Evidence-Based Evidence-Based Medicine and the Medicine and the Medical LibrarianMedical Librarian

Frank Domino, MD

Associate Professor, Community & Family Medicine

Len Levin, MS LIS, MA, AHIP

Manager, Educational Programming

Jim Comes, MSLS, Ed.D

Associate Director REIS

A skeptical Family A skeptical Family Physician approaches you Physician approaches you to “do a Medline search to to “do a Medline search to see if Cranberry Juice to see if Cranberry Juice to

Prevent UTIs.” Prevent UTIs.”

Where do you look to Where do you look to determine if Cranberry determine if Cranberry Juice Prevent A UTI?Juice Prevent A UTI?We will look at this in We will look at this in

greater detail latergreater detail later

Think about…Think about… Clinical questions that you Clinical questions that you

have received from a have received from a patron recently or that you patron recently or that you are curious about.are curious about.

We will be collecting some We will be collecting some of YOUR examples in a of YOUR examples in a little while to use for hands-little while to use for hands-on searching later this on searching later this afternoonafternoon

ObjectivesObjectives

Become familiar with the history and Become familiar with the history and growth of Evidence-Based medicine.growth of Evidence-Based medicine.

Understand Evidence-Based terminology.Understand Evidence-Based terminology. Be able to select appropriate Evidence-Be able to select appropriate Evidence-

Based resources.Based resources. Have an opportunity to learn and apply Have an opportunity to learn and apply

basic statistical techniques used in basic statistical techniques used in evaluating the Evidence-Based literature. evaluating the Evidence-Based literature.

What is: What is:

Evidence Based Medicine?Evidence Based Medicine?

Evidence Based MedicineEvidence Based Medicine

Sackett: Integrating individual Sackett: Integrating individual expertise with the best available expertise with the best available clinical evidence from systematic clinical evidence from systematic

research.research.Domino: Basing the care of Domino: Basing the care of patients on clinical research patients on clinical research

whose outcomes are our main whose outcomes are our main priority.priority.

History of EBMHistory of EBM Traditional Deductive Reasoning (the Traditional Deductive Reasoning (the oldold

way)way) If you understood the Pathophysiology andIf you understood the Pathophysiology and had a treatment that addressed this, thenhad a treatment that addressed this, then using that treatment would improve the using that treatment would improve the

disease.disease.

Evidence Based ReasoningEvidence Based Reasoning If there is a preponderance of data, when If there is a preponderance of data, when

viewed in aggregate (published and viewed in aggregate (published and unpublished) that supports a treatment for a unpublished) that supports a treatment for a disease, then can it be safely used.disease, then can it be safely used.

Old Paradigm: Old Paradigm:

If you know problemIf you know problemAndAnd

You have a solution to the problemYou have a solution to the problemThenThen

Using the solution will solve the problem.Using the solution will solve the problem.

Analogy: The trash (the problem) will be Analogy: The trash (the problem) will be taken out to the curb if you ask your taken out to the curb if you ask your

teenager (solution)teenager (solution)

First “Clinical Trial”First “Clinical Trial”

Scurvy trials in 1747

•Sea Water

•Vinegar

•Lemons & Limes

•Elixir Vitriol (Copper Sulfate)

•Garlic & Mustard

•Cider

First “Meta-Analysis”

BMJ, 1904

Dr. Joseph Bell & Sherlock Holms

Evidence-Based Medicine, my dear Watson?

PSHA

W!

Flexner Report

1910

Very first RCT

Published by the British Medical Journal in 1948

Archie CochraneArchie Cochrane

Archie Cochrane’s seminal book on EBM

“Cochrane estimated that fewer than 10% of medical interventions were supported by objective evidence…”

Dickerson K, Manheimer E The Cochrane Collaboration: evaluation of health care and services using systematic reviews of the results of randomized controlled trials. Clinical Obstetrics and Gynecology, 41(2):316 – add date

Iain Chalmers

Mid to late 1980’s

•Developed Oxford Database of Perinatal Trials

•(1989)Published Effective Care in Pregnancy & Childbirth. 1st Systematic Review

Founded in 1993 in the United Kingdom

EBM not without criticsEBM not without critics

1995 Lancet editorial states that “EBM…revolutionaries…demand to have [EBM] hallowed as the new orthodoxy…” and that they “…deplore attempts to foist [EBM] of the profession as a discipline…”

This article is Friday’s headlines

Why is EBM new?Why is EBM new?

