and health professionals and policy experts. Among the patients, defaulters and good performing patients were equally interviewed. Also, as the interviews progressed in the Indian setting, it was realized that alternate medicine practices may also play a role in secondary prevention of CVDs. Therefore, we intended interviewing at least a few AYUSH (Ayurveda, Yoga, Unani, Siddha and Homoeopathy) doctors in addition to the allopathic doctors.
Step 3: Recruitment process
The potential participants were approached through emails, telephone, in-person, and appointments made for a 40-45 minute interview. Patients were identified through the consulting physicians and their OPD visits.
Step 4: Tools
The developed tool was first pilot tested on a small number of subjects both in Delhi and Hamilton. Important modifications were incorporated into the interview guide, and will continue to be, as the process of interview guide development is an iterative one. The interviews are audio-recorded. Additional notes and non-verbal cues were also recorded by the interviewer. All recordings were transcribed in the local language and converted to English for uniformity. Transcribed data do not contain personal identifiers.
Step 5: Key stakeholder Interviews conducted
New Delhi, India
Step 6: Analysis plan
A conceptual framework was initially developed based on the protocol (Annexure 1). The transcriptions were manually analyzed to elicit appropriate themes and subthemes. A coding strategy based on Phenomenology approach was developed. Appropriate codes and sub codes are being generated.
A sampling strategy was prepared (Annexure 3). However, customized iterations were incorporated/made as deemed appropriate. Interim analysis wasconducted at three different levels:
Peer-reviewed publication of the systematic review, qualitative interviews, context-specific policy briefs as well as full reports will be produced. We will pro-actively engage with media (television, radio, print media, social media) for disseminating the major findings of our systematic review. Via existing knowledge networks, institutional support (PHFI and PHRI) and the World Heart Federation, appropriate contacts and media outlets will be identified and engaged with.
The overarching goal of this program is to reduce the morbidity and mortality of cardiovascular diseases (CVD) through the increased use of evidence-based, secondary-prevention medicines. This program will initially focus on coronary heart disease (HAD), with plans for expansion to stroke and congestive heart failure. The current feasibility study serves as a pilot to:
Cardiovascular disease (CVD) is the leading cause of all non-communicable disease (NCD) deaths, and is projected to increase by 15% worldwide between 2010 and 2030. A wealth of evidence and international guidelines support the use of low-cost, evidence-based medication, for the management of established CVD.
A multi-faceted, evidence-based, adaptable intervention that is focused on increased prescription of medications at the point of care and long-term follow-up with patients through structured messaging has the potential to significantly increase the prescription of secondary prevention medications and sustain their use of among patients with cardiovascular disease. This program will assess the prescription pattern and medication use to impact on the World Heart Federation’s goal of achieving 25% reduction in premature mortality by 2025, using software applications. It also has the potential to be adaptable across countries, and customizable to other healthcare conditions such as heart failure, stroke or rheumatic heart disease.
The current pilot study is planned to conduct in three community healthcare centers in Shanghai.The intervention comprises of 1) an easy to use mobile app-based, provider-level decision support system to increase secondary preventative medication use. When the physician sees a patient who meets inclusion criteria, the app can be activated to help guide the use of evidence-based medications for that patient. They can also easily enrol the patient into the TAKEmeds program. 2) Patients identified by participating providers will receive automated, periodic, evidence-based, tailored text messages or calls (if they cannot read messages) about consistent medication use and lifestyle modification (including smoking cessation) via text-messaging.
After completing the app and messages development, we implemented the quasi-experimental pilot with a pre-post design in Longhua community healthcare center, Xuhui District in Shanghai (n=98) and Hainan Nongken General Hospital (tier-three hospital) in Haikou, Hainan Province (n=92). The Hainan site was made possible with additional funding from Duke Kunshan University and both sites followed the same protocol. The study intervention comprises of 1) an easy-to-use mobile app-based provider-level decision support system to increase the prescription rates of evidence-based medicines, and 2) automated, evidence-based text messages or voice calls delivered for 12 weeks. We conducted baseline and follow-up surveys to examine changes in patient medication adherence and lifestyle factors. We used semi- structured interviews and surveys to obtain qualitative feedback from physicians and patients. The ethical approval was obtained from Fudan University, Hainan Nongken General Hospital and Duke University.
The team is currently collecting follow up data (to be completed by December 2015), data analysis and results dissemination are planned through June, 2016.
At the end of study, we are able to generate:
Further, the cooperation with Fudan University and Hainan Nongken General Hospital enables us to establish close partnerships with them. The School of Public Health in Fudan University ranks top three in China and they have wide network in hospitals and community healthcare centers in Shanghai. Hainan Nongken General Hospital is one of the few tier-three hospitals in Hainan Province, where the cardiovascular disease burden is high but resources are scarce. The established relationships will definitely be valuable assets to future research activities.
We have submitted two abstracts. The first one was submitted in October to World Congress of Cardiology & Cardiovascular Diseases 2016, to be held in Mexico June 4-7th. The abstract introduced our research methodology and presented the preliminary results of the 20 patients from Shanghai. The second one was submitted in October to the 2016 Annual Consortium of Universities for Global Health Conference to be held in San Francisco, April 9-11th. This abstract presented the technology development process of the app and messages.
