e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.

BACKGROUND: During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent. METHODS: A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research. RESULTS: Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions. CONCLUSION: e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.

Longer-term effectiveness of systemic family therapy compared with treatment as usual for young people after self-harm: An extended follow up of pragmatic randomised controlled trial.

BACKGROUND: Self-harm in adolescents is common and repetition frequent. Evidence for effective interventions to reduce self-harm is limited. Long term follow-up of existing studies is rare. METHODS: Extended follow up, from 18 to at least 36-months, of the SHIFT trial: a pragmatic, multi-centre, individually-randomised, controlled trial involving young people (11-17) who had self-harmed at least twice and presented to Child & Adolescent Mental Health Services (CAMHS). SHIFT evaluated manualised family therapy (FT) versus treatment as usual (TAU) in reducing repetition of self-harm leading to hospital attendance 18 months post-randomisation.We obtained ONS mortality data, adult mental health data, and further details of hospital attendance from routine Hospital Episode Statistics (HES) data plus researcher follow-up. We assessed longer-term differences in outcome using multivariable Cox Proportional Hazards regression analysis, and assessed all-cause mortality and morbidity relating to hospital attendances for reasons other than self-harm. STUDY REGISTRATION: ISRCTN 59793150. OUTCOMES: The original sample of 832 were randomised between April 2010 and December 2013. Extended follow-up continued until February 2017 for a median 55·4 months (range 0-82·5 months), providing post 18-month data for 804 (96·6%) participants, of whom 785 (94·4%) had a minimum of 36-months follow-up.There was no evidence of a between-group difference in the primary outcome during the extended follow-up period (Hazard Ratio (HR) 1·03; 95% CI: 0·83, 1·28; p-value=0·78), consistent with our findings in the original trial with 18 months follow-up (HR 1·14, 95% CI 0·87, 1·49; p-value 0·33). There was a reduced rate of self-harm in older participants aged 15-17 (HR 0·7, 95% CI 0·56, 0·88), as compared with those aged 11-14; and significantly increased rates of self-harm in participants whose index episode combined self-injury and poisoning (HR 1·8, 95% CI 1·2, 2·7). Two deaths were reported during the extended follow up period. INTERPRETATION: For adolescents referred to CAMHS after self-harm, having self-harmed at least once before, trial FT confers no benefits over TAU in reducing subsequent hospitalisation for self-harm over 18 months or 36 months. FUNDING: NIHR HTA Reference: 07/33/01.

The feasibility of using the EQ-5D-3L with adults with mild to moderate learning disabilities within a randomized control trial: a qualitative evaluation.

BACKGROUND: In trials incorporating a health economic evaluation component, reliable validated measures for health-related quality of life (HRQOL) are essential. The EQ-5D is the preferred measure for cost-effectiveness analysis in UK trials. This paper presents a qualitative evaluation of the use of the EQ-5D-3L in a feasibility randomised control trial with participants who had a mild- to  moderate learning disability and type 2 diabetes. METHODS: Researchers administered the EQ-5D-3L to 82 participants at baseline and 77 at follow-up. After each interview, researchers rated the ease of administering the EQ-5D-3L and made free-text entries on the administration experience. For a subset of 16 interviews, researchers audio-recorded more detailed journal entries. Ease of administration data were analysed using descriptive statistics. Free-text responses were subject to a basic content analysis. The EQ-5D-3L-related journal entries were transcribed, coded and analysed thematically. RESULTS: Over half of participants were perceived to experience difficulty answering some or all of the items in the EQ-5D-3L (60% at baseline; 54% at follow-up). Analysis of the free-text entries and audio journals identified four themes that question the use of the EQ-5D-3L in this population. The first theme is related to observations of participant intellectual ability and difficulties, for example, in understanding the wording of the measure. Theme 2 is related to the normalisation of adjustments for impairments, which rendered the measure less sensitive in this population. Theme 3 is related to researcher adaptation and non-standard administration. An overarching fourth theme was identified in that people with learning disabilities were viewed as 'unreliable witnesses' by both researchers and supporters. CONCLUSIONS: It is recommended that the EQ-5D-3L should not be used in isolation to assess health-related quality of life outcomes in trials research in adults with a learning disability. Further research is required to develop and evaluate a version of the EQ-5D appropriate for this population in trials research. It is unrealistic to expect that adjustments to the wording alone will deliver an appropriate measure: supporter or researcher involvement will almost always be required. This requirement needs to be factored into the development and administration guidelines of any new version of the EQ-5D for adults with a learning disability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41897033 [registered 21 January 2013].

Characterizing adults with Type 2 diabetes mellitus and intellectual disability: outcomes of a case-finding study.

AIMS: To report the results of a case-finding study conducted during a feasibility trial of a supported self-management intervention for adults with mild to moderate intellectual disability and Type 2 diabetes mellitus, and to characterize the study sample in terms of diabetes control, health, and access to diabetes management services and support. METHODS: We conducted a cross-sectional case-finding study in the UK (March 2013 to June 2015), which recruited participants mainly through primary care settings. Data were obtained from medical records and during home visits. RESULTS: Of the 325 referrals, 147 eligible individuals participated. The participants' mean (sd) HbA1c concentration was 55 (15) mmol/mol [7.1 (1.4)%] and the mean (sd) BMI was 32.9 (7.9) kg/m2 , with 20% of participants having a BMI >40 kg/m2 . Self-reported frequency of physical activity was low and 79% of participants reported comorbidity, for example, cardiovascular disease, in addition to Type 2 diabetes. The majority of participants (88%) had a formal or informal supporter involved in their diabetes care, but level and consistency of support varied greatly. Post hoc exploratory analyses showed a significant association between BMI and self-reported mood, satisfaction with diet and weight. CONCLUSIONS: We found high obesity and low physical activity levels in people with intellectual disability and Type 2 diabetes. Glycaemic control was no worse than in the general Type 2 diabetes population. Increased risk of morbidity in this population is less likely to be attributable to poor glycaemic control and is probably related, at least in part, to greater prevalence of obesity and inactivity. More research, focused on weight management and increasing activity in this population, is warranted.

