Parents' and Adolescents' Preferences for Intensified or Reduced Treatment in Randomized Lymphoblastic Leukemia Trials.

BACKGROUND: When offered participation in clinical trials, families of children with cancer face a delicate balance between cure and toxicity. Since parents and children may perceive this balance differently, this paper explores whether adolescent patients have different enrollment patterns compared to younger children in trials with different toxicity profiles. PROCEDURE: Age-dependent participation rates in three consecutive, randomized childhood leukemia trials conducted by the Nordic Society of Paediatric Haematology and Oncology were evaluated. The ALL2000 dexamethasone/vincristine (Dx/VCR) trial tested treatment intensifications to improve cure, and the back-to-back ALL2008 6-mercaptopurine (6MP) and ALL2008 PEG-asparaginase (ASP) trials tested treatment intensifications (6MP) and toxicity reduction without compromising survival (ASP). Patient randomization and toxicity data were prospectively registered by the treating physicians. RESULTS: Parents of young children favored treatment intensifications (Dx/VCR: 12% refusal; 6MP: 14%; ASP: 21%), whereas parents of adolescents favored treatment reductions (Dx/VCR: 52% refusal; 6MP: 30%; ASP: 8%). Adolescents were more likely to refuse intensification trials than young children (adjusted ORs 6.3; P < 0.01 [Dx/VCR] and 2.1; P = 0.04 [6MP]). Adolescents were less likely to refuse the ASP trial, with varying effect size depending on the length of the preceding consolidation treatment (adjusted OR for median consolidation length 0.15; P = 0.01). Younger children participated more frequently in only 6MP than in only ASP (14% vs. 5%), and adolescents vice versa (2% vs. 17%; P = 0.001). CONCLUSIONS: Parents' and adolescents' divergent inclinations toward intensified or reduced therapy emphasize the necessity of actively involving adolescents in the informed consent process, which should also address motives for trial participation.

European legislation impedes critical care research and fails to protect patients' rights.

The European Clinical Trials Directive requires an informed consent from the patient or a proxy in drug trials. Although informed consent is a valuable tool to protect patients' rights in clinical trials, this requirement largely impedes research in critical care settings, and if pursued in this context, it does not provide the patient with adequate protection. Instead of insisting on informed consent, we suggest that the focus should be shifted towards two other ethically relevant elements in human experimentation: risk assessment and selection of research subjects. When reviewing protocols in which a waiver of consent is deemed necessary, the Ethical Review Board should ensure that non-therapeutic risks are minimal, that the research is specifically designed to benefit critically ill patients, and that it cannot be conducted under circumstances where an informed consent can be obtained. If the European Directive is changed accordingly, this permits clinical trials in critical care settings, while adequate protection from risky non-therapeutic procedures is ensured and exploitation of the patient as an easily accessible research subject is prevented.

Bedside rationing by general practitioners: a postal survey in the Danish public healthcare system.

BACKGROUND: It is ethically controversial whether medical doctors are morally permitted to ration the care of their patients at the bedside. To explore whether general practitioners in fact do ration in this manner we conducted a study within primary care in the Danish public healthcare system. The purpose of the study was to measure the extent to which general practitioners (GPs) would be willing to factor in cost-quality trade-offs when prescribing medicine, and to discover whether, and if so to what extent, they believe that patients should be informed about this. METHODS: Postal survey of 600 randomly selected Danish GPs, of which 330 responded to the questionnaire. The Statistical Package for the Social Sciences (SPSS, version 14.0) was used to produce general descriptive statistics. Significance was calculated with the McNemar and the chi-square test. The main outcome measures of the study were twofold: an assessment of the proportion of GPs who, in a mainly hypothetical setting, would consider cost-quality trade-offs relevant to their clinical decision-making given their economic impact on the healthcare system; and a measure of the extent to which they would disclose this information to patients. RESULTS: In the hypothetical setting 95% of GPs considered cost-quality trade-offs relevant to their clinical decision-making given the economic impact of such trade-offs on the healthcare system. In all 90% stated that this consideration had been relevant in clinical decision-making within the last month. In the hypothetical setting 55% would inform their patients that they considered a cost-quality trade-off relevant to their clinical decisions given the economic impact of such trade-offs on the healthcare system. The most common reason (68%) given for not wanting to inform patients about this matter was the belief that the information would not prove useful to patients. In the hypothetical setting cost-quality trade-offs were considered relevant significantly more often in connection with concerns about costs to the patient (86%) than they were in connection with concerns about costs to the healthcare system (55%; p < 0.001). CONCLUSION: Although readiness to consider cost-quality trade-offs relevant to clinical decisions is prevalent among GPs in Denmark, only half of GPs would disclose to patients that they consider this relevant to their clinical decision-making. The results of this study raise two important ethical problems. First, under Danish law physicians are required to inform patients about all equal treatments. The fact that only a few GPs would inform their patients about all of the relevant treatments therefore seems to contravene Danish law. Second, it is ethically controversial that physicians act as economic gatekeepers.

Patients' perceptions of informed consent in acute myocardial infarction research: a Danish study.

Seeking informed consent from patients in the acute phase of acute myocardial infarction (AMI) poses an ethical challenge due to the fact that these patients are under stress and require urgent medical attention. The very procedure of informed consent, which is supposed to protect eligible patients, may in fact cause harm due to a potential delay in the provision of therapy. Whether or not informed consent can and should be obtained under these particular circumstances is far from evident. Patients participating in various large-scale AMI trials have been enrolled with, as well as without, informed consent in recent years. Little is known, however, about how patients experience the informed consent process in the emergency situation of an AMI. This paper reports the results from qualitative interviews with 32 patients, who had to decide whether or not to participate in a large multi-centre clinical trial in Denmark. We analyse to what extent patients found the informed consent process acceptable as well as how various factors influenced their experience of the consent process. We argue that it is morally sound to involve those patients in a brief and concise informed consent process and that consent should be sought in such trials. Finally, we discuss how future AMI trials may nonetheless be improved by accommodating some of the concerns of the patients.

Research report: do general practitioners tell their patients about side effects to common treatments?

The principle of respect for patients' autonomy, or right to self-determination, has gained increasing importance in health care legislation during the last decade. To respect this principle the patients' informed consent to a proposed treatment is required. In relation to ordinary treatments in general practice, where several reasonable alternatives may be available and where non-treatment may be an acceptable alternative, this requirement is at least as strong as in other parts of the health care system. In this context, information about side effects may be crucial for the patient's decision to accept a proposed treatment or not. The aims of this study were to investigate the extent to which general practitioners in Denmark inform their patients about possible side effects without being asked when a common treatment is proposed. We also wished to examine the relation between physicians' estimation of the severity and frequency of these side effects, and their willingness to inform patients spontaneously as well as their preferred reasons for choosing to inform or not inform the patients. A questionnaire was sent to a random sample of 450 Danish general practitioners. The respondents differed considerably with regard to their willingness to inform patients about side effects but they were significantly more likely to give the information spontaneously if they considered the side effects frequent than when side effects were considered rare. In contrast, estimations of severity did not seem to be of any importance. The majority of the respondents informed their patients primarily to enable them to react appropriately to the side effects in question or to make sure that the patient would comply with the treatment. These findings indicate that the information given to patients about side effects by Danish general practitioners is not in accordance with the principle of respect for the patients' autonomy and not in accordance with the requirements of Danish legislation.