How To Analyse A Clinical Paper CHRIS DAVIDSON BRIGHTON UK
Transcription
How To Analyse A Clinical Paper CHRIS DAVIDSON BRIGHTON UK
How To Analyse A Clinical Paper CHRIS DAVIDSON BRIGHTON UK Why do we read original scientific papers? 2 y Inform clinical practice y Investigate new drugs/procedures y Find causes / risk factors for disease y Part of a research project y Pass examinations y Get promotion! REFERENCE: How to read a paper: The basis of Evidence-Based Medicine. Trisha Greenhalgh. Blackwell 4th Edition 2010 EFIM Clin. Research Course 2013 How to read a Paper y What was the Research Question? { Why was the Study needed? y What was the Study Design? { EFIM Clin. Research Course 2013 Was the Design appropriate? 3 What was the Research Design? y Primary Studies { Experiments { Clinical Trials { Surveys y Secondary Studies { Overviews (metaanalysis etc.) { Guidelines { Decision Analyses { Economic Analyses EFIM Clin. Research Course 2013 4 Broad Fields of Research 5 y Therapy: Drugs or Procedures { Preferred Design: RCT y Diagnosis: evaluation new test { Preferred Design: Cross-section Survey y Screening { Preferred Design: Cross-section Survey y Prognosis { Preferred Design: Longitudinal Survey y Causation { Preferred Design: Cohort / Case-Control Study y Psychometric studies { Preferred Design: Qualitative Study REFERENCE: How to read a paper: The basis of Evidence-Based Medicine. REFERENCE: How to read a paper: The basis of Evidence-Based Medicine. Trisha Greenhalgh. Blackwell 3rdrdEdition 2006 Trisha Greenhalgh. Blackwell 3 Edition 2006 EFIM Clin. Research Course 2013 Why are Randomised Controlled Trials (RCTs) considered so important? 6 THEY MINIMISE THE EFFECT OF CONFOUNDING VARIABLES EFIM Clin. Research Course 2013 RCTs : Statistics for the Amateur… 7 y Do the patients selected reflect the ‘Real World’? { y Inclusion/exclusion criteria { Compare demography / Rx in each Are there significant numbers of ‘drop-outs’ or ‘cross-over’ patients? { Are the statistical tests appropriate? { Are the studied groups comparable clinically? { y y Side-effects or patient/doctor preference EFIM Clin. Research Course 2013 y Parametric vs nonParametric data Is the p-value appropriate with multiple tests (p < 0.05 can occur every 20 tests by chance) Is the difference seen clinically relevant? { RELATIVE and ABSOLUTE differences Clinical Relevance of Trial results 8 From: Trial and Error: How to Avoid Commonly Encountered Limitations of Published Clinical Trials J Am Coll Cardiol. 2010;55(5):415-427. doi:10.1016/j.jacc.2009.06.065 EFIM Clin. Research Course 2013 Invasive compared with non-invasive treatment in unstable coronary artery disease: FRISC II prospective randomised multicentre study FRagmin and Fast Revascularisation during InStability in Coronary artery disease (FRISC II) Investigators* THE LANCET • Vol 354 • August 28, 1999 B a c k g r o u n d: In unstable coronary-artery disease early invasive procedures are common, despite lack of evidence for the superiority of this approach. W e compared an early invasive with a non-invasive treatment strategy in unstable coronary-artery disease . I n t e r p r e t a t i o n: The early invasive approach should be the preferred strategy in most patients with unstable coronary artery disease who have signs of ischaemia on electrocardiography or raised biochemical markers of myocardial damage. EFIM Clin. Research Course 2013 9 FRISC II Trial - Patients 10 EFIM Clin. Research Course 2013 FRISC II Trial: Results 11 Figure 3: Probability of death or myocardial infarction in invasive and non-invasive groups EFIM Clin. Research Course 2013 FRISC II Results 14 P = 0.031 12 RELATIVE RISK REDUCTION P = 0.045 10 % Events at 6 months 12.1 - 9.4 /12.1 = 22.3 % 8 6 P = 0.10 4 12.1 - 9.4 = 2.7 % 2 0 Intervention Control ABSOLUTE RISK REDUCTION Combined M. Infarct Death 9.4 12.1 7.8 10.1 1.9 2.9 EFIM Clin. Research Course 2013 12 FRISC II Study EFIM Clin. Research Course 2013 13 y MACE { { { Death Myocardial Infarction Re-vascularisation Used as a Quality standard for laboratories and published research in cardiac intervention J. Am. Coll. Cardiol. 