Choosing and evaluating randomisation methods in clinical trials: a qualitative study.

BACKGROUND: There exist many different methods of allocating participants to treatment groups during a randomised controlled trial. Although there is research that explores trial characteristics that are associated with the choice of method, there is still a lot of variety in practice not explained. This study used qualitative methods to explore more deeply the motivations behind researchers' choice of randomisation, and which features of the method they use to evaluate the performance of these methods. METHODS: Data was collected from online focus groups with various stakeholders involved in the randomisation process. Focus groups were recorded and then transcribed verbatim. A thematic analysis was used to analyse the transcripts. RESULTS: Twenty-five participants from twenty clinical trials units across the UK were recruited to take part in one of four focus groups. Four main themes were identified: how randomisation methods are selected; researchers' opinions of the different methods; which features of the method are desirable and ways to measure method features. Most researchers agree that the randomisation method should be selected based on key trial characteristics; however, for many, a unit standard is in place. Opinions of methods were varied with some participants favouring stratified blocks and others favouring minimisation. This was generally due to researchers' perception of the effect these methods had on balance and predictability. Generally, predictability was considered more important than balance as adjustments cannot be made for it; however, most researchers felt that the importance of these two methods was dependent on the design of the study. Balance is usually evaluated by tabulating variables by treatment arm and looking for perceived imbalances, predictability was generally considered much harder to measure, partly due to differing definitions. CONCLUSION: There is a wide variety in practice on how randomisation methods are selected and researcher's opinions on methods. The difference in practice observed when looking at randomisation method selection can be explained by a difference in unit practice, and also by a difference in researchers prioritisation of balance and predictability. The findings of this study show a need for more guidance on randomisation method selection.

Navigating complexity of the medication management system within the home setting-a functional resonance analysis method (FRAM) analysis of people with dementia and their carers' experiences.

BACKGROUND: There is a strong imperative to support people with dementia to live independently in their homes for as long as possible. A starting point is to understand how they manage medications on a daily basis. AIM: To understand how people with dementia and their informal carers manage medications within the home setting to inform the identification of opportunities to improve medication management. METHODS: A qualitative study using the Functional Resonance Analysis Method (FRAM). Interview data with people with dementia and informal carers were analysed to (i) Identify and describe key functions, (ii) identify and describe variability in performing key functions, and its potential consequences and (iii) map performance variability to Resilient Healthcare capacities. RESULTS AND DISCUSSION: A FRAM model was developed and consisted of 14 interdependent key functions. The interdependent nature of functions, and the different nature and sources of variability in how each key function was performed highlighted the level of complexity of the medication management system within the home setting. The medication system was managed almost entirely by the person with dementia and/or their informal carers. This shows the lack of system-level controls to support the safe functioning of the medication management system in the home setting. CONCLUSION: Future work will develop a comprehensive FRAM model that includes the perspectives of health and social care professionals and those from the third sectors to underpin the development of a range of system recommendations to strengthen resilience in the medication management system within the home setting.

Widening participation - recruitment methods in mental health randomised controlled trials: a qualitative study.

BACKGROUND: Barriers to mental health research participation are well documented including distrust of services and research; and stigma surrounding mental health. They can contribute to a lack of diversity amongst participants in mental health research, which threatens the generalisability of knowledge. Given the recent widespread use of the internet in medical research, this study aimed to explore the perspectives of key partners on the use of online (e.g. social media) and offline (e.g. in-person) recruitment as an approach to improving diversity in mental health randomised controlled trials (RCTs). METHODS: Face-to-face and online interviews/focus groups with researchers working in mental health and Patient and Public Involvement partners in the United Kingdom. Recordings were transcribed and analysed using a combination of inductive and deductive thematic analysis. RESULTS: Three focus groups and three interviews were conducted with a total N = 23 participants. Four overarching themes were identified: (1) recruitment reach; (2) Demographic factors that affect selection of recruitment method; (3) safety of technology, and; (4) practical challenges. Five main factors were identified that affect the choice of recruitment method: age, complexity of mental health problem and stigma, cultural and ethnicity differences and digital divide. The use of online methods was considered more accessible to people who may feel stigmatised by their mental health condition and with a benefit of reaching a wider population. However, a common view amongst participants was that online methods require closer data monitoring for quality of responders, are not fully secure and less trustworthy compared to offline methods that enable participants to build relationships with health providers. Funding, staff time and experience, organisational support, and technical issues such as spam or phishing emails were highlighted as practical challenges facing online recruitment. All participants agreed that using a hybrid approach tailored to the population under study is paramount. CONCLUSIONS: This study highlighted the importance of offering a flexible and multifaceted recruitment approach by integrating online with offline methods to support inclusivity and widening participation in mental health research. The findings will be used to develop considerations for researchers designing RCTs to improve recruitment in mental health research.

