Evolving values in ethics and global health research.

Over the past 25 years, the ethics of international health research have shifted from addressing narrow issues such as cultural differences in informed consent practices towards a greater emphasis on development and social justice. We anticipate that the next 'era' in international research ethics will involve an intensification of this focus on the role of research in achieving global justice. Three values, in particular, will shape how ethics considerations should evolve: solidarity; respect for Southern innovation; and commitment to action. We expect continuing debate on whether researchers and research sponsors should recognise more than a minimal set of obligations for the care and benefit of research participants and their communities. As the debate about the role of research in development intensifies, we expect to see new and more elaborate mechanisms for financing on-going access to beneficial interventions, ancillary care and other research-related benefits, as well as a greater involvement in research funding by developing country governments and private foundations. Ethics review and oversight need to reflect on these new values and on ways of operationalising them, or risk becoming marginalised in the research process.

Payment to healthy volunteers in clinical research: the research subject's perspective.

Although there is much discussion regarding the ethics of making payments to healthy volunteers for participating in clinical research, little data are available from the point of view of the volunteers as to what they would consider to be fair payment. The objectives of this study were to determine healthy volunteers' estimates of appropriate payments for participation in hypothetical clinical trials in order to explore the reasoning behind these estimates and to examine the association between volunteer demographics and payment expectations. Sixty participants with previous experience as healthy volunteers in research studies were presented with four hypothetical studies and interviewed about their impressions of burden and risks involved in the studies. They were also asked to estimate an appropriate payment to the volunteers for each of the studies. For each of the studies, the payment estimates made by the participants varied over a wide range. However, each individual tended to be consistent in estimate placement within this range. No demographic factor was significantly associated with the estimated study payment. Subjects frequently mentioned risk and logistical burden as factors that should determine payment levels. Healthy volunteer subjects appear to have individualized yet consistent methods of arriving at estimates of payments for participating in clinical studies. These estimates are based on each subject's perception of study burden and associated risk.

Understanding respect: learning from patients.

BACKGROUND: The importance of respecting patients and participants in clinical research is widely recognised. However, what it means to respect persons beyond recognising them as autonomous is unclear, and little is known about what patients find to be respectful. OBJECTIVE: To understand patients' conceptions of respect and what it means to be respected by medical providers. DESIGN: Qualitative study from an academic cardiology clinic, using semistructured interviews with 18 survivors of sudden cardiac death. RESULTS: Patients believed that respecting persons incorporates the following major elements: empathy, care, autonomy, provision of information, recognition of individuality, dignity and attention to needs. CONCLUSIONS: Making patients feel respected, or valued as a person, is a multi-faceted task that involves more than recognising autonomy. While patients' views of respect do not determine what respect means, these patients expressed important intuitions that may be of substantial conceptual relevance.

Balancing justice and autonomy in clinical research with healthy volunteers.

In clinical research, ethics review generally first examines whether study risks are reasonable in light of benefits provided. Through informed consent, then, prospective subjects consider whether the risk/benefit balance and procedures are reasonable for them. Unique ethics issues emerge in clinical research with healthy volunteers. Certain types of studies only recruit healthy volunteers as participants. Phase 1 studies, for example, including first time in human studies of investigational drugs and vaccines, generally are conducted in healthy volunteers. Although such research carries inherent and often unknown risks, healthy subjects provide the most efficient target population in which to conduct such research, as these volunteers generally are free of concurrent diseases or medications that could confound interpretation of toxicity. Other studies enrolling healthy volunteers often are simply looking for the most scientifically sound population for the study of normal human physiology.

Identification of a novel nephropathogenic infectious bronchitis virus in Israel.

A novel infectious bronchitis variant, designated as IS/885/00, associated with nephritis, was isolated from outbreaks in 23 broiler farms in Israel. The virus was first identified by reverse transcriptase-polymerase chain reaction and showed a distinct restriction fragment length polymorphism pattern from previously described Israeli isolates. Sequence analysis of the S1 gene and the deduced amino acid sequence revealed 97.2% protein similarity to genotype IS/ 720/99 and 71.6% similarity to the vaccine strain H120, the only strain permitted for use in this country. A database search in GenBank revealed a closely related isolate from Egypt, Egypt/Beni-Seug/01, with 96.6% similarity. Other published nephropathogenic infectious bronchitis virus strains/isolates shared less than 77% similarity with IS/885/00. A vaccine protection test in specific-pathogen-free chicks indicated 91% protection to the trachea and only 25% protection to the kidneys in vaccinated birds challenged with IS/885/00.

The influence of reovirus sigma C protein diversity on vaccination efficiency.