We plan to submit two papers to be published in international journals: the first one about how we developed the app and messages will be submitted to Journal of Medical Engineering & Technology (invited) before February 1, 2016. This paper is expected to publish in September 2016. The second paper that presents the results of the study will be submitted by June 2016.
We will seek more funding for a second and third phase of the TAKEmeds project if the initial findings turn out to be promising. The second phase will formally test the feasibility and acceptability of the two systems in a sample of providers and patients in several selected LMICs with a total of 30 physicians and 300 patients. It will last 6 to 12 months with patient follow-up for 3 months. In terms of the third phase, we propose a cluster randomized, factorial-design controlled trial to investigate the efficacy of the intervention. The primary outcome will be the proportion of patients taking three or more out of four classes of medications at 12 months. The estimated sample size will be 2400 patients.
WikiMeds: Increasing Transparency to Promote use of Medicines for Secondary Prevention of Cardiovascular Disease
During the pilot phase, the specific aims are:
An estimated 17 million people die from cardiovascular diseases (CVD) every year. Beta-blockers, angiotensin converting enzyme (ACE-inhibitors), statins, and aspirin, have been proven to reduce mortality and recurrent cardiovascular events after a myocardial infarction (MI) or a stroke. These medications are widely recommended for the management of patients with CVD and their risk factors, yet their use is not optimal. Data from the Prospective Urban Rural Epidemiology (PURE) study involving 17 high, middle, and low income countries reported that among CVD patients in the community several years after a
stroke or those with coronary artery disease, only 25% were using antiplatelet drugs, 17% Beta Blockers, 20% ACE inhibitor or ARB, and 15% were using statins. This is worse in low and middle-income countries than high-income countries.
One of the targets of the Global Action Plan (GAP) proposed by the World Health Organization (WHO) is an 80% availability of affordable basic technologies and essential medications to combat non-communicable diseases. Providing access to affordable essential medications in developing countries is also a target to the Millennium Development Goals (MDG). While access is necessary for medication use, it is not sufficient. Barriers for the use of medicines include patient-, provider-, and health system-level factors, as has been documented in the case of hypertension. Health system barriers include price,
availability, and affordability of medicines. The health system can be adversely influenced by lack of transparency in the procurement process, supply chain, and ultimate purchase of medications by patients. Pricing variability is evident across countries and within countries. In addition, counterfeit medications have been reported in high-income countries, as well as low- and middle-income countries. Our WikiMeds intervention therefore aims to increase transparency in medicine governance and thereby increase the use of quality medicines among people with CVD.
It is expected that WikiMeds will provide patients with information regarding the availability and effectiveness of generic medications recommended for the secondary prevention of CVD, locations to buy these medications at a cheaper cost, and the importance of using these medications. Informed patients will ask their providers to prescribe the medications indicated for their condition. With improved information regarding price, quality, and availability, patients will also ask for generic medications at lower prices. From the price and quality information on WikiMeds, patients will be able to identify pharmacies that sell these medications at a lower cost and will be able to identify lower quality medications. Patients will provide feedback to the WikiMeds platform regarding prices and quality of medications they purchase from the pharmacies, which will then use crowdsourcing technology to magnify and consolidate patients’ reviews/feedback, with the aim of making these issues known to a large public audience and, ultimately, the administrators of the health system who then have the power and obligation to enact changes at the health system level.
The increased demand for better quality generic medications at a lower price will likely translate into private pharmacies lowering their prices and increasing availability of high quality generic medications at lower prices. This will also apply pressure on the public sector to improve their procurement strategies of generic medications and negotiate lower prices. This pressure might even force the public sector to lower taxes and mark ups of medications. This framework assumes that providing patients with this information and empowering them to make choices will translate in more available and more affordable medications. It will also improve provider prescription practices with the overall aim of increasing use of secondary prevention medications.
Choosing the pilot country and facilities: For overall feasibility of the study, a single country, Bangladesh has been selected for piloting. The pilot was initiated in one urban (Mirpur), one rural (Sirajgonj), and one peri-urban (Kamrangirchar) community. Facilities covered include the public and private sectors.
Developing budget and timeline: A detailed budget and specific timeline has been created for the coming year to cover aims 1 and 2 of the proposal.
Permission from the local authorities: The permission from NGO Affairs Bureau and ethical clearance from Bangladesh Medical Research Council have been taken before initiating the study. Currently, we are obtaining the permission letters for getting information from the public facilities.
Developing list of stakeholders and medications: List of stakeholders in Bangladesh and medication list has been selected. For study purposes the following categories of people were selected:
Developing consent form, survey guideline, and questionnaires: The study consists of three types of methods:
For the study purpose, a consent form has been developed which incorporates all the questionnaires and survey instruments. The questionnaires and the survey tool have been created after having in-depth discussion and literature review.
Field-testing of the questionnaire: An extensive field testing is currently going on from the 2nd of December with all the questionnaires in the selected areas.
As mentioned earlier, the local permission process took a little extra time, therefore the study started little late then anticipated.
