Building an Opt-Out Model for Service-Level Consent in the Context of New Data Regulations.

The General Data Protection Regulation (GDPR) was introduced in 2018 to harmonize data privacy and security laws across the European Union (EU). It applies to any organization collecting personal data in the EU. To date, service-level consent has been used as a proportionate approach for clinical trials, which implement low-risk, routine, service-wide interventions for which individual consent is considered inappropriate. In the context of public health research, GDPR now requires that individuals have the option to choose whether their data may be used for research, which presents a challenge when consent has been given by the clinical service and not by individual service users. We report here on development of a pragmatic opt-out solution to this consent paradox in the context of a partner notification intervention trial in sexual health clinics in the UK. Our approach supports the individual's right to withhold their data from trial analysis while routinely offering the same care to all patients.

Protocol for a cluster randomised control trial evaluating the efficacy and safety of treatment for latent tuberculosis infection in recent migrants within primary care: the CATAPuLT trial.

BACKGROUND: The identification and treatment of LTBI is a key component of the WHO's strategy to eliminate TB. Recent migrants from high TB-incidence countries are recognised to be at risk TB reactivation, and many high-income countries have focused on LTBI screening and treatment programmes for this group. However, migrants are the group least likely to complete the LTBI cascade-of-care. This pragmatic cluster-randomised, parallel group, superiority trial investigates whether a model of care based entirely within a community setting (primary care) will improve treatment completion compared with treatment in specialist TB services (secondary care). METHODS: The CATAPuLT trial (Completion and Acceptability of Treatment Across Primary Care and the community for Latent Tuberculosis) randomised 34 general practices in London, England, to evaluate the efficacy and safety of treatment for LBTI in recent migrants within primary care. GP practices were randomised to either provide management for LTBI entirely within primary care (GPs and community pharmacists) or to refer patients to secondary care. The target recruitment number for individuals is 576. The primary outcome is treatment completion (defined as taking at least 90% of antibiotic doses). The secondary outcomes assess adherence, acceptance of treatment, the incidence of adverse effects including drug-induced liver injury, the rates of active TB, patient satisfaction and cost-effectiveness of LTBI treatment. This protocol adheres to the SPIRIT Checklist. DISCUSSION: The CATAPuLT trial seeks to provide implementation research evidence for a patient-centred intervention to improve treatment completion for LTBI amongst recent migrants to the UK. TRIAL REGISTRATION: NCT03069807, March 2017, registered retrospectively.

Ethics and social acceptability of a proposed clinical trial using maternal gene therapy to treat severe early-onset fetal growth restriction.

OBJECTIVE: To evaluate the ethical and social acceptability of a proposed clinical trial using maternal uterine artery vascular endothelial growth factor (VEGF) gene therapy to treat severe early-onset fetal growth restriction (FGR) in pregnant women. METHODS: We conducted a literature review on the ethics and legality of experimental treatments in pregnant women, in particular advanced therapeutics. Issues that were identified from the literature helped develop interview guides for semistructured, qualitative interviews, carried out in four European countries, with 34 key stakeholders (disability groups, professional bodies and patient support groups) and 24 women/couples who had experienced a pregnancy affected by severe early-onset FGR. RESULTS: The literature review identified two main questions: 'is it ethical to give a pregnant woman a potentially risky treatment from which she does not benefit directly?' and 'is it ethical to treat a condition of the unborn child, who may then be born with a serious disability when, without treatment, they would have died?'. The review concluded that there were no ethical or legal objections to the intervention, or to a trial of this intervention. Overall, respondents viewed the proposed trial in positive terms. Women were generally interested in participating in clinical trials that conferred a potential benefit to their unborn child. The risk of disability of the premature child was a concern, but not considered a major stumbling block for maternal VEGF gene therapy. CONCLUSIONS: This study did not identify any fundamental or insurmountable objections to a trial of maternal gene therapy for severe early-onset FGR. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Clinician and service user perceptions of implementing contingency management: a focus group study.

BACKGROUND: Contingency management (CM), despite the evidence base for its effectiveness, remains controversial, with sub-optimal implementation. In 2007, UK guidelines recommended the use of CM in publicly funded services, but uptake has also been minimal. Previous surveys of service providers suggest differences in opinions about CM, but to date there has been no published involvement of service users in this debate. METHOD: Focus group methodology was used to explore systematically the attitudes, concerns and opinions of staff and service users about the use of CM, in publicly funded substance misuse services, to identify the key areas that may be influential in terms of implementation and outcome. Data were analysed thematically using the constant comparative method. RESULTS: 70 staff and service users participated in 9 focus groups. 15 themes of discussion around CM were identified, grouped into four categories: how CM was aligned to the philosophy of substance misuse services; the practicalities of implementation; wider ethical concerns; and how participants perceived the evidence for effectiveness. CONCLUSIONS: Robust process evaluation in different treatment systems is needed to define the active components of CM for implementation. Involvement of service users in this process is essential and is likely to provide valuable insights into the mechanism of action of CM and its effectiveness and uptake within complex treatment systems.

