Background The CONSORT statement is intended to improve reporting of randomised controlled trials and focuses on minimising the risk of bias (internal validity). The applicability of a trial’s ...results (generalisability or external validity) is also important, particularly for pragmatic trials. A pragmatic trial (a term first used in 1967 by Schwartz and Lellouch) can be broadly defined as a randomised controlled trial whose purpose is to inform decisions about practice. This extension of the CONSORT statement is intended to improve the reporting of such trials and focuses on applicability. Methods At two, two-day meetings held in Toronto in 2005 and 2008, we reviewed the CONSORT statement and its extensions, the literature on pragmatic trials and applicability, and our experiences in conducting pragmatic trials. Recommendations We recommend extending eight CONSORT checklist items for reporting of pragmatic trials: the background, participants, interventions, outcomes, sample size, blinding, participant flow, and generalisability of the findings. These extensions are presented, along with illustrative examples of reporting, and an explanation of each extension. Adherence to these reporting criteria will make it easier for decision makers to judge how applicable the results of randomised controlled trials are to their own conditions. Empirical studies are needed to ascertain the usefulness and comprehensiveness of these CONSORT checklist item extensions. In the meantime we recommend that those who support, conduct, and report pragmatic trials should use this extension of the CONSORT statement to facilitate the use of trial results in decisions about health care.
Another Brick in the Wall … no More! Breaking the Sex Bias De Paoli, M.; Gardner, H.R.; Treweek, S.
Clinical oncology (Royal College of Radiologists (Great Britain)),
December 2022, 2022-12-00, 20221201, Letnik:
34, Številka:
12
Journal Article
Aim
To establish patient factors associated with a successful colon capsule endoscopy (CCE) test.
Method
This prospective cohort study used data collected from patients who underwent CCE as part of ...the ScotCap evaluation prior to April 2020. A CCE was defined as successful if the capsule visualized the whole colon and rectum (complete test) with sufficient bowel cleansing to permit assessment of the colonic mucosa (adequate bowel preparation). Factors from patients in symptomatic and surveillance groups were analysed for associations with a successful test, complete test, adequate bowel preparation and requirement for further procedure using univariate, multivariate logistic, least absolute shrinkage and selection operator regression.
Results
Data from 263 symptomatic and 137 surveillance patients were analysed. There was an association between a symptomatic patient's age and a successful test (OR = 0.97, 95% CI: 0.95–0.99), adequate bowel preparation (OR = 0.97, 95% CI: 0.94–1.00) and further procedure requirement (OR = 1.04, 95% CI: 1.02–1.06). An association was found, for symptomatic patients, between a faecal immunochemical test result in the range 10–399 μg/g and a further procedure (OR = 2.32, 95% CI: 1.23–4.48). In patients undergoing surveillance for previous colorectal cancer (OR = 0.42, 95% CI: 0.18–0.97), had previous bowel resection surgery (OR = 0.43, 95% CI: 0.19–0.98) or took a beta blocker medication (OR = 0.32, 95% CI: 0.11–0.88), an association was found with further procedure requirement.
Conclusions
Among symptomatic patients, younger age was associated with obtaining a successful CCE test. Clinicians could consider patient selection based on these results to improve the rate of successful testing in clinical practice.
Suboptimal or slow recruitment affects 30-50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled ...trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN.
TRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3) intervention acceptability assessments with recruiters to neonatal trials.
TRAIN, accompanied by a comprehensive intervention manual, has been designed for online or in-person delivery. TRAIN can be offered to recruiters before trial recruitment begins or as refresher sessions during a trial. The intervention consists of five core learning outcomes which are addressed across three core training units. These units are the trial protocol (Unit 1, 50 min, trial-specific), understanding randomisation (Unit 2, 5 min, trial-generic) and approaching and engaging with parents (Unit 3, 70 min, trial-generic). Eleven recruiters to neonatal trials registered to attend the acceptability assessment training workshops, although only four took part. All four positively valued the training Units and resources for increasing recruiter preparedness, knowledge, and confidence. More flexibility in how the training is facilitated, however, was noted (e.g., training divided across two workshops of shorter duration). Units 2 and 3 were considered beneficial to incorporate into Good Clinical Practice Training or as part of induction training for new staff joining neonatal units.
TRAIN offers a comprehensive co-produced training and education intervention for recruiters to neonatal trials. TRAIN was deemed acceptable, with minor modification, to neonatal trial recruiters. The small number of recruiters taking part in the acceptability assessment is a limitation. Scale-up of TRAIN with formal piloting and testing for effectiveness in a large cluster randomised trial is required.
Evidence to support decisions on trial processes is minimal. One way to generate this evidence is to use a Study Within A Trial (SWAT) to test trial processes or explore methodological uncertainties. ...SWAT evidence relies on replication to ensure sufficient power and broad applicability of findings. Prompt reporting is therefore essential; however, SWAT publications are often the first to be abandoned in the face of other time pressures. Reporting guidance for embedded methodology trials does exist but is not widely used. We sought therefore to build on these guidelines to develop a straightforward, concise reporting standard, which remains adherent to the CONSORT guideline.
