Andreas Reis

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone. Guidelines on LTBI for low TB incidence countries – essential element of the @WHO #EndTB strategy and TB elimination http://ow.ly/RW8xn

Evidence-informed recommendations to reduce dissemination bias in clinical research: conclusions from the OPEN (Overcome failure to Publish nEgative fiNdings) project based on an international consensus meeting

Background Dissemination bias in clinical research severely impedes informed decision-making not only for healthcare professionals and patients, but also for funders, research ethics committees, regulatory bodies and other stakeholder groups that make health-related decisions. Decisions based on incomplete and biased evidence cannot only harm people, but may also have huge financial implications by wasting resources on ineffective or harmful diagnostic and therapeutic measures, and unnecessary research. Owing to involvement of multiple stakeholders, it remains easy for any single group to assign responsibility for resolving the problem to others. Objective To develop evidence-informed general and targeted recommendations addressing the various stakeholders involved in knowledge generation and dissemination to help overcome the problem of dissemination bias on the basis of previously collated evidence. Methods Based on findings from systematic reviews, document analyses and surveys, we developed general and targeted draft recommendations. During a 2-day workshop in summer 2013, these draft recommendations were discussed with external experts and key stakeholders, and refined following a rigorous and transparent methodological approach. Results Four general, overarching recommendations applicable to all or most stakeholder groups were formulated, addressing (1) awareness raising, (2) implementation of targeted recommendations, (3) trial registration and results posting, and (4) systematic approaches to evidence synthesis. These general recommendations are complemented and specified by 47 targeted recommendations tailored towards funding agencies, pharmaceutical and device companies, research institutions, researchers (systematic reviewers and trialists), research ethics committees, trial registries, journal editors and publishers, regulatory agencies, benefit (health technology) assessment institutions and legislators. Conclusions Despite various recent examples of dissemination bias and several initiatives to reduce it, the problem of dissemination bias has not been resolved. Tailored recommendations based on a comprehensive approach will hopefully help increase transparency in biomedical research by overcoming the failure to disseminate negative findings.

The contribution of ethics to public health

While ethics in health care dates back at least to the times of Hippocrates, Sun Si Miao,1 and Ibn Sina (Avicenna),2 the field of “bioethics” did not emerge until after World War Two. The birth of bioethics was stimulated by a confluence of factors. First, the Nazis’ medical experiments on concentration camp prisoners heightened concerns about the vulnerability of human subjects in medical research. Second, rapid advances in medicine, including reproductive health, organ transplantation and genetics, raised questions about the purpose and limits of medical technology. Third, post-war civil rights movements led to growing attention to the power imbalances between physicians and patients and the corresponding need to empower patients to control their own health-care decisions. In recent years, there have been efforts to broaden the scope of ethical analysis in health care to focus more directly on public-health issues.3 In contrast to the traditional emphasis of bioethicists on the physician–patient relationship, public-health ethics focuses on the design and implementation of measures to monitor and improve the health of populations. In addition, public-health ethics looks beyond health care to consider the structural conditions that promote or inhibit the development of healthy societies. From a global perspective, key issues in public health ethics include the following: Disparities in health status, access to health care and to the benefits of medical research – For example, questions about resource allocation depend in part on value judgments about the relative importance of small improvements in quality of life for a large portion of the population as compared with a life-saving intervention that would benefit only a few people. Responding to the threat of infectious diseases – Efforts to contain the spread of infectious diseases raise difficult questions about the appropriateness of restricting individual choices to safeguard other people’s welfare. Examples include the use of isolation and quarantine for tuberculosis and pandemic influenza. International cooperation in health monitoring and surveillance – The implementation of the International Health Regulations4 reflects the commitment of countries to collective action in the face of public-health emergencies. Defining the scope of countries’ obligations to act collectively, and determining how those obligations should be enforced, will inevitably raise difficult ethical dilemmas. Exploitation of individuals in low-income countries – Current practices in medical research, for example, may expose participants to significant risks without a benefit for themselves or their communities. Defining and enforcing foreign research sponsors’ obligations to local participants is therefore a critical ethical issue. In the area of organ transplantation, the growing practice of “transplant tourism” exposes individuals living in poverty to significant health risks while also raising broader questions about the commodification of the human body. Health Promotion – The growing public-health threats of noncommunicable diseases, including those caused in part by unhealthy behaviours such as smoking, poor diet or lack of exercise, have raised the question of the extent to which public-health authorities should interfere with personal choices on health. Participation, transparency, and accountability – As an ethical matter, the process by which decisions are made is as important as the outcome of the decisions. In the area of medical research, much attention has been devoted in recent years to strengthening systems for informed consent and community oversight. Once such systems are in place, the next step will be to develop mechanisms for evaluating their effectiveness. Since it was founded 60 years ago, ethics has been at the heart of WHO’s mission to protect and promote the global community’s health. Activities in ethics have been undertaken by many programmes and departments, as well as WHO’s regional offices. For example, in 1994, the Regional Office for the Americas (AMRO/PAHO) created a regional programme on bioethics5,6 In 2002, WHO’s Director-General Dr Gro Harlem Brundtland created an Ethics and Health Initiative, which has since served as a focal point for the ethics activities throughout the organization. Examples include the publication of Guidance on ethics and equitable access to HIV treatment and care (jointly with UNAIDS)7 and of Ethical considerations in developing a public health response to pandemic influenza.8 WHO also contributes to regional capacity-strengthening efforts in ethics, in close collaboration with Member States. For example, the project Networking for Ethics on Biomedical Research in Africa (NEBRA) sought to strengthen African countries’ capacity to engage in effective ethical review processes.9 Articulating ethical and evidence-based policy options is one of WHO’s six core functions.10 WHO’s 60th anniversary and the 30th anniversary of Alma-Ata provide a particular opportunity to reflect on ethical values and dilemmas arising in the field of public health. ■