The upcoming activities of the project includes the following:
PISCO: Developing a dynamic online library of NCD policies and actions to track progress towards the 25×25 goals
To develop a dynamic online library of NCD policies and actions to coordinate and track progress towards 25×25 goals, with an initial effort on policies to address salt intake. Our specific objectives are to:
Non-communicable diseases (NCDs) cause 36 million deaths yearly and account for over half of deaths in all regions except sub-Saharan Africa. In 2011, the UN General Assembly adopted a political declaration that committed its member states to the prevention and control of NCDs. Subsequently, countries agreed to adopt nine global targets, including an overarching target of reducing premature mortality from cardiovascular diseases, chronic respiratory diseases, cancers, and diabetes by 25% relative to their 2010 levels by 2025 (i.e., 25×25 target). Countries also agreed on targets for selected NCD risk factors: tobacco use, salt intake, harmful alcohol use, obesity, raised blood glucose and diabetes, raised blood pressure, and physical inactivity.
Reducing NCD risk factors and meeting the 25×25 target can be achieved through cost-effective national and regional policies that address factors including access, pricing, and advertising, among others. According to the WHO, decisions, plans, and actions undertaken to achieve specific health care goals within a society are referred to as health policies. Clear health policies should outline priorities and the expected roles of different groups while building consensus and informing people (WHO, 2015). Furthermore, policies can be considered to be ‘best buy’ policies if their implementation is highly cost-effective, cheap, feasible and culturally acceptable. Tobacco use is the most policy-responsive of targeted risk factors, with major successes in tobacco control in many countries. Less is known about other NCD policies like salt intake and physical activity.
High blood pressure (hypertension) is a global public health problem, causing 9.4 million deaths around the world annually. It is a major risk factor for CVD and high salt intake is a major contributor to high blood pressure. Furthermore independent of its effect on blood pressure, a high salt intake has also been shown to increase the risk of stroke, renal disease and left ventricular hypertrophy. Lowering dietary salt helps to lower the blood pressure and this has been shown to be an important determinant of the decrease in CVD mortality in some high-income countries (Elliot et al., 1996; Zhou et al., 2003; He & MacGregor, 2009). Salt reduction strategies is a best buy in the prevention of NCDs as it has been estimated that if salt consumption is reduced by 6 g/day, up to 2.5 million deaths could be prevented each year (He & MacGregor, 2009). Although salt reduction policies in some high-income countries like Finland, France, Ireland, Japan and the United Kingdom, have demonstrated some positive, measurable results, locally applicable salt reduction or substitution strategies are needed in low- and middle-income countries where salt intake remains high, with countries like India and South Africa taking initial steps to reduce salt intake through policy efforts. As a whole, however, these policy efforts have not been coordinated across regions or risk factors.
In 2012, the World Health Organization launched the Global Database on the Implementation of Nutrition Action (GINA), an interactive database that allows users to access information on the implementation of policies and interventions related to nutrition in member UN countries. As of May 2013, over 3,500 policies and actions in over 176 countries were included on the website, which facilitates comparison of commitments and actions for global nutrition. To our knowledge, there is not currently a similar effort to compare policy commitments with implemented action in the global NCD effort to achieve 25×25.
We propose to develop an online database of NCD-related policies that would support a more integrated approach to policy formulation and monitoring of progress in the global effort to prevent and control NCDs in the 25×25 and post-2015 development agendas.
The proposed policy database is an intended resource for three primary audiences: (1) policy-makers in member states who are involved in developing and implementing NCD-related policies in their countries; (2) researchers seeking to investigate the health and mortality impacts of implementation of selected population-based interventions/policies, and estimated the financial costs of their implementation under different scenarios; (3) policy organizations such as the World Heart Federation and UN foundation who are seeking to track global and national progress in specific policy actions to meet their targets for NCD risk factors by 2025. Ideally, the database will not only identify synergies and gaps in policy implementation for 25×25, but also foster discussions towards improved planning and coordination and the promotion of the most effective policies.
Identifying relevant policies and actions
We will use evidence based search strategies to identify national and regional (i.e., state or provincial) policies on salt reduction in the target countries of Canada, India, and Peru. These policies will include key documents (paper copies as well as Web-published) in English. To identify these relevant policies, we will:
Constructing the database
We will conduct qualitative key informant interviews to obtain information about what features stakeholders would consider important in such a platform, barriers they encounter in searching policies when conducting policy audits, perception of the policy landscape surrounding salt reduction etc. This information will be taken into consideration and all obtained policy documents and actions will be organized and thematically categorized using a relevant analysis framework and ATLAS.ti. We will begin with the following set of broad categories including: country, state or province (if applicable), policy or action title, type (action vs. policy), and date of adoption. We will provide a hyperlink to relevant policy or action documents, when available. For each policy or action, we will further provide information on the implementing organization, date of adoption (if applicable), and a summary of the goals, objectives or targets that relate to NCD prevention. Though the pilot study will be limited to information on policies and actions on salt intake for NCD prevention in English language, the shell database will be developed so that it can include multilingual uploads and information and information on policies/actions related to other major risk factors for NCDs.