An iterative process was used to develop the guideline. This included initial meetings with key stakeholders, development of an initial guideline, pilot testing of draft guidelines, further iteration and pilot testing, and finalisation of the guideline.
We developed a reporting guideline applicable to randomised SWATs, including replications of previous evaluations. The guideline follows the Consolidated Standards for Reporting Trials (CONSORT) statement and provides example text to ensure ease and clarity of reporting across all domains.
The SWAT reporting guideline will aid authors, reviewers, and journal editors to produce and review clear, structured reports of randomised SWATs, whilst also adhering to the CONSORT guideline.
EQUATOR Network - Guidelines Under Development ( https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials/#SWAT ). Registered on 25 March 2021.
Urinary incontinence (UI) is highly prevalent in nursing and residential care homes (CHs) and profoundly impacts on residents' dignity and quality of life. CHs predominantly use absorbent pads to ...contain UI rather than actively treat the condition. Transcutaneous posterior tibial nerve stimulation (TPTNS) is a non-invasive, safe and low-cost intervention with demonstrated effectiveness for reducing UI in adults. However, the effectiveness of TPTNS to treat UI in older adults living in CHs is not known. The ELECTRIC trial aims to establish if a programme of TPTNS is a clinically effective treatment for UI in CH residents and investigate the associated costs and consequences.
This is a pragmatic, multicentre, placebo-controlled, randomised parallel-group trial comparing the effectiveness of TPTNS (target n = 250) with sham stimulation (target n = 250) in reducing volume of UI in CH residents. CH residents (men and women) with self- or staff-reported UI of more than once per week are eligible to take part, including those with cognitive impairment. Outcomes will be measured at 6, 12 and 18 weeks post randomisation using the following measures: 24-h Pad Weight Tests, post void residual urine (bladder scans), Patient Perception of Bladder Condition, Minnesota Toileting Skills Questionnaire and Dementia Quality of Life. Economic evaluation based on a bespoke Resource Use Questionnaire will assess the costs of providing a programme of TPTNS. A concurrent process evaluation will investigate fidelity to the intervention and influencing factors, and qualitative interviews will explore the experiences of TPTNS from the perspective of CH residents, family members, CH staff and managers.
TPTNS is a non-invasive intervention that has demonstrated effectiveness in reducing UI in adults. The ELECTRIC trial will involve CH staff delivering TPTNS to residents and establish whether TPTNS is more effective than sham stimulation for reducing the volume of UI in CH residents. Should TPTNS be shown to be an effective and acceptable treatment for UI in older adults in CHs, it will provide a safe, low-cost and dignified alternative to the current standard approach of containment and medication.
ClinicalTrials.gov, NCT03248362. Registered on 14 August 2017. ISRCTN, ISRCTN98415244. Registered on 25 April 2018. https://www.isrctn.com/.
Melanoma is common; 15,906 people in the UK were diagnosed with melanoma in 2015 and incidence has increased fivefold in 30 years. Melanoma affects old and young people, with poor prognosis once ...metastatic. UK guidelines recommend people treated for cutaneous melanoma receive extended outpatient, hospital follow up to detect recurrence or new primaries. Such follow up of the growing population of melanoma survivors is burdensome for both individuals and health services. Follow up is important since approximately 20% of patients with early-stage melanoma experience a recurrence and 4-8% develop a new primary; the risk of either is highest in the first 5 years. Achieving Self-directed Integrated Cancer Aftercare (ASICA) is a digital intervention to increase total-skin-self-examination (TSSE) by people treated for melanoma, with usual follow up.
We aim to recruit 240 adults with a previous first-stage 0-2C primary cutaneous melanoma, from secondary care in North-East Scotland and the East of England. Participants will be randomised to receive the ASICA intervention (a tablet-based digital intervention to prompt and support TSSE) or control group (treatment as usual). Patient-reported and clinical data will be collected at baseline, including the modified Melanoma Worry Scale (MWS), the Hospital Anxiety and Depression Scale (HADs), the EuroQoL 5-dimension 5-level questionnaire (EQ-5D-5 L), and questions about TSSE practice, intentions, self-efficacy and planning. Participants will be followed up by postal questionnaire at 3, 6 and 12 months following randomization, along with a 12-month review of clinical data. The primary timepoint for outcome analyses will be12 months after randomisation.
If the ASICA intervention improves the practice of TSSE in those affected by melanoma, this may lead to improved psychological well-being and earlier detection of recurrent and new primary melanoma. This could impact both patients and National Health Service (NHS) resources. This study will determine if a full-scale randomised controlled trial can be undertaken in the UK NHS to provide the high-quality evidence needed to determine the effectiveness of the intervention. ASICA is a pilot study evaluating the effectiveness of the practice of digitally supported TSSE in those affected by melanoma.
