A systematic review of economic evaluations alongside studies within a trial (SWATs) for improving recruitment and retention in randomised controlled trials

Aim To review the cost-effectiveness of strategies to improve participant recruitment and retention in randomised controlled trials. Methods All included studies from the latest Cochrane recruitment and retention reviews were considered. To identify articles published since the Cochrane reviews, electronic databases were searched until March 2021. Hand searching of conference databases and journals was also undertaken. The inclusion criteria included Studies within a Trial (SWATs). The main outcome was the incremental cost-effectiveness ratio (ICER). Quality assessment of papers used the Cochrane risk of bias 1 tool. The CRD guidance was used to assess the quality of economic evaluation. Random-effect meta-analyses were undertaken. The GRADE certainty of evidence was applied for each strategy, and Trial Forge Guidance 2 was used for strategies included in meta-analyses to evaluate the uncertainty of the findings. Cost-effectiveness ranks summarise the cost-effectiveness of all strategies. Results We identified 6569 records and included 29 SWATs (earliest conducted in 1999 and latest in 2021) including more than 35,800 participants. There is no strategy we would recommend trial teams and researchers adopt with complete statistical certainty. Recruitment strategies which could be cost-effective include financial incentives, trial-branded pens, telephone reminders and pre-notification leaflets. Retention strategies which could be cost-effective include vouchers and trial-branded pens. Conclusion Future SWATs should replicate existing recruitment and retention strategies, rather than evaluate novel ones. We recommend that economic evaluations be carried out alongside all future SWATs, costs and benefits be recorded transparently, and the cost-effectiveness of existing recruitment or retention strategies be evaluated

Knee Replacement Bandaging Study (KReBS) Evaluating the effect of a Two-layer Compression Bandage System on Knee Function following Total Knee Arthroplasty: Study Protocol for a Randomised Controlled Trial

Background Data from a feasibility study suggests that the use of an inelastic, short-stretch compression bandage following total knee arthroplasty is a safe technique that may improve patient reported health outcomes, and that it is feasible to recruit to a full-scale study. Methods We will conduct a randomised controlled trial (RCT) of 2600 adult patients, which has 80% power to detect a 1 point difference in the Oxford Knee Score (a patient self-reported assessment of knee pain and function) at 52 weeks. Short stretch compression bandaging will be compared with standard wool and crepe bandaging following total knee arthroplasty. Recruitment will take place in orthopaedic units across the United Kingdom. Secondary outcomes include the EQ-5D-5L and EQ-5D-3L scores, pain, length of hospital stay and complications. Discussion The KReBS trial is a large study which aims to contribute to the evidence-base for informing clinical decisions for the use of compression bandaging following knee arthroplasty. Trial registration The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN 87127065). Date of registration was 20/02/2017 (http://www.isrctn.com/ISRCTN87127065). Keywords Knee replacement; arthroplasty; compression bandage; randomised controlled tria

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors

Background: The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments. Methods: The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed. Findings: Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7–1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04–0·17; p=0·0003) in men and 0·06 units per year (0·01–0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21–0·25) in men and 0·14 units per year (0·12–0·15) in women (both p<0·0001). More frequent donation resulted in more deferrals for low haemoglobin (odds ratio per week shorter inter-donation interval 1·19 [95% CI 1·15–1·22] in men and 1·10 [1·06–1·14] in women), and lower mean haemoglobin (difference per week shorter inter-donation interval −0·84 g/L [95% CI −0·99 to −0·70] in men and −0·45 g/L [–0·59 to −0·31] in women) and ferritin concentrations (percentage difference per week shorter inter-donation interval −6·5% [95% CI −7·6 to −5·5] in men and −5·3% [–6·5 to −4·2] in women; all p<0·0001). No differences were observed in quality of life, serious adverse events, or self-reported symptoms (p>0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p<0·0001). Interpretation: During a period of up to 4 years, shorter inter-donation intervals and more intensive reminders resulted in more blood being collected without a detectable effect on donors' mental and physical wellbeing. However, donors had decreased haemoglobin concentrations and more self-reported symptoms compared with the initial 2 years of the trial. Our findings suggest that blood collection services could safely use shorter donation intervals and more intensive reminders to meet shortages, for donors who maintain adequate haemoglobin concentrations and iron stores. Funding: NHS Blood and Transplant, UK National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Effectiveness and cost-effectiveness of offering a chair-based yoga programme in addition to usual care in older adults with multiple long-term conditions : a pragmatic, parallel group, open label, randomised controlled trial

