Approaches and experiences implementing remote, electronic consent at the Leeds Clinical Trials Research Unit.

BACKGROUND: Use of electronic methods to support informed consent ('eConsent') is increasingly popular in clinical research. This commentary reports the approach taken to implement electronic consent methods and subsequent experiences from a range of studies at the Leeds Clinical Trials Research Unit (CTRU), a large clinical trials unit in the UK. MAIN TEXT: We implemented a remote eConsent process using the REDCap platform. The process can be used in trials of investigational medicinal products and other intervention types or research designs. Our standard eConsent system focuses on documenting informed consent, with other aspects of consent (e.g. providing information to potential participants and a recruiter discussing the study with each potential participant) occurring outside the system, though trial teams can use electronic methods for these activities where they have ethical approval. Our overall process includes a verbal consent step prior to confidential information being entered onto REDCap and an identity verification step in line with regulator guidance. We considered the regulatory requirements around the system's generation of source documents, how to ensure data protection standards were upheld and how to monitor informed consent within the system. We present four eConsent case studies from the CTRU: two randomised clinical trials and two other health research studies. These illustrate the ways eConsent can be implemented, and lessons learned, including about differences in uptake. CONCLUSIONS: We successfully implemented a remote eConsent process at the CTRU across multiple studies. Our case studies highlight benefits of study participants being able to give consent without having to be present at the study site. This may better align with patient preferences and trial site needs and therefore improve recruitment and resilience against external shocks (such as pandemics). Variation in uptake of eConsent may be influenced more by site-level factors than patient preferences, which may not align well with the aspiration towards patient-centred research. Our current process has some limitations, including the provision of all consent-related text in more than one language, and scalability of implementing more than one consent form version at a time. We consider how enhancements in CTRU processes, or external developments, might affect our approach.

Posterior cervical foraminotomy versus anterior cervical discectomy for Cervical Brachialgia: the FORVAD RCT.

Background: Posterior cervical foraminotomy and anterior cervical discectomy are routinely used operations to treat cervical brachialgia, although definitive evidence supporting superiority of either is lacking. Objective: The primary objective was to investigate whether or not posterior cervical foraminotomy is superior to anterior cervical discectomy in improving clinical outcome. Design: This was a Phase III, unblinded, prospective, United Kingdom multicentre, parallel-group, individually randomised controlled superiority trial comparing posterior cervical foraminotomy with anterior cervical discectomy. A rapid qualitative study was conducted during the close-down phase, involving remote semistructured interviews with trial participants and health-care professionals. Setting: National Health Service trusts. Participants: Patients with symptomatic unilateral cervical brachialgia for at least 6 weeks. Interventions: Participants were randomised to receive posterior cervical foraminotomy or anterior cervical discectomy. Allocation was not blinded to participants, medical staff or trial staff. Health-care use from providing the initial surgical intervention to hospital discharge was measured and valued using national cost data. Main outcome measures: The primary outcome measure was clinical outcome, as measured by patient-reported Neck Disability Index score 52 weeks post operation. Secondary outcome measures included complications, reoperations and restricted American Spinal Injury Association score over 6 weeks post operation, and patient-reported Eating Assessment Tool-10 items, Glasgow-Edinburgh Throat Scale, Voice Handicap Index-10 items, PainDETECT and Numerical Rating Scales for neck and upper-limb pain over 52 weeks post operation. Results: The target recruitment was 252 participants. Owing to slow accrual, the trial closed after randomising 23 participants from 11 hospitals. The qualitative substudy found that there was support and enthusiasm for the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial and randomised clinical trials in this area. However, clinical equipoise appears to have been an issue for sites and individual surgeons. Randomisation on the day of surgery and processes for screening and approaching participants were also crucial factors in some centres. The median Neck Disability Index scores at baseline (pre surgery) and at 52 weeks was 44.0 (interquartile range 36.0-62.0 weeks) and 25.3 weeks (interquartile range 20.0-42.0 weeks), respectively, in the posterior cervical foraminotomy group (n = 14), and 35.6 weeks (interquartile range 34.0-44.0 weeks) and 45.0 weeks (interquartile range 20.0-57.0 weeks), respectively, in the anterior cervical discectomy group (n = 9). Scores appeared to reduce (i.e. improve) in the posterior cervical foraminotomy group, but not in the anterior cervical discectomy group. The median Eating Assessment Tool-10 items score for swallowing was higher (worse) after anterior cervical discectomy (13.5) than after posterior cervical foraminotomy (0) on day 1, but not at other time points, whereas the median Glasgow-Edinburgh Throat Scale score for globus was higher (worse) after anterior cervical discectomy (15, 7, 6, 6, 2, 2.5) than after posterior cervical foraminotomy (3, 0, 0, 0.5, 0, 0) at all postoperative time points. Five postoperative complications occurred within 6 weeks of surgery, all after anterior cervical discectomy. Neck pain was more severe on day 1 following posterior cervical foraminotomy (Numerical Rating Scale - Neck Pain score 8.5) than at the same time point after anterior cervical discectomy (Numerical Rating Scale - Neck Pain score 7.0). The median health-care costs of providing initial surgical intervention were £2610 for posterior cervical foraminotomy and £4411 for anterior cervical discectomy. Conclusions: The data suggest that posterior cervical foraminotomy is associated with better outcomes, fewer complications and lower costs, but the trial recruited slowly and closed early. Consequently, the trial is underpowered and definitive conclusions cannot be drawn. Recruitment was impaired by lack of individual equipoise and by concern about randomising on the day of surgery. A large prospective multicentre trial comparing anterior cervical discectomy and posterior cervical foraminotomy in the treatment of cervical brachialgia is still required. Trial registration: This trial is registered as ISRCTN10133661. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 21. See the NIHR Journals Library website for further project information.

