Pediatric clinical drug trials in low-income countries: key ethical issues.

Potential child participants in clinical research trials in low-income countries are often vulnerable because of poverty, high morbidity and mortality, inadequate education, and varied local cultural norms. However, vulnerability by itself must not be accepted as an obstacle blocking children from the health benefits that may accrue as an outcome of sound clinical research. As greater emphasis is placed on evidence-based treatment of children, it should be anticipated that there will be a growing call for agreement on principles to guide clinical investigations in low-income countries. There is now general acceptance of the view that children must be protected from non-evidence-based interventions and from substandard treatments. The questions remaining relate to how best to stimulate clinical research activity that will serve the needs of infants, children, and youth in developing countries and how best to assign priority to ethically sound research that will meet their clinical requirements. In low-income countries, 39 % of citizens are 13 years of age or younger, and consequently it is certain that clinical investigations of some new therapeutic products will be conducted there more frequently. This review offers some suggestions for approaches that will help to achieve more effective ethical consideration, including (1) improving the quality of research ethics boards; (2) fostering collaborative partnerships among important stakeholders; (3) making concerted efforts to build capacity; (4) improving the quality of the consent and waiver process; and (5) developing improved governance for harmonized ethics platforms. Continuing support by international organizations is required to sustain the establishment and maintenance of stronger research ethics boards to protect children enrolled in clinical trials. This review underscores the importance of developing a culture of solidarity and true partnership between developed and low-income country organizations, which will allow all those involved, and especially child patients, to benefit from the advancement of therapeutics.

Disclosure of incidental findings in cancer genomic research: investigators' perceptions on obligations and barriers.

Although there has been significant research surrounding incidental findings (IFs), the guidelines and information provided to investigators remain unspecific, unclear, and often generalize the course of action to everyone in the field. We explored the perceptions and experiences of investigators regarding the return of IFs in genetic research. Researchers and clinician-researchers were invited to participate in semi-structured telephone interviews in Quebec and Ontario. Twenty professionals participated, and thematic analysis was used to analyze the transcriptions. Four contextual elements emerged: (i) degree of significance of results, (ii) respect for persons, (iii) infrastructure implications, and (iv) professional responsibilities. Our findings demonstrate that all investigators raised similar contextual elements surrounding the return of IFs. However, some nuances in participants' experiences of the understanding of professional responsibilities also emerged. Because of the existing nuances, a one-size-fits-all approach is inappropriate, suggesting that context ought to be considered in decisions about IFs.

Funding considerations for the disclosure of genetic incidental findings in biobank research.

The use of biobanks in biomedical research has grown considerably in recent years. As a result of the increasing analysis of tissue samples stored in biobanks, there has also been an increase in the probability of discovering-in addition to the research target-incidental findings (IF). We identified 23 laws, policies and guidelines from international, regional and national organizations that provide guidance or identify the need for the disclosure of IF to research participants. We analyzed these instruments to determine their contemplation of the funding considerations for the disclosure of IF, examining their guidance for who discloses and the extent of researcher responsibilities. We found that the available normative documents provide little guidance to researchers and biobanks for how they should address cost and funding concerns associated with IF disclosure. It is therefore essential that the research and policy communities think through the financial implications of imposing an ethical responsibility to disclose IF. Concerted efforts should be made by policymakers, ethicists, researchers, clinicians and research institutions to develop detailed funding recommendations, potentially universal in application, to aid in the disclosure of IF, and we provide recommendations on steps that can be taken to ensure full consideration of these issues.

[Promoting public involvement to increase the legitimacy in health policy decisions]. / Favoriser l'implication du public pour accroître la légitimité des prises de décision en matière de politiques de santé?

The participation of the public in the elaboration of politics has become unavoidable in most countries. The Universal Declaration on Bioethics and Human Rights of UNESCO, adopted by the General conference in 2005, makes the public a paramount aspect in the decision making in bioethics. In the case of explanatory research, based on political analysis and guidelines on the newborn screening programs from different countries, we have examined how the "public" is defined (who is the public?), what are the levels of privileged engagement, and what are the objectives sought out by this public participation? In general terms, we have noticed that the terms "consultation", "engagement", "participation" and "partnership" are often used as though they were synonymous, that the "public" is rarely well defined and that the levels of engagement from the public are variable. However, in spite of these findings, it appears that this willingness to respect the choice of individuals and to implicate the population in the debates or in the elaboration of health policies is motivated by the pursuit of values. These last few, although not frequently explicitly named to justify the initiative to involve the public constitute the source of these initiatives. In summary, it is evident that the moral values result in a significant difference in the answers that a population will give to the issues raised in a given domain and that these are often values that participation of the public looks to better identify and to integrate into health policies.