Piloting the online platform
We will develop and pilot an online format for the database that will include searchable library of policies and actions in member states and a series of data visualizations that facilitate comparison of commitments and actions. In addition, end-users will be able to upload policies directly onto the database. For sustainability we plan to link it up to WHF website with a system that flags up when new policies are added using keywords such as health, policy, NCD etc.
Establish new collaborations for health modeling
An important next step following this pilot project is to map policies and actions against potential or realized health benefits and costs. Through existing relationships with the World Heart Federation, we will begin to establish new collaborations with population health modeling groups at the WHO that are currently developing methods to assess the population health benefits of various scenarios. Future outputs could include website data visualization of potential – or realized – health benefits of specific policies or actions in member countries.
EQUI-MEDS: Physico-chemical equivalence of generic antihypertensive medicines in Nigeria
To inform the evidence-base and catalyse global debate about the physico-chemical equivalence of generic anti-hypertensive medicines available in retail outlets in Nigeria.
Burden of hypertension
High blood pressure (BP), often termed hypertension, is one of the most important public health problems worldwide affecting one billion people, three quarters of which live in the low income and middle income countries. High BP is also the leading cause of cardiovascular disease (CVD) and is responsible for 13% of deaths globally. In most individuals, adequate management and control of BP is associated with a reduction in deaths and disability from a number of conditions including cerebrovascular, cardiovascular, and renal disease. Therefore, prevention and optimal management of high BP in the general population is paramount to the achievement of the World Heart Federation (WHF) goal of reducing premature CVD mortality by 25% by the year 2025 and to the World Health Organization (WHO) goal of reducing premature mortality from non-communicable diseases (NCDs) by 25% by the year 2025. Most importantly, widespread access to good quality antihypertensive medicines is a critical to successful implementation of effective BP control.
Substandard medicines are defined as medicines that do not meet the legally required quality specifications of a country’s regulators. In recent years it has emerged that the availability of substandard medicines is widespread and is a crucial public health problem in developing countries. In these countries, half of the medicines for major diseases, such as Malaria, have been found to be substandard in quality and it is concerning that they often have little or no active ingredient. In more developed countries, medicine safety is generally more highly regulated but substandard medicines still exist and have been shown to result in thousands of adverse reactions and some deaths. The problem of modern-day substandard medicines was first highlighted in 1985 at a conference in Nairobi. Unfortunately, the market of substandard generic medicines has continued to grow and has indeed spread all over the world during the last decade. According to the World Health Organisation (WHO), 25% of all medicines available in developing countries are substandard. Substandard generic medicines are a major contributor and have been shown to constitute 40-50% of all medicine supplies in Nigeria and Pakistan and one-third of all antibiotics and anti-malarial medicines in Nigeria and Thailand. A government led study in India has shown that 9% of medicines are substandard, with 15,000 generics manufacturers in India. The problem is widespread but the extent of the issue as it relates to antihypertensive medicines remains unclear.
Substandard generic medicines share a huge market as estimated by WHO at more than US$35 billion which represents more than 15% of the pharmaceutical market worldwide. More than 60% of the market generated from substandard medicines comes from developing countries (35-90% in south East Asia). Substandard medicine products provide attractive opportunities for producers because the financial benefits are high, production costs are relatively low and the risks limited. Producers are generally able to prepare large batches of the substandard medicines before moving on to start-up another opportunity in a different location. In addition, substandard medicines are generally easily transportable, have high value per unit and their quality cannot be scientifically or legally assessed without a quality testing laboratory. For all these reasons developing countries, including Nigeria, are targets for producers and traders.
Substandard antihypertensive medicines
Almost all kinds of medicines can be substandard however, most existing studies have investigated anti-malarial medicines and antibiotics. The US Pharmacopoeia drug quality and information program listed anti-hypertensive medicines among a class of possible substandard medicines in the African region. A study carried out in Philippines found that the antihypertensive medicine Adalat (Nifedipine) was one of the top five counterfeit medications. However, there is currently very little research being done to assess the quality of generic antihypertensive medicines. Importantly, given that people with high BP often require lifelong adherence to indicated medicines, the problem of substandard anti-hypertensive medicines is potentially a serious public health issue.
In summary, the WHF have set a target of reducing avoidable CVD mortality by 25% by 2025 and a priority area for achieving that target is improved BP management and control. Availability of and access to quality anti-hypertensive medicines globally is therefore a vital strategy needed to achieve the target. However, there is currently a scarcity of knowledge about the quality of antihypertensive medicines available in developing countries. Such information is important for enforcing laws to ensure quality of generic anti-hypertensive medicines. In this proposal we propose to conduct a pilot study that catalyses global debate about the physico-chemical equivalence of generic antihypertensive medicines available in the retail market of a developing country.
In this research work, a mixed methods design will be adopted, which include literature search, landscape assessment, collection and analysis of medicine samples. Ethics approval will be obtained from relevant institutions in the three areas being investigated.
