Charles Weijer

OBJECTIVE: To describe the issues faced, and how they were addressed, by the University of Toronto Critical Care Medicine Program/Joint Centre for Bioethics Task Force on Appropriate Use of Life-Sustaining Treatment. The clinical problem addressed by the Task Force was dealing with requests by patients or substitute decision makers for life-sustaining treatment that their healthcare providers believe is inappropriate. DESIGN: Case study. SETTING: The University of Toronto Joint Centre for Bioethics/Critical Care Medicine Program Task Force on Appropriate Use of Life-Sustaining Treatment. PARTICIPANTS: The 24-member Task Force included physician and nursing leaders from five critical care units, bioethicists, a legal scholar, a health administration expert, a social worker, and a hospital public relations professional. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our specific lessons learned include a) a policy focus on process; b) use of a negotiation and mediation model, rather than a hospital ethics committee model, for this process; and c) the policy development process is itself a negotiation, so we recommend equal involvement of interested groups including patients, families, and the public. CONCLUSIONS: This article describes the key issues faced by the Task Force while developing its policy. It will provide a useful starting point for other groups developing policy on appropriate use of life-sustaining treatment

Recent guidelines from the US National Institutes of Health (NIH) mandate the inclusion of adequate numbers of women in clinical trials. Ought such standards to apply internationally? Walzer's theory of justice is brought to bear on the problem, the first use of the theory in research ethics, and it argues for broad application of the principle of adequate representation. A number of practical conclusions for research ethics committees (RECs) are outlined. Eligibility criteria in clinical trials ought to be justified by trial designers. Research ethics committees ought to question criteria that seem to exclude unnecessarily women from research participation. The issue of adequate representation should be construed broadly, so as to include consideration of the representation of the elderly, persons with HIV, mental illness and substance abuse disorders in clinical research.

The revelation that data obtained for the US-based National Surgical Adjuvant Breast and Bowel Project (NSABP) from subjects enrolled at Hôpital Saint-Luc in Montreal was falsified has eroded public trust in research. Institutions can educate researchers and help prevent unethical research practices by establishing procedures to monitor research involving human subjects. Research monitoring encompasses four categories of activity: annual reviews of continuing research, monitoring of informed consent, monitoring of adherence to approved protocols and monitoring of the integrity of data. The authors describe characteristics of research projects that may call for monitoring procedures in each category. The form taken by such monitoring depends on the nature of the protocol. Although appropriate research monitoring requires substantial investment of personnel and financial resources, it is required under guidelines regulating research involving human subjects in Canada. Research monitoring is a step forward in re-establishing public confidence in medical research

Medical research involving human subjects raises complex ethical, legal and social issues. Investigators sometimes find that their obligations with respect to a research project come into conflict with their obligations to individual patients. The ethical conduct of research rests on 3 guiding principles: respect for persons, beneficience, and justice. Respect for persons underlies the duty to obtain informed consent from study participants. Beneficence demands a favourable balance between the potential benefits and harms of participation. Justice requires that vulnerable people not be exploited and that eligible candidates who may benefit from participation not be excluded without good cause. Studies must be designed in a way that ensures the validity of findings and must address questions of sufficient importance to justify the risks of participation. In any clinical trial there must be genuine uncertainty as to which treatment arm offers the most benefit, and placebo controls should not be used if effective standard therapies exist. Researchers have a responsibility to inform themselves about the ethical, legal and policy standards that govern their activities. When difficulties arise, they should consult the existing literature and seek the advice of experts in research ethics

