Trials

Adaptive designs: current status, future outlook

Andy Grieve

An adaptive seamless phase II/III clinical trial design incorporating short-term endpoint information

Nigel Stallard

Flexible trial design in practice – dropping and adding arms in STAMPEDE: a multi-arm multi-stage randomised controlled trial

Matthew R Sydes, Nicholas D James, Malcolm D Mason, Noel W Clarke, Claire Amos, John Anderson, Johann de Bono, David P Dearnaley, John Dwyer, Gordana Jovic, Alastair Ritchie, Martin Russell, Karen Sanders, George Thalmann, Mahesh KB Parmar

Optimal design for multi-arm multi-stage clinical trials

James MS Wason, Thomas Jaki

Model selection and sample size adaptation: HYPAZ trial

Simon Bond, Adrian Mander, Duncan Jodrell, Joseph Cheryian

How Cancer Research UK is adapting to adaptive designs

Julie Hearn, Nicola Keat, Kate Law, Rowena Sharpe

The importance of planning for a seamless transition in an adaptive phase II randomised trial

Andrea Marshall, Janet A Dunn, Julie Fletcher, Helen B Higgins, Christopher J Poole

Software tools for implementing simulation studies in adaptive seamless designs: introducing R package ASD

Nick Parsons, Tim Friede, Susan Todd, Nigel Stallard

Adverse effects

Stephen JW Evans

Eliciting harms data from trial participants: how perceptions of illness and treatment mediate recognition of relevant information to report

Elizabeth N Allen, Karen I Barnes, Adiel Mushi, Isolide Massawe, Sarah G Staedke, Ushma Mehta, Lasse S Vestergaard, Martha M Lemnge, Clare I Chandler

Anti-epileptic drug harms: issues for meta-analysis

Catrin Tudur Smith, Arif Shukralla, Sarah Donegan, Karla Hemming, Graham A Powell, Paula Williamson, Anthony Marson

Adverse event reporting in randomised trials of neuropathic pain: challenges for clinical usefulness of safety data

Victoria R Cornelius, Odile Sauzet, Salma Ayis, Joy Ross, Paul Farquhar-Smith, Ruth A Branford, John E Williams, Janet L Peacock

Documentation of adverse events in non-commercial trials of intravitreal injection of anti-VEGF drugs to treat wet age-related macular degeneration (AMD)

Barnaby C Reeves, Wendy Underwood, Heike Cappel-Porter, Sarah Baos, Chris A Rogers, Michael Arnott, Simon P Harding, Usha Chakravarthy, Alex E Foss

Using biomarkers prospectively in adaptive clinical trials

Donald A Berry

Data modeling methods in clinical trials: experiences from the clinical trial methods in neurodegenerative diseases project

Athanasios Anastasiou, Emmanuel Ifeachor, John Zajicek

Stratified medicine in practice: review of predictive biomarkers in European Medicines Agency (EMA) indications

Kinga Malottki, Mousumi Biswas, Jon Deeks, Richard Riley, Charles Craddock, Lucinda Billingham

Designing a preliminary adaptive study to inform a biomarker trial in Psoriasis

Andrew T Prevost, Jack Bowden

Selection of subjects for clinical trials in Alzheimer’s disease and mild cognitive impairment with machine learning analysis of MRI and CSF biomarkers

Javier Escudero, John P Zajicek, Emmanuel Ifeachor

Comparing diagnostic tests and biomarkers: trials in people with discordant test results

Richard Hooper, Karla Díaz-Ordaz, Andrea Takeda, Khalid Khan

Choice of transformation for modelling non-linear continuous biomarkers

Deborah D Stocken, Lucinda J Billingham, Philip J Johnson, Nick Freemantle

Statistical issues in the analysis of non-pharmacological therapy trials with clustering by care-provider or therapy group

Chris Roberts

Stratified randomisation: a hidden form of clustering?

Brennan C Kahan, Tim P Morris

A review of methodology for sample size calculations in cluster randomised trials

Clare Rutterford, Sandra Eldridge, Andrew Copas

Clustering in surgical trials – database of intra-cluster correlations

Jonathan A Cook, Thomas Bruckner, Graeme S MacLennan, Christoph M Seiler

Sample size in cluster randomised trials with unequal clusters

Ivana Holloway, Amanda Farrin

Sample size determination through power simulation; practical lessons from a stepped wedge cluster randomised trial (SW CRT)

Munyaradzi Dimairo, Mike Bradburn, Stephen J Walters

Coping with clustering in sample size calculations

Rebecca Playle, Mark Kelly, Robert Newcombe, Kerry Hood

Equivalence and non inferiority trials

Ralph B D’Agostino Sr

Is there a danger of “biocreep” with non-inferiority trials?

