Some implications of genetic biomarkers in occupational epidemiology and practice

This paper addresses the use of genetic biomarkers in occupational epidemiology and some of the scientific, ethical, and social implications for epidemiologists and practitioners to consider, including issues involving individual risk estimation, the communication of epidemiologic results, and the translation of epidemiologic data into clinical or occupational health practice. Three scenarios from the occupational setting illustrate some of these issues and implications. The scenarios involve glutathione-S-transferase theta 1 (GSTT1) and hematopoietic cancer in hospital workers, human leukocyte antigen coding for glutamic acid in the 69th position (HLA DPB1(E69)) and chronic beryllium disease in beryllium workers, and peripheral myelin protein 22 (PMP22) deletion and carpal tunnel syndrome in railroad track workers. Epidemiologic research involving genetic biomarkers requires the application of genetic tests and can be considered on a continuum between basic sciences and clinical and occupational and public health practice for which questions of test relevance, validity, and utility become important.     

Challenges of worker notification in neurotoxic studies of the central nervous system.

Researchers who study the central nervous system (CNS) face special challenges in notifying study participants about the research results. There are human research guidelines regarding the communication of information to subjects at the outset of a CNS research study. Yet there are few guidelines on how to communicate to the subject the research findings and the interpretation of individual results at the study's conclusion. The research subjects may desire detailed information, unequivocal conclusions, understandable interpretations, and clear suggestions about what to do next. Fulfilling these needs, however, is not a simple task for the researcher because outcomes are predicated on statistical uncertainty and the research tests may not be appropriate for individual assessment. We describe methods we have used to communicate with research subjects in two CNS neurotoxic field studies. We suggest that further research examine this important notification process.     

Notification of workers at high risk: an emerging public health problem.

During the last two decades, an increasing number of epidemiologic studies have found cohorts of workers to be at high risk of work-related chronic diseases, especially cancers. These studies frequently have led to the broad recognition of occupational hazards and eventually to the prevention of exposures to such hazards. Generally, however, the individual cohort members found to be at high risk have not been notified of study results, and programs of medical intervention or of palliative services directed at these individual workers have not been developed. Recently, the issue of whether or not workers have a right to be notified more directly about known health hazards to which they may have been exposed has emerged as a major, unresolved question in public health policy. Issues of concern include the criteria that should guide notifications; whom, when, and how to notify; and who should pay for notification and follow-up services. This commentary discusses the scientific, ethical, economic, and institutional aspects of worker notification, and describes three new demonstration projects that have provided notification and intervention for workers at high risk of bladder, colon, and lung cancer.     

Risk to researchers in qualitative research on sensitive topics: issues and strategies

Traditionally, risk assessments in research have been limited to examining the risks to the research participants. Although doing so is appropriate and important, there is growing recognition that undertaking research can pose risks to researchers as well. A grounded theory study involving a range of researchers who had undertaken qualitative health research on a sensitive topic was completed. Analysis of the in-depth, face-to-face unstructured individual interviews with 30 Australian public health researchers provided evidence that researchers do confront a number of physical and emotional risks when undertaking research. Training, preparation, and supervision must be taken into account so that the risk to researchers can be minimized. Researchers need to consider occupational health and safety issues in designing research projects that deal with physical and emotional risks. Recommendations for professional supervision, policy development, and minimum training standards for researchers are provided.     

To tell or not to tell: the ethical dilemmas of HIV test notification in epidemiologic research.

Epidemiologic studies involving HIV (human immunodeficiency virus) antibody testing create ethical dilemmas, particularly about notifying asymptomatic seropositive subjects. Four study designs address this problem: mandatory notification, optional notification, anonymous testing, and blind testing. No single design consistently optimizes the trade-off between valid and ethical research. Each strategy differs substantially from the others in its effect on response rates, bias, ability to perform longitudinal studies, numbers of subjects who learn their test results, and the number of subjects counseled about HIV risk reduction. Both local institutional review boards and potential subjects of study (and their sexual partners) should participate in decisions regarding the conduct of sensitive AIDS (acquired immunodeficiency syndrome) research.     

Regulations of 23 December 1986 for the implementation of the General Law on health, in the field of health research

This document presents the text of health legislation approved in Mexico on December 23, 1986, setting forth ethical issues and professional responsibilities in the area of health research. Health research is conceptualized as activities that contribute to knowledge regarding biological and physiological processes in humans; knowledge of the links between the causes of disease, medical practice, and social structures; prevention and control of health problems; evaluation of the harmful effects of the environment on health; the study of techniques recommended or used for the delivery of health services; and the production of goods for the health sector. Title 1 of these regulations outlines responsibilities of the Secretariat of Health and calls for the establishment of an Inter-Institutional Commission on Health Research. Title II defines ethical aspects of research on human subjects, with separate provisions for research involving minors, incompetent persons, women of childbearing age, pregnant women, women during labor or childbirth, nursing mothers, embryos, stillborn fetuses, and cadavers. In general, research is permissible on human subjects only if it confers health benefits and carries minimal risks. Title III sets forth regulations on research on new prophylactic, diagnostic, therapeutic, and rehabilitative methods, while Title IV concerns the biosafety of research. Clinical research in the field of pharmacology must include 4 phases preceded by full preclinical studies. Finally, Title V of this legislation defines the duties of internal committees in health institutions.     