Ottawa Rules: Ottawa Rules: Study of Patient OutcomesStudy of Patient Outcomes

Ankle Injury Standard of CareAnkle Injury Standard of CareX-ray all Ankle SprainsX-ray all Ankle Sprains

Cost: $$$$$Cost: $$$$$Result: Ottawa RulesResult: Ottawa Rules

2. What EBM is 2. What EBM is NOTNOT

A MEDLine A MEDLine

abstract that supports abstract that supports

a treatment based upona treatment based upon

One researcher’s conclusionsOne researcher’s conclusions

Remember: Statistically Significant does NOT equal Clinically Significant

Lead Article May 8, 2002 JAMA

2 IQ Tests: WAIS & BPP<1 month 99.42-3 months 101.74-6 months 102.37-9 months 106.0>9 months 104.0

P=0.003 all F tests

Wall Street Journal, N Y Times, Washington Post“Breastfeeding Increases I.Q.”

EBM focuses on EBM focuses on Patient Focused OutcomesPatient Focused Outcomes

Which of the following is a PFO?Which of the following is a PFO?

1.1. Using HMG CoA RI (statins) lowers Using HMG CoA RI (statins) lowers Apolipoprotein (a) levels.Apolipoprotein (a) levels.

2.2. Screening CXR’s identify Lung CancerScreening CXR’s identify Lung Cancer

3.3. Smoking Cessation counseling leads Smoking Cessation counseling leads to increased quit rates to increased quit rates

EBM focuses on EBM focuses on Patient Focused OutcomesPatient Focused Outcomes

Which of the following is a PFO?Which of the following is a PFO?1.1. Using HMG CoA RI (statins) lowers Using HMG CoA RI (statins) lowers

Apolipoprotein (a) levels.Apolipoprotein (a) levels.2.2. Screening CXR’s identify Lung CancerScreening CXR’s identify Lung Cancer

3.3. Smoking Cessation counseling Smoking Cessation counseling leads to increased quit ratesleads to increased quit rates

PFO: Actual BenefitsPFO: Actual Benefits, rather than , rather than theoretical or intermediate benefitstheoretical or intermediate benefits

Traditional Reasoning Lead to Traditional Reasoning Lead to False ConclusionsFalse Conclusions

EBM Reasoning looks at EBM Reasoning looks at Patient Outcomes:Patient Outcomes:

Mortality, Mortality,

Morbidity, Morbidity,

RiskRisk

Which is the best agent to get rid of Which is the best agent to get rid of Ear Wax???Ear Wax???

A. CerumenexA. Cerumenex B. Hydrogen Peroxide B. Hydrogen Peroxide C. Baking SodaC. Baking Soda D. Oil (Mineral, Olive, WD 40)D. Oil (Mineral, Olive, WD 40) E. ColaceE. Colace

Burton, et al. Cochrane DSR 2004 & Robinson, et al. J Otolaryngol 1990; 18(6): 263

Who Misleads the Public the Who Misleads the Public the Most?Most?

A. Television DramasA. Television Dramas B. Medical JournalsB. Medical Journals C. Pharmaceutical IndustryC. Pharmaceutical Industry D. News MediaD. News Media

Schwartz, et al. Annals of Int. Med. 2004; 140(3): 226

Nothing is new….Nothing is new….

““Believe nothing that you see in the Believe nothing that you see in the newspapers… newspapers…

...if you see anything in them that you know ...if you see anything in them that you know is true, begin to doubt it at once.”is true, begin to doubt it at once.”

Sir William OslerSir William Osler

What Percent of Americans Would What Percent of Americans Would Prefer a Total Body CT Scan Over Prefer a Total Body CT Scan Over

$1000.00 Check?$1000.00 Check?

A. 10%A. 10% B. 30%B. 30% C. 50%C. 50% D. 70%D. 70% E. 90%E. 90%

Schwartz, et al. JAMA 2004; 291(1): 71

What are the Actual Causes of What are the Actual Causes of Death in the US?Death in the US?