Legal liability and the uncertain nature of risk prediction: the case of breast cancer risk prediction models.

BACKGROUND: The rapidity of technological change in genetics is not always matched by the uptake of this new knowledge into practice. Increasing genetic knowledge has already led to legal liability for those who have not used it properly, such as not informing patients or their families of potential genetic risk. A similar outcome is also of concern in the case of risk prediction models used for hereditary breast cancer. RESULTS: No legal case has directly addressed the use of risk prediction models. However, as genetic medicine and risk prediction models become more widely used, the prospect of a lawsuit will also increase. Current case law is instructive on the circumstances under which medical liability actions could be pursued and circumstances under which liability is unlikely, such as the provision of faulty family history information by a patient. CONCLUSIONS: There is existing case law on family history and genetics that parallels in many respects the use of risk prediction models. However, the idea of a bad 'prediction' is a difficult legal concept. Outside of a plain misuse or failure to use a risk prediction model when circumstances clearly required it, there is little legal guidance presently available to determine the risk for medical liability.

Family history tools in primary care: does one size fit all?

Family health history (FHH) has potential value in many health care settings. This review discusses the potential uses of FHH information in primary care and the need for tools to be designed accordingly. We developed a framework in which the attributes of FHH tools are mapped against these different purposes. It contains 7 attributes mapped against 5 purposes. In considering different FHH tool purposes, it is apparent that different attributes become more or less important, and that tools for different purposes require different implementation and evaluation strategies. The context in which a tool is used is also relevant to its effectiveness. For FHH tools, it is unlikely that 'one size fits all', although appreciation of different purposes, users and contexts should facilitate the development of different applications from single FHH platforms.

Informed consent in the context of pharmacogenomic research: ethical considerations.

Although the scientific research surrounding pharmacogenomics (PGx) has been relatively plentiful, the ethical research concerning this discipline has developed rather conservatively. Following investigation of the ethical, legal and social issues (ELSI) of PGx research, as well as consulting with key stakeholders, we identified six outstanding ethical issues raised by the informed consent process in PGx research: (1) scope of consent; (2) consent to 'add-on' studies; (3) protection of personal information; (4) commercialization; (5) data sharing; and (6) potential risks stemming from population-based research. In discussing these six areas as well as offering specific considerations, this article offers a solid base from which future practical guidelines for informed consent in PGx research can be constructed. As such, this effort works toward filling the ELSI gap and provides ethical support to the numerous PGx projects undertaken by researchers every year.

Communicating pharmacogenetic research results to breastfeeding mothers taking codeine: a pilot study of perceptions and benefits.

Sixty-two codeine-prescribed breastfeeding mothers from a pharmacogenetic study were interviewed regarding the communication of individual CYP2D6 genotype results and overall research findings. All participants wanted to receive the results of their individual genetic tests; however, individuals placed different values on the usefulness of this information toward future medical decisions. Receiving one's pharmacogenetic test results was not associated with a negative psychosocial impact. Thirty-three percent of the participants wished to withhold these results from their physicians. Participants' expectations seem to dictate the extent of transparency of pharmacogenetic research results.

Framing genomics, public health research and policy: points to consider.

Genetic information can be used to target interventions that improve health and prevent disease. Indeed, the results of population genomics research could be useful for public health and national pandemic plans. Yet, firm scientific evidence originating from such research and the indicators of the role of health determinants, gene-gene and gene-environment interaction remain to be assessed and validated before being integrated into pandemic plans or public health programmes. It is not clear what is the role of the State in research on the elucidation of the determinants of gene-gene and gene-environment interactions and how, when, and if such data can be accessed and used for such planning. Over a period of 3 years, we sought to address these questions by gathering data and literature relevant to research in public health genomics, preparing issues papers and, finally, consulting with stakeholders on a provisional 'points to consider' document at various times. Examining in turn the issues of privacy, State powers, stakeholder perceptions, and public participation, we propose in this article, for each of these themes, a series of recommendations aiming to provide guidance on the role of the State in the use of genomic information for public health research, prevention and planning.

Researchers' perceptions of the ethical implications of pharmacogenomics research with children.