Potential penalties for health care professionals who refuse to work during a pandemic.

THE SEVERE ACUTE RESPIRATORY SYNDROME (SARS) EPIdemic and the spread of avian influenza have generated renewed interest in health care professionals’ (HCPs’) obligations to work during a pandemic. However, most discussions of this issue have occurred on a relatively abstract level of ethical analysis, with less attention to what should actually happen to HCPs who are unwilling to work. Should HCPs who refuse to work be fired from their jobs? Should they lose their licenses? Should they go to jail? It is a real possibility that some HCPs may refuse to work during a pandemic. Working during pandemics could place HCPs—and, by extension, their families—at significant risk of infection. Protective measures like masks may reduce the risk, but some HCPs were infected during the SARS crisis even after such measures were implemented. Even though most HCPs continued to work during the SARS epidemic despite the risks, survey results indicate that a substantial number of HCPs would be unwilling to work under comparable conditions. This commentary argues that the penalties for refusing to work during a pandemic should be limited to those an HCP would face for refusing to treat patients with contagious infections in nonpandemic situations. This argument is important because some states, such as Maryland and South Carolina, have enacted laws that authorize license revocations, fines, or even imprisonment for HCPs who disobey public health officials’ orders to work during public health emergencies. These penalties would apply even to HCPs whose occupations do not ordinarily encompass clinical responsibilities, or to HCPs who are not currently part of the workforce—for example, physicians or nurses who are taking time off from work to care for their children. These laws seem unjustified.

Ethical aspects of malaria control and research

Malaria currently causes more harm to human beings than any other parasitic disease, and disproportionally affects low-income populations. The ethical issues raised by efforts to control or eliminate malaria have received little explicit analysis, in comparison with other major diseases of poverty. While some ethical issues associated with malaria are similar to those that have been the subject of debate in the context of other infectious diseases, malaria also raises distinct ethical issues in virtue of its unique history, epidemiology, and biology. This paper provides preliminary ethical analyses of the especially salient issues of: (i) global health justice, (ii) universal access to malaria control initiatives, (iii) multidrug resistance, including artemisinin-based combination therapy (ACT) resistance, (iv) mandatory screening, (v) mass drug administration, (vi) benefits and risks of primaquine, and (vii) malaria in the context of blood donation and transfusion. Several ethical issues are also raised by past, present and future malaria research initiatives, in particular: (i) controlled infection studies, (ii) human landing catches, (iii) transmission-blocking vaccines, and (iv) genetically-modified mosquitoes. This article maps the terrain of these major ethical issues surrounding malaria control and elimination. Its objective is to motivate further research and discussion of ethical issues associated with malaria—and to assist health workers, researchers, and policy makers in pursuit of ethically sound malaria control practice and policy.

