Kirsty Sprange

Lifestyle Matters for maintenance of health and wellbeing in people aged 65 years and over: study protocol for a randomised controlled trial

BackgroundHealthy, active ageing is strongly associated with good mental wellbeing which in turn helps to prevent mental illness. However, more investment has been made into research into interventions to prevent mental illness than into those designed to improve mental wellbeing. This applied research programme will provide high quality evidence for an intervention designed to improve and sustain mental wellbeing in older adults.Methods/DesignThis study was a multi-centre, pragmatic, two-arm, parallel group, individually randomised controlled trial to determine the population benefit of an occupational therapy based intervention for community living people aged 65 years or older. Participants (n = 268) will be identified in one city in the North of England and in North Wales through GP mail-outs, signposting by local authority, primary care staff and voluntary sector organisations and through community engagement. Participants will be randomised to one of two treatment arms: an intervention (Lifestyle Matters programme); or control (routine access to health and social care). All participants will be assessed at baseline, 6 and 24 months post-randomisation. The primary outcome, which is a person reported outcome, is the SF-36 Mental Health dimension at six months post randomisation. Secondary outcome measures have been selected to measure psychosocial, physical and mental health outcomes. They include other dimensions of the SF36, EQ-5D-3L, Brief Resilience Scale, General Perceived Self Efficacy Scale, PHQ-9, de Jong Gierveld Loneliness Scale, Health and Social Care Resource Use and the wellbeing question of the Integrated Household Survey 2011. A cost effectiveness analysis will investigate the incremental cost per Quality Adjusted Life Years (QALYs) of the Lifestyle Matters intervention compared with treatment as usual.DiscussionThe questions being posed through this research are important given the increasing numbers of older people, pressure on the public purse and the associated need to support good health in the extended lifespan. The proposed trial will determine the clinical and cost effectiveness of the intervention delivered in a UK context. The results will support commissioners and providers with decisions about implementation.Trial registrationCurrent Controlled Trials ISRCTN67209155

A preventative lifestyle intervention for older adults (Lifestyle Matters): a randomised controlled trial

Abstract Objectives to test whether an occupation-based lifestyle intervention can sustain and improve the mental well-being of adults aged 65 years or over compared to usual care, using an individually randomised controlled trial. Participants 288 independently living adults aged 65 years or over, with normal cognition, were recruited from two UK sites between December 2011 and November 2015. Interventions lifestyle Matters is a National Institute for Health and Care Excellence recommended multi-component preventive intervention designed to improve the mental well-being of community living older people at risk of decline. It involves weekly group sessions over 4 months and one to one sessions. Main outcome measures the primary outcome was mental well-being at 6 months (mental health (MH) dimension of the SF-36). Secondary outcomes included physical health dimensions of the SF-36, extent of depression (PHQ-9), quality of life (EQ-5D) and loneliness (de Jong Gierveld Loneliness Scale), assessed at 6 and 24 months. Results data on 262 (intervention = 136; usual care = 126) participants were analysed using intention to treat analysis. Mean SF-36 MH scores at 6 months differed by 2.3 points (95 CI: −1.3 to 5.9; P = 0.209) after adjustments. Conclusions analysis shows little evidence of clinical or cost-effectiveness in the recruited population with analysis of the primary outcome revealing that the study participants were mentally well at baseline. The results pose questions regarding how preventive interventions to promote well-being in older adults can be effectively targeted in the absence of proactive mechanisms to identify those who at risk of decline. Trial Registration ISRCTN67209155.

The NICE Medical Technologies Evaluation Programme (MTEP): manufacturer submission challenges

The purpose of this report was to explore and describe the challenges that healthcare sector manufacturers face when producing a submission to the NICE Evaluation Pathway (EP) Programme for medical technologies. The EP Programme was developed to evaluate new and innovative medical technologies to inform adoption of efficient and cost effective devices and diagnostics in the NHS. The premise was to produce recommendations based on a similar process currently used for pharmaceutical products. A submission requires manufacturers to complete a data capture template collating high quality clinical and cost effectiveness evidence for their device. This includes indicating how the device integrates into current NHS clinical pathways and how it performs in relation to current best practice. The time scale for completion of a submission is an approximated 6 weeks. Particular consideration was given to small and medium enterprises (SMEs), and availability and access to resources and skills. A consultation process was undertaken to ascertain the opinion of small, medium and large manufacturers in the healthcare sector who could potentially submit an application to the EP programme. The results of this process would highlight any real or perceived barriers identified by manufacturers that could prevent them from submitting to the new EP programme. The EP programme was renamed after preparation of this report to the Medical Technologies Evaluation Programme (MTEP), and details are available here: http://www.nice.org.uk/mt.