Cervical brachialgia is pain that starts in the neck and passes down into the arm. Although most people with cervical brachialgia recover quickly, in some patients pain persists, and in 15% of patients pain is so severe that they are unable to work. In the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial, we investigated two neck surgeries used to treat this problem: posterior cervical foraminotomy (surgery from the back of the neck) and anterior cervical discectomy (surgery from the front of the neck). This trial aimed to find out if one of them is better than the other at relieving pain and more cost-effective for the National Health Service. We assessed patients' quality of life 1 year after their surgery and how their pain changed over the course of the year. We also measured the number of complications patients had in the first 6 weeks after their operation. Recruitment was slow and so the trial was stopped early, after only 23 patients from 11 hospitals had been randomly allocated to the two surgery groups. We had planned to recruit 252 participants to the trial; the number of participants we were able to recruit in practice was too small to enable us to determine which surgery is better at relieving pain. To find out why the trial had struggled to recruit, we asked hospital staff and participants about their experiences. We found that hospital staff sometimes struggled to organise everything needed to randomise patients on the day of surgery. Some staff also found it difficult to randomise patients as they had an opinion on which surgery they thought the patient should receive. The data collected in the trial will still be useful to help design future research. Finding out which surgery is better at relieving pain remains important, and the data we have collected will support answering this question in future.

Pressure Relieving Support Surfaces: a Randomised Evaluation 2 (PRESSURE 2): using photography for blinded central endpoint review.

BACKGROUND: PRESSURE 2 is a randomised evaluation of the clinical and cost-effectiveness of two types of mattress for the prevention of pressure ulcers (PUs). The primary clinical endpoint was time to development of a category ≥2 PU. The current 'gold standard' for PU identification is expert clinical assessment. Due to the mattress appearance, a blinded assessment of the endpoint is not possible. This poses a risk to the internal validity of the study. A possible approach is to use photographs of skin sites, with central blinded review. However, there are practical and scientific concerns including patients' consent to photographs, burden of data collection, photograph quality, data completeness and comparison of photographs to the current 'gold standard'. This paper reports the findings of the PRESSURE 2 photographic validation sub-study. METHOD: Where consent was obtained, photographs were taken of all category ≥2 PUs on the first presentation to assess over-reporting, and for the assessment of under-reporting, a random sample of 10% patients had an assessment by an independent clinical assessor who also photographed two skin sites. The staff were trained in taking and transferring photographs using standardised procedures and equipment. A card included in the photograph recorded participant details and a 'greyscale' for correction of white balance during processing. Three blinded reviewers assessed the photographs and rated how confident they were in their assessment. RESULTS: The trial recruited 2029 patients; 85% consented to photography, and 532 photographs were received and used in the blinded central review. The level of confidence varied by skin classification with more confidence observed when the skin was assessed as being less severe than a category ≥2 PU. Overall, there was a very good reliability compared to the gold standard expert clinical assessment (87.8%, kappa 0.82). CONCLUSION: Study findings have usefully informed the scientific and practical issues of blinded assessment of PU status to reducing the risk of bias in medical device trials. The reliability of central blinded expert photography was found to be 'very good' (PABAK). Photographs have been found to be an acceptable method of data validation for participants. Methods to improve the quality of photographs would increase the confidence in the assessments. TRIAL REGISTRATION: ISRCTN Registry ISRCTN01151335 . Registered on 19 April 2013.