A. Motor Vehicle AccidentsA. Motor Vehicle Accidents B. FirearmsB. Firearms C. Infectious Disease (including HIV/AIDS)C. Infectious Disease (including HIV/AIDS) D. TobaccoD. Tobacco E. Poor Diet & Physical InactivityE. Poor Diet & Physical Inactivity

ARF = [PARF = [P0 0 + + ΣΣPPi i (RR(RRii)) – 1] / [P)) – 1] / [P0 0 + + Σ Σ PPi i (RR(RRii)])]

Mokdad, et al. JAMA 2004; 291(10): 1238

Leading Diseases to Cause Leading Diseases to Cause Death in the US: 2000Death in the US: 2000

Heart DiseaseHeart Disease 29.6%29.6% Malig. NeoplasmMalig. Neoplasm 23.0%23.0% CVACVA 7.0% 7.0% COPDCOPD 5.1% 5.1% InjuriesInjuries 4.1% 4.1% Diabetes MellitusDiabetes Mellitus 2.9% 2.9% Infectious Disease Infectious Disease 2.7% 2.7%

Minino, et al. Natl Vital Stat Rep. 2002; 50:1-120

Which had the Best Efficacy for the Which had the Best Efficacy for the Acute Treatment of MigraineAcute Treatment of Migraine

A. Ketoprofen 75 mgA. Ketoprofen 75 mg B. Ketoprofen 150 mgB. Ketoprofen 150 mg C. Zolmitriptan 2.5 mgC. Zolmitriptan 2.5 mg D. PlaceboD. Placebo

Dib, M. et al. Neurology 2002. 58(1): 1660

Ketoprofen 75 mgKetoprofen 75 mg

Equal to Zolmitriptan in Efficacy at 2 hours:Equal to Zolmitriptan in Efficacy at 2 hours: HeadacheHeadache Associated Headache SymptomsAssociated Headache Symptoms Impaired Work CapacityImpaired Work Capacity Need for further Rescue MedicineNeed for further Rescue Medicine Recurrence for Relieved AttacksRecurrence for Relieved Attacks

BUT:BUT: 50% less Adverse Events/Side Effects50% less Adverse Events/Side Effects

Which Intervention had the Which Intervention had the greatest Effect on Fall Riskgreatest Effect on Fall Risk

In Senior Populations (60 Yrs)In Senior Populations (60 Yrs)

A. Bisphosphonates (Alendronate, etc)A. Bisphosphonates (Alendronate, etc) B. Removal of “Throw Rugs”B. Removal of “Throw Rugs” C. CalcitoninC. Calcitonin D. Vitamin D SupplementsD. Vitamin D Supplements

Bischoff-Ferrari, H. et al. JAMA 2004; 291(16): 1999

Meta Analysis: Vitamin D on Falls 400-800 IU per day

Presentation: the forest plotPresentation: the forest plot

Estimate and confidence interval for each study

Estimate and confidence for the meta-analysis

Direction of effect

Scale (effect measure)

Line of no effect

Estimates with 95% confidence intervals

0.2 1.0 5

Favours LR Favours control

Risk ratio

Kennedy 1997

Locke 1952A

Lopes 1997

Reynolds 1998

Seiberth 1994

Non Specific Aches and Vitamin DNon Specific Aches and Vitamin D

Observational Study of Out Patients with Observational Study of Out Patients with persistent, nonspecific musculoskeletal pain persistent, nonspecific musculoskeletal pain 93% of population were deficient (</= 20ng/mL)93% of population were deficient (</= 20ng/mL) 100% of African Am, Hispanic & Am. Indians 100% of African Am, Hispanic & Am. Indians

were deficientwere deficient 28% were Severely Deficient (< 8ng/mL)28% were Severely Deficient (< 8ng/mL) Season was NOT a factor Season was NOT a factor 55% were UNDER age 30 years55% were UNDER age 30 years Male = Female; Inc. Risk for ChildbearingMale = Female; Inc. Risk for Childbearing

Colorectal AdenomasColorectal Adenomas

In patients with History of Colorectal In patients with History of Colorectal adenomas, adenomas,

Only in Patients At or Above Median Serum Only in Patients At or Above Median Serum Vit. D, Calcium => Vit. D, Calcium =>

Recurrence Relative Risk = 0.71 Recurrence Relative Risk = 0.71 [95%CI=0.57-.89][95%CI=0.57-.89]

Calcium Supplementation + Vitamin D Calcium Supplementation + Vitamin D status reduce risk of Colorectal Adenomasstatus reduce risk of Colorectal Adenomas

Which is the WEAKEST Predictor Which is the WEAKEST Predictor of CAD?of CAD?

