Welcome to the Centre for Biostatistics...

Welcome to the Centre for Biostatistics Showcase

Weds 3rd May 2017

Programme

13:40 Prof Richard Emsley “The Clinical Trials Unit”

13:50 Dr Jamie Sergeant “The Manchester Musculoskeletal Biomedical Research Unit”

14:00 Dr Sarah Cotterill “Working with the NIHR CLAHRC Greater Manchester”

14:10 “What we do” Session 1:

Matthew Gittins, Liz Howarth, Jack Wilkinson, Calvin Heal

14:30 Tea and Coffee

Programme

14:50 Prof Andy Vail “The Biostatistics Collaboration Unit”

15:00 Dr David Reeves “The National School of Primary Care Research”

15:10 Prof Carlo Berzuini “Causal inference and its use in biomedical research”

15:20 Dr Matthias Pierce “The North West Hub for Trials Methodology Research”

15:30 Sarah Rhodes “The Research Design Service”

15:40 “What we do” Session 2:

Antonia Marsden, Fiona Holland, Stephen Pye, Hui Guo

16:00 End

Manchester Academic Health Science

Centre Trials Co-ordination Unit (CTU)

Professor Richard Emsley Deputy Director, MAHSC CTU Centre for Biostatistics, School of Health Sciences

What is the MAHSC CTU?

• Hosted by Christie NHS Trust since 2000

– Relocating to University by end 2017

• Funding from:

– MAHSC partners

– National Institute for Health Research CTU Support Funding

– University of Manchester (£1.2m)

– Health Innovation Manchester (£370k)

• New management team and structure

UK Clinical Trials Units

• Specialist units with a specific remit to design, conduct, analyse and publish clinical trials & other well-designed studies

• Currently 50 registered CTUs (46 Full/4 provisional)

www.ukcrc-ctu.org.uk

Pre Trial

• Statistics & Methodology

• Feasibility

• Budget

• Timely submission to Fun and constitution of IDSMC & TSC

• Liaison with Sponsor

• Trial supplies

Set-up

• Protocol development

• Coordinate meetings of oversight committees

• Liaise with sponsor

• Management of trial supplies

• CRF and database development

• Trial approval – ethical, institutional

• Establish/maintain Essential Documents centrally

• Site initiation and ongoing communication

Recruitment and follow-up • Primary contact

• Safety monitoring/ reporting

• Progress reports, amendment notification

• Monitor accrual

• Database support, data query resolution

• Interim and final analysis

• Reports for oversight committees

• Notification of the end of the trial

• Archiving arrangements

What does a CTU do?

Biostatistics input into CTU

• Trial design options

• Sample size/power

• Statistical analysis plans

• Statistical analysis

• Report during the trial

• Our model is to cost a senior and junior

statistician in each proposal

• Contact us as early as possible!

Areas of statistical expertise

1. Early phase oncology trials

– New Senior Lecturer in Clinical Trial Statistics

2. Efficacy and mechanisms evaluation

– Causal inference methods

– Precision medicine

3. Health Technology Assessment

Find out more at:

http://www.mahsc.ac.uk/

The NIHR Manchester Musculoskeletal

Biomedical Research Unit (BRU)

…and other stories

Jamie Sergeant

Lecturer in Biostatistics

Contents

• About me

• NIHR Manchester Musculoskeletal Biomedical

Research Unit (BRU)

• NIHR Manchester Biomedical Research Centre

(BRC)

• Biostatistics teaching and learning

…all with a focus on collaboration

About me

• Training in Maths and Statistics

• Qualified teacher

• Experience in risk prediction:

– breast cancer

– musculoskeletal diseases

• Interest in statistics:

– teaching and learning

– communication

NIHR Manchester Musculoskeletal

Biomedical Research Unit (BRU)

• 2012-2017

• £4.9m NIHR funding

• “Treating arthritis: right first time”

• Understanding why some patients

respond to certain treatments and

do not

BRU example: Predicting non-response to

methotrexate in rheumatoid arthritis

• Methotrexate is cheap and

effective for many…but not all

• Idea: predict who is unlikely to

respond to methotrexate

– earlier access to alternative drugs

– prevent disease progression

• Data: Rheumatoid Arthritis

Medication Study (RAMS)

BRU example: Predicting non-response to

methotrexate in rheumatoid arthritis

• Methods: multivariable

regression prediction model

• Results:

