NOURISH, Nutritional OUtcomes from a Randomised Investigation of Intradialytic oral nutritional Supplements in patients receiving Haemodialysis: a pilot randomised controlled trial

Background The study was done to assess the feasibility of conducting a trial evaluating the use of an intradialytic oral nutritional supplement (ONS) on nutritional status. Methods The study design is a single centre, parallel group, external pilot randomised controlled trial (RCT). The setting was at a haemodialysis unit in Sheffield, UK. The aim was to recruit 30 trial participants to allow at least 12 evaluable patients per arm, but the actual study sample consisted of 10 adults with a body mass index (BMI) ≤22 kg/m2, receiving thrice weekly haemodialysis. All participants received nutritional advice from a renal dietitian as per usual practice. The intervention included the provision of an intradialytic ONS. Feasibility outcomes included recruitment to time and retention of participants along with palatability of ONS. Secondary outcomes were clinical parameters to obtain variance and estimates of effect size to inform the sample size calculation for a definitive trial. Results Recruitment was undertaken for a fixed period of 6 weeks. Rates were lower than expected mainly due to ineligibility with only 7% of screened patients (19/265) being eligible and 4% (10/265) of these being recruited. Due to the small proportion of patients eligible for the trial, all haemodialysis patients at the specified unit were assessed for eligibility. Data completion rates were low for session questionnaires (23%). Sample sizes derived from variance in secondary outcome measure of handgrip strength and adjusted for a dropout rate of 20% indicate that 189 patients would be required for a definitive RCT, requiring 19 UK haemodialysis units to participate. Conclusions A definitive RCT is feasible with some adaptation to exclusion criteria and methodology. The exclusion criteria could be adapted to include an increase in upper limit for BMI. The use of questionnaires at each dialysis session may not be feasible but the inclusion of appetite and supplement consumption data collection at the main assessments would provide similar outcome data. Quality of life assessment using SF-12 would be acceptable

Nonlocality vs. complementarity: a conservative approach to the information problem

A proposal for resolution of the information paradox is that "nice slice" states, which have been viewed as providing a sharp argument for information loss, do not in fact do so as they do not give a fully accurate description of the quantum state of a black hole. This however leaves an information *problem*, which is to provide a consistent description of how information escapes when a black hole evaporates. While a rather extreme form of nonlocality has been advocated in the form of complementarity, this paper argues that is not necessary, and more modest nonlocality could solve the information problem. One possible distinguishing characteristic of scenarios is the information retention time. The question of whether such nonlocality implies acausality, and particularly inconsistency, is briefly addressed. The need for such nonlocality, and its apparent tension with our empirical observations of local quantum field theory, may be a critical missing piece in understanding the principles of quantum gravity.Comment: 11 pages of text and figures, + references. v2 minor text. v3 small revisions to match final journal versio

Scientific mindfulness: a foundation for future themes in international business

We conceptualize new ways to qualify what themes should dominate the future IB research agenda by examining three questions: Whom should we ask? What should we ask and which selection criteria should we apply? What are the contextual forces? We propose scientific mindfulness as the way forward for generating themes in IB research

Building a recruitment database for asthma trials: a conceptual framework for the creation of the UK Database of Asthma Research Volunteers

Funded by Asthma UK as part of the Asthma UK Centre for Applied Research (AUK-AC-2012-01). In addition, BN, IS, CS and AS acknowledge the support of the Farr Institute, which is funded by the MRC and its consortium of funders

A re-randomisation design for clinical trials

Background: Recruitment to clinical trials is often problematic, with many trials failing to recruit to their target sample size. As a result, patient care may be based on suboptimal evidence from underpowered trials or non-randomised studies. Methods: For many conditions patients will require treatment on several occasions, for example, to treat symptoms of an underlying chronic condition (such as migraines, where treatment is required each time a new episode occurs), or until they achieve treatment success (such as fertility, where patients undergo treatment on multiple occasions until they become pregnant). We describe a re-randomisation design for these scenarios, which allows each patient to be independently randomised on multiple occasions. We discuss the circumstances in which this design can be used. Results: The re-randomisation design will give asymptotically unbiased estimates of treatment effect and correct type I error rates under the following conditions: (a) patients are only re-randomised after the follow-up period from their previous randomisation is complete; (b) randomisations for the same patient are performed independently; and (c) the treatment effect is constant across all randomisations. Provided the analysis accounts for correlation between observations from the same patient, this design will typically have higher power than a parallel group trial with an equivalent number of observations. Conclusions: If used appropriately, the re-randomisation design can increase the recruitment rate for clinical trials while still providing an unbiased estimate of treatment effect and correct type I error rates. In many situations, it can increase the power compared to a parallel group design with an equivalent number of observations

