Ivana Holloway

Cluster Randomized Controlled Trial: Clinical and Cost-Effectiveness of a System of Longer-Term Stroke Care

Background and Purpose— We developed a new postdischarge system of care comprising a structured assessment covering longer-term problems experienced by patients with stroke and their carers, linked to evidence-based treatment algorithms and reference guides (the longer-term stroke care system of care) to address the poor longer-term recovery experienced by many patients with stroke. Methods— A pragmatic, multicentre, cluster randomized controlled trial of this system of care. Eligible patients referred to community-based Stroke Care Coordinators were randomized to receive the new system of care or usual practice. The primary outcome was improved patient psychological well-being (General Health Questionnaire-12) at 6 months; secondary outcomes included functional outcomes for patients, carer outcomes, and cost-effectiveness. Follow-up was through self-completed postal questionnaires at 6 and 12 months. Results— Thirty-two stroke services were randomized (29 participated); 800 patients (399 control; 401 intervention) and 208 carers (100 control; 108 intervention) were recruited. In intention to treat analysis, the adjusted difference in patient General Health Questionnaire-12 mean scores at 6 months was −0.6 points (95% confidence interval, −1.8 to 0.7; P=0.394) indicating no evidence of statistically significant difference between the groups. Costs of Stroke Care Coordinator inputs, total health and social care costs, and quality-adjusted life year gains at 6 months, 12 months, and over the year were similar between the groups. Conclusions— This robust trial demonstrated no benefit in clinical or cost-effectiveness outcomes associated with the new system of care compared with usual Stroke Care Coordinator practice. Clinical Trial Registration— URL: http://www.controlled-trials.com. Unique identifier: ISRCTN 67932305.

Protocol of a cluster randomized trial evaluation of a patient and carer-centered system of longer-term stroke care (LoTS care)

Rationale Despite recognition of the importance of the longer-term consequences of stroke, services addressing these needs remain poorly developed. There are persuasive arguments that a community-based orientation to poststroke care, to assess, support, and coordinate relevant services, might be more helpful in minimizing longer-term stroke morbidity. To address this, an evidence-based system of care has been developed that aims to meet the longer-term needs for stroke survivors and their carers living at home in the community. Aims The study aims to evaluate the clinical and cost-effectiveness of a purposely developed system of care for stroke patients and their carers living in the community. Design This is a cluster randomized, controlled trial. The trial aimed to recruit 800 patients (and their carers, if appropriate) in 32 stroke services across the United Kingdom. The system of care is delivered by health professionals undertaking a community-based liaison or coordinating role for stroke patients (termed ‘stroke care coordinators’). Stroke care coordinators in stroke services randomized to the intervention group were trained to deliver the system of care, while those randomised to the control group continued to deliver current practice. Study outcomes The primary outcome is patient emotional health measured using the General Health Questionnaire 12 at six-months after recruitment. Secondary outcomes include cost-effectiveness, patient functional health and carer emotional health, with final follow-up at 12 months. Current status Thirty-two stroke services were randomized and 800 patients and 208 carers were recruited from 29 services. Follow-up is ongoing, and trial results are expected in early 2013.

The DARS (Dopamine Augmented Rehabilitation in Stroke) trial: protocol for a randomised controlled trial of Co-careldopa treatment in addition to routine NHS occupational and physical therapy after stroke.

BackgroundStroke has a huge impact, leaving more than a third of affected people with lasting disability and rehabilitation remains a cornerstone treatment in the National Health Service (NHS). Recovery of mobility and arm function post-stroke occurs through re-learning to use the affected body parts and/or learning to compensate with the lesser affected side. Promising evidence suggests that the addition of Co-careldopa to physical therapy and occupational therapy may improve the recovery of arm and leg movement and lead to improved function.Methods/designDopamine Augmented Rehabilitation in Stroke (DARS) is a multi-centre double-blind, randomised, placebo, controlled clinical trial of Co-careldopa in addition to routine NHS occupational therapy and physical therapy as part of early stroke rehabilitation. Participants will be randomised on a 1:1 basis to either Co-careldopa or placebo. The primary objective of the trial is to determine whether the addition of six weeks of Co-careldopa treatment to rehabilitation therapy can improve the proportion of patients who can walk independently eight weeks post-randomisation.DiscussionThe DARS trial will provide evidence as to whether Co-careldopa, in addition to routine NHS occupational and physical therapy, leads to a greater recovery of motor function, a reduction in carer dependency and advance rehabilitation treatments for people with stroke.Trial registrationISRCTN99643613 assigned on 4 December 2009.

Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial

BackgroundUp to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). Of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping™ (DCM™) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM™ is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM™ in the UK is urgently needed.Methods/designA pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCM™) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation.DiscussionThe protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message.Trial registrationCurrent Controlled Trials ISRCTN82288852. Registered on 16 January 2014.Full protocol version and date: v7.1: 18 December 2015.

