Reporting on data monitoring committees in neonatal randomised controlled trials is inconsistent

Aim: To evaluate the reported use of Data Monitoring Committees (DMCs), the frequency of interim analysis, pre-specified stopping rules and early trial termination in neonatal randomised controlled trials (RCTs). Methods: We reviewed neonatal RCTs published in four high impact general medical journals, specifically looking at safety issues including documented involvement of a DMC, stated interim analysis, stopping rules and early trial termination. We searched all journal issues over an 11-year period (2003-2013) and recorded predefined parameters on each item for RCTs meeting inclusion criteria. Results: Seventy neonatal trials were identified in four general medical journals: Lancet, New England Journal of Medicine (NEJM), British Medical Journal and Journal of American Medical Association (JAMA). 43 (61.4%) studies reported the presence of a DMC, 36 (51.4%) explicitly mentioned interim analysis; stopping rules were reported in 15 (21.4%) RCTs and 7 (10%) trials were terminated early. The NEJM most frequently reported these parameters compared to the other three journals reviewed. Conclusion: While the majority of neonatal RCTs report on DMC involvement and interim analysis there is still scope for improvement. Clear documentation of safety related issues should be a central component of reporting in neonatal trials involving newborn infants.

Principles and prejudice: The erosion of fairness in admissibility determinations relating to historic child sexual abuse trials in Ireland

This thesis interrogates the construction of fairness to the accused in historic child sexual abuse trials in Ireland. The protection of fairness is a requirement of any trial that claims to adhere to the rule of law. Historic child sexual abuse trials, in which the charges relate to events that are alleged to have taken place decades previously, present serious challenges to the ability of the trial process to safeguard fairness. They are a litmus test of the courts’ commitment to fairness. The thesis finds that in historic abuse trials fairness to the accused has been significantly eroded and that therefore the Irish Courts have failed to respect the core of the rule of law in these most serious of prosecutions. The thesis scrutinises two bodies of case law, both of which deal with the issue of whether evidence should reach the jury. First, it examines the decisions on applications brought by defendants seeking to prohibit their trial. The courts hearing prohibition applications face a dilemma: how to ensure the defendant is not put at risk of an unfair trial, while at the same time recognising that delay in reporting is a defining feature of these cases. The thesis traces the development of the prohibition case law and tracks the shifting interpretations given to fairness by the courts. Second, the thesis examines what fairness means in the superior courts’ decisions regarding the admissibility of the following kinds of evidence, each of which presents particular challenges to the ability of the trial to safeguard fairness: evidence of multiple complainants; evidence of recovered memories and evidence of complainants’ therapeutic records. The thesis finds that in both bodies of case law the Irish courts have hollowed out the meaning of fairness. It makes proposals on how fairness might be placed at the heart of courts’ decisions on admissibility in historic abuse trials. The thesis concludes that the erosion of fairness in historic abuse trials is indicative of a move away from the liberal model of criminal justice. It cautions that unless fairness is prioritised in historic child sexual abuse trials the legitimacy of these trials and that of all Irish criminal trials will be contestable.

Pharmacotherapy optimization in older patients by a structured clinical pharmacist assessment and intervention

