Ethical and policy issues in cluster randomized trials: rationale and design of a mixed methods research study

<p>Abstract</p> <p>Background</p> <p>Cluster randomized trials are an increasingly important methodological tool in health research. In cluster randomized trials, intact social units or groups of individuals, such as medical practices, schools, or entire communities – rather than individual themselves – are randomly allocated to intervention or control conditions, while outcomes are then observed on individual cluster members. The substantial methodological differences between cluster randomized trials and conventional randomized trials pose serious challenges to the current conceptual framework for research ethics. The ethical implications of randomizing groups rather than individuals are not addressed in current research ethics guidelines, nor have they even been thoroughly explored. The main objectives of this research are to: (1) identify ethical issues arising in cluster trials and learn how they are currently being addressed; (2) understand how ethics reviews of cluster trials are carried out in different countries (Canada, the USA and the UK); (3) elicit the views and experiences of trial participants and cluster representatives; (4) develop well-grounded guidelines for the ethical conduct and review of cluster trials by conducting an extensive ethical analysis and organizing a consensus process; (5) disseminate the guidelines to researchers, research ethics boards (REBs), journal editors, and research funders.</p> <p>Methods</p> <p>We will use a mixed-methods (qualitative and quantitative) approach incorporating both empirical and conceptual work. Empirical work will include a systematic review of a random sample of published trials, a survey and in-depth interviews with trialists, a survey of REBs, and in-depth interviews and focus group discussions with trial participants and gatekeepers. The empirical work will inform the concurrent ethical analysis which will lead to a guidance document laying out principles, policy options, and rationale for proposed guidelines. An Expert Panel of researchers, ethicists, health lawyers, consumer advocates, REB members, and representatives from low-middle income countries will be appointed. A consensus conference will be convened and draft guidelines will be generated by the Panel; an e-consultation phase will then be launched to invite comments from the broader community of researchers, policy-makers, and the public before a final set of guidelines is generated by the Panel and widely disseminated by the research team.</p

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Mode of Slip and Crust–mantle Interaction at Oceanic Transform Faults

Oceanic transform faults, connecting offset mid-ocean spreading centres, rupture quasi-periodically in earthquakes up to about magnitude M 7.0 that are often preceded by foreshocks. In addition to seismic slip, a large portion of slip takes place as aseismic creep, which likely influences initiation of large earthquakes. Although oceanic transform faults are one of the major types of plate boundaries, the exact mode of slip and interaction between the seismic and aseismic motion remains unclear. Here we present a detailed model of the mode of slip at oceanic transform faults based on data acquired from a recent temporary deployment of ocean-bottom seismometers at the Blanco Transform Fault and existing regional and teleseismic observations. In the model, the crustal part of the fault is brittle and fully seismically coupled, while the fault in the mantle, shallower than the depth of the 600 °C isotherm, creeps partially and episodically. The creep activates small asperities in the mantle that produce seismic swarms. Both mantle and the crustal zones release most of the plate-motion strain during large-magnitude earthquakes. Large earthquakes appear to be preceded by a brief episode of shallow mantle creep, accompanied by seismic swarms, which explains the observation of foreshocks and shows that mantle creep likely influences initiation of large seismic events

Change in functioning outcomes as a predictor of the course of depression: a 12-month longitudinal study

PURPOSE: Functioning is a necessary diagnostic criterion for depression, and thus routinely assessed in depressive patients. While it is highly informative of disorder severity, its change has not been tested for prognostic purposes. Our study aimed to analyze to what extent early functioning changes predict depression in the mid-term. METHODS: Longitudinal study (four occasions: baseline, 1, 3, and 12 months) of 243 patients with depressive symptomatology at three different services (primary care, outpatients, and hospital). Functioning was assessed on the first three occasions using the Global Assessment of Functioning (GAF), the WHODAS-2.0, and a self-reported functioning (SRF) rating scale. Growth mixture modeling of initial assessments served to estimate individual person-change parameters of each outcome. Person-growth parameters were used as predictors of major depressive episode at 12 months in a logistic regression model, adjusted by sex, age, healthcare level, and depression clinical status at third month. Predictive accuracy of all measures was assessed with area under the receiver operating curve (AUC). RESULTS: Of the 179 patients who completed all assessments, 58% had an active depression episode at baseline and 20% at 12 months (64% non-recoveries and 36% new onsets). Individual trends of change in functioning significantly predicted patient depression status a year later (AUCWHODAS = 0.76; AUCGAF = 0.92; AUCSRF = 0.93). CONCLUSIONS: Longitudinal modeling of functioning was highly predictive of patients' clinical status after 1 year. Although clinical and patient-reported assessment had high prognostic value, the use of very simple patient-reported outcome measures could improve case management outside specialized psychiatric services