Multiple Interventions for Diabetic Foot Ulcer Treatment Trial (MIDFUT): study protocol for a randomised controlled trial.

INTRODUCTION: Diabetes affects more than 425 million people worldwide with a lifetime risk of diabetic foot ulcer (DFU) of up to 25%. Management includes wound debridement, wound dressings, offloading, treatment of infection and ischaemia, optimising glycaemic control; use of advanced adjuvant therapies is limited by high cost and lack of robust evidence. METHODS AND ANALYSIS: A multicentre, seamless phase II/III, open, parallel group, multi-arm multi-stage randomised controlled trial in patients with a hard-to-heal DFU, with blinded outcome assessment. A maximum of 447 participants will be randomised (245 participants in phase II and 202 participants in phase III). The phase II primary objective will determine the efficacy of treatment strategies including hydrosurgical debridement ± decellularised dermal allograft, or the combination with negative pressure wound therapy, as an adjunct to treatment as usual (TAU), compared with TAU alone, with patients randomised in a 1:1:1:2 allocation. The outcome is achieving at least 50% reduction in index ulcer area at 4 weeks post randomisation.The phase III primary objective will determine whether one treatment strategy, continued from phase II, reduces time to healing of the index ulcer compared with TAU alone, with participants randomised in a 1:1 allocation. Secondary objectives will compare healing status of the index ulcer, infection rate, reulceration, quality of life, cost-effectiveness and incidence of adverse events over 52 weeks post randomisation. Phase II and phase III primary endpoint analysis will be conducted using a mixed-effects logistic regression model and Cox proportional hazards regression, respectively. A within-trial economic evaluation will be undertaken; the primary economic analysis will be a cost-utility analysis presenting ICERs for each treatment strategy in rank order of effectiveness, with effects expressed as quality-adjusted life years.The trial has predefined progression criteria for the selection of one treatment strategy into phase III based on efficacy, safety and costs at 4 weeks. ETHICS AND DISSEMINATION: Ethics approval has been granted by the National Research Ethics Service (NRES) Committee Yorkshire and The Humber - Bradford Leeds Research Ethics Committee; approved 26 April 2017; (REC reference: 17/YH/0055). There is planned publication of a monograph in National Institute for Health Research journals and main trial results and associated papers in high-impact peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN64926597; registered on 6 June 2017.

Pressure Relieving Support Surfaces for Pressure Ulcer Prevention (PRESSURE 2): Clinical and Health Economic Results of a Randomised Controlled Trial.