Introduction: Older individuals are particularly vulnerable to potentially inappropriate prescribing (PIP), drug related problems (DRPs) and adverse drug reactions (ADRs). A number of different interventions have been proposed to address these issues. However to-date there is a paucity of well-designed trials examining the impact of such interventions. Therefore the aims of this work were to: (i) establish a baseline PIP prevalence both nationally and internationally using the STOPP, Beers and PRISCUS criteria, (ii) identify the most comprehensive method of assessing PIP in older individuals, (iii) develop a structured pharmacist intervention supported by a computer decisions support system (CDSS) and (iv) examine the impact of this intervention on prescribing and incidence of ADRs. Results: This work identified high rates of PIP across all three healthcare settings in Ireland, 84.7% in the long term care, 70.7% in secondary care and 43.3% in primary care being reported. This work identified that for a comprehensive assessment of prescribing to be undertaken, an amalgamation of all three criteria should be deployed simultaneously. High prevalences of DRPs and PIP in older hospitalised individuals were identified. With 82.0% and 76.3% of patients reported to have at least one DRP or PIP instance respectively. The structured pharmacist intervention demonstrated a positive impact on prescribing, with a significant reduction MAI scores being reported. It also resulted in the intervention patients’ having a reduced risk of experiencing an ADR when compared to the control patients (absolute risk reduction of 6.8 (95% CI 1.5% - 12.3%)) and the number needed to treat = 15 (95% CI 8 - 68). However the intervention was found to have no significant effect on length of stay or mortality rate. Conclusion: This work shows that PIP is highly prevalent in older individuals across three healthcare settings in Ireland. This work also demonstrates that a structured pharmacist intervention support by a dedicated CDSS can significantly improve the appropriateness of prescribing and reduce the incidence of ADRs in older acutely ill hospitalised individuals.

Reforming the legal framework for clinical trials with neonates in Ireland: a children’s rights approach

This thesis assesses the current regulatory framework regarding clinical trials with neonates in Ireland from a children’s rights perspective, as derived from the UN Convention on the Rights of the Child 1989 (UN CRC) and its supporting instruments. The focus on neonates in the thesis is due to the particular need for clinical research with this group of children, their dependency on others for their protection and the lack of attention which has been given to them in the regulatory framework. The importance of children’s rights in this area is linked to the role of human rights in the regulation of clinical research in general. A rights-based approach is of great practical relevance in reforming law, policy and practice. For example, the CRC contains a set of commonly agreed legal benchmarks which can be used to assess the current framework and shape recommendations for reform. In this way, it provides a set of binding norms under international law, which must be complied with by states and state actors in all law, policy and practice affecting children. However, the contribution which a children’s rights approach could make to the regulation of research with children has not, to date, been explored in detail. This thesis aims to address this gap by developing a set of children’s rights-based benchmarks, which are used to assess the Irish regulatory framework for clinical trials with neonates and to develop recommendations for reform. The purpose of the analysis and recommendations is to assess Ireland’s compliance with international children’s rights law in the area and to analyse the potential of children’s rights to effectively address inadequacies in the Irish framework. The recommendations ultimately aim to develop a framework which will enhance the protection of neonates’ rights in this important area of children’s lives.

Career choice in medicine

Background: Career Choice in Medicine is an important and problematic topic. Medical education has been framed as professional identity development, yet career choice has not been viewed as a matter of identity. My primary aim was to offer new insights by exploring career choice using Figured Worlds theory, a socio-cultural theory of identity. Graduate retention is a challenge for many countries, including Ireland. My secondary aim was to address a gap in the data on postgraduate trainees in Ireland and to use the Irish case to illustrate points transferable to other contexts. Methodology & Methods: This was a predominantly qualitative Mixed Methods programme of research. My qualitative studies were oriented towards social constructionism. I collated existing data from the Royal College of Physicians of Ireland (RCPI) and HSE-MET to describe trainees and their career paths. I surveyed Basic Specialist Training trainees (n=333) about their career plans. I surveyed new trainees (n=527) about their expectations of training and all RCPI trainees about their experiences of training (n=1246). I conducted semi-structured interviews with 18 medical students and doctors. A subgroup (n=6) provided longitudinal data. Figured Worlds theory and Gee’s discourse tools were used for analysis. Results: I have used the case of medical training and career choice in Ireland to explain how social, political and cultural context, and day to day experiences in the cultural world of medicine, shaped doctors’ career choices. My qualitative findings described a unifying model of career choice, consisting of priming, exposure, positioning and open-endedness, which can guide the design of interventions to shape and support career choice. Conclusion: My original contribution has been to demonstrate the fruitfulness of framing career choice in terms of identity development. This represents a turn in the conversation about career choice, which brings new starting points and moves the dialogue forward.