Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings

Peer reviewedPublisher PD

Simple imputation methods were inadequate for missing not at random (MNAR) quality of life data

Acknowledgements We thank the patients who took part in the RECORD study, without whose help this study would not have been possible. The MRC funded the central organisation of RECORD, and Shire Pharmaceuticals Group plc funded the drugs, which were manufactured by Nycomed Ltd. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. Shona Fielding is also currently funded by the Chief Scientist Office on a Research Training Fellowship (CZF/1/31). The views expressed are, however, not necessarily those of the funding body.Peer reviewedPublisher PD

Game of Stones:feasibility randomised controlled trial of how to engage men with obesity in text message and incentive interventions for weight loss

Objectives To examine the acceptability and feasibility of narrative text messages with or without financial incentives to support weight loss for men. Design Individually randomised three-arm feasibility trial with 12 months’ follow-up. Setting Two sites in Scotland with high levels of disadvantage according to Scottish Index for Multiple Deprivation (SIMD). Participants Men with obesity (n=105) recruited through community outreach and general practitioner registers. Interventions Participants randomised to: (A) narrative text messages plus financial incentive for 12 months (short message service (SMS)+I), (B) narrative text messages for 12 months (SMS only), or (C) waiting list control. Outcomes Acceptability and feasibility of recruitment, retention, intervention components and trial procedures assessed by analysing quantitative and qualitative data at 3, 6 and 12 months. Results 105 men were recruited, 60% from more disadvantaged areas (SIMD quintiles 1 or 2). Retention at 12 months was 74%. Fewer SMS+I participants (64%) completed 12-month assessments compared with SMS only (79%) and control (83%). Narrative texts were acceptable to many men, but some reported negative reactions. No evidence emerged that level of disadvantage was related to acceptability of narrative texts. Eleven SMS+I participants (31%) successfully met or partially met weight loss targets. The cost of the incentive per participant was £81.94 (95% CI £34.59 to £129.30). Incentives were acceptable, but improving health was reported as the key motivator for weight loss. All groups lost weight (SMS+I: −2.51 kg (SD=4.94); SMS only: −1.29 kg (SD=5.03); control: −0.86 kg (SD=5.64) at 12 months). Conclusions This three-arm weight management feasibility trial recruited and retained men from across the socioeconomic spectrum, with the majority from areas of disadvantage, was broadly acceptable to most participants and feasible to deliver

Stable carbon isotopes of dissolved inorganic carbon for a zonal transect across the subpolar North Atlantic Ocean in summer 2014

The stable carbon isotope composition of dissolved inorganic carbon (δ13CDIC) in seawater was measured in samples collected during June–July 2014 in the subpolar North Atlantic. Sample collection was carried out on the RRS James Clark Ross cruise JR302, part of the “Radiatively Active Gases from the North Atlantic Region and Climate Change” (RAGNARoCC) research programme. The observed δ13CDIC values for cruise JR302 fall in a range from −0.07 to +1.95 ‰, relative to the Vienna Pee Dee Belemnite standard. From duplicate samples collected during the cruise, the 1σ precision for the 341 results is 0.08 ‰, which is similar to our previous work and other studies of this kind. We also performed a cross-over analysis using nearby historical δ13CDIC data, which indicated that there were no significant systematic offsets between our measurements and previously published results. We also included seawater reference material (RM) produced by A. G. Dickson (Scripps Institution of Oceanography, USA) in every batch of analysis, enabling us to improve upon the calibration and quality-control procedures from a previous study. The δ13CDIC is consistent within each RM batch, although its value is not certified. We report δ13CDIC values of 1.15 ± 0.03 ‰ and 1.27 ± 0.05 ‰ for batches 141 and 144 respectively. Our JR302 δ13CDIC data can be used – along with measurements of other biogeochemical variables – to constrain the processes that control DIC in the interior ocean, in particular the oceanic uptake of anthropogenic carbon dioxide and the biological carbon pump. Our δ13CDIC results are available from the British Oceanographic Data Centre – doi:10.5285/22235f1a-b7f3-687f-e053-6c86abc0c8a6

Marketing and clinical trials: a case study.

BACKGROUND: Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. METHODS: Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. RESULTS: The case study demonstrates that trials need various categories of people to buy in - hence, to be successful, trialists must embrace marketing strategies to some extent. CONCLUSION: The performance of future clinical trials could be enhanced if trialists routinely considered these factors

Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial : FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)

Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Fullthickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery. Methods/Design: Patients with stage 2–3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity ≤ 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events. Discussion: FILMS will provide high quality evidence on the role of ILM peeling in FTMH surgery. Trial registration: This trial is registered with Current Controlled Trials ISRCTN number 33175422 and Clinical Trials.gov identifier NCT00286507.Chief Scientist Office, Scotland (project ref no CZH/4/235), NHS GrampianPeer reviewedPublisher PD

Where do we go from here? - Opportunities and barriers to the career development of trial managers: a survey of UK-based trial management professionals

BackgroundClinical trials commonly have a dedicated trial manager and effective trial management is essential to the successful delivery of high-quality trials. Trial managers have diverse experience and currently there is no standardised structured career pathway. The UK Trial Managers’ Network (UKTMN) surveyed its members to understand what is important to them with respect to career development since this would be important in the development of any initiative intended to develop a skilled workforce.MethodsWe conducted an online survey of UKTMN members, who are trial management professionals, working on academic-led trials in the UK. Members were asked what they perceive as opportunities and barriers to career development. Two reminders were sent to facilitate completion of the survey, and responders were offered the opportunity to enter a prize draw for waived fees at the UKTMN annual meeting. Data were analysed descriptively by using Stata (version 15.1), and free-text responses were reviewed for themes.ResultsThe survey was sent to 819 UKTMN members; 433 responses were received, although 13 were from non-UKTMN members; thus 420 respondents' data were included in analyses. Respondents were representative of UKTMN membership; however, more responses were received by trial managers based in registered clinical trials units (CTUs). The top three opportunities for career development were (i) training, (ii) helping design trials and (iii) undertaking relevant qualifications. The top three barriers were (i) funding, (ii) few opportunities to get involved in development activities aside from managing a trial and (iii) unclear organisational career pathway. Almost all respondents (401/420, 95.4%) considered career development either very or quite important. Although all respondents had a day-to-day role in managing trials, there was huge disparity between job titles.ConclusionCareer development is important to trial managers yet there is a lack of a structured pathway. The enablers and disablers to career development for trial managers should be clearly considered by the clinical trial community and, in particular, employers, sponsors and funders in order to develop a highly skilled workforce of trial managers, who are key to the delivery of trials