BACKGROUND: Pressure ulcers (PUs) are complications of serious acute/chronic illness. Specialist mattresses used for prevention lack high quality effectiveness evidence. We aimed to compare clinical and cost effectiveness of 2 mattress types. METHODS: Multicentre, Phase III, open, prospective, parallel group, randomised controlled trial in 42 UK secondary/community in-patient facilities.2029 high risk (acutely ill, bedfast/chairfast and/or Category 1 PU/pain at PU site) adult in-patients were randomised (1:1, allocation concealment, minimisation with random element) factors including: centre, PU status, facility and consent type. Interventions were alternating pressure mattresses (APMs) or high specification foam (HSF) for maximum treatment phase 60 days. Primary outcome was time to development of new PU Category ≥ 2 from randomisation to 30 day post-treatment follow-up in intention-to treat population. Trial registration: ISRCTN 01151335. FINDINGS: Between August 2013 and November 2016, we randomised 2029 patients (1016 APMs: 1013 HSF) who developed 160(7.9%) PUs. There was insufficient evidence of a difference between groups for time to new PU Category ≥ 2 Fine and Gray Model Hazard Ratio HR = 0.76, 95%CI0.56-1.04); exact P = 0.0890; absolute difference 2%). There was a statistically significant difference in the treatment phase time to event sensitivity analysis, Fine and Gray model HR = 0.66, 95%CI, 0.46-0.93; exact P = 0.0176); 2.6% absolute difference). Economic analyses indicate that APM are cost-effective.There were no safety concerns. INTERPRETATION: In high risk (acutely ill, bedfast/chairfast/Category 1 PU/ pain on a PU site) in-patients, we found insufficient evidence of a difference in time to PU development at 30-day final follow-up, which may be related to a low event rate affecting trial power. APMs conferred a small treatment phase benefit. Patient preference, low PU incidence and small group differences suggests the need for improved targeting of APMs with decision making informed by patient preference/comfort/rehabilitation needs and the presence of potentially modifiable risk factors such as being completely immobile, nutritional deficits, lacking capacity and/or altered skin/Category1 PU.

Comparing alternating pressure mattresses and high-specification foam mattresses to prevent pressure ulcers in high-risk patients: the PRESSURE 2 RCT.

BACKGROUND: Pressure ulcers (PUs) are a burden to patients, carers and health-care providers. Specialist mattresses minimise the intensity and duration of pressure on vulnerable skin sites in at-risk patients. PRIMARY OBJECTIVE: Time to developing a new PU of category ≥ 2 in patients using an alternating pressure mattress (APM) compared with a high-specification foam mattress (HSFM). DESIGN: A multicentre, Phase III, open, prospective, planned as an adaptive double-triangular group sequential, parallel-group, randomised controlled trial with an a priori sample size of 2954 participants. Randomisation used minimisation (incorporating a random element). SETTING: The trial was set in 42 secondary and community inpatient facilities in the UK. PARTICIPANTS: Adult inpatients with evidence of acute illness and at a high risk of PU development. INTERVENTIONS AND FOLLOW-UP: APM or HSFM - the treatment phase lasted a maximum of 60 days; the final 30 days were post-treatment follow-up. MAIN OUTCOME MEASURES: Time to event. RESULTS: From August 2013 to November 2016, 2029 participants were randomised to receive either APM (n = 1016) or HSFM (n = 1013). Primary end point - 30-day final follow-up: of the 2029 participants in the intention-to-treat population, 160 (7.9%) developed a new PU of category ≥ 2. There was insufficient evidence of a difference between groups for time to new PU of category ≥ 2 [Fine and Gray model HR 0.76, 95% confidence interval (CI) 0.56 to 1.04; exact p-value of 0.0890 and 2% absolute difference]. Treatment phase sensitivity analysis: 132 (6.5%) participants developed a new PU of category ≥ 2 between randomisation and end of treatment phase. There was a statistically significant difference in the treatment phase time-to-event sensitivity analysis (Fine and Gray model HR 0.66, 95% CI 0.46 to 0.93; p = 0.0176 and 2.6% absolute difference). Secondary end points - 30-day final follow-up: new PUs of category ≥ 1 developed in 350 (17.2%) participants, with no evidence of a difference between mattress groups in time to PU development, (Fine and Gray model HR 0.83, 95% CI 0.67 to 1.02; p-value = 0.0733 and absolute difference 3.1%). New PUs of category ≥ 3 developed in 32 (1.6%) participants with insufficient evidence of a difference between mattress groups in time to PU development (Fine and Gray model HR 0.81, 95% CI 0.40 to 1.62; p = 0.5530 and absolute difference 0.4%). Of the 145 pre-existing PUs of category 2, 89 (61.4%) healed - there was insufficient evidence of a difference in time to healing (Fine and Gray model HR 1.12, 95% CI 0.74 to 1.68; p = 0.6122 and absolute difference 2.9%). Health economics - the within-trial and long-term analysis showed APM to be cost-effective compared with HSFM; however, the difference in costs models are small and the quality-adjusted life-year gains are very small. There were no safety concerns. Blinded photography substudy - the reliability of central blinded review compared with clinical assessment for PUs of category ≥ 2 was 'very good' (kappa statistic 0.82, prevalence- and bias-adjusted kappa 0.82). Quality-of-life substudy - the Pressure Ulcer Quality of Life - Prevention (PU-QoL-P) instrument meets the established criteria for reliability, construct validity and responsiveness. LIMITATIONS: A lower than anticipated event rate. CONCLUSIONS: In acutely ill inpatients who are bedfast/chairfast and/or have a category 1 PU and/or localised skin pain, APMs confer a small treatment phase benefit that is diminished over time. Overall, the APM patient compliance, very low PU incidence rate observed and small differences between mattresses indicate the need for improved indicators for targeting of APMs and individualised decision-making. Decisions should take into account skin status, patient preferences (movement ability and rehabilitation needs) and the presence of factors that may be potentially modifiable through APM allocation, including being completely immobile, having nutritional deficits, lacking capacity and/or having altered skin/category 1 PU. FUTURE WORK: Explore the relationship between mental capacity, levels of independent movement, repositioning and PU development. Explore 'what works for whom and in what circumstances'. TRIAL REGISTRATION: Current Controlled Trials ISRCTN01151335. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 52. See the NIHR Journals Library website for further project information.