Clinical Trials.gov, NCT03328247 . Registered on 1 November 2017.
EuroFIT is a gender-sensitised, health and lifestyle program targeting physical activity, sedentary time and dietary behaviours in men. The delivery of the program in football clubs, led by the ...clubs' community coaches, is designed to both attract and engage men in lifestyle change through an interest in football or loyalty to the club they support. The EuroFIT program will be evaluated in a multicentre pragmatic randomised controlled trial (RCT), for which ~1000 overweight men, aged 30-65 years, will be recruited in 15 top professional football clubs in the Netherlands, Norway, Portugal and the UK. The process evaluation is designed to investigate how implementation within the RCT is achieved in the various football clubs and countries and the processes through which EuroFIT affects outcomes.
This mixed methods evaluation is guided by the Medical Research Council (MRC) guidance for conducting process evaluations of complex interventions. Data will be collected in the intervention arm of the EuroFIT trial through: participant questionnaires (n = 500); attendance sheets and coach logs (n = 360); observations of sessions (n = 30); coach questionnaires (n = 30); usage logs from a novel device for self-monitoring physical activity and non-sedentary behaviour (SitFIT); an app-based game to promote social support for physical activity outside program sessions (MatchFIT); interviews with coaches (n = 15); football club representatives (n = 15); and focus groups with participants (n = 30). Written standard operating procedures are used to ensure quality and consistency in data collection and analysis across the participating countries. Data will be analysed thematically within datasets and overall synthesis of findings will address the processes through which the program is implemented in various countries and clubs and through which it affects outcomes, with careful attention to the context of the football club.
The process evaluation will provide a comprehensive account of what was necessary to implement the EuroFIT program in professional football clubs within a trial setting and how outcomes were affected by the program. This will allow us to re-appraise the program's conceptual base, optimise the program for post-trial implementation and roll out, and offer suggestions for the development and implementation of future initiatives to promote health and wellbeing through professional sports clubs.
ISRCTN81935608 . Registered on 16 June 2015.
Abstract
Background
Myotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (
DMPK
) gene. The OPTIMISTIC clinical trial ...demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Through a process of reverse engineering, this study aims to identify druggable molecular biomarkers associated with the clinical improvement in the OPTIMISTIC cohort.
Methods
Based on full blood samples collected during OPTIMISTIC, we performed paired mRNA sequencing for 27 patients before and after the CBT intervention. Linear mixed effect models were used to identify biomarkers associated with the disease-causing CTG expansion and the mean clinical improvement across all clinical outcome measures.
Results
We identified 608 genes for which their expression was significantly associated with the CTG-repeat expansion, as well as 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes associated with both returned to more normal levels in patients who benefited the most from CBT. This main finding has been replicated based on an external dataset of mRNA data of DM1 patients and controls, singling these genes out as candidate biomarkers for therapy response. Among these candidate genes were
DNAJB12
,
HDAC5
, and
TRIM8
, each belonging to a protein family that is being studied in the context of neurological disorders or muscular dystrophies. Across the different gene sets, gene pathway enrichment analysis revealed disease-relevant impaired signaling in, among others, insulin-, metabolism-, and immune-related pathways. Furthermore, evidence for shared dysregulations with another neuromuscular disease, Duchenne muscular dystrophy, was found, suggesting a partial overlap in blood-based gene dysregulation.
Conclusions
DM1-relevant disease signatures can be identified on a molecular level in peripheral blood, opening new avenues for drug discovery and therapy efficacy assessments.
Pregnancy is a life stage where excess weight gain may occur and the postpartum period is often characterised by weight retention. The aim of the current study was to evaluate the feasibility of ...undertaking a randomised controlled trial of a weight loss intervention (WeighWell) in postpartum women living in areas of social disadvantage.
The study aimed to recruit 60 women who were not pregnant, 6-18 months postpartum with a body mass index >25 kg/m(2) living in areas of deprivation within Tayside, UK. Recruitment strategies focused on visits to community groups; writing directly to postpartum women living in areas of deprivation and primary care teams who covered the most deprived 15% of the population and advertising in community settings. The 12-week intervention used motivational interviewing techniques to promote an energy deficit diet and increased physical activity, delivered by three face-to-face consultations plus three structured telephone calls.
Of 142 women screened, 63 were eligible and 52 (83%) were recruited and randomised to an intervention (n=29) or comparison group (n=23). Over the 12-week intervention, body weight changed significantly by -1.6 ± 2.0 kg in the intervention group compared with +0.2 ± 2.2 kg in the comparison group, indicating the potential efficacy of the intervention. Loss to follow-up was 24% in the intervention group and 39% for the comparison group.
The findings support the development of a definitive trial that embraces personalised recruitment strategies and the development of approaches to improve retention over a clinically relevant intervention period.
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