Monitoring Progress towards Universal Health Coverage at Country and Global Levels

Universal health coverage (UHC) has been defined as the desired outcome of health system performance whereby all people who need health services (promotion, prevention, treatment, rehabilitation, and palliation) receive them, without undue financial hardship. UHC has two interrelated components: the full spectrum of good-quality, essential health services according to need, and protection from financial hardship, including possible impoverishment, due to out-of-pocket payments for health services. Both components should benefit the entire population.This paper summarizes the findings from 13 country case studies and five technical reviews, which were conducted as part of the development of a global framework for monitoring progress towards UHC.The case studies show the relevance and feasibility of focusing UHC monitoring on two discrete components of health system performance: levels of coverage with health services and financial protection, with a focus on equity. These components link directly to the definition of UHC and measure the direct results of strategies and policies for UHC. The studies also show how UHC monitoring can be fully embedded in often existing, regular overall monitoring of health sector progress and performance. Several methodological and practical issues related to the monitoring of coverage of essential health services, financial protection, and equity, are highlighted. Addressing the gaps in the availability and quality of data required for monitoring progress towards UHC is critical in most countries.

Summary Points

• The overall goal of universal health coverage (UHC) is that all people obtain the good-quality essential health services, including promotion, prevention, treatment, rehabilitation, and palliation, that they need without enduring financial hardship.
• A global UHC monitoring framework, developed by WHO and the World Bank Group in interaction with the process that led to this PLOS Collection, was used in 13 country case studies, underpinned by five technical reviews.
• The UHC monitoring framework focuses on the simultaneous monitoring of coverage of the population with essential health services and with financial protection against catastrophic out-of-pocket health payments, stratified by wealth quintile, place of residence, and sex.
• Most countries focus on regular monitoring of a set of tracer indicators for priority health services, as well as the occurrence of financial hardship and impoverishment due to out-of-pocket health expenses. The indicators generally follow international standards of measurement and can be used for global comparisons.
• Most countries do not have an explicit framework for UHC monitoring. The monitoring of UHC is, however, partially embedded in regular overall health sector progress and performance reviews which include health system inputs, service delivery, and health status indicators.
• There are major gaps in the availability and quality of data required for monitoring progress towards UHC. Countries mostly rely on international survey programs or national surveys to obtain disaggregated data on coverage and financial protection indicators, complemented by health facility data, but often the frequency and contents of these surveys are not sufficient to meet the country''s information needs.
• Monitoring progress towards the two components of UHC will be complementary and critical to achieving desirable health outcome goals, such as ending preventable deaths and promoting healthy life expectancy, and also reducing poverty and protecting household incomes.

     

Beyond UHC: Monitoring Health and Social Protection Coverage in the Context of Tuberculosis Care and Prevention

Tuberculosis (TB) remains a major global public health problem. In all societies, the disease affects the poorest individuals the worst. A new post-2015 global TB strategy has been developed by WHO, which explicitly highlights the key role of universal health coverage (UHC) and social protection. One of the proposed targets is that “No TB affected families experience catastrophic costs due to TB.” High direct and indirect costs of care hamper access, increase the risk of poor TB treatment outcomes, exacerbate poverty, and contribute to sustaining TB transmission. UHC, conventionally defined as access to health care without risk of financial hardship due to out-of-pocket health care expenditures, is essential but not sufficient for effective and equitable TB care and prevention. Social protection interventions that prevent or mitigate other financial risks associated with TB, including income losses and non-medical expenditures such as on transport and food, are also important. We propose a framework for monitoring both health and social protection coverage, and their impact on TB epidemiology. We describe key indicators and review methodological considerations. We show that while monitoring of general health care access will be important to track the health system environment within which TB services are delivered, specific indicators on TB access, quality, and financial risk protection can also serve as equity-sensitive tracers for progress towards and achievement of overall access and social protection.

This paper is part of the PLOS Universal Health Coverage Collection.

