1. Vanderbilt Sports Medicine SELECTING LITERATURE An Evidence-Based Medicine Approach Kurt P. Spindler, MD Professor & Vice Chair, Orthopaedics Director, Vanderbilt Sports Medicine & Ortho PCC Head Team Physician, Vanderbilt University B+JD Young Investigators Initiative May 13-15, 2005

2. Why EBM Select Literature? 1. 1.Identify clinically relevant problem! 2. 2.Limit selection BIAS in peer- review paper 3. 3.Learn hierarchy clinical studies 4. 4.Develop hypothesis from best study designs 5. 5.Caveat: still need to play to study sections bias for innovation and “clinical importance”

3. Is There Evidence in Literature Supporting EBM Approach for ORTHOPAEDICS? 1. 1.JBJS-A, Jan 2003 Editorial (Heckman) Introducing levels of evidence Five levels Four study types 2. 2.AJSM, 2002 Abstract Format (Reider) Background Hypothesis STUDY DESIGN: list Methods / Results / Conclusion Clinical relevance

4. GOAL: Reach for Peaks! EBM approach review clinical literature Concepts apply basic science Application template

5. Basics Title Author Reference HYPOTHESIS – –PRIMARY – –SECONDARY

6. Type of Study Treatment Diagnosis Screening Prognosis Causation

7. CLINICAL PRACTICE In vitro cell/matrix gene biomechanic THOUSANDS In vivo relevant animal models biology healing biomechanic safety TENS OF THOUSANDS Controlled Clinical Trials outcomes complications risk/benefit cost/benefit HUNDREDS OF THOUSANDS Study Design: Cost: ExtremeCAUTION MAYBE YES: EBM

8. Clinical QUESTION Determines Study Design ResearchExample Preferred Study Design TherapyAutograft choiceRCT DiagnosisLabral tear Cross-sectional survey Screening Role flexibility as injury risk Cross-sectional survey Prognosis Predictors OA after ACLR Longitudinal cohort study Risk Factor Risk OA Div I Athlete Cohort or case control

9. 1° HYPOTHESIS OR PREFERRED TOPIC RESEARCH [EXAMPLES] RESEARCH DESIGN TREATMENT [DRUG, PREVEN-RCT TION, SURG] Diagnosis [dx test]Cross-sect survey Screening [value of test]Cross-sect survey PROGNOSIS [DISEASE, INJURY,LONGITUDINAL CONDITION]COHORT Causation [exposure to... ]Cohort or case-control Study Type with Preferred Design

10. Sports Medicine Question H o : Anterior knee pain after ACL reconstruction is dependent on autograft choice between Ham vs PT What do you believe? Approach to literature review: – –Select articles that support your bias? – –What is research topic? – –Treatment choice – –Focus review -- RCTs

11. Traditional Hierarchy of Clinical Treatment Studies 1. 1.RCT (randomized controlled trials) = only computer or random # table acceptable 2. 2.Cohort: two or more groups selected basis differences exposure to “agent” and f/u 3. 3.Case control: pts particular disease/condition identified + “matched” control 4. 4.Cross-sectional: data collected single timepoint 5. 5.Case reports/series: medical hxs one or more patients with condition/tx reported on

12. Why do Treatment Studies Need Control Group? 1. 1.Basics Scientific Method! 2. 2.If no control group: tx is same, better, or worse than what? 3. 3.Quality of “control” group one measure of validity of results 4. 4.Unfortunately majority orthopaedic literature lack control group -- case series

13. Anterior Knee Pain S/P ACL Recon H o :Autograft choice Ham vs PT EBM Review: Systematic review nine RCTs Ref: Spindler AJSM 2004 Answer:NO DIFFERENCE 8/9 studies! Caveat: a. a.Kneeling pain > PT 4/4 studies! b. b.Bynum PT ACL Recon  PF pain Preop = 40%, Postop = 20%, p < 0.05

14. Basic Science Grant 1. 1.FOCUS LITERATURE EBM 2. 2.HYPOTHESIS: focus EBM key clinical problem 3. 3.BEST STUDY DESIGN TOPIC – –Clinical relevance—systematic reviews – –Background—related topics – –Prelim data—review similar studies – –Design—metrics, techniques, alternatives – –Stats—method, sample size or power

15. How to Identify Bias Study BIAS Example Allocation groupsSelectionFail randomize InterventionPerformanceFail control confounding variables Follow-upExclusionNot uniform or (or Transfer)inadequate (<70%) OutcomesDetectionDissimilar evaluation independent examiner? Validated question- naire?

16. Definition of Bias 1. 1.SELECTION or SUSCEPTIBILITY = difference in comparison groups secondary to incomplete randomization 2. 2.PERFORMANCE = differences in care provided apart from intervention being evaluated 3. 3.EXCLUSION or TRANSFER = differences in withdrawal from trial 4. 4.DETECTION = different evaluation for outcomes best independent examiner or blinding examiner or validated outcome questionnaire self-administered

17. Sports Medicine Examples Bias 1. 1.SELECTION: ACL tr pt self-select OR vs Nonop tx = evaluate OA Soccer teams self-select ACL inj prevention training, then report difference incidence ACL tr 2. 2.PERFORMANCE: Report outcome of meniscal allograft or autologous chondrocytes fail control concomitant ACL recon or HTO! 3. 3.EXCLUSION OR TRANSFER: Report conclusions based <70% f/u outcome variable

18. Statistical and Clinical Significance Outcomes Absolute If ns power = ( ) Clinically Absolute If ns power = ( ) Clinically Outcome/Result Difference P for ( ) diff significant a.b.c.d.

19. Examples Statistical Significance vs Clinical Significance 1. 1.Primary H o and each AIM determine sample size by choosing a clinically meaningful difference in a single result or outcome measure chosen 2. 2.Instrumented Laxity (KT 1000) ACL Recon Graft Choice Literature studies powered detect 1 mm side to side difference (n ≈ 70) How many surgeons would change practice if results 1 mm (few) vs 2 mm (some) vs 3 mm (many) 3. 3.Thus clinical significance is based on both individual and “consensus” scientific community 4. 4.Power or sample size set at 80% avoid Type II (  ) error

20. Ideal vs Reality in Study Section NIAMS has no study section for clinical research/outcomes. If your systematic review does not support perceived bias think twice. Recommend refocus support bias. Clinical significance vs statistical significance not well understood by basic science study sections. Plethora funded NIAMS studies without clinical significance but positive statistical results. Seek expert funded opinion on your grant.

21. Pearls 1. 1.Develop ideas methods, results, statistics from best EBM in literature review based on realities previously discussed. 2. 2.Retrospective review “your” cases! Establish sample size Timelines to complete Generate methods 3. 3.Consult statistician BEFORE begin study!

22. Summary 1. 1.EBM review literature 2. 2.Generate hypothesis (H o ) 3. 3.Construct preliminary AIMS 4. 4.Review literature modify H o and AIMS 5. 5.Develop TEAM 6. 6.CONSULT STATISTICIAN 7. 7.Clinical retrospective reviews clinical pts, variation, outcomes

24. References Wright JG: JBJS-Am 2000 Hurwitz SR: JBJS-Am 2000 McLeod RS: Surgery 1996 Greenhalgh T: How to Read a Paper. Br Med J 2001 Lang TA and Secic M: How to Report Statistics in Medicine. ACP 1997 Spindler K, Johnson R, Reider B: ICL AOSSM 2002