Ethical issues in public health surveillance: a systematic qualitative review

BackgroundPublic health surveillance is not ethically neutral and yet, ethics guidance and training for surveillance programmes is sparse. Development of ethics guidance should be based on comprehensive and transparently derived overviews of ethical issues and arguments. However, existing overviews on surveillance ethics are limited in scope and in how transparently they derived their results. Our objective was accordingly to provide an overview of ethical issues in public health surveillance; in addition, to list the arguments put forward with regards to arguably the most contested issue in surveillance, that is whether to obtain informed consent.MethodsEthical issues were defined based on principlism. We assumed an ethical issue to arise in surveillance when a relevant normative principle is not adequately considered or two principles come into conflict. We searched Pubmed and Google Books for relevant publications. We analysed and synthesized the data using qualitative content analysis.ResultsOur search strategy retrieved 525 references of which 83 were included in the analysis. We identified 86 distinct ethical issues arising in the different phases of the surveillance life-cycle. We further identified 20 distinct conditions that make it more or less justifiable to forego informed consent procedures.ConclusionsThis is the first systematic qualitative review of ethical issues in public health surveillance resulting in a comprehensive ethics matrix that can inform guidelines, reports, strategy papers, and educational material and raise awareness among practitioners.

How should ethics be incorporated into public health policy and practice

The ethical obligations of those who work for health are as old as the health professions themselves; indeed, the commitment to place the interests of clients above all else is one of the hallmarks of professionalism. Ethical prescriptions are found in many cultures, such as the oath and associated writings of Hippocrates in ancient Greece and the writings of the medieval Jewish philosopher Maimonides. Though originating with the professions, ethical duties are of concern to society in general, and their violation – as by the doctors who conducted experiments in the Nazi prison camps – can constitute human rights as well as ethical violations. In response to the tremendous expansion of the powers of medicine and biomedical science in the 20th century, the new field of bioethics emerged in the 1960s, first in North America and western Europe and eventually around the world. With contributions not only from moral philosophers but also from physicians, nurses and other health professionals, social and natural scientists and lawyers, bioethics has become a field of major concern. Health professionals, health authorities and the public debate the issues raised by organ and tissue transplantation, unequal access to life-saving medicines, new reproductive technologies and vast increases in the numbers and types of clinical trials. While abundant analysis and official guidelines have been produced on most of the ethical issues in health care and research, until recently the field of public health received relatively little attention among ethicists. Similarly, while ethical questions have always been an implicit part of public health practice, the idea of incorporating a formal process of ethical deliberation into public health policy-making remains relatively new. As the ethics of public health receives greater attention, new paradigms and methods of ethical analysis will have to be developed. In particular, whereas medical ethics has traditionally aimed to protect individual interests in the context of the physician–patient relationship, public health ethics focuses on the design and implementation of measures to monitor and improve the health of broader populations. In addition, public health ethics must look beyond health care per se to consider the structural conditions, and social and economic determinants that promote or inhibit the development of healthy societies. Incorporating ethical analysis into public health raises many challenging questions. For example, what does ethical analysis add to public health beyond legal or public policy analysis? Is the law itself subject to a process of ongoing ethical scrutiny? When ethicists appeal to “values”, who gets to decide which values are worthy of protection or how these values should be prioritized in cases of conflict? How should ethical analysis address the tension between universal principles and culturally specific values, and find common ground among individuals from diverse cultural backgrounds? Such questions have practical implications for how public health policies are designed, implemented and evaluated. For example, when public health authorities make decisions about allocating limited resources, they will implicitly or explicitly determine which principles and values underlie those decisions. Such decisions also vary according to the processes by which they are made and to what extent the public, nongovernmental and international organizations, and national or regional governments participate in these processes. A Bulletin theme issue, to be published in August 2008, will provide a forum for examining these and related issues. The goal of this theme issue is to explore how ethical considerations have been and should be incorporated into decision-making about public health issues. The Bulletin encourages the submission of papers covering practical examples that illustrate how ethical questions have been addressed at the domestic and international levels. For example, how have governments or professional associations used ethical analysis to evaluate health-care workers’ obligations during influenza pandemics? What does ethics have to say about the use of financial incentives to increase the supply of organs for transplantation? In general, we seek to publish specific examples of structures and processes that have been used for ethical deliberation, combined with a candid examination of these options’ advantages and drawbacks. Contributions from authors from developing countries are particularly welcome. It is hoped that the papers in this issue will help national policy-makers reflect on the need to consider ethics in formulating and implementing health policies, while also providing best practices that can be adapted to specific national contexts. The issue will provide a forum for units at WHO headquarters and regional offices that have engaged in ethical analysis of their programmes to share their work. Finally, the empirical basis of the papers will provide much-needed data about global efforts to address ethical issues and the impact these efforts are having on the health of populations. The deadline for submissions is 11 January 2008. All submissions will go through the Bulletin’s peer review process. ■