PURPOSE/OBJECTIVES: To examine differences in nursing care received by patients with breast cancer enrolled in clinical trials and those not enrolled in clinical trials. DESIGN: Retrospective review of clinic charts. SETTING: Oncology outpatient department of a tertiary-care hospital. SAMPLE: 90 women with early stage breast cancer. The mean age of the women was 53 years. More than half of the women (51 of 90) were treated in a clinical trial. METHODS: Retrospective chart review of all the nurse-patient clinic encounters for a six-month period from date of cancer diagnosis. The content of each encounter was coded using a modified version of the Nursing Action Classification System. MAIN RESEARCH VARIABLES: Nursing interventions (i.e., assessment, medical scheduling, psychosocial scheduling, reassurance, and teaching) and phone calls. FINDINGS: Women enrolled in clinical trials had more phone interactions with nursing staff (p = 0.003) and received teaching (p < 0.001) and reassurance (p = 0.005) from nursing staff more often than women not enrolled in clinical trials. Controlling for age and stage of disease, teaching (p < 0.001), and reassurance (p = 0.10) were the primary differences in nursing care between the patients enrolled in clinical trials and those not enrolled. CONCLUSION: Differences in nursing care received exist between patients with breast cancer enrolled in clinical trials and those not enrolled. IMPLICATIONS FOR NURSING PRACTICE: Both teaching and reassurance are important components of caring for patients with cancer and are associated with treatment compliance. If the results of this study are confirmed, measures must be employed to ensure that all patients receive optimal care

The definition of the study population for a clinical trial via the criteria for trial eligibility has implications for the validity of the study and its applicability to clinical practice. Though issues of equity regarding the selection of subjects for research have long been a concern of ethicists, issues regarding the impact of subject selection on a trial's generalizability have only recently attracted ethical scrutiny. After a review of the history of the ethics of subject selection, I focus on three empirical questions regarding the generalizability of clinical trials. (1) What proportion of diseased populations are studied in clinical trials? (2) How are subjects selected for clinical trial participation (and what are the main barriers to participation)? (3) Are clinical trial participants comparable to non-participants? Finally, the role of the Institutional Review Board--Research Ethics Board in Canada--in assessing the generalizability of clinical research is discussed.

As scientists target communities for research into the etiology, especially the genetic determinants of common diseases, there have been calls for the protection of communities. This paper identifies the distinct characteristics of aboriginal communities and their implications for research in these communities. It also contends that the framework in the Belmont Report is inadequate in this context and suggests a fourth principle of respect for communities. To explore how such a principle might be specified and operationalized, it reviews existing guidelines for protecting aboriginal communities and points out problems with these guidelines and areas for further work

OBJECTIVE: Pilot study to characterize treatment differences between patients treated in clinical trials and those treated in a clinical setting. Previous studies have shown higher survival rates for participants in trials of cancer therapy. This difference is observed even after rates are adjusted for important covariates such as age and stage of disease. DESIGN: Retrospective chart review. SETTING: Oncology outpatient department in a tertiary care hospital. PATIENTS: Ninety women 18 to 70 years of age with early-stage breast cancer who were diagnosed in 1990. Fifty-one of the women were treated through clinical trials and 39 were treated outside of clinical trials. OUTCOME MEASURES: Number of blood tests, telephone calls, clinic visits and imaging procedures as well as intensity of chemotherapy and use of radiation therapy. The age of the patient and the stage of disease were important covariates. RESULTS: After the analysis was controlled for patient age and stage of disease, patients treated through a clinical trial were more likely to receive standard-dose chemotherapy (p = 0.020, 95% confidence interval 1.20 to 200.73) and more frequent blood tests (p < 0.001, 95% confidence interval 1.02 to 1.13) than other patients treated in the clinic. CONCLUSIONS: Our results provide a plausible mechanism for the observed survival advantage for participants in clinical trials in oncology. Further study is called for. If these results are confirmed, they have important implications for informed consent to participate in clinical trials and for clinical practice

The practice of surgical trainees operating in developing countries is gaining interest in the medical community. Although there has been little analysis about the ethical impact of these electives, there has been some concerns raised over the possible exploitation of trainees and their patients. An ethical review of this practice shows that care needs to be taken to prevent harm. Inexperienced surgeons learning surgical skills in developing countries engender greater risk of violating basic ethical principles. Advanced surgical trainees who have already achieved surgical competence are best qualified to satisfy these ethical issues. All training programs need to develop a structured ethical review for international electives to protect their trainees and their patients from harm