Primrose Beryl, Werner Vach

Choice of randomisation time-point in non-inferiority studies of reduced treatment duration: experience from the SCOT study

Jim Paul, Tim Iveson, Rachel Midgley, Andrea Harkin, Michelle Masterton, Laura Alexander, Jim Cassidy

The evolution of and challenges in defining the clinical endpoint in tuberculosis treatment trials with non-inferiority designs

Patrick PJ Phillips, Angela Crook, Andrew J Nunn

Challenges of defining a non-inferiority margin: a case study of non-inferiority randomized controlled trials of oral anti-thrombolytic agents for prophylaxis of venous thromboembolic events after orthopedic surgery

Grace Wangge, Olaf H Klungel, Kit CB Roes, Antonius de Boer, Arno W Hoes, Mirjam J Knol

The STAR trial: can quality of life benefit offset any survival detriment?

Fiona Collinson, Janet Brown, Christopher McCabe, Julia Brown, Sandy Tubeuf, Barbara Potrata, Jenny Hewison, Ines Rombach, Peter Selby, Catherine Olivier, Helen Howard, Walter Gregory

The ABC of non-inferiority margin setting: an investigation of approaches

Steven A Julious

Streamlining regulation of clinical trials – update on the Academy of Medical Sciences review and government’s response

Gary A Ford

Interim reports for data monitoring committee review vs final reports for regulatory filing

KyungMann Kim

A practical solution to ‘Continuing Care Site’ issues in neonatal clinical trials – a pragmatic approach to regulatory and research governance review

Kayleigh Morgan, Ed Juszczak, Ursula Bowler

Exploring the ethical and practical challenges of conducting clinical trials in care home settings

Fiona Wood, Hayley Prout, Arun Acharjya, Jacqueline Nuttall, Kerry Hood, Christopher Butler

Risk-adapted approaches to the management of clinical trials: guidance from the Department of Health (DH)/Medical Research Council(MRC)/Medicines and Healthcare Products Regulatory Agency (MHRA) Clinical Trials Working Group

Sarah Meredith, Martyn Ward, Gillian Booth, Andrew Fisher, Carrol Gamble, Heather House, Martin Landray

Using economic modelling to contribute to the prioritisation and design and clinical trials: ready for prime time

Mark Sculpher

Analysis of adverse events and quality of life data for an economic evaluation of adjuvant chemotherapy in colorectal cancer: when can we stop collecting?

Kathleen A Boyd, Andrew H Briggs, Jim Paul, Tim Iveson, Rachel Midgely, Andrea Harkin, Gaynor Bates, Laura Alexander, Jim Cassidy

What is the value of collecting detailed costing data in clinical trials?

Helen Dakin, Giselle Abangma, Sarah Wordsworth

Bayesian analysis of trial-based cost-effectiveness in the presence of missing data: effects of including covariates on efficiency of estimation in the ASTER trial

Linda Sharples, Christopher Jackson, Ella Wheaton, Robert Rintoul

HERALD (Health Economics using Routine Anonymised Linked Data)

Muhammad J Husain, Sinead Brophy, Steven Macey, Leila M Pinder, Mark D Atkinson, Roxanne Cooksey, Ceri J Phillips, Stefan Siebert

Estimation of cost-effectiveness in randomised controlled trials when not all participants allocated to active intervention receive it

Chris Metcalfe

How best to handle the evidence in a cost-effectiveness analysis of TAVI in the UK

Aileen Murphy, Elizabeth Fenwick, Andrew Briggs, Matthew Neilson

The influence of CONSORT on the quality of reporting of randomised controlled trials: an updated review

Lucy Turner, David Moher, Larissa Shamseer, Laura Weeks, Jodi Peters, Amy Plint, Douglas G Altman, Kenneth F Schulz

What can available randomised controlled trials evaluating monitoring strategies tell us about the design and analysis of future trials?

