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The Ebola outbreak that has devastated parts of west Africa represents an unprecedented challenge for research and ethics. Estimates from the past three decades emphasise that the present effort to contain the epidemic in the three most affected countries (Guinea, Liberia, and Sierra Leone) has been insufficient, with more than 24,900 cases and about 10,300 deaths, as of March 25, 2015. Faced with such an exceptional event and the urgent response it demands, the use of randomised controlled trials (RCT) for Ebola-related research might be both unethical and infeasible and that potential interventions should be assessed in non-randomised studies on the basis of compassionate use. However, non-randomised studies might not yield valid conclusions, leading to large residual uncertainty about how to interpret the results, and can also waste scarce intervention-related resources, making them profoundly unethical. Scientifically sound and rigorous study designs, such as adaptive RCTs, could provide the best way to reduce the time needed to develop new interventions and to obtain valid results on their efficacy and safety while preserving the application of ethical precepts. We present an overview of clinical studies registered at present at the four main international trial registries and provide a simulation on how adaptive RCTs can behave in this context, when mortality varies simultaneously in either the control or the experimental group.

Background Socio-economic inequalities in mortality are well established, yet the contribution of intermediate risk factors that may underlie these relationships remains unclear. We evaluated the role of multiple modifiable intermediate risk factors underlying socio-economic-associated mortality and quantified the potential impact of reducing early all-cause mortality by hypothetically altering socio-economic risk factors. Methods Data were from seven cohort studies participating in the LIFEPATH Consortium (total n = 179 090). Using both socio-economic position (SEP) (based on occupation) and education, we estimated the natural direct effect on all-cause mortality and the natural indirect effect via the joint mediating role of smoking, alcohol intake, dietary patterns, physical activity, body mass index, hypertension, diabetes and coronary artery disease. Hazard ratios (HRs) were estimated, using counterfactual natural effect models under different hypothetical actions of either lower or higher SEP or education. Results Lower SEP and education were associated with an increase in all-cause mortality within an average follow-up time of 17.5 years. Mortality was reduced via modelled hypothetical actions of increasing SEP or education. Through higher education, the HR was 0.85 [95% confidence interval (CI) 0.84, 0.86] for women and 0.71 (95% CI 0.70, 0.74) for men, compared with lower education. In addition, 34% and 38% of the effect was jointly mediated for women and men, respectively. The benefits from altering SEP were slightly more modest. Conclusions These observational findings support policies to reduce mortality both through improving socio-economic circumstances and increasing education, and by altering intermediaries, such as lifestyle behaviours and morbidities.

ObjectiveThe general purpose for ethics consultations is to deliberate on issues on medical and scientific research and act towards the safeguard of the patient's rights and dignity. With the implementation of European Union (EU) Regulation 536/2014 on clinical trials and cost and time-optimization, the nature of consultations and the bodies they are carried out might be to some extent affected. Accordingly, we sought to gain an updated perspective on the current role and current practices of ethics consultations nationwide in both clinical and research settings.MethodsThe study was carried forth by a three-step mixed-method approach: i) review of policies/regulations for ethics committee (EC) nationwide; ii) a structured survey on ethics consultation activity completed by each EC during 2016; iii) incorporated into the third part, a qualitative assessment with a selected sample of 8 key-informants for a semi-structured interview, discussing EC history, the ethics consultation function, and the professional experience of consultants.ResultsReview of the policies/regulations promoted by ECs showed that 72,6% (n = 69) of all the ECs (N = 95) being actually capable of providing ethics consultation service by policy.71 ECs (74.7%) responded to the survey on ethics consultation requests; among them, 48 (67.6%) provided ethics consultations of which 23 (23/48) actually received requests for this service in the year 2016. Many ECs did not have a structured database in place to provide precise figures of requests received in the last year nor of their contents.ConclusionTo date, ethics consultation in clinical and research practice is largely underappreciated and not well understood by users. The consultants themselves lack a comprehensive vision of work carried out in their field, and bioethics training programs to keep them updated. Despite clinical ethics consultation services should not necessarily be mandatory, following the recent EU Regulation on clinical trials, institutional ethics consultation bodies should be re-evaluated.

Background: The ECRAN (European Communication on Research Awareness Needs) project was initiated in 2012, with support from the European Commission, to improve public knowledge about the importance of independent, multinational, clinical trials in Europe. Methods: Participants in the ECRAN consortium included clinicians and methodologists directly involved in clinical trials; researchers working in partnership with the public and patients; representatives of patients; and experts in science communication. We searched for, and evaluated, relevant existing materials and developed additional materials and tools, making them freely available under a Creative Commons licence. Results: The principal communication materials developed were:

AimsMost public health agencies and learned societies agree that the prostate-specific antigen (PSA) test in asymptomatic men should not be recommended, on account of its potential for harm. Yet PSA is still widely used as a screening test and is not being abandoned. This remains a significant public health issue, and citizens’ engagement is needed. This study was designed to produce a deliberation on the PSA screening test by a citizens’ jury.MethodsFifteen citizens were selected and balanced for sex, age, and education. They received an information booklet and participated in a two-day meeting with experts to reach a deliberation on the question “Should the National Health Service discourage or recommend PSA as an individual screening test for prostate cancer in men 55–69 years old?”. A facilitator ran the jurors’ discussion.ResultsAll except three of the jurors decided that the National Health Service should discourage the use of PSA as an individual screening test for prostate cancer in 55–69 year-old men. The jury was particularly convinced by the uncertainty of the test outcomes, the utility of the test, and its cost/benefit ratio. Before the meeting 60% of jurors would have recommended the test to a relative, and all the male jurors would have done so. After the meeting these percentages fell to 15% and 12%.ConclusionsThis experience confirms the feasibility and effectiveness of delegating to a group of citizens the responsibility to decide on public health issues on behalf of the community. Public health authorities should invest in information campaigns aimed at the public and in educational initiatives for physicians. This also provided an opportunity to disseminate information on screening, over-diagnosis, and over-treatment.