Developing guidance for a risk-proportionate approach to blinding statisticians within clinical trials: a mixed methods study.

BACKGROUND: Existing guidelines recommend statisticians remain blinded to treatment allocation prior to the final analysis and that any interim analyses should be conducted by a separate team from the one undertaking the final analysis. However, there remains substantial variation in practice between UK Clinical Trials Units (CTUs) when it comes to blinding statisticians. Therefore, the aim of this study was to develop guidance to advise CTUs on a risk-proportionate approach to blinding statisticians within clinical trials. METHODS: This study employed a mixed methods approach involving three stages: (I) a quantitative study using a cohort of 200 studies (from a major UK funder published between 2016 and 2020) to assess the impact of blinding statisticians on the proportion of trials reporting a statistically significant finding for the primary outcome(s); (II) a qualitative study using focus groups to determine the perspectives of key stakeholders on the practice of blinding trial statisticians; and (III) combining the results of stages I and II, along with a stakeholder meeting, to develop guidance for UK CTUs. RESULTS: After screening abstracts, 179 trials were included for review. The results of the primary analysis showed no evidence that involvement of an unblinded trial statistician was associated with the likelihood of statistically significant findings being reported, odds ratio (OR) 1.02 (95% confidence interval (CI) 0.49 to 2.13). Six focus groups were conducted, with 37 participants. The triangulation between stages I and II resulted in developing 40 provisional statements. These were rated independently by the stakeholder group prior to the meeting. Ten statements reached agreement with no agreement on 30 statements. At the meeting, various factors were identified that could influence the decision of blinding the statistician, including timing, study design, types of intervention and practicalities. Guidance including 21 recommendations/considerations was developed alongside a Risk Assessment Tool to provide CTUs with a framework for assessing the risks associated with blinding/not blinding statisticians and for identifying appropriate mitigation strategies. CONCLUSIONS: This is the first study to develop a guidance document to enhance the understanding of blinding statisticians and to provide a framework for the decision-making process. The key finding was that the decision to blind statisticians should be based on the benefits and risks associated with a particular trial.

Blinding of study statisticians in clinical trials: a qualitative study in UK clinical trials units.

BACKGROUND: Blinding is an established approach in clinical trials which aims to minimise the risk of performance and detection bias. There is little empirical evidence to guide UK clinical trials units (CTUs) about the practice of blinding statisticians. Guidelines recommend that statisticians remain blinded to allocation prior to the final analysis. As these guidelines are not based on empirical evidence, this study undertook a qualitative investigation relating to when and how statisticians should be blinded in clinical trials. METHODS: Data were collected through online focus groups with various stakeholders who work in the delivery and oversight of clinical trials. Recordings of the focus groups were transcribed verbatim and thematic analysis was used to analyse the transcripts. RESULTS: Thirty-seven participants from 19 CTUs participated in one of six focus groups. Four main themes were identified, namely statistical models of work, factors affecting the decision to blind statisticians, benefits of blinding/not blinding statisticians and practicalities. Factors influencing the decision to blind the statistician included available resources, study design and types of intervention and outcomes and analysis. Although blinding of the statistician is perceived as a desirable mitigation against bias, there was uncertainty about the extent to which an unblinded statistician might impart bias. Instead, in most cases, the insight that the statistician offers was deemed more important to delivery of a trial than the risk of bias they may introduce if unblinded. Blinding of statisticians was only considered achievable with the appropriate resource and staffing, which were not always available. In many cases, a standard approach to blinding was therefore considered unrealistic and impractical; hence the need for a proportionate risk assessment approach identifying possible mitigations. CONCLUSIONS: There was wide variation in practice between UK CTUs regarding the blinding of trial statisticians. A risk assessment approach would enable CTUs to identify risks associated with unblinded statisticians conducting the final analysis and alternative mitigation strategies. The findings of this study will be used to design guidance and a tool to support this risk assessment process.