BACKGROUND: This paper presents the results of an exploratory qualitative study that assesses Canadian pediatric researchers' perceptions of a pre-selected group of ethical issues raised by pharmacogenomics research with children. METHODS: As a pilot study, we conducted semi-structured telephone interviews with Canadian pediatric pharmacogenomic researchers. The interviews were guided by the following themes: (1) benefits and risks of inclusion, (2) the consent/assent process, and (3) the return of research results. RESULTS: Issues about assent, consent, risks and benefits, as well as the communication of results were addressed by the respondents. Some issues, such as the unique vulnerability of children, the long term privacy concerns associated with biobanking, additional core elements that need to be discussed and included in the consent/assent forms, as well as the challenges of communicating research results in a pediatric research were not explicitly identified by the respondents. CONCLUSION: Further consideration should be given to address the ethical challenges of including children in pharmacogenomics research. This exploratory study indicates that further guidance is needed if children are to be protected and yet benefit from such research.

Ethical, legal, and social issues in health technology assessment for prenatal/preconceptional and newborn screening: a workshop report.

Prenatal/preconceptional and newborn screening programs have been a focus of recent policy debates that have included attention to ethical, legal, and social issues (ELSIs). In parallel, there has been an ongoing discussion about whether and how ELSIs may be addressed in health technology assessment (HTA). We conducted a knowledge synthesis study to explore both guidance and current practice regarding the consideration of ELSIs in HTA for prenatal/preconceptional and newborn screening. As the concluding activity for this project, we held a Canadian workshop to discuss the issues with a diverse group of stakeholders. Based on key workshop themes integrated with our study results, we suggest that population-based genetic screening programs may present particular types of ELSIs and that a public health ethics perspective is potentially highly relevant when considering them. We also suggest that approaches to addressing ELSIs in HTA for prenatal/preconceptional and newborn screening may need to be flexible enough to respond to diversity in HTA organizations, cultural values, stakeholder communities, and contextual factors. Finally, we highlight a need for transparency in the way that HTA producers move from evidence to conclusions and the ways in which screening policy decisions are made.

[The ethical implications of conserving biological samples]. / Les implications éthiques de la conservation des échantillons biologiques.

The conservation and use of biological samples become more and more frequent all around the world. Biobanks of human body substances (blood, urine, DNA, tissues, cells, etc.), and personal data associated with them are created. They have a double character as they are collections of both human biological samples and personal data. In some cases, the gametes, reproductive tissues, embryos, foetal tissue after abortion or even specimens of dead donors are collected and conserved. Although biobanks raise hopes in both the development of new therapies, new drugs and their integration into clinical medicine, they also point to concerns related to ethical questions such as: the principles of information, the consent of the persons concerned, the confidentiality about the personal data, and in some cases discrimination and stigmatisation. Other ethical aspects could raise gradually as research advance. Research being carried out on human sample requires informed free consent from the person who should be able to consent. The donor must be sufficiently informed about the process of research, the purpose, benefits and the risks involved in participating in this research. In the case of persons unable to give consent such minors or persons with mental disabilities, special measures are undertaken. Once the consent was given, the right of withdrawal has been consistently supported by the various declarations and regulations, but some oppose this right for a number of reasons particularly in the case of research on the samples without risk of physical exposure. In this case the notion of human body integrity is different than in research involving therapeutic or clinical intervention. In the case of withdrawal of consent, the samples should be destroyed, but the anonymous results arising from them and their analysis are not affected. What is the case for future uses? Should the researcher obtain again the consent from the donor for a secondary use of the samples? This is a matter of debate in the public and scientific communities. In Morocco, research activities on humans are undertaken in the absence of legal framework. Among the ethical issues, the most frequent in Morocco are related to the informed and explicit consent. Illiteracy, which concerns half of the population, and the economic vulnerability of the largest proportion of the patient make the informed and explicit consent questionable. In this paper we aimed to describe the use and conservation of human biological samples in Morocco and to determine the ethical questions raised in this context. An anonymous questionnaire was sent to biologists working in the different laboratories. The response rate was only 59.2%. The human biological samples are generally used for diagnosis and clinical follow-up. The storage period ranged from 3 months to 1 year, it does not exceed one year. The percentage of conservation of biological samples in the laboratory for one year is 67% and no basic criterion is maintained in the selection of samples. All laboratories obtained their samples directly from patients; no exchange or duplicate samples were undertaken between institutions. The analyses performed on the stored samples are biochemical and immunological. The genetic analyses accounted for only 35% of the total samples. The laboratories involved a researcy activity accounted for only 13.6%. Some of them answered they had not obtained in a systematic manner the consent of the persons concerned. These results indicated a lack of information and guidance on bioethics in Morocco.

Genetics and Society Project.

