Welcome to the Centre for Biostatistics Showcaseresearch.bmh.manchester.ac.uk/biostatistics/aboutus/Centrefor... · Calvin Heal. Centre for Biostatistics Showcase 2017 Non-pharmacological

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

http://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

[email protected]

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


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


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

http://www.dimblebycancercare.org/


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


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 PhD: Nia Coupe

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

are overweight or obese

• Supervisors

– Sarah Peters

– Sarah Cotterill


• ‘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.


NIHR CLAHRC GM

Project reports and papers:

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








Matthew Gittins

Lecturer in Biostatistics [email protected]

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.


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


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