Pressure ulcers (PUs) are patches of damaged skin, mainly caused by sitting/lying in one position. PUs are graded based on how serious they are, ranging from red patches (category 1) through small skin breaks/blisters (category 2) to serious wounds (category 4). Special mattresses are used to help prevent PUs. This study compared alternating pressure mattresses (APMs) with high-specification foam mattresses (HSFMs), to see which is better at preventing PUs. The study included adults admitted to hospital for acute illness who were at a high risk of developing PUs. Patients were randomly allocated to HSFM or APM. Nurses checked patients' skin and recorded changes. A total of 132 patients developed at least one new PU of category ≥ 2 before the end of treatment (60 days maximum). Of these, 53 patients were allocated to the APM arm and 79 to the HSFM arm, a difference of 2.6%. This is a small but significant difference. Nurses looked at patients' skin again 30 days after the patient had stopped using a trial mattress. At this point, 160 patients had at least one new PU (of category ≥ 2). Of these, 70 patients were allocated to the APM arm and 90 to the HSFM arm, a very small difference of 2.0%. Some patients asked to change mattresses; this happened more in the APM group. This study focused on high-risk patients; however, only a small number of people developed PUs, suggesting that prevention is possible with either mattress. Results also suggest that certain groups of patients may benefit more from APMs, for example people who cannot give consent or who have skin redness. When planning prevention and choosing mattresses, professionals and patients need to consider a number of factors, such as comfort, existing PUs and people's ability to self-care. Further research is recommended to understand what sort of prevention works, for whom and in what circumstances.

Comparison of generic and disease-specific measures in their ability to detect differences in pressure ulcer clinical groups.

Patient-reported outcomes can be included as end points in pressure ulcer (PU) intervention trials to provide information to inform decision-making and improve the lives of patients. However, the challenge for researchers and clinicians is identifying and choosing an appropriate instrument for each particular application that suits their research questions and clinical context. To provide researchers and clinicians with the information needed to inform choice of patient-reported outcome measures, we compared a generic and disease-specific measures' ability to discriminate between clinical groups known to differ, and determined their responsiveness to change. We performed analyses on a subset of patients recruited to the PRESSURE 2 trial that completed the pressure ulcer quality of life instrument-prevention version (PU-QOL-P) and Short Form 12 Questionnaire (SF12) measures at baseline and 30-day posttreatment. Known-group validity and responsiveness-to-change analyses were conducted. The analysis sample consisted of 617 patients that completed both measures at baseline. Known-group validity revealed that some PU-QOL-P symptoms and function scales differentiated between people with category 2 PUs and those without PUs. A less meaningful pattern of results was observed for the SF12 scales, suggesting that the PU-QOL-P is more sensitive to differences between PU and non-PU populations. Responsiveness analysis revealed that the PU-QOL-P was more responsive in detecting disease severity than the SF12. The PU-QOL-P provides a standardized method for assessing PU-specific symptoms and functioning outcomes and is suitable for quantifying the benefits of PU interventions from the patient's perspective. Generic measures are useful for group comparisons of global quality of life domains. Choice of measure for each particular application should be determined by the purpose of the measurement and the information required.

