Systematic reviews and randomised trials: influencing public policy

Slide 1: Systematic reviews and randomised trials: influencing public policy 2 April 2008 Professor Mike Clarke UK Cochrane Centre Clinical Trial Service Unit, University of Oxford School of Nursing and Midwifery, Trinity College Dublin

Slide 2: Evidence Based Health Care • Is not only about systematic reviews of randomised trials of the effects of interventions • These provide one component of evidence based health care: an estimate of the effects of treatment • However, reliable knowledge of which interventions are beneficial, which are harmful and which have little or no effect is vital to well informed decision making • Reliable knowledge comes from reliable evidence, which needs to minimise chance and bias

Slide 3: • What role should the findings of randomised trials and systematic reviews have in influencing public policy? • What role should the conduct of randomised trials and systematic reviews have as part of public policy?

Slide 4: Answering these questions with ... • Examples of dilemmas faced by public policy • Some possible solutions • Some real findings • Resources that can help

Slide 5: Example

Slide 6: Sub-arachnoid haemorrhage What is the best way to stop the aneurysm from bleeding again?

Slide 7: International Sub-arachnoid haemorrhage trial ISAT

Slide 8: ISAT Endovascular coiling versus Neurosurgical clipping

Slide 9: Endovascular coiling 1073 patients Neurosurgical clipping 1070 patients

Slide 10: Endovascular coiling 1073 patients Neurosurgical clipping 1070 patients

Slide 11: Endovascular coiling 1073 patients Neurosurgical clipping 1070 patients RANDOMIZED

Slide 12: Is this worthwhile?

Slide 13: 25 20 Death Neurosurgery Cumulative percentage 15 Endovascular 5 10 Log-rank P=0.03 0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 Time since randomisation (months)

Slide 14: ISAT Dead or dependent at one year Neurosurgery 31% Endovascular 24%

Slide 15: Endovascular coiling Use of endovascular coils 1990 ~0% 2007 75-85%

Slide 16: Treatments for stroke: from suggestion through randomised trials to routine clinical practice Carotid endarterectomy Carotid angioplasty Aspirin - 20 prevention Dipyridamole + asp - 20 prevention Thienopyridines - 20 prevention Aspirin - acute stroke Neuroprotection - acute stroke Heparin - acute stroke Warfarin in AF - 20 prevention Warfarin in SR - 20 prevention Thrombolysis - acute stroke BP  - 20 prevention BP  - acute stroke Cholesterol  - 20 prevention Coiling ruptured aneurysms 1920 1930 1940 1950 1960 1970 1980 1990 2000

Slide 17: Example

Slide 18: Pregnancy What’s the difference between midwifery led care and consultant led care?

Slide 19: MidU Study

Slide 20: MidU Midwifery led care versus Consultant led care

Slide 21: Midwifery led care versus Consultant led care

Slide 22: Midwifery led care versus Consultant led care

Slide 23: Midwifery led care versus Consultant led care 1500 women

Slide 24: Midwifery led care versus Consultant led care 1500 women RANDOMIZED

Slide 25: Is this worthwhile?

Slide 26: MidU Results ?

Slide 27: Why were ISAT and MidU so sure that the answer was not already available? Systematic reviews

Slide 28: Systematic reviews

Slide 29: What is a systematic review? • Scientific research • Seeks to minimise bias • Avoids undue emphasis on a single trial • Maximises the power of previous research

Slide 30: Why do we need systematic reviews? • Overwhelming amount of healthcare literature • New research is rarely reported in context • Reliable knowledge is essential for better health care • Better health care is essential for better health.

Slide 31: Overwhelming amount of healthcare literature

Slide 32: “Over two million articles are published annually in the biomedical literature in over 20,000 journals - literally a small mountain of information, [a stack] would rise 500 metres” Mulrow. Systematic Reviews (BMJ Publishing Group, 1995)

Slide 33: health

Slide 36: Example

Slide 37: Early (operable) breast cancer Does tamoxifen reduce the risk of cancer recurrence and death?

Slide 38: Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) Overview Tamoxifen versus no immediate tamoxifen 30 years of research 88% of worldwide data in the overview 56 randomized trials 48,000 women 18,000 deaths

Slide 39: Tamoxifen vs no tamoxifen, 1998

Slide 40: Avoiding undue emphasis on individual trials

Slide 41: How sure are we about this treatment?

Slide 42: How sure are we about this treatment?

Slide 43: Tamoxifen for 5 years (ER+), 2005 Recurrence Breast cancer death

Slide 44: Tamoxifen versus no immediate tamoxifen ER+, All ages: Breast cancer mortality over a decade 25% 50% Tamoxifen (5 years) 18% 38%

Slide 45: Is this worthwhile?

Slide 48: What resources are available to help?

Slide 50: Cochrane Database of Systematic Reviews Issue 1, 2008 Contains the full text for • 3300 full Cochrane reviews • 1800 protocols for Cochrane reviews

Slide 51: The Cochrane Library Regional subscriptions Australia Scotland India South Africa Ireland Spain Denmark Wales England Wyoming Finland Northern Ireland HINARI Norway INASP Saskatchewan BIREME

Slide 52: Cochrane Systematic Reviews •Plain language summary •Methodological quality •Structured abstract •Results •Background •Discussion •Objectives •Authors’ conclusions •Eligibility criteria  Implications for practice  Studies  Implications for research  Participants •Acknowledgements  Interventions  Outcome measures •Potential conflict of interest •Search strategy •References •Methods •Tables •Description of studies •Analyses

Slide 53: Cochrane Systematic Reviews •Plain language summary •Methodological quality •Structured abstract •Results •Background •Discussion •Objectives •Authors’ conclusions •Eligibility criteria  Implications for practice  Studies  Implications for research  Participants •Acknowledgements  Interventions  Outcome measures •Potential conflict of interest •Search strategy •References •Methods •Tables •Description of studies •Analyses

Slide 54: Implications for Practice (2006) All Cochrane reviews 2801 Intervention works 1305 (47%) Intervention doesn’t work 206 (7%) Uncertain 1409 (50%) Only use in research 84 (3%)

Slide 55: Implications for Research (2005) All Cochrane reviews 2535 Types of intervention 2079 (82%) Types of participant 765 (30%) Types of outcome 1315 (52%) No more research 82 (3%)

Slide 56: Is this worthwhile?

Slide 57: National Institute for Health Research Estimate of costs • Contribution to the infrastructure costs of Cochrane Review Groups in the UK: £10,000 per review • Commissioning of a review under the Health Technology Assessment programme: £140,000 per review

Slide 58: Use of Cochrane reviews in UK guidelines and policy 54 NICE guidelines: 572 citations to Cochrane reviews 49 SIGN guidelines: 271 citations 12 Health Evidence Bulletins (Wales): 234 citations 56 Royal College’s guidelines: 226 citations 130 Clinical Knowledge Summaries: 518 citations 91 NHS HTA Reports: 306 citations

Slide 59: Influencing public policy: You are important • What role do you want the findings of randomised trials and systematic reviews to have in influencing public policy? • What role do you want the conduct of randomised trials and systematic reviews to have as part of public policy?

Slide 60: Better evidence

Slide 61: Better evidence better knowledge and policy

Slide 62: Better evidence better knowledge and policy better health care

Slide 63: Better evidence better knowledge and policy better health care better health

Slide 64: Some web addresses The Cochrane Collaboration www.cochrane.org The Cochrane Library www.thecochranelibrary.com

Slide 65: Some web addresses The Cochrane Collaboration www.cochrane.org The Cochrane Library www.thecochranelibrary.com