Improving recruitment to a study of telehealth management for long-term conditions in primary care: two embedded, randomised controlled trials of optimised patient information materials

Background: Patient understanding of study information is fundamental to gaining informed consent to take part in a randomised controlled trial. In order to meet the requirements of research ethics committees, patient information materials can be long and need to communicate complex messages. There is concern that standard approaches to providing patient information may deter potential participants from taking part in trials. The Systematic Techniques for Assisting Recruitment to Trials (MRC-START) research programme aims to test interventions to improve trial recruitment. The aim of this study was to investigate the effect on recruitment of optimised patient information materials (with improved readability and ease of comprehension) compared with standard materials. The study was embedded within two primary care trials involving patients with long-term conditions. Methods: The Healthlines Study involves two linked trials evaluating a telehealth intervention in patients with depression (Healthlines Depression) or raised cardiovascular disease risk (Healthlines CVD). We conducted two trials of a recruitment intervention, embedded within the Healthlines host trials. Patients identified as potentially eligible in each of the Healthlines trials were randomised to receive either the original patient information materials or optimised versions of these materials. Primary outcomes were the proportion of participants randomised (Healthlines Depression) and the proportion expressing interest in taking part (Healthlines CVD). Results: In Healthlines Depression (n = 1364), 6.3 % of patients receiving the optimised patient information materials were randomised into the study compared to 4.0 % in those receiving standard materials (OR = 1.63, 95 % CI = 1.00 to 2.67). In Healthlines CVD (n = 671) 24.0 % of those receiving optimised patient information materials responded positively to the invitation to participate, compared to 21.9 % in those receiving standard materials (OR = 1.12, 95 % CI = 0.78 to 1.61). Conclusions: Evidence from these two embedded trials suggests limited benefits of optimised patient information materials on recruitment rates, which may only be apparent in some patient populations, with no effects on other outcomes. Further embedded trials are needed to provide a more precise estimate of effect, and to explore further how effects vary by trial context, intervention, and patient population

Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials

BACKGROUND: Randomized controlled trials play a central role in evidence-based practice, but recruitment of participants, and retention of them once in the trial, is challenging. Moreover, there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies. As with other healthcare initiatives, the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives, which for recruitment would mean embedding a recruitment trial within an ongoing host trial. Systematic reviews indicate that such studies are rare. Embedded trials are largely delivered in an ad hoc way, with interventions almost always developed in isolation and tested in the context of a single host trial, limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to researchers working in different contexts. METHODS/DESIGN: The Systematic Techniques for Assisting Recruitment to Trials (START) program is funded by the United Kingdom Medical Research Council (MRC) Methodology Research Programme to support the routine adoption of embedded trials to test standardized recruitment interventions across ongoing host trials. To achieve this aim, the program involves three interrelated work packages: (1) methodology - to develop guidelines for the design, analysis and reporting of embedded recruitment studies; (2) interventions - to develop effective and useful recruitment interventions; and (3) implementation - to recruit host trials and test interventions through embedded studies. DISCUSSION: Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or, potentially, other types of intervention linked to trial conduct. It will also increase the evidence base for two types of recruitment intervention. TRIAL REGISTRATION: The START protocol covers the methodology for embedded trials. Each embedded trial is registered separately or as a substudy of the host trial

Successful recruitment to trials : findings from the SCIMITAR+ Trial

BACKGROUND: Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. METHODS: SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. RESULTS: Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. CONCLUSIONS: This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment

Cultural and leadership predictors of corporate social responsibility values of top management: A GLOBE study of 15 countries.

This paper examines cultural and leadership variables associated with corporate social responsibility values that managers apply to their decision-making. In this longitudinal study, we analyze data from 561 firms located in 15 countries on five continents to illustrate how the cultural dimensions of institutional collectivism and power distance predict social responsibility values on the part of top management team members. CEO visionary leadership and integrity were also uniquely predictive of such values. Journal of International Business Studies (2006) 37, 823–837. doi:10.1057/palgrave.jibs.8400230