Background People with multiple long-term conditions are more likely to have poorer health-related quality of life (HRQOL). Yoga has the potential to improve HRQOL. Gentle Years Yoga© (GYY) is a chair-based yoga programme for older adults. We investigated the effectiveness and cost-effectiveness of the GYY programme in older adults with multiple long-term conditions. Methods In this pragmatic, multi-site, open, randomised controlled trial, we recruited older adults aged ≥65 years with ≥2 long-term conditions from 15 primary care practices in England and Wales. Participants were randomly assigned to usual care control or a 12-week, group-based, GYY programme delivered face-to-face or online by qualified yoga teachers. The primary outcome was HRQOL (assessed with EQ-5D-5L) over 12 months. Secondary outcomes included anxiety, depression, falls, loneliness, healthcare resource use, and adverse events. Results Between October 2019 and October 2021, 454 participants were randomly assigned to the intervention (n=240) and control (n=214) groups. Seven GYY courses were delivered face-to-face and 12 courses were delivered online. The mean number of classes attended among all intervention participants was nine (SD 4, median 10). In our intention-to-treat analysis (n=422), there was no statistically significant difference between trial groups in the primary outcome of HRQOL (adjusted difference in mean EQ-5D-5L = 0.020 [favouring intervention]; 95% CI -0.006 to 0.045, p=0.14). There were also no statistically significant differences in key secondary outcomes. No serious, related adverse events were reported. The incremental cost-effectiveness ratio was £4,546 per quality-adjusted life-year (QALY) and the intervention had a 79% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY. Conclusions The offer of a 12-week chair-based yoga programme in addition to usual care did not improve HRQOL in older adults with multiple long-term conditions. However, the intervention was safe, acceptable, and probably cost-effective

Home environmental assessments and modification delivered by occupational therapists to reduce falls in people aged 65 years and over : the OTIS RCT

Background: Falls and fall-related fractures in older people are highly prevalent and a major contributor to morbidity and cost to individuals and society. There is only one small pilot trial evaluating the effectiveness of a home hazard assessment and environmental modification in the UK. This trial reported a reduction in falls as a secondary outcome; no economic evaluation was undertaken. The results therefore need confirming and a cost-effectiveness analysis undertaking. Objectives: To determine the clinical and cost-effectiveness of a home hazard assessment and environmental modification delivered by occupational therapists for preventing falls in community-dwelling people aged over 65 at risk of falling, relative to usual care. Design: A pragmatic, multicentre, modified cohort randomised controlled trial with an economic evaluation and qualitative study. Setting: Eight NHS trusts in primary and secondary care in England. Participants: In total, 1331 participants were randomised (intervention, n=430; usual care group, n=901) via a secure, remote service. Blinding was not possible. Interventions: All participants received a falls prevention leaflet and routine care from their General Practitioner. The intervention group were additionally offered one home environmental assessment and modifications recommended or provided to identify and manage personal fall-related hazards, delivered by an occupational therapist. Main outcome measures: The primary outcome was the number of falls per participant over the 12 months from randomisation. The secondary outcomes were the proportion of fallers and multiple fallers, time to fall, fear of falling, fracture rate, health-related quality of life and cost-effectiveness. Results: The primary analysis included all 1331 randomised participants and indicated weak evidence of a difference in fall rate between the two groups, with an increase in the intervention group relative to usual care (adjusted incidence rate ratio 1.17, 95% CI 0.99 to 1.38; p=0.07). A similar proportion of participants in the intervention group (57.0%) and the usual care group (56.2%) reported at least one fall over 12 months. There were no differences in any of the secondary outcomes. The base case cost-effectiveness analysis from an NHS and personal social services perspective found that, on average per participant, the intervention was associated with additional costs (£18.78, 95% CI £16.33 to £21.24), but was less effective (mean QALY loss -0.0042, 95% CI -0.0041 to -0.0043). Sensitivity analyses demonstrated uncertainty in these findings. No serious, related adverse events were reported. The intervention was largely delivered as intended but recommendations were followed to a varying degree. Limitations: Outcome data were participant self-reported, which may have led to inaccuracies in the reported falls data. Conclusions: We found no evidence that an occupational therapist-delivered home assessment and modification reduced falls in this population of over 65 year old, community-dwelling participants deemed at risk of falling. The intervention was more expensive and less effective than usual care, therefore does not provide a cost-effective alternative. Future work: Evaluation of falls prevention advice in a higher risk population, perhaps those previously hospitalised for a fall, or given by other professional staff could be justified. Trial registration: ISRCTN2220213

Home hazard assessment and environmental modification to prevent falls in older people : the OTIS trial