The ethics of mandatory vaccination against influenza for health care workers.

Vaccination of health care workers (HCW) in long-term care results in indirect protection of patients who are at high-risk for influenza. The voluntary uptake of influenza vaccination among HCW is generally low. We argue that institutions caring for frail elderly have the responsibility to implement voluntary programmes for vaccination against influenza of HCW. When uptake falls short a mandatory programme may be justified. The main justification stems from the duty of care givers not to harm one's patient when one knows there is a significant risk of harm and the intervention to reduce this chance has a favourable balance of benefit over burdens and risks.

Are meticillin-resistant Staphylococcus aureus bloodstream infection targets fair to those with other types of healthcare-associated infection or cost-effective?

UK National Health Service Trust hospitals are required to report meticillin-resistant Staphylococcus aureus bloodstream infection (MRSA BSI) and also have targets for their reduction. We argue that the MRSA BSI target influences local priorities, and that the high priority given to control of MRSA BSI is not fair or cost-effective when account is taken of the much larger number of patients who develop other types of serious hospital-acquired infection. Reasons for infection control priorities should be made explicit. Use of a formal and reasoned process of priority setting would also counteract the potential distortion of local priorities by national targets.

An analysis of decision letters by research ethics committees: the ethics/scientific quality boundary examined.

OBJECTIVES: The performance of NHS research ethics committees (RECs) is of growing interest. It has been proposed that they confine themselves to "ethical" issues only and not concern themselves with the quality of the science. This study aimed to identify current practices of RECs in relation to scientific issues in research ethics applications. METHODS: Letters written by UK RECs expressing provisional or unfavourable opinions in response to submitted research applications were sampled from the research ethics database held by the Central Office for Research Ethics Committees. Ethnographic content analysis (ECA) was used to develop a coding framework. QSR N6 software was used to facilitate coding. RESULTS: "Scientific issues" were raised in 104 (74%) of the 141 letters in our sample. The present data suggest that RECs frequently considered scientific issues and that judgments of these often informed their decisions about approval of applications. Current processes of peer review seemed insufficient to reassure RECs about the scientific quality of applications they were asked to review. CONCLUSIONS: This study provides evidence that scientific issues are frequently raised in letters to researchers and are often considered a quality problem by RECs. In the discussion, the authors reflect on how far issues of science can and should be distinguished from those of ethics and the policy implications.

Interventions for improving patients' trust in doctors and groups of doctors.

BACKGROUND: Trust is a fundamental component of the patient-doctor relationship and is associated with increased satisfaction, adherence to treatment, and continuity of care. It is not clear if there are interventions known to be effective in enhancing patient trust in doctors. OBJECTIVES: To assess the effects of interventions intended to improve a patient's trust in the doctor or a group of doctors. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1 2003), MEDLINE(1966 to week 4 2003), EMBASE (1985 to July 2003), Health Star (1975 to July 2004), PsycINFO (1967 to July 2004), CINAHL (1982 to June 2003), LILACS (1982 to April 2003), African Trials Register (1948 to April 2003), African Health Anthology (1924 to April 2003), Dissertation Abstracts International (1861 to April 2003) and the bibliographies of studies assessed for inclusion. We also searched the bibliographies of studies assessed for inclusion, and contacted researchers active in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs), controlled clinical trials, controlled before and after studies, and interrupted time series studies of interventions (informative, educational, behavioural, organisational) directed at doctors or patients (or carers) where trust was assessed as a primary or secondary outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Three RCTs, all published in English and set in North American primary care, and involving 1916 participants, were included. There was considerable heterogeneity in terms of aims, format and content of the interventions. One trial of a training intervention for family doctors to improve communication behaviours (20 doctors assessed by 414 patients) showed no effect on trust. The other two interventions were patient focussed. One explored the impact on trust of disclosing physician incentives to patients (n= 918) in a Health Maintenance Organisation (HMO) and showed no diminution in trust. Another investigated the effect of induction visits on new HMO members' (n=564) trust in their HMO doctors. Trust in doctors rose compared with control following the visit for one type of induction visit, the group visit (Trust out of 10 (standard deviation (SD)) was 8.8 (1.5) and 7.1 (2.2), difference 1.7, (95% confidence interval 1.22 to 2.18)). However there were many drop-outs and analysis was not on intention to treat. AUTHORS' CONCLUSIONS: Overall there remains insufficient evidence to conclude that any intervention may increase or decrease trust in doctors. Further trials are required to explore the impact of policy changes, guidelines and specific doctors' training on patients' trust.

Differential effects of intra-midbrain raphe and systemic 8-OH-DPAT on VTA self-stimulation thresholds in rats.