A. C Reactive ProteinA. C Reactive Protein B. Total CholesterolB. Total Cholesterol C. Tobacco AbuseC. Tobacco Abuse D. Systolic Blood Pressure D. Systolic Blood Pressure

Danesh, et al. NEJM 2004; 350(14): 1387

CDC Recommendations 2003CDC Recommendations 2003

Predictive Only in Intermediate Risk Predictive Only in Intermediate Risk Patients (10-20% risk over 10 Years)Patients (10-20% risk over 10 Years)

Low < 1.0 mg/LLow < 1.0 mg/L High > 3.0 mg/LHigh > 3.0 mg/L Order only the HS-CRP; if elevated, repeat Order only the HS-CRP; if elevated, repeat

two weeks aparttwo weeks apart If > 10 mg/L, repeat and Rule Out InfectionIf > 10 mg/L, repeat and Rule Out Infection Of Of NO valueNO value in those with Known CAD in those with Known CAD

True or False: True or False:

Angioplasty is Better than Exercise Angioplasty is Better than Exercise at Preventing CAD Progressionat Preventing CAD Progression

TRUETRUE FALSEFALSE

CAD:CAD:Cardiac Rehab (exercise) vs Cardiac Rehab (exercise) vs

Angioplasty w/StentingAngioplasty w/Stenting

RCT 100 male patients </= 70 c Stable CAD to RCT 100 male patients </= 70 c Stable CAD to 12 months Exercise vs Stent12 months Exercise vs Stent

Exercise = 20 min bicycle/dayExercise = 20 min bicycle/day Event Free Survival: 88% vs 70%Event Free Survival: 88% vs 70% $3400 vs $6900$3400 vs $6900

Hambrecht, et al. Circulation 2004; 109: 1371Hambrecht, et al. Circulation 2004; 109: 1371

So Far:So Far:

Introduction & History of EBMIntroduction & History of EBM What EBM ISWhat EBM IS What EBM is NOTWhat EBM is NOT Patient Oriented Evidence, rather then Patient Oriented Evidence, rather then

focusing on intermediate informationfocusing on intermediate information Visual representation of evidence (Forest Visual representation of evidence (Forest

Plot)Plot)

5 Minute Break5 Minute Break

Medical LiteratureMedical Literature

Descriptive Explanatory

Case Studies Observational Experimental

Cohort Study RCT

Case Control Study

Cross Sectional Study

Study TypesStudy Types

Clinical TrialClinical Trial

Prospective==== Prospective==== Absolute RisksAbsolute Risks

Cohort StudyCohort Study

Prospective Study=== Prospective Study=== Relative Relative RisksRisks

Case Control StudyCase Control Study

Retrospective Study== Retrospective Study== Odds of Odds of RiskRisk

Review ArticlesReview Articles

1.1. Traditional ReviewTraditional Review: Summaries of : Summaries of literature literature Problems:Problems:

? all the relevant evidence? all the relevant evidence Author’s bias Author’s bias What the What the American Family PhysicianAmerican Family Physician was was

2.2. EBM Review: UpToDate, EBM Review: UpToDate, AFPAFPExpert in a field summarizes the current, Expert in a field summarizes the current,

EBM based literature, EBM based literature, Reviewed by an Editorial Team to verify Reviewed by an Editorial Team to verify

contentcontent

What is a Systematic Review?What is a Systematic Review?(Oxman, JAMA, 1994)(Oxman, JAMA, 1994)

Type of Review with explicit criteria for selecting Type of Review with explicit criteria for selecting the studies includedthe studies included

Structured format for consistent presentation of Structured format for consistent presentation of information information