According to the 2006 Census, the Federal Republic of Nigeria has a population of about 140 million. It has an area is 923,772 square kilometres (about 356,700 square miles). It is the most densely populated country in Africa and represents about 20% of the total population of sub-Saharan Africa. Although Nigeria has a large number of ethnic groups (approximately 250) the three dominants are the Hausas in the North, Yorubas in the West and Ibos in the Eastern part of Nigeria. We purposively selected a state from each 3 geopolitical zones (Kano, Osun State, Enugu states). Kano state has a population of approximately 9 million. It’s a major industrial center of the North part of Nigeria. Osun State has populations of approximately 3 million and the people are mostly traders, artisans and farmers. Enugu State is one the five Ibos states with population of over 3 million people. The chosen areas of Nigeria have been previously identified as a “hotspot” for availability of substandard antimalarial medicines and also affords practical benefits for this pilot study given the location of our team members and the connections available. In addition, Nigeria has relatively ‘porous’ borders, a huge population, a high level of corruption and ease of medication purchase. However, this proposal identifies the first step in a broader program of work and debate related to the quality of antihypertensive medicines available in developing countries.
Objective 1: Assessment of health systems and contextual features
To examine and understand health systems and contextual features that may enable availability of substandard antihypertensive medicines we will;
1. Map the local supply chain of antihypertensive medicines and explore medicine regulation to determine factors enabling substandard medicines. To do this we will conduct interviews with key informants and analyse publically available local policy documents in order to obtain a legal and administrative overview.
2. Document presence and reasons for expired or degraded medicines at the point of collection, stockouts of generally available samples and the cost of medicines
3. Review the content of patient information leaflets as well as the way it is presented, to determine whether they are user friendly.
Objective 2: Physico-chemical equivalence
To identify which generic brands to include for sampling we will initially review the five classes of anti-hypertensive medicines (Calcium channel blockers, beta blockers, ACE inhibitors, ARBs and centrally acting drugs) based on information available through the National Agency Food and Drug Administration and Control (NAFDAC) agency. We will then determine the most commonly prescribed medicines in each class through a combination of literature searches and through consultations with local clinicians/experts and key opinion leaders. We will randomly select 10 generics from each class for collection.
In each of the three states we will obtain a list of local government areas from which we will randomly select one rural and one urban area. Therefore, across the three states we will then have a total of six local government areas (three rural and three urban). We will then using geographical mapping to divide each of the included local government areas into four geographical regions or quadrants ie, north, east, south and west. Therefore, in each state we will identify eight regions (four from the rural local government area and four from the urban local government area). This will give a total of 24 regions for sampling across the three states. From within each the 24 geographical regions, one pharmacy shop and one patent medicine store will be randomly selected. To do this we will use GIS software to create a mesh of points from the respective regions. Therefore, in total there will be two retail outlets from each of the 24 geographical regions giving a total of 48 retail outlets altogether. We estimate approximately 10 samples will be obtained for each medicine class from each outlet however, we acknowledge this will vary between outlets. Physical and chemical equivalence will be measured (methods described elsewhere). Descriptive statistics will be carried out for comparing the generic medicines on their physical and chemical characteristics with the reference product (medicine). In addition, we will compare equivalence in rural versus urban areas and based on retail type (namely pharmacy or other ‘local drug outlet’).
Blood Pressure-HOME MONitoring Intervention Trial and Outcomes Research
Control of hypertension in low- and middle-income countries is poor. It has been documented that home blood pressure management significantly lowers blood pressure (BP) when compared to usual care in high-income countries. In a high-income country, one study of home blood pressure management (n=527) showed, at 6 months after intervention, a decrease in systolic blood pressure (SBP) 12.9 (95%CI 10.4-15.5) in self-management group vs. 9.2 mmHg (95%CI 6.7-11.8) in control group. The decrease in SBP was even higher at 12 months after intervention: 17.6 mmHg (95%CI 14.9-20.3) and 12.2 mmHg (95%CI 9.4-14.9), respectively. This strategy for blood pressure measurement has been incorporated into NICE guidelines in the United Kingdom. As such, our research question is relevant to public health efforts and clinical practice.
Recent data suggests that the utility of home blood pressure monitors may be limited in resource-restricted settings in the US. However, there is limited data from low- and middle-income countries. One recent clinical trial in Mexico and Honduras documented that individuals using a BP monitor combined with automated interactive voice response messages, had SBP levels 4.2 mmHg (95%CI -9.1, 0.7; p=0.09) lower on average than control group. Furthermore, a subgroup of individuals with low literacy showed a higher decrease, 8.8 mmHg (95%CI -14.2, -3.4; p=0.002). However, this study had important limitations such as short duration of follow up, small sample (n=181), and limited interface with the health care system.
The potential impact of this work is high because of the high global burden of hypertension in low- and middle- income countries; thereby, identification of innovative and effective strategies to control blood pressure is critical. To the best of our knowledge, our study aims to be one of the first to provide evidence of the feasibility and utility of home blood pressure management to optimize blood pressure management in these settings. Figure 1 shows our conceptual framework for the relationships between home blood pressure management context and blood pressure. We hypothesize that self management will optimize management of blood pressure in a low income setting by reducing delays in medication titration and improving adherence to antihypertensive medication.
There are important implications of this work regardless of whether the findings are negative or positive. A positive result provides much needed information about the feasibility and possible importance of dose titration, and the role of home blood pressure monitors in accomplishments. A negative result will provide information about the barriers and facilitators of self-management in low- and middle-income study.