– easily-measurable predictors used

to predict non-response

– patient anxiety of particular interest

• Next: additional genetic and

biological predictors

NIHR Manchester Biomedical Research

Centre (BRC)

• 2017-2022

• £28.5m NIHR funding

• 7 themes

• 3 cross cutting themes

BRC themes

• Advanced radiotherapy

• Cancer precision medicine

• Cancer prevention and early detection

• Dermatology

• Hearing health

• Musculoskeletal diseases

• Respiratory diseases

BRC cross cutting themes

• Rapid translational incubator

• Biomarker platforms

• Informatics and data sciences

Biostatistics teaching and learning

• Context:

– Students have statistics learning needs

– Staff have statistics teaching needs

• Actions:

– Training course aimed at non-statisticians teaching

statistics: “Strategies for teaching statistics”

– Pilot of “Stats Buddy” offering specialist support to

non-specialist staff

…and clinical training for non-clinicians

Any questions?

Jamie Sergeant

Lecturer in Biostatistics

jamie.sergeant@manchester.ac.uk

CLAHRC Greater Manchester 23

NIHR CLAHRC Greater

Manchester Sarah Cotterill

Sarah Rhodes

Eva Batistatou

Nia Coupe

Centre for Biostatistics Showcase – 3 May 2017

CLAHRC Greater Manchester 25 CLAHRC Greater Manchester 25

OSCARSS

• Organising Support for CARers of Stroke Survivors

• Cluster randomised controlled trial (RCT)

• Partnership Between CLAHRC GM and Stroke Association

• Statistician - Sarah Rhodes:

–Design of cluster RCT

–Trial Management

–CLAHRC Workshop on design of

implementation research

CLAHRC Greater Manchester 26 CLAHRC Greater Manchester 26

Wound Audit

• Audit of prevalence of complex wounds and their

treatment

• Partnership between GM CLAHRC and 5 NHS Primary

Care Trusts

• Statistician - Sarah Rhodes:

–Analysis of large data set

–Dissemination to NHS Trusts

–Paper on ‘Better Value Wound Care’

–Using results to plan future work

CLAHRC Greater Manchester 27 CLAHRC Greater Manchester 27

End of Life: Carer Survey

• The contributions of family care-giving at end of life: A national post-

bereavement census survey of cancer carers

• Partnership between CLAHRC GM and Dimbleby Cancer Care

• Statistician – Eva Batistatou

- Analysis of the census survey of cancer carers

- Dissemination of results

- Plan of future work

CLAHRC Greater Manchester 28 CLAHRC Greater Manchester 28

Type 2 Diabetes Prevention

• Evaluation of NHS Diabetes Prevention Programme

– Salford pathfinder.

• Partnership between CLAHRC GM and Salford

health trusts, local authority and voluntary sector.

Funded by Public Health England.

• Mixed methods study: literature review, analysis of

routine data and qualitative interviews.

• Principal Investigator – Sarah Cotterill

CLAHRC Greater Manchester 29 CLAHRC Greater Manchester 29

Diabetic neuropathy screening

• Corneal confocal microscopy (CCM) for screening and early

assessment of diabetic neuropathy

• Partnership between CLAHRC GM and Heidelberg Engineering.

• Feasibility study in 4 opticians (400 patients)

• Statistician – Sarah Cotterill

– Research design

– Project management team

– Contribution to analysis

– Reports, papers

CLAHRC Greater Manchester 30 CLAHRC Greater Manchester 30

CLAHRC PhD: Nia Coupe

• SMART-C: commitments to promote behaviour change in people who

are overweight or obese

• Supervisors

– Sarah Peters

– Sarah Cotterill

CLAHRC Greater Manchester 31 CLAHRC Greater Manchester 31

• ‘TIDieR or Messier? Exploring the utility of TIDieR beyond trials’

• TIDieR template used in 6 CLAHRC GM projects

• Findings:

–We found the TIDieR tool to be a useful tool for applied research

outside the context of clinical trials and we have identified four

amendments to enhance its utility

• Authors: Sarah Cotterill, Sarah Knowles, Anne-Marie Martindale,

Rebecca Elvey, Nia Coupe, Susan Howard, Paul Wilson, Michael

Spence.