2008;51;701-707 EFIM Clin. Research Course 2013 14 EFIM Clin. Research Course 2013 15 Composite End-Points 16 Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials Ferreira-Gonzalez et al BMJ 2007 334; 786 EFIM Clin. Research Course 2013 ARISTOTLE Trial N Engl J Med 2011; 365:981-992 17 EFIM Clin. Research Course 2013 So how to critically appraise? 18 3 STEPS EFIM Clin. Research Course 2013 Appraisal Tools 19 y Critical Appraisal Skills Programme { http://www.casp-uk.net/homepage/ y Evidence based medicine: Tool kit University of Alberta { http://www.ebm.med.ualberta.ca/ EFIM Clin. Research Course 2013 CASP website: http://www.casp-uk.net EFIM Clin. Research Course 2013 20 EFIM Clin. Research Course 2013 21 ARISTOTLE Trial N Engl J Med 2011; 365:981-992 22 y Group A: study methods and patient selection y Group B: study results y Group C: study design and conclusions EFIM Clin. Research Course 2013 ARISTOTLE Study DISCUSSION ARISTOTLE Trial: patient characteristics 24 EFIM Clin. Research Course 2013 ARISTOTLE Trial: patient characteristics 25 EFIM Clin. Research Course 2013 CHADS‐2 Score in AF 26 RISK FACTOR Cardiac Failure Hypertension Age >75 years Diabetes Stroke / TIA JAMA 2001;285:2864 – 2870. Madrid 2012 SCORE 1 1 1 1 2 CHADS‐2 Score in AF 27 ESC recommendation 2010: Treat if Score 2 or more Madrid 2012 ARISTOTLE Trial 28 EFIM Clin. Research Course 2013 ARISTOTLE Trial 29 EFIM Clin. Research Course 2013 ARISTOTLE Trial: time course 30 EFIM Clin. Research Course 2013 ARISTOTLE Trial: time course 31 EFIM Clin. Research Course 2013 ARISTOTLE Trial: sub-group analysis 32 EFIM Clin. Research Course 2013 33 EFIM Clin. Research Course 2013 Aristotle Trial: Conclusions 34 y Study Objectives met: { Non-inferiority to standard care warfarin { Significantly fewer heamorrhagic CVAs { Fewer serious haemorrhages { [No increase in MI] EFIM Clin. Research Course 2013 Aristotle Trial: Conclusions (2013) 35 y METHODS { Non_inferiority design { Definition haemorrhagic stroke { Representative sample { Interaction with anti platelet drugs { Double blind INR? { Control group comparable EFIM Clin. Research Course 2013 Aristotle Trial: Conclusions (2013) 36 y RESULTS { Withdrawal and lost patients low { INR 66% { Stroke positive but especially haemorrhagic stroke { Haemorhagic events significantly lower { 81% adverser outcomes { 33% serious adverse events EFIM Clin. Research Course 2013 Aristotle Trial: Conclusions (2013) 37 y DISCUSSION { Target INR levels important { Absolute vs relative risks { No cost effective ananlysis EFIM Clin. Research Course 2013 Aristotle Trial: Conclusions (2012) 38 y BUT { Stroke (primary endpoint) not clearly defined { Discrepancy between haemorrhagic stroke and cerebral haemorrhages { Other haemorrhagic complications (60%) not detailed { Further details necessary about drop-outs (>25%) { Further details on warfarin control (especially at the time of events) { ?heterogeneity from Asian recruits (INR control, % cerebral haemorhages). EFIM Clin. Research Course 2013 From: Influence of Global Region on Outcomes in Heart Failure Beta-Blocker Trials J Am Coll Cardiol. 2011;58(9):915-922. doi:10.1016/j.jacc.2011.03.057 Figure Legend: Major β-Blocker Trials (A) Overall results. (B) The United States versus the rest of the world (ROW). BEST = β-Blocker Evaluation of Survival Trial; CIBIS-II = Cardiac Insufficiency Bisoprolol Study; COPERNICUS = Carvedilol Prospective Randomized Cumulative Survival trial; MERIT-HF = Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure. Date of download: 6/13/2013 Copyright © The American College of Cardiology. All rights reserved. ARISTOTLE Study IS THIS A LANDMARK STUDY?