What empirical research has been undertaken on the ethics of clinical research in India? A systematic scoping review and narrative synthesis.

INTRODUCTION: The post-2005 rise in clinical trials and clinical research conducted in India was accompanied by frequent reports of unethical practices, leading to a series of regulatory changes. We conducted a systematic scoping review to obtain an overview of empirical research pertaining to the ethics of clinical trials/research in India. METHODS: Our search strategy combined terms related to ethics/bioethics, informed consent, clinical trials/research and India, across nine databases, up to November 2019. Peer-reviewed research exploring ethical aspects of clinical trials/research in India with any stakeholder groups was included. We developed an evidence map, undertook a narrative synthesis and identified research gaps. A consultation exercise with stakeholders in India helped contextualise the review and identify additional research priorities. RESULTS: Titles/Abstracts of 9699 articles were screened, full text of 282 obtained and 80 were included. Research on the ethics of clinical trials/research covered a wide range of topics, often conducted with little to no funding. Studies predominantly examined what lay (patients/public) and professional participants (eg, healthcare staff/students/faculty) know about topics such as research ethics or understand from the information given to obtain their consent for research participation. Easily accessible groups, namely ethics committee members and healthcare students were frequently researched. Research gaps included developing a better understanding of the recruitment-informed consent process, including the doctor-patient interaction, in multiple contexts and exploring issues of equity and justice in clinical trials/research. CONCLUSION: The review demonstrates that while a wide range of topics have been studied in India, the focus is largely on assessing knowledge levels across different population groups. This is a useful starting point, but fundamental questions remain unanswered about informed consent processes and broader issues of inequity that pervade the clinical trials/research landscape. A priority-setting exercise and appropriate funding mechanisms to support researchers in India would help improve the clinical trials/research ecosystem.

Moral Distress and Austerity: An Avoidable Ethical Challenge in Healthcare.

Austerity, by its very nature, imposes constraints by limiting the options for action available to us because certain courses of action are too costly or insufficiently cost effective. In the context of healthcare, the constraints imposed by austerity come in various forms; ranging from the availability of certain treatments being reduced or withdrawn completely, to reductions in staffing that mean healthcare professionals must ration the time they make available to each patient. As austerity has taken hold, across the United Kingdom and Europe, it is important to consider the wider effects of the constraints that it imposes in healthcare. Within this paper, we focus specifically on one theorised effect-moral distress. We differentiate between avoidable and unavoidable ethical challenges within healthcare and argue that austerity creates additional avoidable ethical problems that exacerbate clinicians' moral distress. We suggest that moral resilience is a suitable response to clinician moral distress caused by unavoidable ethical challenges but additional responses are required to address those that are created due to austerity. We encourage clinicians to engage in critical resilience and activism to address problems created by austerity and we highlight the responsibility of institutions to support healthcare professionals in such challenging times.

Methodology and Myopia? Some Praise, a Problem, and a Plea.

In "A Conceptual Model for the Translation of Bioethics Research and Scholarship," Debra Mathews et al. aim to "begin an important discussion" about how to measure success in bioethics, and in doing so they set out a typology of bioethics research and scholarship with the arguably correct assumption that we cannot evaluate success in bioethics without first understanding what its goals are. I think the authors are correct in their claim that, in the current academic climate, having work in bioethics deemed a success is likely to hinge, in some way, on its being translated into practice and having impact. I want, however, to add a critical voice in the form of three considerations that I feel ought to be attended to before the work progresses further, the first being that the typology Mathews et al. propose is highly problematic. Although there is a burgeoning literature on "empirical bioethics" methodologies that blend empirical and conceptual work, the typology appears to ignore this.

Systematic evaluation of the patient-reported outcome (PRO) content of clinical trial protocols.

BACKGROUND: Qualitative evidence suggests patient-reported outcome (PRO) information is frequently absent from clinical trial protocols, potentially leading to inconsistent PRO data collection and risking bias. Direct evidence regarding PRO trial protocol content is lacking. The aim of this study was to systematically evaluate the PRO-specific content of UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme trial protocols. METHODS AND FINDINGS: We conducted an electronic search of the NIHR HTA programme database (inception to August 2013) for protocols describing a randomised controlled trial including a primary/secondary PRO. Two investigators independently reviewed the content of each protocol, using a specially constructed PRO-specific protocol checklist, alongside the 'Standard Protocol Items: Recommendations for Interventional Trials' (SPIRIT) checklist. Disagreements were resolved through discussion with a third investigator. 75 trial protocols were included in the analysis. Protocols included a mean of 32/51 (63%) SPIRIT recommendations (range 16-41, SD 5.62) and 11/33 (33%) PRO-specific items (range 4-18, SD 3.56). Over half (61%) of the PRO items were incomplete. Protocols containing a primary PRO included slightly more PRO checklist items (mean 14/33 (43%)). PRO protocol content was not associated with general protocol completeness; thus, protocols judged as relatively 'complete' using SPIRIT were still likely to have omitted a large proportion of PRO checklist items. CONCLUSIONS: The PRO components of HTA clinical trial protocols require improvement. Information on the PRO rationale/hypothesis, data collection methods, training and management was often absent. This low compliance is unsurprising; evidence shows existing PRO guidance for protocol developers remains difficult to access and lacks consistency. Study findings suggest there are a number of PRO protocol checklist items that are not fully addressed by the current SPIRIT statement. We therefore advocate the development of consensus-based supplementary guidelines, aimed at improving the completeness and quality of PRO content in clinical trial protocols.

Patient-reported outcome (PRO) assessment in clinical trials: a systematic review of guidance for trial protocol writers.