We will conduct mixed-methods, implementation science study in adults with uncontrolled high blood pressure, living in low- and middle-income countries. First, we will conduct a qualitative study, followed by a pragmatic, pilot, clinic-based, unblinded, randomized controlled trial of home blood pressure management. Next we will conduct a qualitative study of participant and health care team perceptions about the intervention and implementation process.
For the in-depth semi-structured interviews and focus group discussions, we will include 24 patients, 12 family caregivers, and 12 stakeholders at each of the 5 sites. For the usability testing of monitors and protocols we will include 10 patients and their family caregivers and health care teams at each of the 5 sites. Sampling will be purposive and heterogeneous to capture individuals with family caregivers and those without, and those with longer-standing hypertension (≥3years) and those with a newer diagnosis (< 3years). Study participants will be selected through two stages. In the first stage, outpatient medical clinics will be selected in each city: 1) Gilgit, Pakistan, 2) Delhi, India (North), 3) Bangalore, India (South), 4) Dhaka, Bangladesh, and 5) Douala, Cameroon. Patients from the practices that fall under the inclusion criteria will be invited to participate in the study. Key informants from the health care teams and health care systems will be invited through local contacts.
Interviews and focus group discussions. Health care worker, patient, and family caregiver perspectives will be obtained using two qualitative research techniques: in depth semi-structured interviews and focus group discussions. At least two discussion groups of patients with their family caregivers (n=10-12 participants in each group) will be formed in each city. Individual interviews will be conducted with key informants from the health care systems, including primary care physicians and cardiologists, nurses, community health workers, and administrators. .A focus group discussion guide will be developed collaboratively using literature review, expert input, and local team input. Key informant interviews will use a semi-structured interview guide developed with the same process. The interview guide will be designed to assess whether the heath system will be stressed by our intervention. Guides and protocols will be standardized across sites to ensure cross-national comparisons of qualitative data and data collection will be conducted by individuals trained in conducting qualitative methods. The broad themes that will be examined in our qualitative study are summarized in Figure 1. They include barriers and facilitators to home blood pressure management in low- and middle-income countries. We are interested in factors that may occur on the individual level (e.g., family structure, duration of hypertension, age, access to healthcare) and the provider level (e.g., clinical inertia, practice size, age).
Beta testing of home BP monitors and titration protocols and materials. The study team and local teams will adapt titration protocols and patient materials (such as BP diaries) from prior trials of home BP management so that they are culturally and contextually appropriate. We will choose 5 patients (at least 2 of them will have a family caregiver) at the trial site who meet study inclusion criteria to beta-test the home BP monitor. Clinic staff will be asked to identify 5 patients and their caregivers for this part of the study. Patients and caregivers will be trained and instructed to use the monitors for one week and to record readings. Research staff will observe the participant in the home and use a checklist to document the process. At the end of the week, we will also ask participants for feedback on the experience, and how it could be made better. We will also ask physicians, nurses, community health workers and patients and family caregivers for feedback on the titration protocols and materials. We will have five patients and family caregivers use the titration protocol to determine barriers, facilitators and fidelity to the protocol. We are specifically interested in the appropriateness of the frequency of medication titration, clarity and literacy-appropriateness of instructions, and comfort level of health care team and patient/family caregiver with the actions recommended. We will use standardize checklists and interviews to obtain information from beta-testing.
Practice assessment survey. Clinic sites will be asked to complete a practice survey assessment that will collaboratively be adapted for local use and will be used to identify the strengths and weaknesses of the practice for carrying out quality improvement efforts in BP management.
Study participants will be recruited from medical (out-patient) clinics in a low- income/ low-middle income country (detailed methods described elsewhere). The intervention group (self management) will consist of self-monitoring of BP with self-titration of medication following a predetermined three-step algorithm dependent on the self-monitored BP readings.Participants will receive a home blood pressure monitor and a self-titration plan. They will be trained by designated clinic staff. Participants will be given diaries for recording of readings, and instructions about frequency of measurement and recording blood pressure. As in the TASMIN-SR protocol, each patient in the intervention group will be given an individually tailored three -step algorithm through which to adjust medication according to measured BP. Each step will represent a single medication change (additional medication or increased dose) that will be made at the end of the measurement week. Of note: the qualitative study will be used to inform the acceptability and timing of the three-step titration. Medication choice for the self titration plan will be ratified by the primary physician who will be provided with an algorithm based on clinical guidelines for hypertension. If patients use all three steps of their management plan they will return to their primary care physician and an additional three-step plan will be devised. Medications will not be provided as part of the intervention. Medication procurement in each specific site will be studied as part of Aim 1 and will be documented for participants in both arms of Aim 2.
The control group (usual care) will consist of the participant seeing a designated member of the health care team for routine BP measurement and/or adjustment of medication at the discretion of the health professional.
At the completion of Aim 2, we will recruit a purposive sample of intervention participants (e.g., various ages, sexes, level of fidelity), family caregivers who may have been involved in the HBPM, and a designee from each of the health care teams. We will conduct exploratory qualitative research to understand acceptability, fidelity, satisfaction, challenges, and benefits of the home BP management intervention. Information from this phase of the study will be used to modify and adapt the intervention and trial design for a larger scale implementation trial in different LMIC settings.