Background: Falls in older people are a major cause of morbidity and mortality. There is some evidence to suggest that home hazard assessment and environmental modification delivered by an occupational therapist may reduce falls. The objective of this study was to evaluate the effectiveness of this intervention, relative to usual care. Methods: A pragmatic, two-arm modified cohort randomised controlled trial in eight NHS trusts in primary and secondary care in England. In total 1331 community-dwelling adults aged 65 years and over with a history of falls or fear of falling were randomised in a 2:1 allocation to either usual care plus a falls prevention leaflet (n=901) or to receive the home hazard assessment and environmental modification intervention, plus usual care and a falls prevention leaflet (n=430). The primary outcome was the number of falls per participant over the 12 months from randomization. Secondary outcomes included: proportion of fallers and multiple fallers, time to fall, and fear of falling. Results: All 1331 randomised participants (mean age 80 years, 872 [65.5%] female) were included in the primary analysis. There was a small increase in the rate of falls in the intervention group relative to usual care (adjusted incidence rate ratio 1.17, 95% CI 0.99 to 1.38; p=0.07). A similar proportion of participants in the intervention (57.0%) and usual care group (56.2%) reported at least one fall over 12 months. There were no differences in any of the other secondary outcomes and no serious, related adverse events were reported. Conclusions: Home hazard assessment and environmental modification delivered by an occupational therapist did not reduce falls in community-dwelling older people deemed at higher risk of falling recruited to this trial. ISRCTN registry: ISRCTN22202133 Key words: home hazard assessment and environmental modification, falls prevention, older adults, modified cohort randomized controlled tria

Chair-based yoga programme for older adults with multimorbidity: RCT with embedded economic and process evaluations

Background: Older adults with multimorbidity experience impaired health-related quality of life and treatment burden. Yoga has the potential to improve several aspects of health and well-being. The British Wheel of Yoga’s Gentle Years Yoga© programme was developed specifically for older adults, including those with chronic conditions. A pilot trial demonstrated feasibility of using Gentle Years Yoga in this population, but there was limited evidence of its effectiveness and cost-effectiveness. Objective: To determine the effectiveness and cost-effectiveness of the Gentle Years Yoga programme in addition to usual care versus usual care alone in older adults with multimorbidity. Design: Pragmatic, multisite, individually randomised controlled trial with embedded economic and process evaluations. Setting: Participants were recruited from 15 general practices in England and Wales from July 2019with final follow-up in October 2022. Participants: Community-dwelling adults aged 65 years and over with multimorbidity, defined as two or more chronic health conditions from a predefined list. Interventions: All participants continued with any usual care provided by primary, secondary, community and social services. The intervention group was offered a 12-week programme of Gentle Years Yoga. Main outcome measures: The primary outcome and end point were health-related quality of life measured using the EuroQol-5 Dimensions, five-level version utility index score over 12 months. Secondary outcomes were health-related qualityof life, depression, anxiety, loneliness, incidence of falls, adverse events and healthcare resource use. Results: The mean age of the 454 randomised participants was 73.5 years; 60.6% were female, and participants had a median of three chronic conditions. The primary analysis included 422 participants (intervention, n = 227 of 240, 94.6%; usual care, n = 195 of 214, 91.1%). There was no statistically or clinically significant difference in the EuroQol-5 Dimensions, five-level version utility index score over 12 months: the predicted mean score for the intervention group was 0.729 (95% confidence interval 0.712 to 0.747) and for usual care it was 0.710 [95% confidence interval (CI) 0.691 to 0.729], with an adjusted mean difference of 0.020 favouring intervention (95% CI −0.006 to 0.045, p = 0.14). No statistically significant differences were observed in secondary outcomes, except for the pain items of the Patient-Reported Outcomes Measurement Information System-29. No serious, related adverse events were reported. The intervention cost £80.85 more per participant (95% CI £76.73 to £84.97) than usual care, generated an additional 0.0178 quality-adjusted life-years per participant (95% CI 0.0175 to 0.0180) and had a 79% probability of being cost-effective at the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. The intervention was acceptable to participants, with seven courses delivered face to face and 12 online. Limitations: Self-reported outcome data raise the potential for bias in an unblinded trial. The COVID-19 pandemic affected recruitment, follow-up and the mode of intervention delivery. Conclusions: Although the Gentle Years Yoga programme was not associated with any statistically significant benefits in terms of health-related quality of life, mental health, loneliness or falls, the intervention was safe, acceptable to most participants and highly valued by some. The economic evaluation suggests that the intervention could be cost-effective. Future work: Longer-term cost-effectiveness modelling and identifying subgroups of people who are most likely to benefit from this type of intervention. Trial registration: This trial is registered as ISRCTN13567538. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/94/36) and is published in full in Health Technology Assessment; Vol. 28, No. 53. See the NIHR Funding and Awards website for further award information