Solomon R. Benatar

Reflections and recommendations on research ethics in developing countries

The debate on the ethics of international clinical research involving collaboration with developing countries has achieved a high profile in recent years. Informed consent and universal standards have been most intensively debated. Exploitation and lack of adequate attention to justice in the distribution of risks/harm and benefits to individuals and communities have to a lesser extent been addressed. The global context in which these debates are taking place, and some of the less obvious implications for research ethics and for health are discussed here to broaden understanding of the complexity of the debate. A wider role is proposed for research ethics committees, one that includes an educational component and some responsibility for audit. It is proposed that new ways of thinking are needed about the role of research ethics in promoting moral progress in the research endeavour and improving global health.

Miliary tuberculosis : rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults

PURPOSE The purpose of this study was to determine the clinical and laboratory characteristics, diagnostic methods, and prognostic variables in adults treated for miliary tuberculosis in the rifampicin era. PATIENTS AND METHODS Computerized records of our community-based university teaching hospital over a 10-year period (1978 to 1987) were analyzed. A total of 109 patients were identified, including 12 who did not have miliary nodules on the chest radiograph (all of whom were shown to have hematogenous dissemination). Predisposing conditions were present in 46 patients. RESULTS Clinical features were similar to those of previously reported series. Hematologic abnormalities were common: leukopenia (less than 4 x 10(9)/L) was present in 16 of 107 patients (15%), thrombocytopenia (less than 150 x 10(9)/L) in 24 of 104 (23%), and lymphopenia (less than 1.5 x 10(9)/L) in 82 of 94 (87%). Pancytopenia was found in six patients, three of whom recovered. Disseminated intravascular coagulation occurred in four patients, all of whom died. Adenosine deaminase levels were elevated in only seven of 11 serosal exudates and in seven of 12 samples of abnormal cerebrospinal fluid. Fiberoptic bronchoscopy was diagnostic in 44 of 51 patients (86%), bone marrow examination in 19 of 22 (86%), and liver biopsy in all 10 patients. Twenty-six patients (24%) died of miliary tuberculosis a median of 6 days after starting treatment. Survivors were followed up for a median of 51 weeks. Stepwise logistic regression identified aged (greater than 60 years), lymphopenia, thrombocytopenia, hypoalbuminemia, elevated transaminase levels, and treatment delay as independent predictors of mortality. CONCLUSIONS Miliary tuberculosis commonly causes hematologic derangements, some of which are helpful prognostically. Fiberoptic bronchoscopy compares favorably to liver and bone marrow biopsy in sputum smear-negative cases. Mortality remains high and treatment should be begun as soon as the diagnosis is suspected.

A new look at international research ethics

Editorial by Lansang The normal “standard of care” against which new interventions are tested in medical research has not been formally defined. It is usually taken to mean the “best proved treatment” for any condition under investigation in a trial. We reject the arbitrariness of this notion of the standard of care and offer a more comprehensive alternative. Use of this new standard invokes a new approach to international research ethics that focuses on reducing inequalities in global health. The debate on what constitutes a fair and reasonable standard of care for subjects in developing countries who participate in clinical trials has been rekindled by critics of studies on the transmission of HIV.1-3 They argued that placebo controlled trials of new regimens to prevent the vertical transmission of HIV were unethical because they included a placebo arm rather than “the best proven treatment” available in developed countries. Some commentators considered the criticisms to be unfounded4-6 and associated with imperialistic attitudes.7 The debate made it clear that the high standards of research aspired to have not been adequately defined. It was also marred by simplistic notions of ethics. Although there was justified concern that pressure from the US Food and Drug Administration could “dilute” the Declaration of Helsinki, critics also presumed that whether a trial was ethical could simply be deduced from the text of a declaration. But declarations—such as the Declaration of Helsinki, governing international research ethics—are like constitutions, needing interpretation. Determining what is ethical goes beyond merely following prescriptions and requires moral reasoning: consideration of all relevant aspects of the case in its context, weighing and balancing competing moral requirements, and developing justifiable conclusions. Although more mature insight is gradually emerging into the complexity associated with the ethics of research in developing countries, the debate remains …

Global health ethics: the rationale for mutual caring

Despite spectacular twentieth century scientific and technological progress, the world is more inequitable than it was fifty years ago. This is evident both in terms of access to health care for individuals, and in relation to the health of whole populations. Disparities in wealth and health within and between nations are widening inexorably and the rapidly expanding global economy has failed to reduce poverty among those with little if any access to health care. In this context the Universal Declaration of Human Rights remains an unrealized aspiration for the majority of the worlds people. Given these realities, no single discipline, or body of knowledge is likely to make much difference. For example, approaches based only on neo–liberal economics, as exemplified by the structural adjustment programmes of the World Bank, have not been successful in promoting health equity. The authors believe that an interdisciplinary approach is required, and that bioethics, an interdisciplinary field, can make a contribution towards improving health globally. To do this, the scope of bioethics should be expanded towards a results–oriented global health ethics, based upon widely shared and foundational values that could be carried forward through five transformational approaches.