Workers' response to risk notification

Since 1988, the National Institute for Occupational Safety and Health (NIOSH) has notified workers who were subjects in occupational epidemiology studies of the study findings (“worker notification”). This paper describes seven notifications and the worker's reactions to them. The chemicals of interest in the studies were: carbon monoxide, o-toluidine, bis-chloromethyl ether, polychlorinated biphenyls, cadmium, acid mist, and dioxin. Materials describing the study results were sent to 15,958 subjects who were notified of their increased risk of arteriosclerotic heart disease, bladder cancer, lung cancer, melanoma, kidney dysfunction, laryngeal cancer, all cancers combined, or soft tissue sarcoma. Workers provided feedback via telephone calls, and for three notifications, by postcards containing workers' comments and ratings of the notification materials. The percentage of telephone calls received from notified workers ranged from 0.3% to 3.8%, and the percentage returning postcards ranged from 8.8% to 17.6%. The two largest categories of callers were those with questions about their disease risk (30%) or who reported on their health status (25%). Most of the comments on postcards (26%) were complimentary or expressed appreciation for receiving the letters; reports of ill health were second (20%). A majority (66%) rated the notification materials well done. Few of the callers (5%) requested information on legal issues. Most (85%) did not find the materials, which ranged in reading level from sixth to ninth grade, too hard to read, although 15% reported difficulty reading them. Although this response system was effective in producing some input from workers, its limitation is that respondents may not be representative of all notified workers. However, such information is useful because there are few data on the effects of notifications on workers. © 1995 Wiley-Liss, Inc.     

Issues in notification: Reflections of a public health worker

The objectives of notification are to inform individuals of research results so that they can make informed choices regarding health care and risk reduction behaviors, and to inform workers and employers of results and recommendations in order to take actions to improve workplace health and safety. Many questions confront researchers or public health workers engaged in notification efforts. Who should be notified? What information should be included in notification materials? When should notification occur? How and where should notification take place? What is the socioeconomic context in which notification is occurring? This article presents a public health worker's perspective on these issues. © 1993 Wiley-Liss, Inc.     

Prevention of mental retardation due to PKU: selected aspects of program validity.

Phenylketonuria (PKU) screening of the newborn represents the largest preventive program in the history of public health. Yet traditional indices of program validity cannot be estimated with confidence because of insufficient or equivocal evidence. Large variation of results within and between screening programs invalidates general probability statements. Current issues in PKU screening involve aspects of comprehensiveness, effectiveness, and efficiency of the program. Specific concerns include the risk of missing PKU cases, the interpretation of a positive screening test result, the loss to follow-up of infants with positive screening test results, the validity of diagnostic criteria in regard to the risk for mental retardation, the age at which preventive intervention is initiated, and the consequences of the program for the prevalence of mental retardation in future generations. The major evidence bearing on these questions is reviewed, and it is concluded that the screening program has a high potential for effectiveness and efficiency. Program validity can be optimized and maintained by continuous monitoring of individual program experience, which results in appropriate adjustments of procedures and criteria.     

Exploration of occupational therapists' comfort with client sexuality issues

Sexuality is manifest in nearly every aspect of our daily behaviour and is crucial to self-image. It follows, then, that issues of sexuality are important to consider when providing health care. When an individual experiences ill health, every aspect of that individual needs to be recognized and included in the overall intervention; this includes the client's sexuality. Literature indicates that clients' need for recognition of their sexuality within health care is not often met. Some writers suggest that this need is not being met partly because health professionals, including occupational therapists, are not comfortable with situations involving sexuality, due to a lack of knowledge, experience and positive attitudes. The purpose of this research was to explore these and other factors that might contribute to the comfort level of occupational therapists when they deal with situations involving sexuality. To explore this area, six clinical scenarios involving issues of sexuality were developed from the literature and the authors' experience. Occupational therapists and final year occupational therapy students were asked to review and comment on these situations. Analyses of this data together with data from a focus group, the authors' clinical education placements and informal interviews suggests that, in addition to knowledge, experience and attitudes, there are other factors worthy of further consideration. These factors include: the therapist's perception of his or her role and issues of power and control. This study highlights the need for further innovative inquiry into this interesting and important area.     