Summary Points

1. The WHO has developed a post-2015 Global TB Strategy emphasizing that significant improvement to TB care and prevention will be impossible without the progressive realization of both universal health coverage and social protection. This paper discusses indicators and measurement approaches for both.
2. While access to high-quality TB diagnosis and treatment has improved dramatically in recent decades, there is still insufficient coverage, especially for correct diagnosis and treatment of multi-drug resistant TB.
3. Continued and expanded monitoring of effective coverage of TB diagnosis and treatment is needed, for which further improvements to existing surveillance systems are required.
4. Many households face severe financial hardship due to TB. Out-of-pocket costs for medical care, transport, and food are often high. However, income loss is the largest financial threat for TB-affected households.
5. Consequently, the financial risk protection target in the post-2015 Global TB Strategy—“No TB affected families experience catastrophic costs due to TB”—concerns all direct costs as well as income loss. This definition is more inclusive than the one conventionally used for “catastrophic health expenditure,” which concerns only direct medical costs.

     

Monitoring Intervention Coverage in the Context of Universal Health Coverage

Monitoring universal health coverage (UHC) focuses on information on health intervention coverage and financial protection. This paper addresses monitoring intervention coverage, related to the full spectrum of UHC, including health promotion and disease prevention, treatment, rehabilitation, and palliation. A comprehensive core set of indicators most relevant to the country situation should be monitored on a regular basis as part of health progress and systems performance assessment for all countries. UHC monitoring should be embedded in a broad results framework for the country health system, but focus on indicators related to the coverage of interventions that most directly reflect the results of UHC investments and strategies in each country. A set of tracer coverage indicators can be selected, divided into two groups—promotion/prevention, and treatment/care—as illustrated in this paper. Disaggregation of the indicators by the main equity stratifiers is critical to monitor progress in all population groups. Targets need to be set in accordance with baselines, historical rate of progress, and measurement considerations. Critical measurement gaps also exist, especially for treatment indicators, covering issues such as mental health, injuries, chronic conditions, surgical interventions, rehabilitation, and palliation. Consequently, further research and proxy indicators need to be used in the interim. Ideally, indicators should include a quality of intervention dimension. For some interventions, use of a single indicator is feasible, such as management of hypertension; but in many areas additional indicators are needed to capture quality of service provision. The monitoring of UHC has significant implications for health information systems. Major data gaps will need to be filled. At a minimum, countries will need to administer regular household health surveys with biological and clinical data collection. Countries will also need to improve the production of reliable, comprehensive, and timely health facility data. Please see later in the article for the Editors'' Summary

Summary Points

• Monitoring universal health coverage (UHC) should be integral to overall tracking of health progress and performance, which requires regular assessment of health system inputs (finances, health workforce, and medicines), outputs (service provision), coverage of interventions, and health impacts, as well as the social determinants of health.
• Within this overall context, we propose that UHC monitoring focus on financial protection and intervention coverage indicators, with a strong equity focus. This paper focuses on intervention coverage.
• Progress towards UHC should be tracked using tracer intervention coverage indicators selected on the basis of objective considerations and designed to keep the numbers of indicators small and manageable while covering a range of health interventions to capture the essence of the UHC goal.
• Since UHC is about progressive realization and countries differ in epidemiology, health systems, socioeconomic development, and people''s expectations, the indicator sets will not be the same everywhere.
• Coverage indicators should cover promotion and prevention, as well as treatment, rehabilitation, and palliation. While there are several suitable indicators for the first two, there are major gaps for coverage indicators of treatment, as population need for treatment is difficult to measure.
• A small set of well-established international intervention tracer coverage indicators can be identified for monitoring UHC. Where no good indicators are currently available, proxy indicators and equity analysis of service utilization can provide some insights.
• Special attention needs to be paid to quality of services, either through the tracer indicator itself (referred to as effective coverage) or through additional indicators on quality of services or health impact of the intervention.
• Targets should be set in accordance with baseline, historical rate of progress, and measurement considerations.
• The main data sources of intervention coverage indicators are household surveys and health facility reports. Investments in both are needed to improve the ability of countries to monitor progress towards UHC.
• It is essential to find effective ways of communicating progress towards UHC in ways that are meaningful to the general public and that capture the attention of policy makers.