Emergency medicine research requires the enrollment of subjects with varying decision-making capacities, including capable adults, adults incapacitated by illness or injury, and children. These different categories of subjects are protected by multiple federal regulations. These include the federal Common Rule, the Department of Health and Human Services (DHHS) regulations for pediatric research, and the Food and Drug Administration's (FDA) Final Rule for the Exception from the Requirements of Informed Consent in Emergency Situations. Investigators should be familiar with the relevant federal research regulations to optimally protect vulnerable research subjects, and to facilitate the institutional review board (IRB) review process. IRB members face particular challenges in reviewing emergency research. No regulations exist for research enrolling incapacitated subjects using proxy consent. The wording of the Final Rule may not optimally protect vulnerable subjects. It is also difficult to apply conflicting regulations to a single study that enrolls subjects with differing decision-making capacities. This article is intended as a guide for emergency researchers and IRB members who review emergency research. It reviews the elements of Federal Regulations that apply to consent, subject selection, privacy protection, and the analysis of risks and benefits in all emergency research. It explores the challenges for IRB review listed above, and offers potential solutions to these problems.

The question "When are research risks reasonable in relation to anticipated benefits?" is at the heart of disputes in the ethics of clinical research. Institutional review boards are often criticized for inconsistent decision-making, a problem that is compounded by a number of contemporary controversies, including the ethics of research involving placebo controls, developing countries, incapable adults and emergency rooms. If this pressing ethical question is to be addressed in a principled way, then a systematic approach to the ethics of risk in research is required. Component analysis provides such a systematic approach

Research involving the vulnerable sick raises difficult challenges for investigators and Institutional Review Boards. Exactly who among the ill counts as vulnerable is a matter of judgement, and involves consideration of susceptibility to harm and capacity to provide free and informed consent. A balanced approach is required when protections are considered, and the benefits as well as the risks of research participation must be carefully weighed. A variety of protections for the vulnerable sick in research are available, including enrolling subjects in a study only with a strong justification, ensuring that consent is free and comprehending, and setting limits on the risk to which they may be asked to endure. Discussion of three contemporary controversies, placebo-controlled trials in the psychiatric setting, phase I clinical trials and oncology patients, and emergency room research involving patients incapable of giving consent, highlights the little recognized prominence of risk-benefit issues in the clinical studies in the vulnerable sick

Demands by Patients or their Families for treatment thought to be inappropriate by health care providers constitute an important set of moral problems in clinical practice. A variety of approaches to such cases have been described in the literature, including medical futility, standard of care and negotiation. Medical futility fails because it confounds morally distinct cases: demand for an ineffective treatment and demand for an effective treatment that supports a controversial end (e.g., permanent unconsciousness). Medical futility is not necessary in the first case and is harmful in the second. Ineffective treatment falls outside the standard of care, and thus health care workers have no obligation to provide it. Demands for treatment that supports controversial ends are difficult cases best addressed through open communication, negotiation and the use of conflict-resolution techniques. Institutions should ensure that fair and unambiguous procedures for dealing with such cases are laid out in policy statements

Research in the intensive care unit (ICU) is commonly thought to pose 'serious risk' to study participants. This perception may be at the root of a variety of impediments to the conduct of clinical trials in the ICU setting. Component analysis offers a promising approach to the ethical analysis of ICU research. Because clinical trials commonly involve a mixture of study interventions, therapeutic and nontherapeutic procedures must be analyzed separately. Therapeutic procedures must meet the requirement of clinical equipoise. Risks associated with nontherapeutic procedures must be minimized consistent with sound scientific design, and be deemed reasonable in relation to the knowledge to be gained. When research involves a vulnerable population, such as adults incapable of providing informed consent, nontherapeutic risks are limited to a minor increase over minimal risk. Understood in this way, the incremental risk posed by participation in ICU research may be minimal. This realization has important implications for review by institutional review boards of such research and for the informed consent process

