The impact of an intervention to increase uptake to structured self-management education for people with type 2 diabetes mellitus in primary care (the embedding package), compared to usual care, on glycaemic control: study protocol for a mixed methods study incorporating a wait-list cluster randomised controlled trial

Abstract: Background: Approximately 425 million people globally have diabetes, with ~ 90% of these having Type 2 Diabetes Mellitus (T2DM). This is a condition that leads to a poor quality of life and increased risk of serious health complications. Structured self-management education (SSME) has been shown to be effective in improving glycaemic control and patient related outcome measures and to be cost-effective. However, despite the demonstrated benefits, attendance at SSME remains low. An intervention has been developed to embed SSME called the ‘Embedding Package’. The intervention aims to address barriers and enhance enablers to uptake of SSME at patient, healthcare professional and organisational levels. It comprises a marketing strategy, user friendly and effective referral pathways, new roles to champion SSME and a toolkit of resources. Methods: A mixed methods study incorporating a wait-list cluster randomised trial and ethnographic study, including 66 UK general practices, will be conducted with two intervention start times (at 0 and 9 months), each followed by an active delivery phase. At 18 months, the intervention will cease to be actively delivered and a 12 month observational follow-up phase will begin. The intervention, the Embedding Package, aims to increase SSME uptake and subsequent improvements in health outcomes, through a clear marketing strategy, user friendly and effective referral pathways, a local clinical champion and an ‘Embedder’ and a toolkit of resources for patients, healthcare professionals and other key stakeholders. The primary aim is, through increasing uptake to and attendance at SSME, to reduce HbA1c in people with T2DM compared with usual care. Secondary objectives include: assessing whether there is an increase in referral to and uptake of SSME and improvements in biomedical and psychosocial outcomes; an assessment of the sustainability of the Embedding Package; contextualising the process of implementation, sustainability of change and the ‘fit’ of the Embedding Package; and an assessment of the cost-effectiveness of the Embedding Package. Discussion: This study will assess the effectiveness, cost-effectiveness and sustainability of the Embedding Package, an intervention which aims to improve biomedical and psychosocial outcomes of people with T2DM, through increased referral to and uptake of SSME. Trial registration: International Standard Randomised Controlled Trials Number ISRCTN23474120. Assigned 05/04/2018. The study was prospectively registered. On submission of this manuscript practice recruitment is complete, participant recruitment is ongoing and expected to be completed by the end of 2019

Increasing uptake of structured self-management education programmes for type 2 diabetes in a primary care setting: a feasibility study

Abstract: Background: Structured self-management education (SSME) for people with type 2 diabetes mellitus (T2DM) improves biomedical and psychological outcomes, whilst being cost-effective. Yet uptake in the UK remains low. An ‘Embedding Package’ addressing barriers and enablers to uptake at patient, health care professional and organisational levels has been developed. The aim of this study was to test the feasibility of conducting a subsequent randomised controlled trial (RCT) to evaluate the Embedding Package in primary care, using a mixed methods approach. Methods: A concurrent mixed methods approach was adopted. Six general practices in the UK were recruited and received the intervention (the Embedding Package). Pseudonymised demographic, biomedical and SSME data were extracted from primary care medical records for patients recorded as having a diagnosis of T2DM. Descriptive statistics assessed quantitative data completeness and accuracy. Quantitative data were supplemented and validated by a patient questionnaire, for which two recruitment methods were trialled. Where consent was given, the questionnaire and primary care data were linked and compared. The cost of the intervention was estimated. An integrated qualitative study comprising ethnography and stakeholder and patient interviews explored the process of implementation, sustainability of change and ‘fit’ of the intervention. Qualitative data were analysed using a thematic framework guided by the Normalisation Process Theory (NPT). Results: Primary care data were extracted for 2877 patients. The primary outcome for the RCT, HbA1c, was over 90% complete. Questionnaires were received from 423 (14.7%) participants, with postal invitations yielding more participants than general practitioner (GP) prompts. Ninety-one percent of questionnaire participants consented to data linkage. The mean cost per patient for the Embedding Package was £8.94, over a median follow-up of 162.5 days. Removing the development cost, this reduces to £5.47 per patient. Adoption of ethnographic and interview methods in the collection of data was appropriate, and the use of NPT, whilst challenging, enhanced the understanding of the implementation process. The need to delay the collection of patient interview data to enable the intervention to inform patient care was highlighted. Conclusions: It is feasible to collect data with reasonable completeness and accuracy for the subsequent RCT, although refinement to improve the quality of the data collected will be undertaken. Based on resource use data collected, it was feasible to produce cost estimates for each individual component of the Embedding Package. The methods chosen to generate, collect and analyse qualitative data were satisfactory, keeping participant burden low and providing insight into potential refinements of the Embedding Package and customisation of the methods for the RCT. Trial registration: ISRCTN, ISRCTN21321635, Registered 07/07/2017—retrospectively registered