RATIONALE: Intra-median raphe nucleus (MRN) administration of the 5-HT(1A) receptor agonist 8-OH-DPAT decreases lateral hypothalamic self-stimulation thresholds and is reported to have biphasic effects following systemic administration. These experiments attempted to extend the previous findings to mesolimbic pathway self-stimulation at ventral tegmental area (VTA) electrodes. OBJECTIVES: This study was conducted to provide comparative data for systemic and intra-dorsal raphe nucleus (DRN) and intra-MRN effects of 8-OH-DPAT on VTA self-stimulation. METHODS: Male Sprague-Dawley rats with VTA electrodes were trained to respond for electrical stimulation. Systemic and intra-midbrain raphe 8-OH-DPAT effects on rate-frequency thresholds were measured. Systemic administration of WAY 100635 was used to confirm 5-HT(1A) receptor mediation of 8-OH-DPAT effects. RESULTS: 8-OH-DPAT (0.003-0.3 mg kg(-1) SC) increased rate-frequency thresholds and decreased maximal response rates. WAY 100635 alone (0.0125-0.1 mg kg(-1) SC) did not alter these measures. Intra-DRN and intra-MRN 8-OH-DPAT (5.0 microg) decreased rate-frequency thresholds without altering maximal response rates. Intra-DRN 8-OH-DPAT (0.1-5.0 microg) induced a slight decrease and intra-MRN 8-OH-DPAT a slight increase in locomotor activity. WAY 100635 (0.1 mg kg(-1)) blocked effects of 8-OH-DPAT on VTA self-stimulation. CONCLUSION: These results confirm threshold-decreasing effects of intra-MRN 8-OH-DPAT and extend this to the DRN and to VTA thresholds. Monophasic dose dependent increases in VTA thresholds following systemic 8-OH-DPAT are not equivalent to reports for hypothalamic self-stimulation. Differences between studies may be attributable to stimulation site and/or differences in threshold measurement procedures. Effects of WAY 100635 in this study indicate 5-HT(1A) receptor mediation of these 8-OH-DPAT effects.

Further ethical and social issues in using a cocaine vaccine: response to Hall and Carter.

Evaluation of the potential of a cocaine vaccine requires a detailed understanding of the intended and unintended social consequences of its use. Prospective technology assessment is always difficult, but in the case of treatment and prevention of cocaine addiction we need to understand not only the neuroscience and pharmacology of cocaine addiction, but also social attitudes to drug use and addiction, the social context of drug use, and the factors which make drug use a rational strategy for an addict and make treatment seeking or relapse more or less likely. By considering different scenarios related to differing levels of effectiveness of the vaccine, the authors argue that vaccination will be at best a useful adjunct to existing methods of treatment, rather than a substitute for them.

Current epistemological problems in evidence based medicine.

Evidence based medicine has been a topic of considerable controversy in medical and health care circles over its short lifetime, because of the claims made by its exponents about the criteria used to assess the evidence for or against the effectiveness of medical interventions. The central epistemological debates underpinning the debates about evidence based medicine are reviewed by this paper, and some areas are suggested where further work remains to be done. In particular, further work is needed on the theory of evidence and inference; causation and correlation; clinical judgment and collective knowledge; the structure of medical theory; and the nature of clinical effectiveness.

Bach to the future: response to: Extending preimplantation genetic diagnosis: medical and non-medical uses.

Professor Robertson sketches an elegant framework for policy evaluation and regulation of the use of preimplantation genetic diagnosis for various medical, medical related, and non-medical purposes. In criticism of his position, I argue that the distinction between policy and ethics upon which his argument relies is highly unstable, and the approach taken to ethical evaluation of particular parental interests leaves open many issues which the policy approach would hope to exclude. In conclusion I argue that while his position ultimately fails, the onus is on his critics to come up with a viable and satisfying alternative.

American biofutures: ideology and utopia in the Fukuyama/Stock debate.

Francis Fukuyama, in his Our Posthuman Future, and Gregory Stock, in his Redesigning Humans, present competing versions of the biomedical future of human beings, and debate the merits of more or less stringent regimes of regulation for biomedical innovation. In this article, these positions are shown to depend on a shared discourse of market liberalism, which limits both the range of ends for such innovation discussed by the authors, and the scope of their policy analyses and proposals. A proper evaluation of the human significance and policy imperatives for biomedical innovation needs to be both more utopian in its imagination, and more sophisticated in its political economy. In essence, the Fukuyama/Stock debate tells us more about current US political ideology than it does about the morality of human genetic and biopsychological engineering.

Are antipsychotic drugs the right treatment for challenging behaviour in learning disability?: The place of a randomised trial.

People with learning disability sometimes display challenging behaviour. This can be managed by use of antipsychotic medication or behavioural therapy or both. There is no solid evidence, however, that these therapies are safe and effective. A randomised controlled trial of antipsychotic medication has been proposed to deliver such evidence. However, this presents difficult issues in the ethics of research with learning disabled people. In particular, is a trial the most efficient and fairest way to evaluate practice in this area? This paper reviews the clinical situation, gives the rationale for the trial, and analyses the ethical arguments for and against such a trial.