This paper is part of the PLOS Universal Health Coverage Collection.

     

Effective Coverage: A Metric for Monitoring Universal Health Coverage

A major challenge in monitoring universal health coverage (UHC) is identifying an indicator that can adequately capture the multiple components underlying the UHC initiative. Effective coverage, which unites individual and intervention characteristics into a single metric, offers a direct and flexible means to measure health system performance at different levels. We view effective coverage as a relevant and actionable metric for tracking progress towards achieving UHC. In this paper, we review the concept of effective coverage and delineate the three components of the metric — need, use, and quality — using several examples. Further, we explain how the metric can be used for monitoring interventions at both local and global levels. We also discuss the ways that current health information systems can support generating estimates of effective coverage. We conclude by recognizing some of the challenges associated with producing estimates of effective coverage. Despite these challenges, effective coverage is a powerful metric that can provide a more nuanced understanding of whether, and how well, a health system is delivering services to its populations.

This paper is part of the PLOS Universal Health Coverage Collection.

Summary Points

• Effective coverage unites intervention need, use, and quality into a simple but data-rich metric, reflecting the core components of UHC.
• Effective coverage can be applied to understand the health gains delivered by interventions at a range of levels, from individual benefits to national impact.
• Effective coverage can be measured and used across resource settings. Lower-income countries can harness data from existing survey data to feed into effective coverage estimations.
• The broader use of effective coverage remains hindered by the availability and quality of health data, especially at subnational levels.

     

Health-Related Financial Catastrophe,Inequality and Chronic Illness in Bangladesh

Background

Bangladesh has a high proportion of households incurring catastrophic health expenditure, and very limited risk sharing mechanisms. Identifying determinants of out-of-pocket (OOP) payments and catastrophic health expenditure may reveal opportunities to reduce costs and protect households from financial risk.

Objective

This study investigates the determinants of high healthcare expenditure and healthcare- related financial catastrophe.

Methods

A cross-sectional household survey was conducted in Rajshahi city, Bangladesh, in 2011. Catastrophic health expenditure was estimated separately based on capacity to pay and proportion of non-food expenditure. Determinants of OOP payments and financial catastrophe were estimated using double hurdle and Poisson regression models respectively.

Results

On average households spent 11% of their total budgets on health, half the residents spent 7% of the monthly per capita consumption expenditure for one illness, and nearly 9% of households faced financial catastrophe. The poorest households spent less on health but had a four times higher risk of catastrophe than the richest households. The risk of financial catastrophe and the level of OOP payments were higher for users of inpatient, outpatient public and private facilities respectively compared to using self-medication or traditional healers. Other determinants of OOP payments and catastrophic expenses were economic status, presence of chronic illness in the household, and illness among children and adults.

Conclusion

Households that received inpatient or outpatient private care experienced the highest burden of health expenditure. The poorest members of the community also face large, often catastrophic expenses. Chronic illness management is crucial to reducing the total burden of disease in a household and its associated increased risk of level of OOP payments and catastrophic expenses. Households can only be protected from these situations by reducing the health system''s dependency on OOP payments and providing more financial risk protection.     

Evaluation of progress toward universal health coverage in Myanmar: A national and subnational analysis

BackgroundUniversal health coverage (UHC) encompasses 2 main components: access to essential healthcare services and protection from financial hardship when using healthcare. This study examines Myanmar’s efforts to achieve UHC on a national and subnational level. It is a primer of studying the concept of UHC on a subnational level, and it also establishes a baseline for assessing future progress toward reaching UHC in Myanmar.Methods and findingsThe study uses the Demographic and Health Survey (2015) and the Myanmar Living Conditions Survey (MLCS; 2017) and adapts a previously developed UHC index to provide insights into the main barriers preventing the country’s progress toward UHC. We find a negative correlation between the UHC index and the state/region poverty levels. The equity of access analysis reveals significant pro-rich inequity in access to all essential healthcare services. Socioeconomic status and limited availability of healthcare infrastructure are the main driving forces behind the unequal access to interventions that are crucial to achieving UHC by 2030. Finally, financial risk protection analysis shows that the poor are less likely to use healthcare services, and, once they do, they are at a greater risk of suffering financial catastrophe. Limitations of this study revolve around its correlational, rather than causal, nature.ConclusionsWe suggest a 2-pronged approach to help Myanmar achieve UHC: Government and state authorities should reduce the financial burden of seeking healthcare, and, coupled with this, significant investment in and expansion of health infrastructure and the health workforce should be made, particularly in the poorer and more remote states.