The long-term (24-month) effect on health and well-being of the Lifestyle Matters community-based intervention in people aged 65 years and over: a qualitative study

Objectives To assess the long-term effect on health and well-being of the Lifestyle Matters programme. Design Qualitative study of a subset of intervention arm participants who participated in the Lifestyle Matters randomised controlled trial (RCT). Setting The intervention took place at community venues within two sites in the UK. Participants A purposeful sample of 13 participants aged between 66 and 88 years from the intervention arm of the RCT were interviewed at 24 months post randomisation. Interviews aimed to understand how participants had used their time in the preceding 2 years and whether the intervention had any impact on their lifestyle choices, participation in meaningful activities and well-being. Intervention Lifestyle Matters is a 4-month occupational therapy intervention, consisting of group and individual sessions, designed to enable community living older people to make positive lifestyle choices and participate in new or neglected activities through increasing self-efficacy. Results Interviews revealed that the majority of interviewed participants were reportedly active at 24 months, with daily routines and lifestyles not changing significantly over time. All participants raised some form of benefit from attending Lifestyle Matters, including an improved perspective on life, trying new hobbies and meeting new friends. A number of intervention participants spoke of adapting to their changing circumstances, but there were significant and lasting benefits for 2 of 13 intervention participants interviewed. Conclusion The majority of those who experienced the Lifestyle Matters intervention reported minor benefits and increases in self-efficacy, but they did not perceive that it significantly improved their health and well-being. The two participants who had experienced major benefits also reported having had life-changing events, suggesting that this intervention is most effective at the time when lifestyle has to be reconsidered if mental well-being is to be sustained. Trial registration ISRCTN, ISRCTN67209155, post results.

Recruitment of older adults to three preventative lifestyle improvement studies

BackgroundRecruiting isolated older adults to clinical trials is complex, time-consuming and difficult. Previous studies have suggested querying existing databases to identify appropriate potential participants. We aim to compare recruitment techniques (general practitioner (GP) mail-outs, community engagement and clinician referrals) used in three randomised controlled trial (RCT) studies assessing the feasibility or effectiveness of two preventative interventions in isolated older adults (the Lifestyle Matters and Putting Life In Years interventions).MethodsDuring the three studies (the Lifestyle Matters feasibility study, the Lifestyle Matters RCT, the Putting Life In Years RCT) data were collected about how participants were recruited. The number of letters sent by GP surgeries for each study was recorded. In the Lifestyle Matters RCT, we qualitatively interviewed participants and intervention facilitators at 6 months post randomisation to seek their thoughts on the recruitment process.ResultsReferrals were planned to be the main source of recruitment in the Lifestyle Matters feasibility study, but due to a lack of engagement from district nurses, community engagement was the main source of recruitment. District nurse referrals and community engagement were also utilised in the Lifestyle Matters and Putting Life In Years RCTs; both mechanisms yielded few participants. GP mail-outs were the main source of recruitment in both the RCTs, but of those contacted, recruiting yield was low (< 3%). Facilitators of the Lifestyle Matters intervention questioned whether the most appropriate individuals had been recruited. Participants recommended that direct contact with health professionals would be the most beneficial way to recruit.ConclusionsRecruitment to the Lifestyle Matters RCT did not mirror recruitment to the feasibility study of the same intervention. Direct district nurse referrals were not effective at recruiting participants. The majority of participants were recruited via GP mail-outs, which may have led to isolated individuals not being recruited to the trials. Further research is required into alternative recruitment techniques, including respondent-driven sampling plus mechanisms which will promote health care professionals to recruit vulnerable populations to research.Trial registrationInternational Standard Randomised Controlled Trial Registry, ID: ISRCTN28645428 (Putting Life In Years RCT). Registered on 11 April 2012;International Standard Randomised Controlled Trial Registry, ID: ISRCTN67209155 (Lifestyle Matters RCT). Registered on 22 March 2012;ClinicalTrials.gov, ID: NCT03054311 (Lifestyle Matters feasibility study). Registered retrospectively on 19 January 2017.

Follow-on RifAximin for the Prevention of recurrence following standard treatment of Infection with Clostridium Difficile (RAPID): a randomised placebo controlled trial

Background Clostridium difficile infection (CDI) recurs after initial treatment in approximately one in four patients. A single-centre pilot study suggested that this could be reduced using ‘follow-on’ rifaximin treatment. We aimed to assess the efficacy of rifaximin treatment in preventing recurrence. Methods A multisite, parallel group, randomised, placebo controlled trial recruiting patients aged ≥18 years immediately after resolution of CDI through treatment with metronidazole or vancomycin. Participants received either rifaximin 400 mg three times a day for 2 weeks, reduced to 200 mg three times a day for a further 2 weeks or identical placebo. The primary endpoint was recurrence of CDI within 12 weeks of trial entry. Results Between December 2012 and March 2016, 151 participants were randomised to either rifaximin or placebo. Primary outcome data were available on 130. Mean age was 71.9 years (SD 15.3). Recurrence within 12 weeks was 29.5% (18/61) among participants allocated to placebo compared with 15.9% (11/69) among those allocated to rifaximin, a difference between groups of 13.7% (95% CI −28.1% to 0.7%, p=0.06). The risk ratio was 0.54 (95% CI 0.28 to 1.05, p=0.07). During 6-month safety follow-up, nine participants died in each group (12%). Adverse event rates were similar between groups. Conclusion While ‘follow-on’ rifaximin after CDI appeared to halve recurrence rate, we failed to reach our recruitment target in this group of frail elderly patients, so the estimated effect of rifaximin lacks precision. A meta-analysis including a previous trial suggests that rifaximin may be effective; however, further, larger confirmatory studies are needed.