Technology assessment in dentistry: A comparison of the longevity and cost-effectiveness of inlays

OBJECTIVES An example of technology assessment in dental care by evaluating the (cost-)effectiveness of types of three-surface inlays (gold, laboratory-fabricated ceramic, and chairside CAD/CAM ceramic) is provided. METHODS MEDLINE, EMBASE, and the Cochrane Library were searched for studies published between 1966 and June 2003 that reported annual survival probabilities and annual observations. The longevity of different types of inlays was measured by the number of failure-free years. Annual survival rates from different studies were pooled by weighing the rates of each study by the inverse of the variance of the effect estimate. A cost-effectiveness analysis from the perspective of German private health insurers was performed using billing charges. RESULTS Three, five, and two case series on laboratory-fabricated ceramic, chairside CAD/CAM ceramic, and gold inlays, respectively, were included. Over a 9-year observation period, the number of undiscounted failure-free years was 8.62 (95 percent confidence interval, 8.40-8.85), 8.65 (8.58-8.73), and 8.76 (8.72-8.80) for laboratory-fabricated ceramic, chairside CAD/CAM ceramic, and gold inlays, respectively. Laboratory-fabricated ceramic inlays were the most expensive. CONCLUSIONS While laboratory-fabricated ceramic, chairside CAD/CAM ceramic, and gold inlays had a strikingly similar failure-free survival rate, laboratory-fabricated ceramic inlays had the highest costs and, thus, were less cost-effective than chairside CAD/CAM ceramic and gold inlays.

Developing the ethics of implementation research in health

Implementation research (IR) is growing in recognition as an important generator of practical knowledge that can be translated into health policy. With its aim to answer questions about how to improve access to interventions that have been shown to work but have not reached many of the people who could benefit from them, IR involves a range of particular ethical considerations that have not yet been comprehensively covered in international guidelines on health research ethics. The fundamental ethical principles governing clinical research apply equally in IR, but the application of these principles may differ depending on the IR question, context, and the nature of the proposed intervention. IR questions cover a broad range of topics that focus on improving health system functioning and improving equitable and just access to effective health care interventions. As such, IR designs are flexible and often innovative, and ethical principles cannot simply be extrapolated from their applications in clinical research. Meaningful engagement with all stakeholders including communities and research participants is a fundamental ethical requirement that cuts across all study phases of IR and links most ethical concerns. Careful modification of the informed consent process may be required in IR to permit study of a needed intervention. The risks associated with IR may be difficult to anticipate and may be very context-specific. The benefits of IR may not accrue to the same groups who participate in the research, therefore justifying the risks versus benefits of IR may be ethically challenging. The expectation that knowledge generated through IR should be rapidly translated into health policy and practice necessitates up-front commitments from decision-makers to sustainability and scalability of effective interventions. Greater awareness of the particular ethical implications of the features of IR is urgently needed to facilitate optimal ethical conduct of IR and uniform ethical review.

Latent tuberculous infection: ethical considerations in formulating public health policy.

There is increasing interest in the introduction of public health policies relating to latent tuberculous infection (LTBI). However, there has been little previous systematic engagement with LTBI from an ethical perspective. This article offers a general overview of ethical issues in relation to LTBI, with particular focus on those aspects relevant to the development and implementation of public health policy. Key characteristics of LTBI are discussed from an ethical perspective, with examples of challenging situations for policy makers.