A patient-reported pressure ulcer health-related quality of life instrument for use in prevention trials (PU-QOL-P): psychometric evaluation.

INTRODUCTION: Pressure ulcer-specific patient-reported outcome (PRO) instruments should be used to inform patient care and provide a strong evidence base for interventions aimed at preventing pressure ulcers. The aim was to carry out a comprehensive evaluation of the psychometric properties of a PRO instrument designed to assess symptoms and functional outcomes in patients at high-risk of developing pressure ulcers, the PU-QOL-P instrument. METHODS: We modified the original PU-QOL instrument to be suitable for patients at high risk of pressure ulcer development based on feedback from patients, specialist nurses and PRO methodologists. The modified PU-QOL-P instrument was administered to a sub-set of patients participating in the PRESSURE 2 trial. Patients completed PU-QOL-P and SF12 instruments at baseline, weeks 1 and 3, and 30 days post-treatment. We undertook psychometric evaluation of the modified PU-QOL-P to test scale targeting, scaling assumptions, reliability, validity and responsiveness. RESULTS: The analysis sample consisted of 617 patients that completed both instruments at baseline. We found that the PU-QOL-P instrument, consisting of nine PU-specific outcomes: three symptom and six function scales, meets established criteria for reliability, construct validity, and responsiveness. Internal consistency reliability was high with all scale Cronbach alpha > 0.795 (range 0.795-0.970). The factor analysis mostly supported the six-function scale structure. Scaling assumptions were satisfied; all item-total correlations above 0.30. Convergent validity was confirmed by significant correlations between hypothesized scales as expected. PU-QOL-P scales were responsive to change: mean scale scores from baseline to 30 days post-treatment were statistically significant for all scales apart the daily activities scale (effect sizes ranged from moderate to high). As expected, worse symptoms and functioning was observed in patients who had a category 1 or 2 PU compared to patients who did not have a PU. CONCLUSIONS: The PU-QOL-P provides a standardised method for assessing pressure ulcer-specific symptoms and functional outcomes for quantifying the benefits of associated interventions from the patient's perspective. It can be used in research with adults at risk of pressure ulcer development in all UK healthcare settings.

Pressure RElieving Support SUrfaces: a Randomised Evaluation 2 (PRESSURE 2) photographic validation sub-study: study protocol for a randomised controlled trial.

BACKGROUND: PRESSURE 2 is a randomised evaluation of the clinical and cost effectiveness of two types of pressure relieving mattress for the prevention of pressure ulcers. The primary endpoint is the time to development of a Category ≥2 pressure ulcer. The current 'gold standard' for the identification of a Category ≥2 pressure ulcer is expert clinical assessment. Due to the appearance of the bed, it is not possible to achieve blinding of the endpoint. This therefore poses a risk to the internal validity of the study. A possible approach is to use photographs of skin sites, with central blinded review. However, there are practical and scientific concerns including whether patients would agree to photographs; the burden of data collection; the quality of photographs; the completeness of data; and how the use of photographs compares with the current 'gold standard'. This validation sub-study aims to assess and quantify potential bias in the reporting of the trial endpoint. METHODS/DESIGN: Patients will be specifically asked to consent to photographs being taken of their skin sites. Photographs will be taken at first observation or when patients develop a new Category ≥2 pressure ulcer (to assess over-reporting). A 10% random sample of patients will be identified for additional photographs of two skin sites (one torso and one limb) with and without a pressure ulcer (if present) by an independent assessor (to assess the potential for under-reporting). Staff will be trained to take photographs using a standardised camera and photographic technique. A 'grey scale' will be included in the photo to correct white balance. Photographs will be securely transferred for central review. Photographs will have white balance corrected, and the computer monitor will be calibrated prior to review. Analysis will include assessment of under- and over-reporting, acceptability of photography to patients, secure transfer of data, quality of and confidence in blinded photograph review and sensitivity analysis using photograph assessment of primary outcome. DISCUSSION: This study will use photographs to contribute to the primary outcome of the trial. It will inform our understanding of the acceptability of photography for prevention trials and the possibility of other uses of photographic data in clinical work and research. TRIAL REGISTRATION: ISRCTN, ISRCTN01151335 . Registered on 14 May 2013.