PWE-050 Follow-on rifaximin for the prevention of recurrence in clostridium difficile associated diarrhoea: a randomised controlled trial

Introduction Clostridium difficile associated diarrhoea (CDAD) is a common nosocomial infection that recurs in more than 1 in 4 cases. Garey et al. found that a course of rifaximin after standard therapy reduced relapse rate though not significantly1. We aimed to confirm or refute this finding. Method Design A parallel group, randomised, placebo controlled trial in 23 English hospitals. Funding NIHR RfPB Grant PB-PG-0110–21041. Norgine supplied drug and placebo without charge. Population age ≥18 with resolution of CDAD after treatment with metronidazole or vancomycin. CDAD diagnosis required evidence of toxin production or pseudomembranes at endoscopy. Exclusion criteria: pregnancy or breast feeding; life expectancy <4 weeks; unable to take intervention (hypersensitivity or swallowing disorder);>5 days elapsed since treatment. Randomisation was stratified by hospital using a remote, internet-based system. Participants, clinicians and researchers were blind to allocation. Intervention Rifaximin 1200 mg daily for two weeks then 600 mg daily for two weeks, in three divided doses. Comparator: identical placebo. Primary Outcome: relapse ≤12 weeks after treatment initiation. Sample size The planned sample size was 180 to detect a difference in relapse of 20% (30% placebo, 10% rifaximin) with 80% power, allowing for loss to follow-up of 20%. EudraCT 2012-003205-10; www.clinicaltrials.gov NCT01670149 Results Recruitment occurred December 2012–March 2015. Of 2157 patients screened, 151 were eligible, willing and randomised before funding limits were reached (74 placebo, 77 rifaximin). Primary outcome data were available on 130. Mean age was 71.9 (SD 15.3). 36% were in-patients at start of intervention. 18/61 (29.5%) on placebo relapsed within 12 weeks compared to 11/69 (15.9%) on rifaximin, a difference between groups of −13.7% (95% CI −28.1% to 0.7%, p=0.06). The risk ratio was 0.54 (95% CI 0.28 to 1.05, p=0.07). During 6 month safety follow up 9 participants died in each group (12%). Adverse event rates were similar between groups. Conclusion CDAD relapse rate was 13.7% lower than on placebo. The confidence interval means that lack of effect remains possible but the estimated effect size is similar to Garey’s trial, and those reported for fidaxomicin, with longer follow-up2. Age and mortality rate were higher in our trial which may reflect greater similarity to the population at risk. Comparative trials of cost effectiveness should follow. References . Garey et al. J Antimicrob Chemother 2011;66:2850–2855. . Crook et al. CID 2012;55(S2):S93–103. Disclosure of Interest G. Major: None Declared, L Bradshaw: None Declared, N Boota: None Declared, K Sprange: None Declared, A Jawhari: None Declared, M Diggle: None Declared, A Montgomery: None Declared, R Spiller Conflict with: Norgine Pharmaceuticals Ltd supplied product and comparator free of cost

No drug, no trial? Think again!

A reliable drug supply is essential for trial success, but what happens when part way through the trial your source fails and there is no alternative supplier of the same product. This became the challenge for the seAFOod trial in 2014. seAFOod is a randomised, double-blind, placebo-controlled study to determine whether fish oil (omega-3 EPA) prevents colorectal adenomas, alone or combined with aspirin. Whilst most sites were temporarily suspended to recruitment during 2014, a solution was sought to the EPA IMP problem. Consultation with EME, MHRA, REC and independent oversight committees was key to exploring options for continuing the trial and enabled effective decision making. Once sourcing a different product was agreed, the search was on. With no ‘quick fix’ option available, excellent communication was vital to identify an alternative source of EPA IMP and keep sites engaged and motivated to continue the trial. Once the new product was found it was important to update trial documents and arrange approvals and contracts promptly. Good time management facilitated achievement of key milestones and established realistic expectations within the research team and at sites for continuation of the trial. Finally a series of motivational re-launch events meant the trial met the funders ‘stop/go’ recruitment target ahead of schedule. A supportive funder, motivated Chief Investigator and trial team along with good trial management are paramount. This abstract will demonstrate the successful continuation of the seAFOod trial using an alternative equivalent IMP and present the experience and lessons learned by a Trial Management Group.