Using video reflexive ethnography to explore the use of variable rate intravenous insulin infusions.

BACKGROUND: The use of variable rate intravenous insulin infusion (VRIII) is a complex process that has consistently been implicated in reports of error and consequent harm. Investment in patient safety has focused mainly on learning from errors, though this has yet to be proved to reduce error rates. The Resilient Health Care approach advocates learning from everyday practices. Video reflexive ethnography (VRE) is an innovative methodology used to capture everyday practices, reflect on and thereby improve these. This study set out to explore the use of VRIIIs by utilising the VRE methodology. METHODS: This study was conducted in a Vascular Surgery Unit. VRE methodology was used to collect qualitative data that involved videoing healthcare practitioners caring for patients treated with VRIII and discussing the resulting clips with participants in reflexive meetings. Transcripts of these were subjected to thematic analysis. Quantitative data (e.g. blood glucose measurements) were collected from electronic patient records in order to contextualise the outcomes of the video-observed tasks. RESULTS: The use of VRE in conjunction with quantitative data revealed that context-dependent adaptations (seeking verbal orders to treat hypoglycaemia) and standardised practices (using VRIII guidelines) were strategies used in everyday work. Reflexive meetings highlighted the challenges faced while using VRIII, which were mainly related to lack of clinical knowledge, e.g. prescribing/continuing long-acting insulin analogues alongside the VRIII, and problems with organisational infrastructure, i.e. the wireless blood glucose meter results sometimes not updating on the electronic system. Reflexive meetings also enabled participants to share the meanings of the reality surrounding them and encouraged them to suggest solutions tailored to their work, for example face-to-face, VRIII-focused training. CONCLUSIONS: VRE deepened understanding of VRIII by shedding light on its essential tasks and the challenges and adaptations entailed by its use. Future research might focus on collecting data across various units and hospitals to develop a full picture of the use of VRIIIs.

Modelling the use of variable rate intravenous insulin infusions in hospitals by comparing Work as Done with Work as Imagined.

BACKGROUND: Variable rate intravenous insulin infusions (VRIIIs) are widely used to treat elevated blood glucose (BG) in adult inpatients who are severely ill and/or will miss more than one meal. VRIIIs can cause serious harm to the patient if used incorrectly. Recent safety initiatives have embraced the Resilient Health Care (RHC) approach to safety by understanding how VRIIIs are expected to be used (Work as Imagined, 'WAI') and how it is actually used in everyday clinical care (Work as Done, 'WAD'). OBJECTIVES: To systematically compare WAI and WAD and analyse adaptations used in situ to develop a model explaining VRIII use. METHODS: A qualitative observational study video-recording healthcare practitioners using VRIII. The video data were transcribed and inductively coded to develop a hierarchical task analysis (HTA) to represent WAD. This HTA was compared with a HTA previously developed to represent WAI. The comparison output was used to develop a model of VRIII use. RESULTS: While many of the tasks in the WAD HTA were aligned with the tasks presented in the WAI HTA, some important ones did not. When misalignment was observed, permanent adaptations (e.g. signing as a witness for a changed VRIII's rate without independently verifying whether the new rate was appropriate) and temporary workarounds (e.g. not administering intermediate-acting insulin analogues although the intermediate-acting insulin prescription was not suspended) were the most frequently observed adaptations. The comparison between WAI and WAD assisted in developing a model of VRIII use. The model shed light on strategies used to imagine everyday work (e.g. incident reports, VRIII guidelines), how everyday work was accomplished (e.g. context-dependent adaptations) and how these contributed to both successful and unsuccessful outcomes. CONCLUSIONS: This study provided in-depth understanding of the tasks required while using VRIIIs, and responses and adaptations needed to achieve safer care in a complex environment.

Detailed analysis of 'work as imagined' in the use of intravenous insulin infusions in a hospital: a hierarchical task analysis.