Avian reovirus (ARV) is a disease agent that causes economic losses in the poultry industry. The available vaccines do not confer full protection. One possible reason is the existence in the field of many virulent serotypes with no cross protection. Several ARV strains have been isolated in Israel in the last few years. In this study, we investigated the diversity of the sigma C protein of ARV because this is the most variable protein in the virus and it induces the production of neutralizing antibodies. Sigma C from two virulent isolates was sequenced, cloned, and expressed. The protein sequence differed from the attenuated vaccine strain (strain 1133) but was similar to a U.S. virulent strain (strain 1733). Those differences led to a change in the antigenic index of the protein, mainly at three sites. Sera of infected birds in a field trial and of birds in a controlled experiment vaccinated with the recombinant sigma C protein showed high titers in enzyme-linked immunosorbent assay to the recombinant protein and lower titers to the attenuated vaccine strain. This means that sigma C can be used as a diagnostic tool for the detection of antibodies relevant for protection and in the future as a subunit vaccine. The results of this study highlight the need to reconsider vaccinations against ARV in terms of the strains to be used and of the method of identifying protective antibodies transferred to progeny.

Chicken infectious anemia virus infection in Israeli commercial flocks: virus amplification, clinical signs, performance, and antibody status.

The impact of chicken infectious anemia virus (CIAV) infection on commercial chicken flocks in Israel was examined by analyzing flocks with or without typical CIAV signs, signs of other diseases, or apparently healthy flocks. In 23 flocks (broilers and layers) of ages up to 8 wk, typical signs of CIAV infection (stunting, gangrenous dermatitis, and secondary bacterial infections) were recorded. When permitted by flock owners, in several cases among these 23 flocks the morbidity, mortality, and performance parameters were recorded; the presence of CIAV was detected by polymerase chain reaction (PCR); and the antibody status of parents and broilers was measured. In addition, total mortality, number of birds sold, total kilograms of meat sold, density (kg/m2), mean age at slaughter, daily growth rate in grams, total kilogram of food consumed, food conversion rate, and the European Index were calculated. We also surveyed flocks affected by other diseases, such as tumors, respiratory diseases, or coccidiosis, and flocks with no apparent clinical signs. The latter flocks were negative by CIAV-PCR, indicating that typical CIAV clinical signs are associated with one-step PCR-CIAV amplification. However, a small amount of CIAV might still be present in these flocks, acting to induce the subclinical effects of CIAV infection. These data indicate a link between the presence of virus sequences and typical CIAV signs and strengthen the concept that CIAV infection has a negative economic impact on the chicken industry.

Ethical review of health research: a perspective from developing country researchers.

BACKGROUND: Increasing collaboration between industrialised and developing countries in human research studies has led to concerns regarding the potential exploitation of resource deprived countries. This study, commissioned by the former National Bioethics Advisory Commission of the United States, surveyed developing country researchers about their concerns and opinions regarding ethical review processes and the performance of developing country and US international review boards (IRBs). METHODS: Contact lists from four international organisations were used to identify and survey 670 health researchers in developing countries. A questionnaire with 169 questions explored issues of IRB review, informed consent, and recommendations. RESULTS: The majority of the developing country researchers were middle aged males who were physicians and were employed by educational institutions, carrying out research on part time basis. Forty four percent of the respondents reported that their studies were not reviewed by a developing country IRB or Ministry of Health and one third of these studies were funded by the US. During the review process issues such as the need for local language consent forms and letters for approval, and confidentiality protection of participants were raised by US IRBs in significantly higher proportions than by host country IRBs. CONCLUSION: This survey indicates the need for the ethical review of collaborative research in both US and host countries. It also reflects a desire for focused capacity development in supporting ethical review of research.

An ethics framework for public health.

More than 100 years ago, public health began as an organized discipline, its purpose being to improve the health of populations rather than of individuals. Given its population-based focus, however, public health perennially faces dilemmas concerning the appropriate extent of its reach and whether its activities infringe on individual liberties in ethically troublesome ways. In this article a framework for ethics analysis of public health programs is proposed. To advance traditional public health goals while maximizing individual liberties and furthering social justice, public health interventions should reduce morbidity or mortality; data must substantiate that a program (or the series of programs of which a program is a part) will reduce morbidity or mortality; burdens of the program must be identified and minimized; the program must be implemented fairly and must, at times, minimize preexisting social injustices; and fair procedures must be used to determine which burdens are acceptable to a community.

Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening.