Pressure RElieving Support SUrfaces: a Randomised Evaluation 2 (PRESSURE 2): study protocol for a randomised controlled trial.

BACKGROUND: Pressure ulcers represent a major burden to patients, carers and the healthcare system, affecting approximately 1 in 17 hospital and 1 in 20 community patients. They impact greatly on an individual's functional status and health-related quality of life. The mainstay of pressure ulcer prevention practice is the provision of pressure redistribution support surfaces and patient repositioning. The aim of the PRESSURE 2 study is to compare the two main mattress types utilised within the NHS: high-specification foam and alternating pressure mattresses, in the prevention of pressure ulcers. METHODS/DESIGN: PRESSURE 2 is a multicentre, open-label, randomised, double triangular, group sequential, parallel group trial. A maximum of 2954 'high-risk' patients with evidence of acute illness will be randomised on a 1:1 basis to receive either a high-specification foam mattress or alternating-pressure mattress in conjunction with an electric profiling bed frame. The primary objective of the trial is to compare mattresses in terms of the time to developing a new Category 2 or above pressure ulcer by 30 days post end of treatment phase. Secondary endpoints include time to developing new Category 1 and 3 or above pressure ulcers, time to healing of pre-existing Category 2 pressure ulcers, health-related quality of life, cost-effectiveness, incidence of mattress change and safety. Validation objectives are to determine the responsiveness of the Pressure Ulcer Quality of Life-Prevention instrument and the feasibility of having a blinded endpoint assessment using photography. The trial will have a maximum of three planned analyses with unequally spaced reviews at event-driven coherent cut-points. The futility boundaries are constructed as non-binding to allow a decision for stopping early to be overruled by the Data Monitoring and Ethics Committee. DISCUSSION: The double triangular, group sequential design of the PRESSURE 2 trial will provide an efficient design through the possibility of early stopping for demonstrating either superiority, inferiority of mattresses or futility of the trial. The trial optimises the potential for producing robust clinical evidence on the effectiveness of two commonly used mattresses in clinical practice earlier than in a conventional design. TRIAL REGISTRATION: ISRCTN01151335 . Registered on 14 May 2013. Protocol version: 5.0, dated 25 September 2015 Trial sponsor: Clare Skinner, Faculty Head of Research Support, University of Leeds, Leeds, LS2 9JT; 0113 343 4897; C.E.Skinner@leeds.ac.uk.

The TICOPA protocol (TIght COntrol of Psoriatic Arthritis): a randomised controlled trial to compare intensive management versus standard care in early psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) is estimated to occur in 10-15% of people with psoriasis and accounts for 13% of people attending early arthritis clinics. With an increasing awareness of the poor outcomes associated with PsA and the availability of new effective, but costly, treatments, there is an urgent need to research the optimal treatment for patients with PsA. The aim of the TICOPA study is to establish whether, in treatment naive early PsA patients, "tight control" intensive management with protocol driven therapies and pre-defined objective targets for treatment can improve clinical outcome compared to standard care alone. METHODS/DESIGN: TICOPA is a UK multicentre, open-label, randomised controlled, parallel group trial of 206 patients with early PsA. Patients will be randomised on a 1:1 basis to receive either standard care (12 weekly review) or intensive management (4 weekly review) for a period of 48 weeks. Patients assigned to the intensive management group will follow a strict treatment protocol whereby dose continuation/escalation is determined through the objective assessment of the minimal disease activity (MDA) criteria. Patients assigned to the standard care group will have treatment prescribed as felt appropriate by the treating clinician, with no set protocol. The primary objective of the trial is to compare intensive management with standard care in terms of the proportion of patients achieving an ACR 20 response at 48 weeks post-randomisation, in order to determine whether intensive management has superior clinical efficacy. Key secondary outcomes include ACR 50 and 70, PASI 75 and X-ray Van der Heijde score at 48 weeks post-randomisation along with cost-effectiveness at 12, 24 and 28 weeks. DISCUSSION: The TICOPA trial will provide direct evidence as to whether the use of early and intensive treatment in PsA in routine clinical care leads to an improvement in patients' disease activity and a reduction in radiological joint damage. TRIAL REGISTRATION: ISRCTN30147736, NCT01106079.