Zlatko Nikoloski and colleagues provide analytical insight into Myanmar’s efforts to achieve universal health coverage on a national and sub-national level.     

Equity-Oriented Monitoring in the Context of Universal Health Coverage

Monitoring inequalities in health is fundamental to the equitable and progressive realization of universal health coverage (UHC). A successful approach to global inequality monitoring must be intuitive enough for widespread adoption, yet maintain technical credibility. This article discusses methodological considerations for equity-oriented monitoring of UHC, and proposes recommendations for monitoring and target setting. Inequality is multidimensional, such that the extent of inequality may vary considerably across different dimensions such as economic status, education, sex, and urban/rural residence. Hence, global monitoring should include complementary dimensions of inequality (such as economic status and urban/rural residence) as well as sex. For a given dimension of inequality, subgroups for monitoring must be formulated taking into consideration applicability of the criteria across countries and subgroup heterogeneity. For economic-related inequality, we recommend forming subgroups as quintiles, and for urban/rural inequality we recommend a binary categorization. Inequality spans populations, thus appropriate approaches to monitoring should be based on comparisons between two subgroups (gap approach) or across multiple subgroups (whole spectrum approach). When measuring inequality absolute and relative measures should be reported together, along with disaggregated data; inequality should be reported alongside the national average. We recommend targets based on proportional reductions in absolute inequality across populations. Building capacity for health inequality monitoring is timely, relevant, and important. The development of high-quality health information systems, including data collection, analysis, interpretation, and reporting practices that are linked to review and evaluation cycles across health systems, will enable effective global and national health inequality monitoring. These actions will support equity-oriented progressive realization of UHC.

This paper is part of the PLOS Universal Health Coverage Collection.

Summary Points

• The equitable realization of universal health coverage requires an equity-oriented approach to monitoring; equity advocates should be unified in proposing a technically sound platform for monitoring that is easy to understand and communicate.
• Global monitoring should include complementary dimensions of inequality (such as economic status and urban/rural residence, in addition to sex), adopt a gap or whole spectrum approach, and conceptualize economic-related measures using quintiles.
• Both absolute and relative measures of inequality as well as disaggregated data should be reported, and national averages should be presented alongside inequality monitoring.
• Targets for global monitoring of health inequalities should be based on proportional reduction of absolute inequality.
• Countries can develop capacity for health inequality monitoring by strengthening health information systems for data collection, analysis, reporting, and dissemination.

     

Achieving global mortality reduction targets and universal health coverage: The impact of COVID-19

Wenhui Mao and coauthors discuss possible implications of the COVID-19 pandemic for health aspirations in low- and middle-income countries.

Summary points

• The Coronavirus Disease 2019 (COVID-19) pandemic threatens progress toward a “grand convergence” in global health—universal reduction in deaths from infections and maternal and child health conditions to low levels—and toward achieving universal health coverage (UHC).
• Our analysis suggests that COVID-19 will exacerbate the difficulty of achieving grand convergence targets for tuberculosis (TB), maternal mortality, and, probably, for under-5 mortality. HIV targets are likely to be met.
• By 2035, our analysis suggests that the public sectors of low-income countries (LICs) would only be able to finance about a third of the costs of a package of 120 essential non-COVID-19 health interventions through domestic sources, unless the country increases significantly the priority assigned to the health sector; lower middle-income countries (LMICs) would likewise only be able to finance a little less than half.
• The likelihood of getting back on track for reaching grand convergence and UHC will depend on (i) how quickly COVID-19 vaccines can be deployed in LICs and LMICs; (ii) how much additional public sector health financing can be mobilized from external and domestic sources; and (iii) whether countries can rapidly strengthen and focus their health delivery systems.