Epidemiologic input to environmental risk assessment

Epidemiological data are often rejected for risk assessment purposes because of the lack of accurate exposure data. Animal data are frequently resorted for risk assessment calculations. Such a decision should account for potential errors in animal to human risk extrapolations, which may be of 1 or 2 orders of magnitude or more. Because historical human exposure can usually be estimated with confidence that the errors would be considerably less than 1 order of magnitude, it follows that human studies should generally take precedence over animal studies, even when crude assumptions have to be made concerning human exposure levels. This paper illustrates this with cancer risk assessments for vinyl chloride and antimony, both of which relied on use of the stipulated average cohort exposure levels without use of any individual exposure data for cohort members. Linear extrapolations of risk to low exposures were used in both instances. Non-cancer risk assessments were illustrated by examining results of experimental studies of effects of ozone on ventilatory function. A simple approach, in this case involving visual inspection of study results, was again recommended. Consideration was given to concerns about synergistic effects of low-level exposure to chemical mixtures. Calculations were presented to demonstrate that estimating risks by multiplying effects of individual chemicals produces the same risk estimated by adding effects, provided that exposure levels were sufficiently low for each individual agent. It was concluded that epidemiology has much to offer to environmental health risk assessment, but that epidemiologists need to be more effective in justifying the scientific basis of the design and interpretation of epidemiological studies to laboratory scientists, who frequently reject epidemiological findings for inappropriate reasons.     

Informed consent from cognitively impaired persons participating in research trials: comparative law observations

This article addresses the ethical requirements to be considered when conducting clinical trials involving human subjects whose mental condition limits their ability to understand the information and to express fully autonomous and informed consent. It does not address other categories of vulnerable persons, such as children, or advanced directives concerning end-of-life care. There are many ethical issues entailed in clinical trials involving subjects with mental disabilities: how to obtain informed consent, balancing risks and benefits, balancing individual benefits with collective scientific and social interests, legal representation and many more. This article focuses on the issues surrounding the concept of minimal risk and the relationship between informed consent and risk. These issues are addressed with particular emphasis on the regulations adopted by the European Union and the federal government of the United States of America. The conclusion proposes a list of working criteria.     

Negotiating Occupational Identities while Living with Chronic Rheumatic Disease

The purpose of this study was to explore everyday occupation for five persons living with chronic rheumatic disease. Data were collected through qualitative interviews, followed by participant observations in the subjects’ homes. The data were analysed using a qualitative comparative approach, followed by an interpretation of the results based on narrative theory. Four themes were identified from the analyses: (a) the continuing challenges of everyday occupational life, (b) activities anchored to personal occupational history, (c) everyday occupations mediating personal meaning, and (d) activities involving suspense or unpredictability. The results showed that everyday occupation was a challenge for the participants, as their illness caused considerable variation in pain and functional abilities. This influenced the subjects’ ability to perform occupations of everyday life. Their individual occupational history was closely interwoven with their everyday life and served as the foundation for their way of managing the situation. The everyday occupations of the subjects also served as mediators of their personal values and interests, and they made changes following these issues, not as anticipated due to their changing functional condition. The narrative structure of occupation was found to provide the subjects with opportunities to manage issues concerning their identity and created high-level negotiating skills. Processes of negotiating occupational identities in the subjects’ everyday life are presented and discussed, and may add new knowledge to occupational therapy and occupational science, as well as generating further research questions.     

Randomized controlled trials in environmental health research: ethical issues

Randomized controlled trials (RCTs) are becoming increasingly common in environmental health research. Like all studies involving human subjects, environmental health RCTs raise many ethical challenges, ranging from obtaining informed consent to minimizing risks to protecting privacy and confidentiality. One of the most important issues raised by these studies is whether it is ethical to withhold effective environmental health interventions from research subjects in order to satisfy scientific objectives. Although environmental health investigators usually do not have professional obligations to provide medical care to research subjects, they have ethical obligations to avoid exploiting them. Withholding interventions from research subjects can be ethical, provided that it does not lead to exploitation of individuals or groups. To avoid exploiting individuals or groups, investigators should ensure that research subjects and study populations receive a fair share of the benefits of research.     

Risk and responsibility: ethics,Grimes v Kennedy Krieger,and public health research involving children

The legal case of Grimes v. Kennedy Krieger Institute, Inc, has raised concerns in the public health research community regarding the acceptable level of risk in research involving children, parental authority for informed consent, and exploitation of research subjects for the benefit of public health. We provide an overview of the case and discuss the impact of the court's decision and its possible effect on future research protection policies and practices.     