Faced with rapid advances in human genetics, policy makers are struggling to come to grips with a host of complex ethical, legal and social questions. The HUMGEN website gives policy makers and the public access to legislation, policy, guidelines and recommendations of government and nongovernmental organizations worldwide.

A national survey of use of obstetric procedures and technologies in Canadian hospitals: routine or based on existing evidence?

BACKGROUND: The objective of this national survey was to describe the routine use of procedures and technologies in Canadian hospitals providing maternity care, and to determine the extent to which current use was consistent with the existing evidence and recommended guidelines for maternal and newborn care. METHODS: Representatives of 572 hospitals providing maternity care across Canada were sent questionnaires in the spring and summer of 1993; 523 (91.4%) responded. The primary outcome measures consisted of the self-reported use of obstetric procedures and technologies (perineal shaves, enemas/suppositories, intravenous infusions, initial and continuous electronic fetal heart monitoring, episiotomy rates). Hospitals were grouped according to location, size (number of live births per year), and university affiliation status. RESULTS: The hospitals in the Prairie provinces, in Quebec, and in the Atlantic provinces were significantly less likely than those in Ontario to restrict their use of perineal shaves and enemas to women on admission in labor. Small hospitals were significantly more likely than large hospitals (> 1000 live births) to restrict their use of intravenous infusions, and initial and continuous electronic fetal monitoring. The university-affiliated and nonteaching hospitals were significantly less likely than the university teaching hospitals to have episiotomy rates of less than 40 percent for primiparous women. Small hospitals were more likely than large hospitals to report episiotomy rates of less than 20 percent for multiparous women. CONCLUSIONS: Considerable variations occur in the routine use of obstetric procedures and technologies in Canadian hospitals providing maternity care, according to hospital location, size, and university affiliation status. Despite the existing evidence suggesting that the routine use of these practices and procedures is both unnecessary and potentially harmful, a significant number of Canadian hospitals continued to use them routinely in 1993.

Breast-feeding policies and practices in Canadian hospitals providing maternity care.

OBJECTIVE: To determine the extent to which policies and practices of Canadian hospitals providing maternity care are consistent with the World Health Organization (WHO)/UNICEF 10 Steps to Successful Breastfeeding, the WHO International Code of Marketing of Breast-Milk Substitutes and the WHO/UNICEF Baby Friendly Hospital Initiative. DESIGN: Cross-sectional mailed survey. SETTING: Canada. PARTICIPANTS: Representatives of 572 hospitals providing maternity care across Canada were sent a questionnaire in the spring and summer of 1993, 523 (91.4%) responded. OUTCOME MEASURES: Self-reported implementation of policies and practices concerning infant feeding; hospitals were grouped according to location, size (number of live births per year) and university affiliation status. MAIN RESULTS: Although 58.4% (296/507) of the respondents reported that their hospital had a written policy on breast-feeding, only 4.6% (21/454) reported having one that complied with all of the WHO/UNICEF steps surveyed. This figure dropped to 1.3% (6/453) when compliance with the WHO code (distribution of free samples of formula to formula-feeding and breast-feeding mothers) was added. Hospitals in Quebec and the Prairie provinces were significantly more likely than those in Ontario to give free samples of formula to both breast-feeding (OR 2.39 [95% confidence interval (Cl) 1.39 to 4.09] and 20.22 [95% Cl 9.27 to 44.33] respectively) and formula-feeding mothers (OR 1.82 [95% Cl 1.07 to 3.11] and 8.03 [95% Cl 3.29 to 19.6] respectively), after adjustment for hospital size and university affiliation status. CONCLUSION: There are considerable variations in the implementation of individual WHO steps and provisions of the WHO code according to hospital location, size and university affiliation status. Very few Canadian hospitals meet all of the criteria that would enable them to be considered "baby friendly" according to the WHO/UNICEF definition.

Childhood deaths from toy balloons.

We describe four children who died of suffocation by rubber balloons in Canada between 1983 and 1988. In the United States, at least 121 children have died in a similar manner in the 15 years between 1973 and 1988 according to a report by the US Consumer Product Safety Commission. Although the highest mortality occurred among infants, 30 (25%) of the 121 deaths occurred in children 6 years of age or older. Balloons account for 43% of the approximately 15 childhood deaths related to children's products that are documented each year by the Consumer Product Safety Commission. Toy rubber balloons are thus the leading cause of pediatric choking deaths from children's products. Preventive efforts should be directed toward a ban on this type of balloon and the development of safer alternatives. Meanwhile, public information campaigns should alert parents, physicians, and policymakers to the dangers of toy rubber balloons.