     

HIV Programs for Sex Workers: Lessons and Challenges for Developing and Delivering Programs

There is evidence that HIV prevention programs for sex workers, especially female sex workers, are cost-effective in several contexts, including many western countries, Thailand, India, the Democratic Republic of Congo, Kenya, and Zimbabwe. The evidence that sex worker HIV prevention programs work must not inspire complacency but rather a renewed effort to expand, intensify, and maximize their impact. The PLOS Collection “Focus on Delivery and Scale: Achieving HIV Impact with Sex Workers” highlights major challenges to scaling-up sex worker HIV prevention programs, noting the following: sex worker HIV prevention programs are insufficiently guided by understanding of epidemic transmission dynamics, situation analyses, and programmatic mapping; sex worker HIV and sexually transmitted infection services receive limited domestic financing in many countries; many sex worker HIV prevention programs are inadequately codified to ensure consistency and quality; and many sex worker HIV prevention programs have not evolved adequately to address informal sex workers, male and transgender sex workers, and mobile- and internet-based sex workers. Based on the wider collection of papers, this article presents three major clusters of recommendations: (i) HIV programs focused on sex workers should be prioritized, developed, and implemented based on robust evidence; (ii) national political will and increased funding are needed to increase coverage of effective sex worker HIV prevention programs in low and middle income countries; and (iii) comprehensive, integrated, and rapidly evolving HIV programs are needed to ensure equitable access to health services for individuals involved in all forms of sex work.

Summary Points

• HIV prevention programs for sex workers, especially female sex workers, are cost-effective.
• There are opportunities to further increase the impact of HIV prevention programs for sex workers and to adapt interventions to a changing context.
• Many sex worker HIV prevention programs are insufficiently guided by understanding of epidemic transmission dynamics, situation analyses, and programmatic mapping; receive limited domestic financing in many countries; are inadequately codified to ensure consistency and quality; and have not evolved adequately to address informal sex workers, male and transgender sex workers, and mobile and internet-based sex workers.
• We recommend increasing our understanding of HIV epidemic transmission dynamics, improving situation analyses and programmatic mapping, increasing domestic financing for sex worker HIV prevention programs where feasible, delivering well-codified, comprehensive programs using “Science of Delivery” principles and developing more effective models to reach informal sex workers, male and transgender sex workers, and mobile and internet-based sex workers.
• Given their marginalization, concerted efforts must be made to ensure sex workers have equitable access to HIV prevention, care, and treatment services, as well as wider health services, particularly for STIs, mental health, and addictions.

     

Examining inequities in incidence of catastrophic health expenditures on different healthcare services and health facilities in Nigeria

Objective

There is limited evidence about levels of socio-economic and other differences in catastrophic health spending in Nigeria and in many sub-Saharan African countries. The study estimated the level of catastrophic healthcare expenditures for different healthcare services and facilities and their distribution across socioeconomic status (SES) groups.

Methods

The study took place in four Local Government Areas in southeast Nigeria. Data were collected using interviewer-administered questionnaires administered to 4873 households. Catastrophic health expenditures (CHE) were measured using a threshold of 40% of monthly non-food expenditure. We examined both total monthly health expenditure and disaggregated expenditure by source and type of care.

Results

The average total household health expenditure per month was 2354 Naira ($19.6). For outpatient services, average monthly expenditure was 1809 Naira ($15.1), whilst for inpatient services it was 610 Naira ($5.1). Higher health expenditures were incurred by urban residents and the better-off SES groups. Overall, 27% of households incurred CHE, higher for poorer socioeconomic groups and for rural residents. Only 1.0% of households had a member that was enrolled in a health insurance scheme.

Conclusion

The worse-off households (the poorest SES and rural dwellers) experienced the highest burden of health expenditure. There was almost a complete lack of financial risk protection. Health reform mechanisms are needed to ensure universal coverage with financial risk protection mechanisms.     