Improving the feasibility of stepped-wedge cluster randomised trials: a mixed methods enquiry

Stepped-wedge cluster randomised trials are methodologically complex, and can be logistically challenging, due to the staggered implementation of the intervention. These trials may therefore be more likely than other trials, to encounter issues that make them unable to successfully meet their objectives. Consequently, feasibility studies might be particularly useful for stepped-wedge cluster randomised trials. However, it has not been known what specific aspects of this trial design affect its feasibility, nor to what extent the feasibility of these trials has been investigated. The overarching aim of this thesis, was to improve the feasibility of stepped-wedge cluster randomised trials, by: understanding how the feasibility of these trials has been investigated; identifying the aspects of this trial design that affect its feasibility; investigating a solution to an identified issue; and making recommendations to improve the feasibility of trials of this design. This was achieved through a mixed methods enquiry. Feasibility studies, designed to inform stepped-wedge cluster randomised trials, were identified. The objectives of these studies were examined and the quality of reporting of those that had been published was assessed. The objectives of these studies were rarely specific to the chosen study design. Aspects of the stepped-wedge cluster randomised trial design that could affect its feasibility, were identified from individuals with an involvement, or interest, in trials of this design, through an online questionnaire and interview study. The process for stepped-wedge cluster randomised trials, of balancing prognostic covariates during the randomisation, was identified as a cause for concern for those involved in trials of this design. The use of covariate constrained randomisation for stepped-wedge cluster randomised trials, was therefore investigated using a simulation study. Based on the findings of this thesis, recommendations were made to improve the feasibility of future stepped-wedge cluster randomised trials.</div

Sample size calculations for stepped-wedge cluster randomised trials with unequal cluster sizes

Background The current methodology for sample size calculation for steppedwedge cluster randomised trials (SW-CRTs) is based on the assumption of the clusters being of equal size. However, as is often the case in CRTs, the clusters in SW-CRTs are likely to vary in size which in CRTs of other designs leads to a reduction in power. The effect of an imbalance in cluster sizes on SW-CRTs was not known, nor what an appropriate adjustment to the sample size should be. Trials 2016, Volume 17 Suppl 1 Page 4 of 6 Methods We proposed three adjusted design effects (DEs) for use in the calculation of the sample size for SW-CRTs with varying degrees of imbalance in cluster size, based on those suggested for use in CRTs with unequal cluster sizes. A simulation study was conducted which investigated the effect of unequal cluster sizes on the power of SW-CRTs, when the sample size was calculated using both the standard method and the three proposed adjusted DEs. Results An imbalance in cluster size was not found to significantly affect the power of a SW-CRT, and the proposed adjusted DEs generally resulted in trials that were severely over-powered. Conclusions We recommend that the standard method of sample size calculation for SW-CRTs be used when any imbalance in cluster size is expected to be small. When there is likely to be a large imbalance in cluster size it is recommended that simulations be used to determine if additional clusters are needed

The impact of an intervention to increase uptake to structured self-management education for people with type 2 diabetes mellitus in primary care (the embedding package), compared to usual care, on glycaemic control: study protocol for a mixed methods study incorporating a wait-list cluster randomised controlled trial