Jacqueline Dinnes, Jenny Hewison, Doug Altman, Jon Deeks

Cochrane systematic reviews as a source of information for practice and trials

Mike Clarke, Thomas T Clarke, Lorcan Clarke

Biases in clinical trials with sequential monitoring

Manjula Schou, Ian C Marschner

Making best use of existing evidence when planning trials

Verena Roloff, JPT Higgins

Protecting intellectual property associated with health technology trials – another barrier to multi-centre trials?

Sue Ross, Laura Magee, Stephen Wood

Stopping clinical trials early for futility: retrospective analysis of several randomised clinical studies

Mark Jitlal, Iftekhar Khan, Siow Ming Lee, Allan Hackshaw

The use of systematic reviews in the design of randomised trials

Ashley P Jones, Carrol Gamble, Mike Clarke, Paula R Williamson

Central statistical monitoring in clinical trials

Amy A Kirkwood, Allan Hackshaw

Feasibility of establishing a central repository for the individual participant data from research studies

Catrin Tudur Smith, Kerry Dwan, Mike Clarke, Richard Riley, Douglas Altman, Paula Williamson

Individual participant data meta-analyses compared with meta-analyses based on aggregate data

Catrin Tudur Smith, James Oyee, Maura Marcucci, Maroeska Rovers, Alfonso Iorio, Richard Riley, Paula Williamson, Mike Clarke

What are the characteristics of an application (or team) which are associated with success or failure of an application to the NIHR HTA programme for research funding?

Sheila Turner, Peter Davidson, Louise Dent, Elke Streit, Victoria Bowness

Strategies for handling missing data in randomised trials

Ian R White

Using linear increment models for the imputation of missing composite outcomes in randomized trials

Aidan G O’Keeffe, Daniel M Farewell, Brian DM Tom, Vernon T Farewell

CONSORT: missing missing data guidelines, the effects on HTA monograph reporting

Yvonne Sylvestre

Simulation study - handling missing covariates in the context of external validation

Laura J Bonnett, Tony G Marson, Paula R Williamson, Catrin Tudur-Smith

Patient reported outcomes: past, present, and future

Jane A Scott

The effect of diabetes complications on health-related quality of life: estimating the bias due to unobserved heterogeneity using the UKPDS

Maria L Alva, Alastair Gray, Borislava Mihaylova, Philip Clarke

Patient Reported Outcomes: misinference from ordinal scales?

Mike Horton, Alan Tennant

Making continuous outcomes meaningful to clinicians

Janet L Peacock, Odile Sauzet, Sally M Kerry

Efficiency gains resulting from the ordinal analysis of a functional outcome scale: a case study of a major phase III stroke trial

Gordon D Murray, Else Charlotte Sandset, Philip MW Bath, Eivind Berge

Use of an objective measure of time to recovery after cardiac surgery – the STET randomised controlled trial

Chris A Rogers, Katie Pike, Gianni D Angelini, Barney C Reeves

The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities

Duolao Wang, Con Ariti, Tim Collier, Stuart Pocock

The COMET (Core Outcome Measures in Effectiveness Trials) Initiative

Paula R Williamson, Doug G Altman, Jane M Blazeby, Mike Clarke, Elizabeth Gargon

A mixed methods approach to assess the reliability of a test for the success of blinding in a surgical randomised controlled trial (RCT)

Caroline E Boulind, Kerry Avery, Chris Metcalfe, Nader K Francis, Jane M Blazeby

Patient reported clinical outcomes: the challenges and implications for randomised controlled trials

Suzanne Breeman, Alison McDonald, Gladys McPherson, Graeme MacLennan, Marion Campbell, Kath Starr, Seonaidh Cotton

Treatment effect bias in randomised controlled trials using surrogate outcomes: a preliminary cohort study analysis

Oriana Ciani, Rod S Taylor

Optimising patient recall of adverse events over prolonged time periods

Louise Hiller, Janet A Dunn, Helen B Higgins, Emma Ogburn-Storey, Shrushma Loi, Anne-Laure Vallier, Helena M Earl

Applying Rasch analysis to the SF-36 physical function scale: effect of dependent items

Mike Horton, Alan Tennant

Incorporating patient reported outcomes (PROs) in gastro-intestinal (GI) cancer randomised controlled trials (RCTs): the need for adequate rationale and integrated reporting

Rhiannon C Macefield, Angus GK McNair, Natalie S Blencowe, Sara T Brookes, Jane M Blazeby