The team is presenting the protocol to respective IRBs and will begin with Aim #1 after approval has been received.
FACTc: Financing, Resource Allocations (for full implementation of WHO-FCTC) and Cost of Tobacco Control
To help policymakers establish sustainable mechanisms to fund and accelerate the comprehensive implementation of the FCTC. Objectives: building a straightforward and user-friendly tool to help policymakers and advocates, including MOH officials, in at least 8 countries (and ideally most countries) to accelerate FCTC implementation in the next two years by:
Recognizing that tobacco control is a fundamental investment in human capital, an investment that not only directly leads to enormous public health gains, but also to long-term economic growth, Parties to the Framework Convention of Tobacco Control (FCTC) acknowledged the need for collective action to overcome obstacles that delay FCTC implementation. One of these obstacles is the lack of sustainable resources for FCTC implementation. According to the World Health Organization (WHO), the implementation of the four best buy tobacco control measures (tobacco tax increases, smoke-free policies, package warnings, and advertising bans) in all Low- and Middle-Income countries (LMICs) would cost a mere 11 US cents per year. The estimates include the human resources and physical capital needed to plan, develop, implement, monitor, and enforce the policies (WHO 2011). Currently, international funding (including private donors, aid agencies, and multilateral organizations such as WHO) is only about one US cent per person per year on tobacco control in LMICs. One other cent comes from governments of LMICs that provide funding for tobacco control programs in their countries. The total investment in tobacco control in LMICs at only 2 cents per person per year is, therefore, insufficient compared to current needs (Stoklosa and Ross 2014).
To address these issues, the Parties to the FCTC created a Working Group that convened for the first time at the Sixth Meeting of the Conference of the Parties (COP6) in October 2014. The title of the Working Group is Sustainable Measures to Strengthen Implementation of the FCTC. While the Group found the lack of resources, such as staff and funding, as the major obstacle to implement FCTC measures, the Group also stressed that the country-level information on the cost of the FCTC implementation and the cost of inaction (the current costs of the tobacco epidemic) is lacking. For example, in the FCTC needs assessment conducted on the Parties’ request, there are currently no questions on financial and other resource needs. Therefore, one of the key recommendations of this Group was to provide countries with estimates on the funds needed and the costs of the tobacco epidemic. This information regarding the resource gap between desired and existing funding, and the return on investment to countries that tackle the tobacco epidemic would tremendously support country-level efforts and strengthen capacities to implement the FCTC.
We find that this needs of the Working Group on Sustainable Measures, and eventually the Governments, can to the large extent, be fulfilled. Country-level information on both the funds needed and the cost of inaction for many countries exist. However, it is scattered in multiple literature and platforms and have never been combined in one comprehensive and compelling resource. Such resource could also help countries to identify potential sources of the funding needed to implement the key evidence based provisions of FCTC, including tax revenues. This resource could also help to inform the work of the Sustainable Measures Group, and thus the Governments, by providing the countries with score cards and identifying countries that need the assistance the most.
Besides extensively sharing and discussing the tool with the members of the Sustainable Measures Working Group, global experts and other key stakeholders in tobacco control, the project team will work with a local partner organization in the pilot countries. The team will extensively use the tool and the factsheet/score cards to highlight the country score on the five key components and the level of actions required to achieve the targets for full implementation of the corresponding FCTC measures. The local partner organization will be responsible for disseminating the tool and the factsheet/ score cards through all possible mediums, including online and electronic media. The local partner organization will also help in communicating and seeking collaboration with and reaching out to other target audience in the respective countries in addition to the efforts done by the team members to reach out to the following key target audience with the project progress, outputs and outcomes.
KOMPLY: A Project to Support Compliance with the Smoke-free Law in Bars and Restaurants in Kampala, Uganda
To ensure 100% compliance with the new 100% smoke-free law in bars and restaurants in Kampala, Uganda. To communicate the level of compliance with the indoor 100% smoke-free law in bars and restaurants in Kampala, Uganda to the public, government officials (the Ministry of Health Uganda), and Civil Society Organizations (CSOs) so as to facilitate and enable CSO’s to advocate for stronger compliance of the smoke-free law though the development of resources/ skills tools. This project will also involve the training of the team members from three other countries in Africa (Cameroon, Nigeria, and Rwanda) so that objectives measures of proxy indicators and PM2.5 measurements can be taken there to support future initiatives.
Article 8 of the WHO FCTC requires Parties to adopt and implement legislative and other measures providing for protection from exposure to tobacco smoke in indoor public places, workplaces, public transport, and, as appropriate, other public places.8 As part of the gold-standard of smoke-free laws, designated smoking rooms or ventilation schemes are not permitted, as complete prohibition of smoking in all indoor environments is the only intervention that effectively protects people from the harm of SHS.