Effect of User Charges on Secondary Level Surgical Care Utilization and Out-of-Pocket Expenditures in Haryana State,India

BackgroundGeneration of resources for providing health care services is an important issue in developing countries. User charges in the form of Surgical Package Program (SPP) were introduced in all district hospitals of Haryana to address this problem. We evaluate the effect of this SPP program on surgical care utilization and out-of-pocket (OOP) expenditures.MethodsData on 25437 surgeries, from July 2006 to June 2013 in 3 districts of Haryana state, was analyzed using interrupted time series analysis to assess the impact of SPP on utilization of services. Adjustment was made for presence of any autocorrelation and seasonality effects. A cross sectional survey was undertaken among 180 patients in District hospital, Panchkula during June 2013 to assess the extent of out of pocket (OOP) expenditure incurred, financial risk protection and methods to cope with OOP expenditure. Catastrophic health expenditure, estimated as any expenditure in excess of 10% of the household consumption expenditure, was used to assess the extent of financial risk protection.ResultsUser charges had a negative effect on the number of surgeries in public sector district hospitals in all the 3 districts. The mean out-of-pocket expenditure incurred by the patients was Rs.4564 (USD 74.6). The prevalence of catastrophic expenditure was 5.6%. A higher proportion among the poorest 20% population coped through borrowing money (47.2%), while majority (86.1%) of those belonging to richest quintile paid from their monthly income or savings, or had insurance.ConclusionThere is a need to increase the public financing for curative services and it should be based on the needs of population. Any form of user charge in public sector hospitals should be removed.     

Closing the health equity gap: A role for implementation science?

Beryne Odeny discusses strategies to improve equity in health care and health research.

WHO defines health equity as “the absence of unfair and avoidable or remediable differences in health among population groups defined socially, economically, demographically, or geographically or by other means of stratification” [1]. Yet, contrary to this fundamental aspiration and the international mandate on universal health coverage (UHC), almost 50% of the world’s population does not receive needed health services, and progress toward health equity remains elusive [2].     

Chapter 11: Genome-Wide Association Studies

Genome-wide association studies (GWAS) have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.

What to Learn in This Chapter

• Basic genetic concepts that drive genome-wide association studies
• Genotyping technologies and common study designs
• Statistical concepts for GWAS analysis
• Replication, interpretation, and follow-up of association results

This article is part of the “Translational Bioinformatics” collection for PLOS Computational Biology.

     

Achieving the HIV Prevention Impact of Voluntary Medical Male Circumcision: Lessons and Challenges for Managing Programs

Voluntary medical male circumcision (VMMC) is capable of reducing the risk of sexual transmission of HIV from females to males by approximately 60%. In 2007, the WHO and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended making VMMC part of a comprehensive HIV prevention package in countries with a generalized HIV epidemic and low rates of male circumcision. Modeling studies undertaken in 2009–2011 estimated that circumcising 80% of adult males in 14 priority countries in Eastern and Southern Africa within five years, and sustaining coverage levels thereafter, could avert 3.4 million HIV infections within 15 years and save US$16.5 billion in treatment costs. In response, WHO/UNAIDS launched the Joint Strategic Action Framework for accelerating the scale-up of VMMC for HIV prevention in Southern and Eastern Africa, calling for 80% coverage of adult male circumcision by 2016. While VMMC programs have grown dramatically since inception, they appear unlikely to reach this goal. This review provides an overview of findings from the PLOS Collection “Voluntary Medical Male Circumcision for HIV Prevention: Improving Quality, Efficiency, Cost Effectiveness, and Demand for Services during an Accelerated Scale-up.” The use of devices for VMMC is also explored. We propose emphasizing management solutions to help VMMC programs in the priority countries achieve the desired impact of averting the greatest possible number of HIV infections. Our recommendations include advocating for prioritization and funding of VMMC, increasing strategic targeting to achieve the goal of reducing HIV incidence, focusing on programmatic efficiency, exploring the role of new technologies, rethinking demand creation, strengthening data use for decision-making, improving governments'' program management capacity, strategizing for sustainability, and maintaining a flexible scale-up strategy informed by a strong monitoring, learning, and evaluation platform.