The case for a HRQL core outcome set: outcome reporting bias in oesophageal cancer studies

Rhiannon C Macefield, Marc Jacobs, Natalie S Blencowe, Ida J Korfage, Joanna Nicklin, Sara T Brookes, Mirjam A Sprangers, Jane M Blazeby

Optimising trial monitoring on the AZURE trial

Geraldine A Matthews, Roger Burkinshaw, Claire Davies, Vicky Hiley, Helen C Marshall, Robert E Coleman

Pain assessment: the relationship between pain thresholds and pain severity in osteoarthritis

Vikki Wylde, Shea Palmer, Ian D Learmonth, Paul Dieppe

What have we learned from a decade of patient involvement in OMERACT and its effect on trial outcome assessments?

John R Kirwan, Maarten de Wit

Consumer involvement at the MRC Clinical Trials Unit: results of a survey

Claire L Vale, Lindsay C Thompson, Silvia Forcat, Claire Murphy, Bec Hanley

Public involvement in the design and conduct of clinical trials: a narrative review of case examples

Jonathan Boote, Wendy Baird, Anthea Sutton

Including service users in trials and rigorous studies in health and social care: developing a standard operating procedure for researchers

Bridie Angela Evans, Emma Bedson, Philip Bell, Hayley Hutchings, Lesley Lowes, David Rea, Anne Seagrove, Stefan Siebert, Graham Smith, Helen Snooks, Marie Thomas, Kym Thorne, Ian Russell

Self-help therapy and recovery in psychosis: methodological considerations and service user involvement in a partially randomised preference trial

Samantha Hartley, Gillian Haddock

The development of a DVD to aid patients’ understanding of surgical breast reconstruction clinical trials: QUEST Trials A & B

Judith Mills, Maria Emson, Judith M Bliss, Zoe E Winters

Research to meet the needs of the NHS: a review of published NIHR HTA clinical trials

Amanda Young, Ruairidh Milne, James Raftery, Louise Dent, David Turner, Peter Davidson, Andrew Cook

Identifying appropriate phase II trial designs

Sarah R Brown

Phase II investigation of a PARP inhibitor (olaparib) in castration resistant prostate cancer (CRPC) which incorporates the possibility that treatment effect may be restricted to biomarker defined subgroups

Roger A’Hern, Johann DeBono, Shahneen Sandhu, Eletheria Kalaitzaki, Martine Usdin, Emma E Hall

Design choices for small-scale phase II trials with non-inferiority (NI) intention

Hong Sun, Shu-Fang Hsu Schmitz

A Bayesian dose-finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis

Anne Whitehead, Helene Thygesen, Vladimir Dragalin, John Whitehead

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia

Christina Yap, Lucinda Billingham, Andrew Pettitt

Experiences in the design and implementation of phase II trials in CLL

Dena R Cohen, Peter Hillmen, Julia M Brown, Walter M Gregory

Statistical validation of surrogate outcome measures

Marc Buyse

Investigator led trials: challenges and opportunities

Peter Sandercock

Seven myths of randomisation in clinical trials

Stephen Senn

Alternative approaches to tuberculosis treatment evaluation: the role of pragmatic trials

Daniel J Bratton, Andrew J Nunn

Treatment success in pragmatic randomised controlled trials: a review of trials funded by the UK Health Technology Assessment programme

Louise Dent, James Raftery

Pragmatic trials of non-NHS interventions: experiences from a Randomised Controlled Trial of the Strengthening Families 10-14 UK Programme (SFP10-14 UK)

Jo Holliday, J Segrott, H Rothwell, C Phillips, K Hood, Z Roberts, J Scourfield, S Murphy, D Foxcroft, P Daniels, L Moore

Generalisability of trials of home blood pressure monitoring; a comparison of two UK primary care trials

Sally M Kerry, Hugh S Markus, Teck K Khong, Pippa Oakeshott

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

Helen Marshall, Ivana Holloway, Julia M Brown

Holding onto power: why confidence intervals are not (usually) the best basis for sample size calculations

Chris Metcalfe

Making the most of animal data – improving the prospect of success in pragmatic trials in the neurosciences

Kieren J Egan, Emily S Sena, Hanna M Vesterinen, Malcolm R Macleod

The CORONIS Trial: international study of caesarean section surgical techniques

Edmund Juszczak, Barbara Farrell

Randomised Evaluations of Accepted Choices in Treatment (REACT) trials: large-scale pragmatic trials within databases of routinely collected electronic healthcare records