Prior to the adoption of the FCTC, there was little or no progress in the implementation of smoke-free policies. The 2002 Tobacco Atlas reported that in 2000, not a single nation had implemented a comprehensive smoke-free law. Rather, those nations with any kind of smoke-free law had only partial and/or voluntary restrictions on smoking in some public places or workplaces. The adoption of the FCTC was a strong catalyst for advancement because it put in place the necessary framework to encourage nations to proceed with enacting tobacco control policies. With this, Ireland became the first country to go smoke-free in all public places and workplaces, including restaurants and pubs, on March 29, 2004. Thereafter, many FCTC nations followed suit as ratification took place in great numbers, and scientific evidence became available. Between 2005 and 2014, nearly 50 countries (representing 18% of the world’s population) have enacted or implemented strong smoke-free legislation across the globe.
The magnitude of reductions in smoke in public places is related to the strength and comprehensiveness of Article 8 policies. While 49 countries have implemented smoke-free legislation to the highest level possible (and in-line with article 8 guidelines), and many other countries have partial public locations covered, many countries fall short when it comes to enforcement of, and compliance to, their smoke-free laws. In particular the African region lags behind much of the world in both the implementation and compliance with smoke-free laws. In particular, there are certain venues where exposure is extremely high, such as bars and restaurants. For example, a study in Kenya, Zambia and Mauritius (which included a representative sample of 4,251 smokers) reported that the prevalence of smoking in bars was 83%, 70% and 45% respectively, despite there being smoke-free legislation that includes these establishments. In Uganda, exposure to SHS in bars and restaurants has been estimated to be 62%. Given that in low and middle income countries (LMICs) such as Uganda, tobacco control legislation is susceptible to poor implementation and public sector corruption, and low compliance, civil society and academia have potentially an important role to play in monitoring the adherence to smoke-free legislation, including monitoring compliance and air contamination levels.
Currently, smoking prevalence in Uganda is 10.3% of men, 1.8% of women, and 5.8% overall (0.9 million adults).Although low in relation to other countries, the tobacco industry has turned its’ attention to Africa and WHO predicts that if nothing is done to stop this effort, then smoking prevalence in the African region will only grow.16, 16 The Ugandan government recognized the urgency to move forward with strong tobacco control measures and passed new legislation in 2015 under the Tobacco Control Act 2015. Uganda’s 2015 tobacco control law is a comprehensive set of regulations which include a 100% ban on smoking in indoor public places, workplaces and public transport; prohibition on smoking within 50 meters of all public places; pictorial health warnings, covering 65% of the pack to inform the public of the dangers of tobacco; a ban on the sale of cigarettes to and by persons less than 21 years; a ban on tobacco advertising, promotion and sponsorship (TAPS); requirements that cigarette packs should not be prominently displayed at point-of-sale. The law is supposed to be enforced by officers appointed by the government and will include specific public health officers under the Public Health Act, environmental inspectors from the National Environmental Management Authority (NEMA), standards inspectors from the National Bureau of Standards, customs officers under the Uganda Revenue Authority, and other persons whose duty is to maintain law and order. While the law was adopted in September 2015, it will be implemented in May 2016, yet a period of six months is allowed after implementation until enforcement of the law becomes mandatory (i.e. this will occur in November 2016).
In this project, we aim to gather information on the level of compliance with the smoke-free law at high-risk hospitality venues and on the reasons why a venue does or does not comply with the law. Ultimately, our project intends to monitor and support compliance with the smoke-free law in Uganda, and to share lessons learned with other African colleagues on how to advocate for enforcing smoke-free laws.
Objective and subjective data about compliance with the smoke-free law will be collected, collated and used to engage with a range of stakeholders, such as the government, the public, and civil society organizations (CSOs). This information will be used to guide key parties about how they can act to improve compliance in hospitality environments. Specifically, the results should be used to educate venue owners, policymakers, employees, and/or the general public about the existence of the smoke-free law, the status of compliance, and what they can do to increase compliance.
Moreover, this project will involve training our own team members from other African countries how to measure air quality and other objective proxy indicators of non-compliance so that each member will be able to take measurements in indoor public places. This could be used as evidence to advocate for smoke-free laws where they do not yet exist, and to monitor compliance as smoke-free laws are implemented (or to strengthen laws that are in place but where there is poor compliance).
We intend to engage and collaborate with tobacco control CSOs in Uganda to determine their needs in relation to supporting the implementation of the smoke-free law, and co-design advocacy tools that help improve compliance. We will focus the campaigns around key messages from the study, and will direct the campaign at groups that we identify as important to the success of the smoke-free law. The advocacy tools will take the form of media best suited for our target audience. Potential examples of such a tool include a social media campaign directed at young smokers and their peers, a “Thank You for Not Smoking” poster campaign around bars and restaurants, a public awareness campaign using “100% Smoke-Free” graffiti murals in city centers, stylized “Smoke Free” logos for successfully complying bars and restaurants, and video training sessions for law-enforcement officers outlining key messages of the law.
Identification of CSOs will be undertaken in the stakeholder mapping exercise, however, likely CSOs include: Uganda Health Communication Alliance, Uganda National Consumers Organization, Text to Change, Parliamentary Forum on NCDs, Uganda National Tobacco Control Alliance. The CSOs can use the project findings to design advocacy messages in order to reach the public, restaurant and bar owners, as well as policy makers. The messages will be communicated through platforms such as social media, media press briefings, TV, radio and during meetings.
We will work with key stakeholders and champions on a dissemination and communications plan to include activities such as