Until recently, the gold standard for assessing the efficacy and effectiveness of new medications has been the placebocontrol randomized clinical trial (RCT). However, there are serious ethical concerns about placing patients on a placebo when effective treatments exist. Further, if a new agent is tested only against a placebo, there is no guarantee that it is more effective, or even as effective, as an existing agent. For these and other reasons, ethicists and regulatory bodies have said that, under these circumstances, new drugs should be tested against an active agent. There are three types of such trials: superiority, equivalence, and non-inferiority. In superiority trials, the goal is to establish that the new drug is better (i.e., more effective, or with a more benign side-effect profile) than the standard. Because such trials require much larger sample sizes than placebo-control studies, and are rarely required to bring a drug onto market, they are rarely done. In equivalence trials, the aim is to show that the new and standard agents have similar degrees of effectiveness or adverse events. Due to sample size requirements, most studies of new drugs are non-inferiority trials, in which it is sufficient to demonstrate that the new drug is not significantly worse than the existing ones. However, there are methodological concerns with equivalence and non-inferiority trials, including (a) an inability to determine if the drugs were equally good or equally bad; (b) poorly executed trials with low power can be mistaken for “proving” equivalence or non-inferiority; (c) the equivalence interval is arbitrary; (d) successive non-inferiority trials may lead to a gradual reduction in effectiveness; and (e) often larger trials are necessary. The paper also discusses “add on trials.” It is recommended that, even when existing drugs exist, trials should consist of at least three arms, one of which is a placebo. This paper briefly considers the ethics of placebo, and conditions are stated under which such studies can be conducted.

An economic evaluation was undertaken concurrently with a randomized trial comparing a Caregiver Support Program (CSP) with existing conventional community nursing care for those caring for elderly relatives at home. The differences in resource consumption were compared with changes in caregiver quality of life, as measured by the Caregiver Quality of Life Instrument (CQLI). A 20% difference from baseline in the CQLI favored the experimental (CSP) group, although this did not reach conventional levels of statistical significance. A comparison of improvement in quality of life with costs implies an incremental cost per quality-adjusted life year gained of Canadian $20,000 for the CSP, which compares favorably with other health care interventions. Further, larger studies are required to confirm this result.

Background: Despite widespread use of second-generation cholinesterase inhibitors (CHEIs) for the symptomatic treatment of Alzheimer's disease (AD), little is known about possible long-term effects in different functional domains. This study seeks to assess change in activities of daily living (ADLs) over two years in AD patients treated with CHEIs matched to untreated patients in the same longitudinal cohort study.

Methods: This study is based on the two-year prospective cohort study at the Memory Clinic in Sunnybrook Health Sciences Centre, University of Toronto. Probable AD patients (N = 130: untreated = 65, treated = 65) underwent standardized neuropsychological assessments including the Disability Assessment for Dementia Scale (DAD), at baseline, one-year and two-year follow-up. Groups received a careful evaluation of comorbid illnesses, concomitant medication use, and vascular risk factors.

Results: At baseline, there were no significant differences in demographics and characteristics. Treated patients showed less decline in overall function and in instrumental and basic ADLs. Furthermore, less decline was seen in the overall scores for initiation and planning over two years with moderate to large effect sizes.

Conclusion: These findings have clinical relevance since functional ability has been increasingly recognized as a key outcome variable in AD treatment. It is also of note that the subscores reflecting executive functioning appear to drive these beneficial differences.

Clinical practice guidelines are expanding their scope of authority from clinical decision making to collective policy making, and promise to gain ground as resource allocation tools in coming years. A close examination of how guidelines approach patient selection criteria offers insight into their ethical implications when used as resource allocation or rationing instruments. The purposes of this paper are: a) to examine the structure of allocative reasoning found in clinical guidelines; b) to identify the ethical principles implied and compare how guidelines enact these principles with how explicit systems-level rationing exercises and health policy analyses have approached them; and c) to offer some preliminary suggestions for how these ethical issues might be addressed in the process of guideline development. The resulting framework can be used by guideline developers and users to understand and address some of the ethical issues raised by guidelines for the use of scarce technologies.

Separate groups of children with epilepsy, recruited from a regional pediatric epilepsy database, and their parents were established to discuss their life with epilepsy. Twenty-nine children (aged between 6 years and 10 years 4 months) and 42 of their parents were placed into nine and 17 groups respectively. The participants provided information about their own perceptions of life with epilepsy. Discussions were taped and textual analysis followed to extract, understand, explain, and categorize the health-related quality of life (HRQL) components. The process enabled us to identify the burdens and concerns of children with epilepsy, and to identify five emerging dimensions: (1) the experience of epilepsy, (2) life fulfillment and time use, (3) social issues, (4) impact of epilepsy, and (5) attribution. Identifying and understanding the components of HRQL is crucial for developing an HRQL scale in childhood epilepsy. In addition, this list of elements can help health professionals improve their services by considering and addressing aspects of the epilepsy experience beyond the traditional issues for children with epilepsy and their families.

The purpose of this overview is to appraise the studies on the efficacy and effectiveness of family interventions in decreasing relapse in schizophrenic patients. The studies were identified by means of a computerized MEDLINE search, and the scanning of review articles and the reference lists of the primary articles identified. More than 300 citations were reviewed, and the potentially relevant articles revealed six randomized controlled trials that were included in this meta-analysis. The criteria for selecting potential studies as well as for the meta-analysis were tested by means of an inter-rater reliability check that showed a good agreement between two independent raters (K = 0·83, and K = 0·82, respectively). There were independent assessments of the quality of the studies selected, and data extraction comprised a descriptive information of the study population, the types of interventions, and the relevant outcome measurements. The total number of patients included in the six trials was 350 (181 in the control group and 169 in the experimental group). Regarding the decrease of relapse in the experimental group, the pooled odds ratios and their 95% confidence intervals were: 0·30 (0·06, 0·71) for six months; 0·22 (0·09, 0·37) for nine months; and 0·17 (0·10, 0·35) for the 2-year follow-up. Two to five patients needed to be treated to avert one episode of relapse in a nine-month follow-up. The changes in Expressed Emotion status between experimental and control group combining nine months and one year follow-ups were shown to be marginally significant (P < 0·06), in favour of the experimental group. Emotional over-involvement was also marginally significant (P < 0·07), and there was no statistical difference in the distribution of criticism and hostility. In addition, the experimental group showed a significant increase with drug compliance and a reduction in hospitalization over time. These findings are discussed in light of the potential ingredients in the efficacy of family interventions by focusing on the limitations of using relapse as primary outcome in the assessment of efficacy trials with schizophrenic patients.