Tjeerd-Pieter van Staa, Ben Goldacre, Martin Gulliford, Jackie Cassell, Munir Pirmohamed, Adel Taweel, Brendan Delaney, Liam Smeeth

QUEST Perspective Study (QPS) to measure the understanding by patients and healthcare professionals of surgical breast reconstruction clinical trials: QUEST Trials A & B

Zoe E Winters, Judith Mills, Marie Emson, Judith M Bliss, Rob Horne

Strategic use of new generation antidepressants for depression, SUN(^_^)D : study design and rationale

Naohiro Yonemoto, Tatsuo Akechi, Shinji Shimodera, Mitsuhiko Yamada, Kazuhira Miki, Norio Watanabe, Masatoshi Inagaki, Toshi A Furukawa

Trials in rare diseases: the need to think differently

Lucinda Billingham, Kinga Malottki, Mark Pritchard, Neil Steven

Comparison of anticipated and actual control group outcome in randomised trials in paediatric oncology provides evidence that non-randomised studies are biased in favour of the novel treatment

Veronica Moroz, Jayne Wilson, Keith Wheatley

Recruitment into trials of rare conditions - experiences from the STOP GAP trial

Recruitment to trials - why is it hard and how might we make it less so?

Shaun Treweek

Investigating strategies to improve attendance at screening visits in a randomized trial

Fang Chen, K Rahimi, R Haynes, K Naessens, M Taylor-Clarke, C Murray, Jane Armitage

Rates of recruitment from systematic and opportunistic methods: preliminary results from the DDELPHI study

Melvyn Hillsdon

FARSITE: evaluation of an automated trial feasibility assessment and recruitment tool

Sarah Thew, Gary Leeming, John Ainsworth, Martin Gibson, Iain Buchan

Exploring meaning of participation in a clinical trial in a developing country setting: implications for recruitment

Joanna Reynolds, Peter Mangesho, Lasse S Vestergaard, Clare Chandler

Improving recruitment to clinical trials with a register of a million patients who agree to the use of their clinical records for research in the Scottish Health Research Register (SHARE)

Frank M Sullivan, Shaun Treweek, Anile Grant, Fergus Daly, Donald Nicolson, Brian McKinstry, Janet Hanley, Jenny Ure, Aziz Sheikh

What parents think about being approached about children’s trials, how this differs from what practitioners expect, and what this tells us about enhancing recruitment

Bridget Young, Valerie Shilling, Helen Hickey, Emma Sowden, Rosalind L Smyth, Paula R Williamson

Recruiting patients cost-effectively by mail

Theingi Aung, Helen Cowan, Richard Haynes, Louise Bowman, Jane Armitage

Analysis and validation of a Parkinson’s disease register as a recruitment tool for clinical studies

Camille B Carroll, Amy Palmer, Christine Cosby, John P Zajicek

Recruiting patients with advanced malignant and non-malignant disease: lessons learned from a palliative care RCT

Morag C Farquhar, Barbara Brafman-Kennedy, Irene J Higginson, Sara Booth

Recruitment to the pilot phase of Start2quit – lessons learned

Leanne M Gardner, Hazel Gilbert, Irwin Nazareth

Analysis of patient information leaflets (PILs), used in clinical trials using the Informed Consent Evaluation instrument (ICEi)

Katie Gillies, Wan Huang, Zoe Skea, Seonaidh Cotton

The complexities of maximising recruitment to complex intervention trials in child and adolescent mental health services

David Cottrell, Liz Graham, Amanda Farrin

Can we improve recruitment to trials and informed consent by improving participant information sheets? - A nested RCT

Peter Knapp, Natasha Mitchell, David K Raynor, Jonathan Silcock, Brian Parkinson, Janet Holt, Yvonne Birks, Simon Gilbody

Addressing patient treatment preferences at trial recruitment

Nicola Mills, Julia Wade, Athene J Lane, Freddie C Hamdy, David E Neal, Jenny L Donovan

Releasing interim results from a randomised clinical trial: an example from the QUARTZ trial

Matthew Nankivell, Richard Stephens, Cheryl Pugh, Paula Mulvenna, Rachael Barton, Ruth Langley, Mahesh Parmar

Recruiting ahead of target: What worked in the REEACT trial?