Utilizing the plasma very long chain fatty acid assay, supplemented by mutation analysis and immunofluorescence assay, we determined the number of X-linked adrenoleukodystrophy (X-ALD) hemizygotes from the United States identified each year in the two laboratories that perform most of the assays in this country: the Kennedy Krieger Institute between 1981 and 1998 and the Mayo Clinic Rochester from 1996 to 1998. The minimum frequency of hemizygotes identified in the United States is estimated to be 1:42,000 and that of hemizygotes plus heterozygotes 1:16,800. Our studies involved 616 pedigrees with a total of 12,787 identified at-risk members. Diagnostic assays were performed in 4,169 at-risk persons (33%) and included members of the extended family. Only 5% of male probands and 1.7% of X-ALD hemizygotes were found to have new mutations. The extended family testing led to the identification of 594 hemizygotes and 1,270 heterozygotes. Two hundred fifty of the newly identified hemizygotes were asymptomatic and represent the group in which therapy has the greatest chance of success. Identification of heterozygotes provides the opportunity for disease prevention through genetic counseling. Diagnostic tests should be offered to all at-risk relatives of X-ALD patients and should include members of the extended family.

Health-related quality of life among people with HIV disease: results from the Multicenter AIDS Cohort Study.

To examine the effect of HIV status, symptomatology and CD4+ lymphocyte level on health-related quality of life, the Medical Outcomes Study Short-Form Health Survey (SF-36) was administered to 2,295 gay men enrolled in the Multicenter AIDS Cohort Study (MACS) in 1994. Distinct physical and mental health factors of the SF-36 were found. Seropositive asymptomatic individuals and seropositive individuals with CD4+ lymphocytes > or = 500/mm3 scored as well as seronegative participants on all of the mental health domain scales, but lower on the general health perceptions and physical health composite score. Seropositive individuals with at least one symptom or with CD4+ lymphocytes below 200/mm3 scored significantly lower on all of the SF-36 scales and summary scores than seronegative controls. The SF-36 was found to exhibit similar mental and physical health factors for an adult gay male population to that previously seen in general population samples and in patient groups with other diseases. In conclusion, HIV-positive men who are asymptomatic or have CD4+ lymphocytes above 500/mm3 have similar perceived mental health but worse perceived physical health than seronegative men. HIV-positive men who are symptomatic or have CD4+ lymphocytes below 200/mm3 have worse perceived mental and physical health than seronegative men.

Treatment of human immunodeficiency virus during pregnancy: the shift from an exclusive focus on fetal protection to a more balanced approach.

A review is presented of policy and treatment guidelines for human immunodeficiency virus infection in pregnancy. Interventions that serve the best interests of pregnant women and their fetuses are suggested. Reproductive studies with animals should be done routinely, and more research with pregnant women should be conducted. Women and their health care providers need to shift away from the "therapeutic nihilism" paradigm. All clinical decisions must be made cautiously and thoughtfully, with the understanding that the health needs of the pregnant woman are usually whatever is in the best interest of the developing fetus.

Effect of race on insurance coverage and health service use for HIV-infected gay men.

OBJECTIVE: To determine whether race is associated with health insurance coverage and health service use among gay and bisexual men in the Baltimore center of the Multicenter AIDS Cohort Study. METHODS: Data from eight semiannual study visits between 1991 and 1996 were used. Descriptive, stratified, and logistic regression analyses were conducted to determine whether race is associated with insurance coverage, medical, or dental service use, after controlling for socioeconomic variables. RESULTS: No difference was found between blacks' and whites' likelihood of having health insurance, private insurance, using inpatient, emergency department services, or antiretroviral medications. Whites were more likely to use outpatient services, particularly if CD4 cell counts were high, and were more likely to use dental services, although blacks were more likely to have dental insurance. CONCLUSIONS: Further research must be conducted to examine cultural, social, and psychological factors that help explain why white gay men use more outpatient and dental services, when other service use is unrelated to race. Investigators should be precise when using race as a variable in health services and epidemiologic research, emphasizing when racial differences truly exist versus when the variable race is a surrogate for another factor.

Adolescents and popular culture. A psychodynamic overview.

Adolescents occupy a difficult and seemingly elusive developmental space, which makes them enigmas to most adults, including psychotherapists. Building upon dynamic theory such as that formulated by Winnicott or Erikson, this paper explores the relationship between adolescents and material elements of popular culture within a psychodynamic and developmental framework. Theoretical perspectives are integrated with case material to illustrate some of the roles of popular music and fashion in the lives of teenagers as a means of expression and in potential therapeutic alliance formation, dynamic understanding and working through developmental conflicts in displacement.

HIV testing policies for pregnant women: A roundtable discussion.

AIDS: The Institute of Medicine's (IOM) Committee on Perinatal Transmission of HIV released its report in October 1998. Universal and routine HIV testing with the right of refusal for all pregnant women in the United States was recommended. This recommendation differed from the CDC guidelines in 1995 that recommended universal counseling but only voluntary testing for all pregnant women. Dr. Nancy Kass from the IOM committee and Dr. Howard Minkoff of the Maimonides Medical Center discuss the policy and its implications with Dr. Deborah Cotton, editor of AIDS Clinical Care and IOM committee member. Medical and social advantages of the policy are described, and steps are detailed for implementing IOM's recommendations.^ieng