Abstract: Background: Approximately 425 million people globally have diabetes, with ~ 90% of these having Type 2 Diabetes Mellitus (T2DM). This is a condition that leads to a poor quality of life and increased risk of serious health complications. Structured self-management education (SSME) has been shown to be effective in improving glycaemic control and patient related outcome measures and to be cost-effective. However, despite the demonstrated benefits, attendance at SSME remains low. An intervention has been developed to embed SSME called the ‘Embedding Package’. The intervention aims to address barriers and enhance enablers to uptake of SSME at patient, healthcare professional and organisational levels. It comprises a marketing strategy, user friendly and effective referral pathways, new roles to champion SSME and a toolkit of resources. Methods: A mixed methods study incorporating a wait-list cluster randomised trial and ethnographic study, including 66 UK general practices, will be conducted with two intervention start times (at 0 and 9 months), each followed by an active delivery phase. At 18 months, the intervention will cease to be actively delivered and a 12 month observational follow-up phase will begin. The intervention, the Embedding Package, aims to increase SSME uptake and subsequent improvements in health outcomes, through a clear marketing strategy, user friendly and effective referral pathways, a local clinical champion and an ‘Embedder’ and a toolkit of resources for patients, healthcare professionals and other key stakeholders. The primary aim is, through increasing uptake to and attendance at SSME, to reduce HbA1c in people with T2DM compared with usual care. Secondary objectives include: assessing whether there is an increase in referral to and uptake of SSME and improvements in biomedical and psychosocial outcomes; an assessment of the sustainability of the Embedding Package; contextualising the process of implementation, sustainability of change and the ‘fit’ of the Embedding Package; and an assessment of the cost-effectiveness of the Embedding Package. Discussion: This study will assess the effectiveness, cost-effectiveness and sustainability of the Embedding Package, an intervention which aims to improve biomedical and psychosocial outcomes of people with T2DM, through increased referral to and uptake of SSME. Trial registration: International Standard Randomised Controlled Trials Number ISRCTN23474120. Assigned 05/04/2018. The study was prospectively registered. On submission of this manuscript practice recruitment is complete, participant recruitment is ongoing and expected to be completed by the end of 2019

Reporting of stepped wedge cluster randomised trials: extension of the CONSORT 2010 statement with explanation and elaboration

This report presents the Consolidated Standards of Reporting Trials (CONSORT) extension for the stepped wedge cluster randomised trial (SW-CRT). The SW-CRT involves randomisation of clusters to different sequences that dictate the order (or timing) at which each cluster will switch to the intervention condition. The statement was developed to allow for the unique characteristics of this increasingly used study design. The guideline was developed using a Delphi survey and consensus meeting; and is informed by the CONSORT statements for individual and cluster randomised trials. Reporting items along with explanations and examples are provided. We include a glossary of terms, and explore the key properties of the SW-CRT which require special consideration in their reporting

Proceedings of the First International Conference on Stepped Wedge Trial Design: York, UK, 10 March 2016