Bioethics is currently witnessing unprecedented debate over the moral and legal norms governing the conduct of clinical research. At the center of this debate is the duty of care in clinical research, and its most widely accepted specification, clinical equipoise. In recent work, we have argued that equipoise and cognate concepts central to the ethics of clinical research have been left unnecessarily vulnerable to criticism. We have suggested that the vulnerability lies in the conspicuous absence of an articulated foundation in moral and legal theory of the physician-researcher's duty of care to the patient-subject. We have repeatedly suggested that the requisite foundation is in the ethics of trust and the law of fiduciaries.Curiously, despite the absence of a published thorough exposition of our position, some have preemptively criticized our suggestion that the relationship between physician-researcher and patient-subject is fiduciary. Others have offered their own accounts of the implications of fiduciary law for the relationship.

OBJECTIVE: To apply component analysis, a structured approach to the ethical analysis of risks and potential benefits in research, to published emergency research using a waiver of/exception from informed consent. The hypothesis was that component analysis could be used with a high degree of interrater reliability, and that the vast majority of emergency research would comply with a minimal-risk threshold. METHODS: A Medline search and manual search were done to identify studies using a waiver of/exception from informed consent published between July 1996 and December 2000. A review panel of physicians and bioethicists independently classified nontherapeutic procedures in each study as minimal risk, probably minimal risk, or probably more than minimal risk. RESULTS: Seventy studies using a waiver of/exception from informed consent were identified. A majority of reviewers classified nontherapeutic procedures in 62 studies (88.6%) as minimal risk. Reviewers classified nontherapeutic procedures in six studies (8.6%) as minimal risk or probably minimal risk. In two studies (2.9%), nontherapeutic procedures were classified as probably more than minimal risk. The intraclass correlation coefficient was 0.89 (95% CI = 0.85 to 0.93), indicating very high interrater reliability. CONCLUSIONS: Component analysis can be used with high reliability to review emergency research and may improve the consistency of institutional review board review of emergency research. The vast majority of published emergency research performed using a waiver of/exception from consent complies with a properly-applied minimal-risk threshold. A minimal-risk threshold for nontherapeutic procedures protects subjects better than current U.S. regulations while permitting important emergency research to continue

BACKGROUND: Researchers have a moral responsibility to offer to return research results to participants, but the needs and attitudes of parents and adolescents with cancer in paediatric oncology regarding the issue are relatively unknown.OBJECTIVES: To explore the needs of potential research participants or their guardians with respect to the offer of a return of research results. METHODS: A questionnaire was used in a focus group and in telephone interviews with eight adolescents and 12 parents of children with cancer. The participants were asked to respond to the questions and to comment on the inclusiveness of the questionnaire.RESULTS: The majority of participants (18 of 20) wished to receive research results. Two somewhat unexpected findings are described. First, all participants in the present study felt that it was the primary responsibility of the participant to retain contact with the researchers for the purpose of obtaining research results. Second, few participants (n=2) indicated that the Internet would be a satisfactory way of transmitting these results. One-half of the participants wished to have face-to-face communication of results.CONCLUSIONS: These results provide preliminary guidance for the return of research results to participants and validate the use of the questionnaire in a larger study of this issue

The institutional review board is the social-oversight mechanism charged with protecting research subjects. Performing this task competently requires that the IRB scrutinize informed-consent procedures, the balance of risks and potential benefits, and subject-selection procedures in research protocols. Unfortunately, it may be said that IRBs are spending too much time editing informed-consent forms and too little time analyzing the risks and potential benefits posed by research. This time mismanagement is clearly reflected in the research ethics literature. A review of articles published between 1979 and 1990 in IRB: A Review of Human Subjects Research, for example, reveals a large number of articles on informed consent and confidentiality and considerably fewer on the assessment of risks and potential harms, study design, and subject-selection procedures.