Introducing structured caregiver training in stroke care: findings from the TRACS process evaluation study.

OBJECTIVE: To evaluate the process of implementation of the modified London Stroke Carers Training Course (LSCTC) in the Training Caregivers After Stroke (TRACS) cluster randomised trial and contribute to the interpretation of the TRACS trial results. The LSCTC was a structured competency-based training programme designed to help develop the knowledge and skills (eg, patient handling or transfer skills) essential for the day-to-day management of disabled survivors of stroke. The LSCTC comprised 14 components, 6 were mandatory (and delivered to all) and 8 non-mandatory, to be delivered based on individual assessment of caregiver need. DESIGN: Process evaluation using non-participant observation, documentary analysis and semistructured interviews. PARTICIPANTS: Patients with stroke (n=38), caregivers (n=38), stroke unit staff (n=53). SETTINGS: 10 of the 36 stroke units participating in the TRACS trial in four English regions (Yorkshire, North West, South East and South West, Peninsula). RESULTS: Preparatory cascade training on delivery of the LSCTC did not reach all staff and did not lead to multidisciplinary team (MDT) wide understanding of, engagement with or commitment to the LSCTC. Although senior therapists in most intervention units observed developed ownership of the LSCTC, MDT working led to separation rather than integration of delivery of LSCTC elements. Organisational features of stroke units and professionals' patient-focused practices limited the involvement of caregivers. Caregivers were often invited to observe therapy or care being provided by professionals but had few opportunities to make sense of, or to develop knowledge and stroke-specific skills provided by the LSCTC. Where provided, caregiver training came very late in the inpatient stay. Assessment and development of caregiver competence was not commonly observed. CONCLUSIONS: Contextual factors including service improvement pressures and staff perceptions of the necessity for and work required in caregiver training impacted negatively on implementation of the caregiver training intervention. Structured caregiver training programmes such as the LSCTC are unlikely to be practical in settings with short inpatient stays. Stroke units where early supported discharge is in place potentially offer a more effective vehicle for introducing competency based caregiver training. LINKED TRACS CLUSTER RANDOMISED CONTROLLED TRIAL NUMBER: ISRCTN49208824.

The development of a method for functional assessment of dentures.

AIMS: To design and validate a method of assessing complete dentures from a functional standpoint. SUBJECTS: A random sample of 40 complete denture wearers took part in the study. SETTING: A university clinical department of prosthetic dentistry. INTERVENTION: We undertook a pilot study to refine the protocol and criteria. All participants and their dentures were examined by two authors independently, with no prior knowledge of the patients' complaints. DESIGN: We defined nine clinical factors of functional quality and applied criteria with binary scoring. We analysed the scores for these factors for inter-rater reliability. RESULTS: The method proved simple to apply and took less than 5 minutes to complete. The inter-examiner agreement for all factors was 86% to 100% giving Kappa scores of 0.64 to 1.00 (all Good or Very Good). CONCLUSIONS: This study successfully demonstrates that the technique, which we call the Functional Assessment of Dentures (FAD), can give good inter-examiner reliability. It can therefore be used separately as a routine diagnostic tool and to investigate the relationship between denture qualities and functional 'outcome' such as difficulty eating or dietary selection.

Responsiveness of generic and specific measures of health outcome in low back pain.

STUDY DESIGN: A longitudinal study using patient questionnaires was performed. OBJECTIVE: To compare the discriminatory power and responsiveness of the Aberdeen Back Pain Scale (ABPS), the Roland Disability Questionnaire (RDQ), and the EuroQol in patients with low back pain. SUMMARY OF BACKGROUND DATA: A number instruments specific to low back pain have not been compared for measurement properties. The EuroQol is a widely used generic instrument that has not been compared with specific instruments in patients with back pain. METHODS: A questionnaire incorporating the Aberdeen Back Pain Scale, the Roland Disability Questionnaire, and the EuroQol was completed by patients taking part in a clinical trial of exercise treatments for back pain. Patients completed follow-up questionnaires at 6 weeks, 6 months, and 1 year. The discriminatory power of these instruments was assessed against variables relating to activity limitations, medication, and comorbidity. Responsiveness was assessed using standardized response means. RESULTS: The questionnaire was completed by 187 patients taking part in the clinical trial. The Aberdeen instrument was found to be the most powerful at discriminating between different groups of patients on variables relating to activity limitations, medication, and comorbidity. The specific instruments demonstrated good levels of responsiveness, with the Aberdeen instrument producing the largest standardized response means. The Aberdeen instrument was more responsive to the smaller changes experienced by the control group, but was less powerful than the Roland at measuring differences in the levels of change between the two groups of patients at two of the three follow-up assessments in the trial. The EuroQol demonstrated a moderate level of responsiveness. CONCLUSIONS: The two specific instruments are capable of greater levels of discrimination between groups of patients, and are more responsive over time than the generic EuroQol. The Aberdeen instrument performed most satisfactorily in relation to these criteria, but the Roland instrument was more sensitive to differences between the two groups in the clinical trial. The measurement properties of these two instruments reflect their origin: The Aberdeen instrument is based on clinical questions, whereas the Roland instrument is based on the generic Sickness Impact Profile. Instrument content should be carefullyconsidered when selecting instruments for applications, including clinical trials.