OBJECTIVE: Variable rate intravenous insulin infusions (VRIII) is a high-risk medication that has a potential to cause significant patient harm if used in error. Complex preparation of VRIII in clinical areas and the need for frequent monitoring and adjustment increase the complexity of using VRIII. An emerging approach, called Resilient Healthcare, proposes understanding complexity of work by exploring how work is assumed to be done and compare it with everyday work. This study aimed to explore how VRIII is perceived to be used by healthcare practitioners, focusing on one aspect of Resilient Healthcare: understanding how work is assumed to be done, using a method called hierarchical task analysis (HTA). DESIGN: A qualitative study using document analysis and focus groups. SETTING: A vascular surgery unit in an acute National Health Service teaching hospital in the UK. PARTICIPANTS: Stakeholders/users in different professional roles involved in the process of using VRIII. RESULTS: The HTA showed the complexity of using VRIII and highlighted more than 115 steps required to treat elevated blood glucose. The process of producing hospital-specific guidelines was iterative. Careful consideration was taken to coordinate the development and implementation of guidelines. Documents provided detailed clinical instructions related to the use of VRIII but practitioners selectively used them, often in deference to senior colleagues. Intentional adaptations, for example, proactively asking for a VRIII prescription occurred and were acknowledged as part of providing individualised patient care. CONCLUSION: Using VRIII to treat elevated blood glucose is a complex but necessary process mediated by a range of factors such as organisational influences. Adaptive strategies to mitigate errors were common and future research can build on insights from this study to develop a broader understanding of how VRIII is used and to understand how adaptations are made in relation to the use of VRIII.

Resilient Health Care: a systematic review of conceptualisations, study methods and factors that develop resilience.

BACKGROUND: Traditional approaches to safety management in health care have focused primarily on counting errors and understanding how things go wrong. Resilient Health Care (RHC) provides an alternative complementary perspective of learning from incidents and understanding how, most of the time, work is safe. The aim of this review was to identify how RHC is conceptualised, described and interpreted in the published literature, to describe the methods used to study RHC, and to identify factors that develop RHC. METHODS: Electronic searches of PubMed, Scopus and Cochrane databases were performed to identify relevant peer-reviewed studies, and a hand search undertaken for studies published in books that explained how RHC as a concept has been interpreted, what methods have been used to study it, and what factors have been important to its development. Studies were evaluated independently by two researchers. Data was synthesised using a thematic approach. RESULTS: Thirty-six studies were included; they shared similar descriptions of RHC which was the ability to adjust its functioning prior to, during, or following events and thereby sustain required operations under both expected and unexpected conditions. Qualitative methods were mainly used to study RHC. Two types of data sources have been used: direct (e.g. focus groups and surveys) and indirect (e.g. observations and simulations) data sources. Most of the tools for studying RHC were developed based on predefined resilient constructs and have been categorised into three categories: performance variability and Work As Done, cornerstone capabilities for resilience, and integration with other safety management paradigms. Tools for studying RHC currently exist but have yet to be fully implemented. Effective team relationships, trade-offs and health care 'resilience' training of health care professionals were factors used to develop RHC. CONCLUSIONS: Although there was consistency in the conceptualisation of RHC, methods used to study and the factors used to develop it, several questions remain to be answered before a gold standard strategy for studying RHC can confidently be identified. These include operationalising RHC assessment methods in multi-level and diverse settings and developing, testing and evaluating interventions to address the wider safety implications of RHC amidst organisational and institutional change.

Understanding safety differently: developing a model of resilience in the use of intravenous insulin infusions in hospital in-patients-a feasibility study protocol.

BACKGROUND: Intravenous insulin infusions are considered the treatment of choice for critically ill patients and non-critically ill patients with persistent raised blood glucose who are unable to eat, to achieve optimal blood glucose levels. The benefits of using intravenous insulin infusions as well as the problems experienced are well described in the scientific literature. Traditional approaches for improving patient safety have focused on identifying errors, understanding their causes and designing solutions to prevent them. Such approaches do not take into account the complex nature of healthcare systems, which cannot be controlled solely by following standards. An emerging approach called Resilient Healthcare proposes that, to improve safety, it is necessary to focus on how work can be performed successfully as well as how work has failed. METHODS AND ANALYSIS: The study will be conducted at Oxford University Hospitals NHS Foundation Trust and will involve three phases. Phase I: explore how work is imagined by analysing intravenous insulin infusion guidelines and conducting focus group discussions with guidelines developers, managers and healthcare practitioners. Phase II: explore the interplay between how work is imagined and how work is performed using mixed methods. Quantitative data will include blood glucose levels, insulin infusion rates, number of hypoglycaemic and hyperglycaemic events from patients' electronic records. Qualitative data will include video reflexive ethnography: video recording healthcare practitioners using intravenous insulin infusions and then conducting reflexive meetings with them to discuss selected video footage. Phase III: compare findings from phase I and phase II to develop a model for using intravenous insulin infusions. ETHICS AND DISSEMINATION: Ethical approvals have been granted by the South Central-Oxford C Research Ethics Committee, Oxford University Hospitals NHS Foundation Trust and University of Reading. The results will be disseminated through presentations at appropriate conferences and meetings, and publications in peer-reviewed journals.

