Birmingham Clinical Trials Unit

Jane Daniels

Deputy Director

60 second history• 1996 DH funding to the University

• 1997 Prof Richard Gray: first director

• 2007 UKCRC registered CTU status

• 2012 Prof Jon Deeks becomes director

• 2013 50 staff, 26 trials, £23m total live awards

• >2014 Sustainable growth

Statistics

Programming

Quality Assurance

Colo-proctology

Women’s Health

Renal Disease

Neuro-science

Cardio-vascular

Trauma, Critical Care and Anaesthetics

Pragmatic RCTs Test evaluation

Adaptive and pilot studies

Systematic reviews

Methodology

Research

BCTU Philosophy

Ask a good question

Answer it reliably

EFFECTIVENESS AND COST EFFECTIVENESS OF LEVONORGESTREL RELEASING INTRAUTERINE SYSTEM IN PRIMARY CARE AGAINST STANDARD TREATMENT FORMENORRHAGIAHEAVY MENSTRUAL BLEEDING

Janesh Gupta, Jane Daniels, Lee Middleton, Laura Gennard, Lisa Leighton, Tracy Roberts, Sabina Sanghera, Pelham Barton

with Joe Kai (Nottingham), Helen Pattison (Aston), Richard Gray (Oxford)

Treatment options• Levonorgestrel-

releasing intra-uterine system (LNG-IUS, Mirena® coil)

Standard treatment

• Tranexamic acid

• Mefenamic acid

• Oral contraceptive pill

• Progesterone only pill

Surgery

• Hysterectomy

• Endometrial ablation

Heavy menstrual bleeding

What’s important?

Actual blood loss

Subjective blood loss

Impact on everyday life

Outcomes

- HMB specific questionnaire

- Generic quality of life

- Further treatment (hysterectomy, endometrial ablation)

- Costs

- Acceptability and opinions on treatments

- 6 months, 1, 2, 5 years

A challenging trial2004 – HTA funding starts, trial start-up in era of new regulations

Feb 2005 – Opens to recruitment

July 2006 – Extended to secondary care

July 2009 – Recruitment ended with 571 patients

Jan 2013 – Main trial paper of 2 year follow-up published NEJM 2013;368(2):128-37

Dec 2014 – Aim to publish 5 year follow-up

Results – impact on life

Usual treatment 21 points p<0.001

LNG-IUS 33 points p<0.001

13 points difference (95%CI: 10 to 17), p<0.001

Impact

• Either treatment reduces the burden quickly and the effect is maintained

– Women should seek and be offered treatment

• LNG-IUS is more effective at relieving symptoms, is cost-effective and generally acceptable

• Already being adopted

• NICE guidelines update

Other BCTU work in this area• Ongoing trial of myomectomy versus uterine

artery embolisation for symptomatic fibroids

• Proposed trial of LNG-IUS versus ulipristal for long-term treatment of heavy menstrual bleeding

• Systematic review evidence– for overall benefit of hysterectomy over endometrial

ablation (BMJ 2010; 341:c3929)

– for bipolar radiofrequency ablation amongst endometrial ablation techniques (BMJ 2012;344:e2564)

A LARGE RANDOMISED ASSESSMENT OF THE RELATIVE CLINICAL AND COST-EFFECTIVENESS OF CLASSES OF DRUGS FOR PARKINSON'S DISEASE.

Carl Clarke, Natalie Ives, Cally Rick, Smitaa Patel, Keith Wheatley, Francis Dowling, Versha Cheed, Pui Au, Ryan Ottridge, Adrian Williams

with Richard Gray , Crispin Jenkinson, Alastair Grey, Emma McIntosh (Oxford)

Prescribing by class: 1998-2008

0

10

20

30

40

50

60

70

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

£ m

illi

on

s

Dopamine agonists

Levodopa

COMT inhibitors

MAOB inhibitors

"……the long-term benefits of initial dopamine agonist therapy remain unproven. A very large trial currently under way in the United Kingdom (PD MED) is randomising hundreds of subjects

to initial treatment with LD preparations, dopamine agonists, or selegiline. Five-year follow-up is projected. Widespread changes

in clinical practice should await more trial data.“R.L.Albin, K. A. Frey. Neurology, 2003; 60(3): 390-394

“Further trials are required to compare the initial treatment of PD with levodopa, dopamine agonists and MAOB inhibitors, preferably using quality-of-life and health economics outcome measures. The UK PD MED trial will attempt to address these comparisons.”

NICE's current guidelines on treatment of PD

PD MED

• Pragmatic, ‘real life’ trial

• Flexible randomisation to accommodate preference

• Relevant outcome measures – PDQ39

• Integrated economic assessment

• Long-term follow-up

Randomisation LD DA MAOBI Total

2-way: LD vs. DA 175 173 - 348

2-way: DA vs. MAOBI - 107 107 214

3-way: LD vs. DA vs. MAOBI 353 352 353 1058

Total 528 632 460 1620

Protocol Comparisons

LD vs. LD-sparing 528 878 1406 (87%)

DA vs. MAOBI - 459 460 919 (57%)

LD vs. LD-SPARING THERAPY:

PDQ-39 MOBILITY

wo

rsen

ing

qu

alit

y o

f lif

e

Test for increasing difference over time: p=0.2

Average difference (favours LD): 1.8 points (CI: 0.6 to 3.0); p=0.004

PD MED conclusions

• LD provides

– Greater initial motor control

– Better overall quality of life in short and long term

– Better scores on mobility and other domains

– Greater risk of developing dyskinesias

• MAOBIs are marginally better than DAs

• However, magnitude of effect is below that considered clinically meaningful

Other BCTU work in this area• PD SURG showed deep brain stimulation

improved PDQ-39 scores more than medical treatment at 1 year. Lancet Neurol. 2010 Jun;9(6):581-91

• PD REHAB has completed recruitment of 763 participants, who had occupational and physical therapy or none.

• PD COMM a pilot study of speech and language therapy shows a full study is possible

• PD GEN is the UK’s largest PD biobank

PULSE OXIMETRY AS A SCREENING TEST FOR CONGENITAL HEART DEFECTS IN NEWBORN INFANTS: THE PULSEOX TEST ACCURACY STUDY

Andy Ewer, Jon Deeks, Lee Middleton, Jane Daniels, Alex Vince, Leanne Fulcher, Tracy Roberts, Peter Auguste, Pelham Barton

with Helen Pattison, Rachel Powell (Aston), Khalid Khan, Shakila Thangaratinum (QMUL)

Congenital Heart

Disease

3% all infant mortality

Antenatal detection,Clinical exam

Hypoxaemiain significant/ critical CHD

• Feasiblity of PO as a screening tool in newborn

• Accuracy of PO for diagnosing critical and serious CHD

• Acceptability of PO as a screening method among parents and health professionals.

• Cost effectiveness

20,000 asymptomatic newborns >34 weeks prior to discharge from 6 centres in West Midlands

Summary• 20 055 babies tested

• 195 tested positive (0.96%)

• 26 serious or critical CHD (13%)

• 9 false negatives (8/9 detected by exam prior to discharge)

• 0.8% false positives but 27% had other problems

Summary• PO is safe and feasible in a postnatal ward• PO identifies additional cases of critical/ serious

CHD over clinical exam• PO screening acceptable to parents and staff• PO in addition to clinical exam is cost-effective• Added advantage of detecting other serious, non-

cardiac illnesses

Lancet. 2011 Aug 27;378(9793):785-94Arch Dis Child Fetal Neonatal Ed. 2013;98(1):F59-63Arch Dis Child. 2012;97(3):221-6

Impact