Puvan Tharmanathan, Gwen Brierley, Elizabeth Littlewood, Phil Andersen, Simon Gilbody

Recruiting and retaining medical patients in trials of complex interventions: practical experience of challenges and solutions in three multi-centre trials

Jane Walker, Michael Sharpe

Strategies to reduce attrition in randomised trials

Valerie Brueton, Jayne Tierney, Sally Stenning, Irwin Nazareth, Sarah Meredith, Seeromanie Harding, Greta Rait

Departure from treatment protocol in published randomised controlled trials: a review

Susanna Dodd, Ian White, Paula Williamson

The use of the Medication Event Monitoring System (MEMS) for assessing medication adherence for chronic conditions: use and results from a 12 month trial of patients in remission with ulcerative colitis (UC)

David Gillespie, Kerenza Hood, Andrew Williams, Rachel Stenson, Christopher Probert, Antony Hawthorne

Adherence in a randomised controlled trial comparing liberal and restrictive red blood cell (RBC) transfusion protocols after cardiac surgery (TITRe2)

Katie Pike, Rachel Brierley, Chris A Rogers, Gavin J Murphy, Barney C Reeves

Complexities of retention in primary care randomised trials: A thematic analysis of in-depth interviews

Valerie Brueton, Fiona Stevenson, Claire Vale, Greta Rait

Maximising adherence to study protocol within pharmaco-rehabilitation clinical trials

Suzanne Hartley, Sharon Ruddock, Bipin Bhakta, John Pearn, Lorna Barnard, Alison Fergusson, Dean Langan, Amanda Farrin

Understanding factors influencing questionnaire response rates to maximise retention in a long term complex intervention trial

Athene J Lane, Liz Down, Julia Wade, David Neal, Freddie Hamdy, Jenny Donovan

A key risk indicator approach to central statistical monitoring in multicentre clinical trials: method development in the context of an ongoing large-scale randomized trial

Valdés-Márquez Elsa, Hopewell C Jemma, Landray Martin, Armitage Jane

Survival analysis: coping with non proportional hazards in randomized trials

Patrick Royston, Mahesh KB Parmar

Crossing survival curves: alternatives to the log-rank test

George Bouliotis, Lucinda Billingham

A new measure of predictive ability for survival models

Babak Choodari-Oskooei, Patrick Royston, Mahesh KB Parmar

Evaluation of methods to adjust for treatment switching in clinical trials

Richard Fox, Lucinda Billingham, Keith Abrams

Impact of the censoring distribution on time-to-event problems in the presence of competing risks

Mark W Donoghoe, Val Gebski

A robust parameterisation for the analysis of survival data in the presence of covariates with extreme value observations

Richard Jackson, Trevor Cox

Randomised controlled trials of complex interventions

John Norrie

Designing trials of complex interventions for efficacy and mechanisms evaluation

Richard A Emsley, Jonathan Green, Graham Dunn

How do treatments for chronic fatigue syndrome work? Exploration of instrumental variable methods for mediation analysis in PACE – a randomised controlled trial of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care

Kimberley Goldsmith, Trudie Chalder, Peter White, Michael Sharpe, Andrew Pickles

Statistical design of mental health complex intervention trials

Sabine Landau

Modelling multiple outcomes to improve the detection of causal mediation effects in complex intervention trials

Neil Casey, Simon Thompson, Andrew T Prevost

MATRICS: A Method for Aggregating The Reporting of Interventions in Complex Studies

Kymberley Thorne, Gabi S Jerzembek, Wai-Yee Cheung, David Cohen, Hayley A Hutchings, Frances L Rapport, Anne C Seagrove, John G Williams, Ian T Russell

Understanding the complexity of surgical procedures in RCTs: a pilot study to test the application of the MRC framework for evaluating complex healthcare interventions in the operating theatre

Mark O Eveleigh, Natalie S Blencowe, Nicola Mills, Jane M Blazeby

Designing and analysing pragmatic clinical trials of complex interventions in mental health: challenges and solutions

Amanda J Farrin, Michelle Collinson

A pilot factorial randomised cohort trial of manual therapy or acupuncture for low back pain

Vivienne C Dascanio, Yvonne Birks, David Torgerson

Practical and methodological challenges in the design and implementation of a cluster-randomised feasibility trial of the management of urinary incontinence after stroke

Chris J Sutton, Lois Thomas, Denise Forshaw, Caroline L Watkins