Identification of the high-risk asthmatic patient: Experience with 39 patients undergoing ventilation for status asthmaticus

Thirty-nine asthmatic patients required mechanical ventilation (IPPV) for status asthamticus over a seven and a half year period. We reviewed their clinical records with particular emphasis on the events leading to intermittent positive pressure ventilation (IPPV) and the long-term courses of those patients who survived IPPV. Long delays by patients before seeking medical attention, incomplete assessment of acute attacks, underuse of corticosteroids prior to admission and overuse of sedation were important factors often influencing the necessity for IPPV. Four patients died during IPPV. Of the 35 who survived, 32 were regularly followed in our Respiratory Clinic. Nine patients subsequently died, eight undoubtedly from asthma. Serial measurements of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were retrospectively analyzed to determine patterns of asthma. Of the 23 patients still alive, 14 have well controlled asthma, five have a pattern of persistent airflow obstruction, two have markedly labile asthma, and two have gradually deteriorating airflow obstruction. By contrast, seven patients who died sufficiently long after IPPV to enable categorization of their patterns showed either markedly labile asthma or gradually deteriorating airflow obstruction. None had relatively constant ventilatory function at either normal or suboptimal levels. We suggest that patterns of asthma are useful guides in detecting patients at high-risk. Patterns characterized by markedly labile asthma or gradually deteriorating airflow obstruction appear to be associated with an increased risk of sudden death from asthma.

Health and Health Care in South Africa — 20 Years after Mandela

Twenty years after the fall of apartheid, social and economic disparities persist in South Africa and have a profound effect on the health of the population. HIV infection and tuberculosis remain major health problems, and there are not enough health care workers.

Responsibilities in international research: a new look revisited

Following promulgation of the Nuremberg code in 1947, the ethics of research on human subjects has been a challenging and often contentious topic of debate. Escalation in the use of research participants in low-income countries over recent decades (stimulated by the HIV pandemic and the need to carry out clinical trials expeditiously on large numbers of patients), has intensified the debate on the ethics of international research and led to increasing attention both to exploitation of vulnerable subjects and to considerations of how the 10:90 gap in health and medical research (ie, 90% of resources being spent on 10% of the problems) could be narrowed. In 2000, prompted by the discussions over several years that led to the US NIH launching a capacity building programme on research ethics for members of research ethics committees in developing countries, we advanced a ‘new look’ for the ethics of international research.1 Since then progress has been made on several fronts. First, our ideas—considered somewhat radical and impractical at the time—have been provocatively addressed by scholars who have either contested them or advanced similar conceptions of what obligations international researchers have to research participants and communities in low income countries before, during and after clinical trials. Second, those researchers who have been sympathetic to our ideas have either endeavoured to put these into practice or have investigated the feasibility of doing so. Third, the intractability of the 10/90 gap and the escalation of interest in global health have sensitised many to the need to amplify the uptake of these ideas in practice. Here, we briefly review the conceptual and practical developments in international research ethics. While much conceptual progress has been made (and the concepts are now appearing …

Global Health and the Global Economic Crisis

Although the resources and knowledge for achieving improved global health exist, a new, critical paradigm on health as an aspect of human development, human security, and human rights is needed. Such a shift is required to sufficiently modify and credibly reduce the present dominance of perverse market forces on global health. New scientific discoveries can make wide-ranging contributions to improved health; however, improved global health depends on achieving greater social justice, economic redistribution, and enhanced democratization of production, caring social institutions for essential health care, education, and other public goods. As with the quest for an HIV vaccine, the challenge of improved global health requires an ambitious multidisciplinary research program.

Moral imagination: The missing component in global health

Benatar explores the underlying reasons for our failure to make adequate progress in improving global health.

Towards Progress in Resolving Dilemmas in International Research Ethics

ion that is blind to context while also avoiding the perils of moral relativism. An essential requirement here is to have deeper insights (a difficult task) into when and how it is morally appropriate to take local contexts (ethos/mores) into consideration in applying universal ethical principles. Considerations of major importance will be whether local cultural values inflict harms that could and should be avoided (or are harmless) and whether (or not) they infringe on human rights or abrogate respect for human dignity in the full acknowledgement that these concepts too are not easily defined in acceptable ways to al1.12 Standard of Care It is against this background that a philosophical approach to the standard of care in international research can be reviewed.13 Alex London shows that the controversy about whether or not to use a placebo, when some effective treatment may be available, is more complex than a comparison between local and global standards as reference points. He argues that the controversy also embraces interpretations of the standard of care from what he calls “de facto” and “de jure” perspectives. His morally reasoned analysis can also be depicted as a two dimensional framework (Figure 3). In a sequence of lucid arguments London shows that the debate does not merely take place along the