Summary Points

• Large-scale implementation of voluntary medical male circumcision (VMMC) in 14 priority countries of Eastern and Southern Africa has the potential to significantly reduce heterosexual transmission of HIV to males, saving lives, averting suffering, and avoiding health care costs.
• Resource and capacity constraints pose a serious challenge to the ability of the priority countries to reach their goals for VMMC scale-up.
• The 13 papers in this collection examine issues of service quality, demand creation, cost, and efficiency faced by governments, donors, and programs.
• Systematic, evidence-based management of programs and a dynamic culture of learning are proposed to help meet the challenges of VMMC scale-up.
• Recommendations include greater prioritization and funding of VMMC, strategic targeting and demand creation, a focus on programmatic efficiencies, and exploration of new technologies.
• Further recommendations are for strengthened data use, improving governments'' program management capacity, strategizing for sustainability, and maintaining a flexible scale-up strategy.

     

Ecological Risk Assessment and Quantitative Consequence Analysis

Ecological risk actually refers to two separate things. First, risk to the environment as a result of human activity. Contaminated sites are an example. Second, risk to the biota—flora, fauna, and people—as a result of environmental hazards. Geophysical risk arising from natural hazards is an example. Risk is a combination of likelihoods and consequences. This article examines methods used to quantify the consequences. At the general level, such methods are linked to the methods used to quantify the likelihoods and thus to quantify the risks. It is possible to use the existing frameworks of risk management, health risk assessment, and ecological risk analysis to develop a risk management framework that is suitable for ecological risk assessment. The framework consists of the following steps:

1. Determine concernsby using risk assessment techniques for various scenarios.

2. Identify the consequences by systematically identifying hazards.

3. Undertake calculations by using relevant models.

4. Evaluate certainties, uncertainties, and probabilities involved in the calculations of the vulnerability and of the exposure.

5. Compare with criteriato assess the need for further action.

6. Determine and act on options to control, mitigate, and adapt to the risk.

7. Communicatethe results to those who need to know.

     

Chapter 4: Protein Interactions and Disease

Proteins do not function in isolation; it is their interactions with one another and also with other molecules (e.g. DNA, RNA) that mediate metabolic and signaling pathways, cellular processes, and organismal systems. Due to their central role in biological function, protein interactions also control the mechanisms leading to healthy and diseased states in organisms. Diseases are often caused by mutations affecting the binding interface or leading to biochemically dysfunctional allosteric changes in proteins. Therefore, protein interaction networks can elucidate the molecular basis of disease, which in turn can inform methods for prevention, diagnosis, and treatment. In this chapter, we will describe the computational approaches to predict and map networks of protein interactions and briefly review the experimental methods to detect protein interactions. We will describe the application of protein interaction networks as a translational approach to the study of human disease and evaluate the challenges faced by these approaches.

What to Learn in This Chapter

• Experimental and computational methods to detect protein interactions
• Protein networks and disease
• Studying the genetic and molecular basis of disease
• Using protein interactions to understand disease

This article is part of the “Translational Bioinformatics” collection for PLOS Computational Biology.

     

Chapter 6: Structural Variation and Medical Genomics

Differences between individual human genomes, or between human and cancer genomes, range in scale from single nucleotide variants (SNVs) through intermediate and large-scale duplications, deletions, and rearrangements of genomic segments. The latter class, called structural variants (SVs), have received considerable attention in the past several years as they are a previously under appreciated source of variation in human genomes. Much of this recent attention is the result of the availability of higher-resolution technologies for measuring these variants, including both microarray-based techniques, and more recently, high-throughput DNA sequencing. We describe the genomic technologies and computational techniques currently used to measure SVs, focusing on applications in human and cancer genomics.

What to Learn in This Chapter

• Current knowledge about the prevalence of structural variation in human and cancer genomes.
• Strategies for using microarray and high-throughput DNA sequencing technologies to measure structural variation.
• Computational techniques to detect structural variants from DNA sequencing data.

This article is part of the “Translational Bioinformatics” collection for PLOS Computational Biology.