BACKGROUND: Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers. METHODS AND FINDINGS: We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency. CONCLUSIONS: PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in appropriate trial protocols, in order to facilitate rigorous collection/reporting of PRO data, to effectively inform patient care.

Men, maternity and moral residue: negotiating the moral demands of the transition to first time fatherhood.

This article discusses men's transition to first time fatherhood, with a focus on the way they recognise various in-tension moral demands and negotiate an appropriate role for themselves. The findings are taken from a longitudinal study, drawing on elements of grounded theory, comprising a series of face-to-face and telephone interviews with 11 men over a 9-month period from the 12(th) week of pregnancy to 8 weeks after the birth. The analysis focuses on men's feelings and experience of exclusion and participation, and their response and reaction to that experience. The findings present two descriptive themes, 'on the inside looking in' and 'present but not participating', followed by third theme 'deference and support: a moral response' that exposes the dilemmatic nature of men's experience and explains the participants' apparent acceptance of being less involved. The discussion explores the concept of moral residue, arguing that while deference and support may be an appropriate role for fathers in the perinatal period it may also be a compromise that leads to feelings of uncertainty and frustration, which is a consequence of being in a genuinely dilemmatic situation.

Centre selection for clinical trials and the generalisability of results: a mixed methods study.

BACKGROUND: The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice. METHODS AND FINDINGS: Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists' views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively. CONCLUSIONS: Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize 'generalisability' and incorporate it at the design stage of RCTs so that results are readily transferable to 'real world' practice.

PPI, paradoxes and Plato: who's sailing the ship?

Over the last decade, patient and public involvement (PPI) has become a requisite in applied health research. Some funding bodies demand explicit evidence of PPI, while others have made a commitment to developing PPI in the projects they fund. Despite being commonplace, there remains a dearth of engagement with the ethical and theoretical underpinnings of PPI processes and practices. More specifically, while there is a small (but growing) body of literature examining the effectiveness and impact of PPI, there has been relatively little reflection on whether the concept/practice of PPI is internally coherent. Here, the authors unpick a 'paradox' within PPI, which highlights a tension between its moral and pragmatic motivations and its implementation. The authors argue that this 'professionalisation paradox' means we need to rethink the practice, and purpose, of PPI in research.

Will the NHS continue to function in an influenza pandemic? A survey of healthcare workers in the West Midlands, UK.

BACKGROUND: If UK healthcare services are to respond effectively to pandemic influenza, levels of absenteeism amongst healthcare workers (HCWs) must be minimised. Current estimates of the likelihood that HCWs will continue to attend work during a pandemic are subject to scientific and predictive uncertainty, yet an informed evidence base is needed if contingency plans addressing the issues of HCW absenteeism are to be prepared. METHODS: This paper reports the findings of a self-completed survey of randomly selected HCWs across three purposively sampled healthcare trusts in the West Midlands. The survey aimed to identify the factors positively or negatively associated with willingness to work during an influenza pandemic, and to evaluate the acceptability of potential interventions or changes to working practice to promote the continued presence at work of those otherwise unwilling or unable to attend. 'Likelihood' and 'persuadability' scores were calculated for each respondent according to indications of whether or not they were likely to work under different circumstances. Binary logistic regression was used to compute bivariate and multivariate odds ratios to evaluate the association of demographic variables and other respondent characteristics with the self-described likelihood of reporting to work. RESULTS: The survey response rate was 34.4% (n = 1032). Results suggest absenteeism may be as high as 85% at any point during a pandemic, with potential absence particularly concentrated amongst nursing and ancillary workers (OR 0.3; 95% CI 0.1 to 0.7 and 0.5; 95% CI 0.2 to 0.9 respectively). CONCLUSION: Levels of absenteeism amongst HCWs may be considerably higher than official estimates, with potential absence concentrated amongst certain groups of employees. Although interventions designed to minimise absenteeism should target HCWs with a low stated likelihood of working, members of these groups may also be the least receptive to such interventions. Changes to working conditions which reduce barriers to the ability to work may not address barriers linked to willingness to work, and may fail to overcome HCWs' reluctance to work in the face of what may still be deemed unacceptable risk to self and/or family.

Offering payments, reimbursement and incentives to patients and family doctors to encourage participation in research.

Sometimes researchers fail to meet their recruitment targets, and sometimes it is predicted that recruitment may prove difficult but it is not obvious what ethical latitude researchers have to boost participation by, for instance, paying participants to take part or by paying family doctors to recruit patients to participate. In this paper, we distinguish between payment, reimbursement and inducement. We look first at the ethics of paying research participants. We conclude that payment raises all kinds of ethical difficulties, but that reimbursement-whilst not completely unproblematic-is an ethical requirement. We then look at whether some inducement to participate is acceptable and conclude that it is. We continue by asking whether the same arguments can be applied to encouraging family doctors to recruit patients. We conclude that it is right for family doctors to be reimbursed for the costs of recruiting research participants and also argue that there are fewer problems with paying family doctors to recruit patients than there are with paying research participants. Given, however, that there is a fine line between reimbursement and payment, given the potential for conflicts of interests to arise, and given that even suspicion of such a conflict might undermine trust in doctors, systems of both payment and reimbursement need to be transparent.

L.I.F.E. and D.E.A.T.H.

In this short, rhetorical article, I offer a thought experiment that seeks to make an analogy between 'life' and 'disease'. This article was written whilst under the influence of Nietzsche, and I hope that readers will not mistake the polemical style and the occasional nod towards humour for flippancy. This is a serious subject, and this article attempts to ask, inexplicitly, a serious question. If we do suspend our subjective value judgements about life, and strip away what might be considered the 'dogma' of value in life, what effect might this have on our feelings towards voluntary euthanasia, and what can our reaction to that thought experiment tell us?