Simulated Patient Studies: An Ethical Analysis

Context: In connection with health care reform, the U.S. Department of Health and Human Services commissioned a “mystery shopper,” or simulated patient study, to measure access to primary care. But the study was shelved because of public controversy over “government spying” on doctors. Opponents of the study also raised ethical concerns about the use of deception with human subjects without soliciting their informed consent. Methods: We undertook an ethical analysis of the use of simulated patient techniques in health services research, with a particular focus on research measuring access to care. Using a case study, we explored relevant methodological considerations and ethical principles relating to deceptive research without informed consent, as well as U.S. federal regulations permitting exceptions to consent. Findings: Several relevant considerations both favor and oppose soliciting consent for simulated patient studies. Making research participation conditional on informed consent protects the autonomy of research subjects and shields them from unreasonable exposure to research risks. However, scientific validity is also an important ethical principle of human subjects research, as the net risks to subjects must be justified by the value to society of the knowledge to be gained. The use of simulated patients to monitor access is a naturalistic and scientifically sound experimental design that can answer important policy‐relevant questions, with minimal risks to human subjects. As interaction between researchers and subjects increases, however, so does the need for consent. Conclusions: As long as adequate protections of confidentiality of research data are in place, minimally intrusive simulated patient research that gathers policy‐relevant data on the health system without the consent of individuals working in that system can be ethically justified when the risks and burdens to research subjects are minimal and the research has the potential to generate socially valuable knowledge.     

Patient-led partner notification for syphilis: Strategies used by women accessing antenatal care in urban Bolivia

Maternal syphilis adversely affects close to one million pregnancies worldwide every year with consequences that may include spontaneous abortion, stillbirth, neonatal death, premature birth, neurological impairment and bone deformities of the neonate. In Bolivia, the maternal syphilis rate has been estimated at 4.3% among women with live births and 26% among women with stillbirths. Partner notification is critical to the prevention of maternal re-infection and vertical transmission of syphilis. Patient-led partner notification, also known as patient referral, is the recommended starting point for partner notification programs in resource poor settings because it requires less infrastructure and provider involvement. Though patient referral requires a higher level of engagement on the part of individuals, few studies have examined, in depth, the process of patient-led notification. Further, we found no studies of this type conducted in Bolivia, a country where culturally acceptable and appropriate interventions are needed to control maternal syphilis. This study examined partner notification, for the first time, from the perspective of women accessing treatment for maternal syphilis in Bolivia. Semi-structured interviews were conducted with 18 women who had attempted or planned to attempt notifying their partner. The interview guide was designed to investigate the experience of patient-led partner notification for syphilis with particular emphasis on the strengths and capacities of the participants. Accordingly, we applied an existing theoretical model for individual empowerment in the analysis of the interviews with the participants. This emphasis on the positive, solution-finding capacities of the participants allowed us to investigate the ways in which participants took control over an aspect of concern to their health. More studies are needed which examine successful patient-led strategies for partner notification and their connections with long-term health outcomes.     

Population health needs beyond ratifying the Kyoto Protocol: a look at occupational deprivation

The dramatic impact of climate change is physically and economically affecting the world, a consequence of neglecting scientific information known since the 1960s and 1970s. International discussion has focused on the needs of the physical environment and general health concerns (such addressing greenhouse gas production and population health issues); however, little acknowledgement has yet been made of local human issues, such as the effect of climate change on the mental health of those in rural communities. This commentary takes an occupational science perspective to describe new ways of classifying potential mental health problems associated with climate change and its impact on the rural environment. It challenges policy makers to take a proactive approach to addressing the current impacts of climate change on the future mental health of individuals in rural communities.     

Informative inducement: Study payment as a signal of risk

In research involving human subjects, large participation payments often are deemed undesirable because they may provide ‘undue inducement’ for potential participants to expose themselves to risk. However, although large incentives may encourage participation, they also may signal the riskiness of a study's procedures. In three experiments, we measured people's interest in participating in potentially risky research studies, and their perception of the risk associated with those studies, as functions of participation payment amounts. All experiments took place 2007–2008 with an on-line nationwide sample or a sample from a northeastern U.S. city. We tested whether people judge studies that offer higher participation payments to be riskier, and, if so, whether this increased perception of risk increases time and effort spent learning about the risks. We found that high participation payments increased willingness to participate, but, consistent with the idea that people infer riskiness from payment amount, high payments also increased perceived risk and time spent viewing risk information. Moreover, when a link between payment amount and risk level was made explicit in Experiment 3, the relationship between high payments and perceived risk strengthened. Research guidelines usually prohibit studies from offering participation incentives that compensate for risks, yet these experiments' results indicate that potential participants naturally assume that the magnitude of risks and incentives are related. This discrepancy between research guidelines and participants' assumptions about those guidelines has implications for informed consent in human subjects research.