I1 Introduction Mona Kanaan, Noreen Dadirai Mdege, Ada Keding O1 The HiSTORIC trial: a hybrid before-and-after and stepped wedge design RA Parker, N Mills, A Shah, F Strachan, C Keerie, CJ Weir O2 Stepped wedge trials with non-uniform correlation structure Andrew Forbes, Karla Hemming O3 Challenges and solutions for the operationalisation of the ENHANCE study: a pilot stepped wedge trial within a general practice setting Sarah A Lawton, Emma Healey, Martyn Lewis, Elaine Nicholls, Clare Jinks, Valerie Tan, Andrew Finney, Christian D Mallen, on behalf of the ENHANCE Study Team O4 Early lessons from the implementation of a stepped wedge trial design investigating the effectiveness of a training intervention in busy health care settings: the Thistle study Erik Lenguerrand, Graeme MacLennan, John Norrie, Siladitya Bhattacharya, Tim Draycott, on behalf of the Thistle group O5 Sample size calculation for longitudinal cluster randomised trials: a unified framework for closed cohort and repeated cross-section designs Richard Hooper, Steven Teerenstra, Esther de Hoop, Sandra Eldridge O6 Restricted randomisation schemes for stepped-wedge studies with a cluster-level covariate Alan Girling, Monica Taljaard O7 A flexible modelling of the time trend for the analysis of stepped wedge trials: results of a simulation study Gian Luca Di Tanna, Antonio Gasparrini P1 Tackling acute kidney injury – a UK stepped wedge clinical trial of hospital-level quality improvement interventions Anna Casula, Fergus Caskey, Erik Lenguerrand, Shona Methven, Stephanie MacNeill, Margaret May, Nicholas Selby P2 Sample size considerations for quantifying secondary bacterial transmission in a stepped wedge trial of influenza vaccine Leon Danon, Hannah Christensen, Adam Finn, Margaret May P3 Sample size calculation for time-to-event data in stepped wedge cluster randomised trials Fumihito Takanashi, Ada Keding, Simon Crouch, Mona Kanaan P4 Sample size calculations for stepped-wedge cluster randomised trials with unequal cluster sizes Caroline A. Kristunas, Karen L. Smith, Laura J. Gray P5 The design of stepped wedge trials with unequal cluster sizes John N.S. Matthews P6 Promoting Recruitment using Information Management Efficiently (PRIME): a stepped wedge SWAT (study-within-a-trial) R Al-Shahi Salman, RA Parker, A Maxwell, M Dennis, A Rudd, CJ Weir P7 Implications of misspecified mixed effect models in stepped wedge trial analysis: how wrong can it be? Jennifer A Thompson, Katherine L Fielding, Calum Davey, Alexander M Aiken, James R Hargreaves, Richard J Hayes S1 Stepped Wedge Designs with Multiple Interventions Vivian H Lyons, Lingyu Li, James Hughes, Ali Rowhani-Rahbar S2 Analysis of the cross-sectional stepped wedge cluster randomised trial Karla Hemming, Monica Taljaard, Andrew Forbe

Completeness of reporting and risks of overstating impact in cluster randomised trials: a systematic review

Overstating the impact of interventions through incomplete or inaccurate reporting can lead to inappropriate scale-up of interventions with low impact. Accurate reporting of the impact of interventions is of great importance in global health research to protect scarce resources. In global health, the cluster randomised trial design is commonly used to evaluate complex, multicomponent interventions, and outcomes are often binary. Complete reporting of impact for binary outcomes means reporting both relative and absolute measures. We did a systematic review to assess reporting practices and potential to overstate impact in contemporary cluster randomised trials with binary primary outcome. We included all reports registered in the Cochrane Central Register of Controlled Trials of two-arm parallel cluster randomised trials with at least one binary primary outcome that were published in 2017. Of 73 cluster randomised trials, most (60 [82%]) showed incomplete reporting. Of 64 cluster randomised trials for which it was possible to evaluate, most (40 [63%]) reported results in such a way that impact could be overstated. Care is needed to report complete evidence of impact for the many interventions evaluated using the cluster randomised trial design worldwide

Completeness of reporting and risks of overstating impact in cluster randomised trials: a systematic review

Overstating the impact of interventions through incomplete or inaccurate reporting can lead to inappropriate scale-up of interventions with low impact. Accurate reporting of the impact of interventions is of great importance in global health research to protect scarce resources. In global health, the cluster randomised trial design is commonly used to evaluate complex, multicomponent interventions, and outcomes are often binary. Complete reporting of impact for binary outcomes means reporting both relative and absolute measures. We did a systematic review to assess reporting practices and potential to overstate impact in contemporary cluster randomised trials with binary primary outcome. We included all reports registered in the Cochrane Central Register of Controlled Trials of two-arm parallel cluster randomised trials with at least one binary primary outcome that were published in 2017. Of 73 cluster randomised trials, most (60 [82%]) showed incomplete reporting. Of 64 cluster randomised trials for which it was possible to evaluate, most (40 [63%]) reported results in such a way that impact could be overstated. Care is needed to report complete evidence of impact for the many interventions evaluated using the cluster randomised trial design worldwide