IMPROVDENT: improving dentures for patient benefit. A crossover randomised clinical trial comparing impression materials for complete dentures.

BACKGROUND: According to the UK Adult Dental Health Survey (2009) 15% of adults aged 65-74, 30% aged 75-84 and 47% aged >85 years are edentulous and require complete dentures. Patients' quality of life and nutrition status are affected by poor dentures. The quality of the dental impression is the most important issue for improving the fit and comfort of new dentures. There is paucity of RCT evidence for which impression material is best for complete dentures construction. This study aims to compare two impression materials for effectiveness and cost effectiveness. METHODS/DESIGN: IMPROVDENT is a double-blind crossover trial comparing the use of alginate and silicone, two commonly used denture impression materials, in terms of patient preference and cost-effectiveness. Eighty five edentulous patients will be recruited and provided with two sets of dentures, similar in all aspects except for the impression material used (alginate or silicone). Patients will try both sets of dentures for a two-week period, unadjusted, to become accustomed to the feel of the new dentures (habituation period). Patients will then wear each set of dentures for a period of 8 weeks (in random order) during which time the dentures will be adjusted for optimum comfort. Finally, patients will be given both sets of dentures for a further two weeks to wear whichever denture they prefer (confirmation period).Patients will be asked about quality of life and to rate dentures on function and comfort at the end of each trial period and asked which set they prefer at the end of the habituation period (unadjusted denture preference) and confirmation period (adjusted denture preference). A health economic evaluation will estimate incremental cost-effectiveness ratios of producing dentures from the two materials. A qualitative study will investigate the impact of dentures on behaviour and quality of life. FUNDING: IMPROVDENT is funded by NIHR RfPB (PB-PG-0408-16300). DISCUSSION: This trial aims to provide evidence on the costs and quality of dentures cast from two different commonly used impression materials; the intention is to significantly impact on the quality of denture production within NHS dentistry. TRIAL REGISTRATION: ISRCTN Register: ISRCTN01528038 UKCRN Portfolio ID: 8305.

Pressure and pain in systemic sclerosis/scleroderma--an evaluation of a simple intervention (PISCES): randomised controlled trial protocol.

BACKGROUND: Foot problems associated with Systemic Sclerosis (SSc)/Scleroderma have been reported to be both common and disabling. There are only limited data describing specifically, the mechanical changes occurring in the foot in SSc. A pilot project conducted in preparation for this trial confirmed the previous reports of foot related impairment and reduced foot function in people with SSc and demonstrated a link to mechanical etiologies. To-date there have been no formal studies of interventions directed at the foot problems experienced by people with Systemic Sclerosis. The primary aim of this trial is to evaluate whether foot pain and foot-related health status in people with Systemic Sclerosis can be improved through the provision of a simple pressure-relieving insole. METHODS: The proposed trial is a pragmatic, multicenter, randomised controlled clinical trial following a completed pilot study. In four participating centres, 140 consenting patients with SSc and plantar foot pain will be randomised to receive either a commercially available pressure relieving and thermally insulating insole, or a sham insole with no cushioning or thermal properties. The primary end point is a reduction in pain measured using the Foot Function Index Pain subscale, 12 weeks after the start of intervention. Participants will complete the primary outcome measure (Foot Function Index pain sub-scale) prior to randomisation and at 12 weeks post randomisation. Secondary outcomes include participant reported pain and disability as derived from the Manchester Foot Pain and Disability Questionnaire and plantar pressures with and without the insoles in situ. DISCUSSION: This trial protocol proposes a rigorous and potentially significant evaluation of a simple and readily provided therapeutic approach which, if effective, could be of a great benefit for this group of patients. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN02824122.