Awareness of Physicians and Clinical Pharmacists About ACC/AHA Guidelines for Dyslipidemia Management: A Cross-Sectional Study.

INTRODUCTION: Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality worldwide. Although genetics could contribute to the incidence of CVD, they are mostly acquired conditions. Management of precipitating factors such as hyperlipidemia can prevent CVD. Therefore, clinical guidelines have been used as a tool to improve patient outcomes and minimize practice variation. OBJECTIVE: The objective of this study was to assess health-care providers' (physicians and clinical pharmacists) awareness about the latest edition of the American College of Cardiology/American Heart Association (ACC/AHA) guidelines of dyslipidemia management. MATERIALS AND METHODS: To meet the study objective, a self-administered questionnaire was designed based on the recommendations of the latest edition of the ACC/AHA guidelines for dyslipidemia management. After validation, the questionnaire was distributed to physicians and clinical pharmacists in Al-Ahsa province of Saudi Arabia. RESULTS: Validation of the questionnaire was carried on 10 participants (Cronbach's alpha = 0.816). Seventy-seven participants completed the questionnaire (acceptance rate = 51.33%). The majority of participants knew about the release of the ACC/AHA 2013 guidelines for dyslipidemia (77% of the physicians and 48% of the clinical pharmacist). Inadequate knowledge of the major changes in the dyslipidemia management was observed in both study groups with no significant difference between them (the median score for physicians and pharmacists was 4 out of 10 with a range of 1-9, Z = -0.15, P = 0.88). CONCLUSION: Inadequate level of knowledge about practice-changing recommendations of the recent ACC/AHA guidelines for dyslipidemia management was observed among the study participants. This level of knowledge could result in clinical malpractice and worsen management outcomes. Thus, efforts should be in place to raise awareness about the evidence-based management of dyslipidemia and monitor compliance to guidelines and their implementation outcomes.

Evaluating unfractionated heparin fixed dosing protocol and establishing an institutional therapeutic range for UFH in hospital setting in Jordan.

This study was conducted to evaluate current unfractionated heparin (UFH) dosing regimen and establish an institutional therapeutic range for UFH in a public hospital in Jordan. In the first part, medical records of 241 patients who received UFH were reviewed retrospectively. In the second part, blood samples were withdrawn from 60 patients on UFH, and activated partial thromboplastin time and anti-Xa assay were measured. Most activated partial thromboplastin time readings were not therapeutic (91.4%) and recurrence of thrombosis was reported in 35.3% of patients. In the second part, therapeutic activated partial thromboplastin time range corresponding to the UFH concentration of 0.3 to 0.7 anti-factor Xa unit/mL was 56 to 95 seconds, which corresponds to an activated partial thromboplastin time range of 1.5 of 2.8 times the mean control value. The traditional activated partial thromboplastin time range ratio of 1.5 to 2.5 times the control value can result in subtherapeutic UFH levels.

Implementation of clinical pharmacy services at a university hospital in Jordan.

OBJECTIVE: Clinical pharmacy services are still in the early stages of implementation in the Middle East. This study assessed the implementation of clinical pharmacy services at a major university hospital. METHODS: All recommendations and services provided by clinical pharmacists were recorded for a period of 7 months. KEY FINDINGS: During the study period a total of 3026 patients were followed up and 10,783 recommendations and services were provided. The physicians' rate of acceptance of clinical pharmacists' recommendations was 69.4%. CONCLUSION: The implementation of clinical pharmacy services in this setting was successful and should positively impact patient care.