Poststroke Trajectories: The Process of Recovery Over the Longer Term Following Stroke

We adopted a grounded theory approach to explore the process of recovery experienced by stroke survivors over the longer term who were living in the community in the United Kingdom, and the interacting factors that are understood to have shaped their recovery trajectories. We used a combination of qualitative methods. From the accounts of 22 purposively sampled stroke survivors, four different recovery trajectories were evident: (a) meaningful recovery, (b) cycles of recovery and decline, (c) ongoing disruption, (d) gradual, ongoing decline. Building on the concept of the illness trajectory, our findings demonstrate how multiple, interacting factors shape the process and meaning of recovery over time. Such factors included conception of recovery and meanings given to the changing self, the meanings and consequences of health and illness experiences across the life course, loss, sense of agency, and enacting relationships. Awareness of the process of recovery will help professionals better support stroke survivors.

Economic evaluation of a patient and carer centred system of longer-term stroke care from a cluster randomised trial (the LoTS care trial)

Materials and methods A pragmatic cluster, randomised, controlled trial compared the system of care against usual care. Randomisation was at the level of stroke service. Participants’ use of health/social care services and informal care were measured by self-complete questionnaires at baseline, 6 and 12 months. From these, we estimated and compared individual-level total costs from health/social care and societal perspectives at 6 months, 12 months and over 1 year. Costs were combined with the primary outcome, psychological health (General Health Questionnaire 12; GHQ12), and quality-adjusted life years (QALYs; based on the EQ-5D) to examine cost-effectiveness at 6 months. Costeffectiveness acceptability curves based on the net benefit approach and bootstrapping techniques were used to estimate the probability of cost-effectiveness.

Can follow-up reminders from postal questionnaires help determine the mechanism of missing data in trials?

The issue of missing data is present in every trial. Identification of the missing data mechanism is not straightforward; however it is essential to avoid bias. The mechanism of missing completely at random (MCAR) is seldom appropriate and the distinction between missing at random (MAR) and not at random (MNAR) is not straightforward. Follow-up reminder responses provide excellent source of information for investigating the issue. Improving postal response rates for patient-reported outcome measures often requires some kind of reminder process. Patient-reported outcomes from two stroke rehabilitation cluster randomised trials were used to investigate the usefulness of reminders in the identification of the missing data mechanism. In both trials, the reminder process was set-up from the outset. Missing data in these trials had an intermittent pattern. An approach by Fairclough (2010) was used to determine missingness mechanism. Covariates predicting non-response (from reminderresponders) were first identified to distinguish between MCAR and MAR mechanisms and participants outcome scores were added to model testing for inclusion to check for evidence of MNAR. The advantage of this method is that reminderresponses are considered to be similar to non-responders with the additional benefit of knowing the actual outcome. Furthermore, identification of covariates indicated by this approach can inform the choice of covariates for the appropriate method of data imputation. In trials with potentially high loss to follow-up, reminder strategies can be used not only to minimise loss to follow-up but offer valuable data to examine mechanisms of missingness and ultimately contribute to a robust final analysis.

Sample size in cluster randomised trials with unequal clusters

Objectives The aim of RCTs is to obtain unbiased estimates of treatment effects to answer the question of interest. In a cluster randomised trial (CRT), maximum statistical efficiency is obtained if an equal sized sample from each cluster is selected. In practice, the ability to achieve equal cluster size is an exception rather than the norm. Two CRTs run by the Leeds CTRU; TRACS (Training Caregivers After Stroke) and LoTS Care (Longer Term Stroke Care) are used to demonstrate how this issue can be dealt with practically.

Statistical issues in the design of randomised surgical trials: a practical example of the possible solutions

Methods and results One significant issue for surgical trials is to ensure surgeons recruiting to the trial are over their initial ‘learning curve’. To ensure surgeon competency and minimise any ‘learning curve’ effect, ROLARR only includes surgeons who have performed at least 30 rectal cancer resections (minimum of 10 for each procedure). Randomisation also stratifies by surgeon to ensure balance between arms within each surgeon and within the stage that individual surgeons have reached on the learning curve. To be able to statistically assess the learning curve at analysis, data on time-dependent factors known to influence the learning curve will also be collected prior to and on a regular basis during recruitment. Another issue is blinding. Blinding surgical teams is generally impossible, but blinding patients may be feasible. In ROLARR however, although patients could be initially blinded to their performed surgery, maintaining the blind was felt to be difficult to achieve successfully. ROLARR therefore incorporates objectives measures and central blinded assessments of these measures to reduce potential bias. Timing of randomisation can also be problematic due to the need for theatre planning. Preferably surgery should take place as soon as possible after randomisation however in ROLARR, up to 28 days after surgery has had to be permitted. Monitoring timings will take place to allow prompt action on any possible problems that may introduce bias.