     

Evaluation of portable devices for medicine quality screening: Lessons learnt,recommendations for implementation,and future priorities

Céline Caillet and co-authors discuss a Collection on use of portable devices for the evaluation of medicine quality and legitimacy.

Summary points

• Portable devices able to detect substandard and falsified medicines are vital innovations for enhancing the inspection of medicines in pharmaceutical supply chains and for timely action before they reach patients. Such devices exist, but there has been little to no independent scientific evidence of their accuracy and cost-effectiveness to guide regulatory authorities in choosing appropriate devices for their settings.
• We tested 12 portable devices, evaluated their diagnostic performances and the resources required to use each device in a laboratory.
• We then assessed the utility and usability of the devices in medicine inspectors’ hands in a pharmacy mimicking a real-life Lao pharmacy.
• We then assessed the health and economic benefits of using portable devices compared to not using them in a low- to middle-income setting.
• Here, we discuss the conclusions and practical implications of the multiphase study discussed in this Collection. We discuss the results, highlight the evidence gaps, and provide recommendations on the key aspects to consider in the implementation of portable devices and their main advantages and limitations.

Global concerns over the quality of medicines, especially in low- and middle-income countries (LMICs) are exacerbated by the Coronavirus Disease 2019 (COVID-19) pandemic [1,2]. The World Health Organisation (WHO) estimated that 10.5% of medicines in LMICs may be substandard or falsified (SF) [3]. “Prevention, detection, and response” to SF medical products are strategic priorities of WHO to contribute to effective and efficient regulatory systems [4]. Numerous portable medicine screening devices are available on the market, holding great hope for detection of SF medicines in an efficient and timely manner, and, therefore, might serve as key detection tools to inform prevention and response [5,6]. Screening devices have the potential to rapidly identify suspected SF medical products, giving more objective selection for reference assays, reducing the financial and technical burden. However, little is known regarding how well the existing devices fulfil their functions and how they could be deployed within risk-based postmarketing surveillance (rb-PMS) systems [5–7].We conducted, during 2016 to 2018, a collaborative multiphase exploratory study aimed at comparing portable screening devices. This paper accompanies 4 papers in this PLOS Collection “A multiphase evaluation of portable screening devices to assess medicines quality for national Medicines Regulatory Authorities.” The first article introduced the multiphase study [8]. In brief, 12 devices (S1 Table) were first evaluated in a laboratory setting [9], to select the most field-suitable devices for further evaluation of their utility/usability by Lao medicines inspectors [10]. Cost-effectiveness analysis of their implementation for rb-PMS in Laos was also conducted [11]. The results of these 3 phases were discussed in a multistakeholder meeting in 2018 in Vientiane, Lao PDR (S1 Text). The advantages/disadvantages, cost-effectiveness, and optimal use of screening devices in medicine supply chains were discussed to develop policy recommendations for medicines regulatory authorities (MRAs) and other institutions who wish to implement screening technologies. A summary of the main results of the multiphase study is presented in S2 Table.As far as we are aware, this is the first independent investigation comparing the accuracy and practical use from a public health perspective, of a diverse set of portable medicine quality screening devices. The specific objective(s) for which the portable screening technologies are implemented, their advantages/limitations, costs and logistics, and the development of detailed standard operating procedures and training programmes are key points to be carefully addressed when considering selection and deployment of screening technologies within specific rb-PMS systems (Fig 1).Open in a separate windowFig 1Major proposed considerations for the selection and implementation of medicine quality screening device.Each circle represents a key consideration when purchasing a screening device, grouped by themes (represented by heptagons). When the shapes overlap, the considerations are connected. For example, standard operating procedures are needed for the implementation of devices and should include measures for user safety. The circle diameters are illustrative.Here, we utilise this research and related literature to discuss the evidence, gaps, and recommendations, complementary to those recently published by the US Pharmacopeial Convention [12]. These discussions can inform policy makers, non-governmental organisations, wholesalers/distributors, and hospital pharmacies considering the implementation of such screening devices. We discuss unanswered research questions that require attention to ensure that the promise these devices hold is realised.