CLAHRC Greater Manchester 32 CLAHRC Greater Manchester 32

NIHR CLAHRC GM

Project reports and papers:

http://clahrc-gm.nihr.ac.uk/our-work/

Matthew Gittins

Lecturer in Biostatistics Matthew.Gittins@manchester.ac.uk

PhD – Environmental Epidemiology

Manchester Guardian, 8 December 1952 Wilkins ET. Air Pollution and the London Fog of December, 1952. Ama Archives of Industrial Hygiene and Occupational Medicine. 1954;9(3):247-248.

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OPRA 1996-2012 - 'Core' reporters only

• STRATEGIC - HTA clinical trial aiming to improve the uptake of cervical screening particularly in non-responders at first call.

• SSNAPIEST – Observational study describing and investigating factors that impact on stroke therapy received and the effect on health outcomes.

• THOR - Surveillance scheme monitoring occupational ill-health in the UK particularly attempting to account for excess zeros due to reporter fatigue.

Comparing missing data techniques

for intention-to-treat analyses

Liz Howarth

Missing data is a problem

• RCTs best method to compare treatments

– Complicated by non-compliance & missing data

• Non-compliance not necessarily a problem

– Pragmatic ‘ITT’ analysis ignores compliance

• Missing data IS a problem

– biased estimates, faulty inference

• Can we exploit links between compliance & missingness?

Compliance & missingness

• Some missing data techniques use auxiliary models

– Multiple Imputation

– Inverse Probability Weighting

• Does use of compliance in auxiliary models improve resulting ITT analysis?

Incomplete data ITT analysis Auxiliary model

Simulation study

• Generate data

– outcome & missingness both depend on compliance

• Compare different methods

– With and without compliance in auxiliary model

– ITT analysis on full data used as benchmark

• Bias and variability used as performance measures

PhD Aim: Develop statistical

methodology for the analysis of

complex multistage treatment

data.

Jack Wilkinson. Centre for Biostatistics Showcase 2017

Funder: NIHR

Supervisors: Steve Roberts, Andy Vail

PhD overview

IVF success rates

• 33 different ways of reporting pregnancy rates.

• 9 different ways of reporting live birth rates. Only 51% of websites reported live birth at all, 42% per cycle started – one to HFEA standard.

• 72% presented results without sample sizes, 26% without patient ages, 23% without specifying period. 80% did not report selection criteria.

Chemical Pregnancy 19% of clinics: -per cycle started -per egg recovery -per frozen cycle -per insemination -per transfer -unspecified denominator

Clinical Pregnancy 81% of clinics: -per cycle started -per egg recovery -per frozen cycle -per insemination -per transfer -per cycle -per first cycle -per treatment -unspecified -unspecified (cumulative) -per course of inseminations -per egg recovery (cumulative) -per three cycles -per blastocyst stage achieved -per embryo transferred

Pregnancy (undefined) 21% of clinics: -per cycle started -per frozen cycle -per insemination -per transfer -per cycle -per patient (cumulative) -per three cycles -unspecified denominator -per blastocyst stage achieved

Singleton Pregnancy 2% of clinics: -unspecified denominator

Continuing Pregnancy 2% of clinics: -per cycle started -per frozen cycle

OVERVIEW • Primarily applied statistician. • Cautiously skeptical re: much methodology research. • Given that most research is bad, how can statisticians be

more effective? • Teaching: statistics as reasoning and arguing with data –

not as a maths problem.

Calvin Heal. Centre for Biostatistics Showcase 2017

The effects of arthritis gloves on people with

Rheumatoid Arthritis or Inflammatory Arthritis with

hand pain: a multi-centre randomised controlled trial.

Pressure &

Warmth Warmth

or

For reducing hand pain during day activity.

Calvin Heal. Centre for Biostatistics Showcase 2017

Non-pharmacological interventions for spatial neglect due to

stroke and other non-progressive acquired brain injury in adults

Spatial neglect

• Lack of awareness of objects or people to the left

• Serious symptoms

• Often a result of injury to right cerebral hemisphere

Treatment / Rehabilitation

• Prismatic adaptation

• Transcranial direct-current stimulation

• Video feedback training

• Most treatments relatively new and have

limited evidence

Calvin Heal. Centre for Biostatistics Showcase 2017

A single-blind randomised controlled trial with a four

month and 12 month follow up comparing

Group-Metacognitive Therapy plus usual cardiac

rehabilitation (intervention group) with

usual CR alone (control group).

Background

• Heart attack/failure -> Cardiac rehabilitation

• 69000 patients annually (37% significant anxiety/depressive symptoms)

• Current treatment options have limited benefit

Metacognitive therapy