Cochrane Database of Systematic Reviews—Cochrane Database of Systematic Reviews—MostMost Prestigious Prestigious

http://www.update-software.com/http://www.update-software.com/

What is a Meta-Analysis?What is a Meta-Analysis?(Oxman, JAMA, 1994)(Oxman, JAMA, 1994)

SubclassSubclass of systematic reviews of systematic reviews

Meta-Analyses combine and statistically Meta-Analyses combine and statistically summarize the results of individual studies summarize the results of individual studies

Evidence Pyramid

MOST evidence

LEAST evidence

From SUNY Downstate Medical Research Library http://servers.medlib.hscbklyn.edu/ebm/2100.htm

Basics/Background

Guidelines/Algorithms

Uncommon / very specific topic

Systematic Review:Cochrane, PubMed Sys. Rev.

ACP Journal Club / InfoPOEMS /DARE/Bandolier

UpToDate, eMedicine, Textbooks

USPSTF: AHRQ.GovNat. Guideline C.H.

MEDLINE

Review of common, well-studied problem

C

D

E

EBM review of a recent article

B

Search Algorithm

A

Attendee CasesAttendee Cases

Demonstration of Evidence-Based Demonstration of Evidence-Based ResourcesResources

The Gold StandardThe Gold StandardA resident walks up to your desk and has that there is a patient in her practice coming in today with acute maxillary sinusitis. What does the evidence suggest about a course of antibiotics?

Check out the Cochrane Library via Update Softwarehttp://www.update-software.com/http://www.update-software.com/

Systematic Reviews:Systematic Reviews: A Higher Level of EvidenceA Higher Level of Evidence

An 82 year old female presented a month An 82 year old female presented a month ago with a vesicular rash along her right ago with a vesicular rash along her right

chest wall. chest wall. You diagnosed H. Zoster, but she comes You diagnosed H. Zoster, but she comes back in pain. Your intern wants to know back in pain. Your intern wants to know

the best evidencethe best evidence on on treatingtreating post herpetic neuralgia. post herpetic neuralgia.

ANDANDYou You don’tdon’t subscribe to the Cochrane! subscribe to the Cochrane!

Try PubMed Evidence FiltersTry PubMed Evidence Filters

http://pubmed.gov

AND

You get a call from an NP in You get a call from an NP in the Ambulatory Clinic. A 38 the Ambulatory Clinic. A 38 year old patient wants a to year old patient wants a to be “checked” for Ovarian be “checked” for Ovarian Cancer, as her friend was Cancer, as her friend was

recently diagnosed.recently diagnosed.Your resident wants to Your resident wants to

do something.do something.

Send her to Send her to http://www.ahrq.govhttp://www.ahrq.gov to check to check

out the evidence.out the evidence.

http://www.ahrq.govhttp://www.ahrq.gov

Levels of EvidenceLevels of Evidence A.A.— The USPSTF strongly recommends…. — The USPSTF strongly recommends…. concludes concludes

that benefits substantially outweigh harmsthat benefits substantially outweigh harms..

B.B.— The USPSTF recommends that clinicians provide… — The USPSTF recommends that clinicians provide… concludes that benefits outweigh harmsconcludes that benefits outweigh harms..

C.C.— The USPSTF makes no recommendation for or — The USPSTF makes no recommendation for or against routine provision of [the service]. … against routine provision of [the service]. … concludes concludes that the balance of benefits and harms is too close to that the balance of benefits and harms is too close to justify a general recommendationjustify a general recommendation..

D.D.— The USPSTF recommends against … — The USPSTF recommends against … is ineffective is ineffective or that harms outweigh benefitsor that harms outweigh benefits..

I.I.— The USPSTF concludes that the evidence is — The USPSTF concludes that the evidence is insufficient to recommend for or against … insufficient to recommend for or against … the balance the balance of benefits and harms cannot be determinedof benefits and harms cannot be determined..

An orthopaedic attending sends you an e-mail and wants to know if his professional society or any other organization has written guidelines for knee arthroplasty.

You use the National Guideline Clearinghouse to conduct a search

http://www.guidelines.gov

Evidence-Based Guidelines

She proudly recalls a studyShe proudly recalls a study

About using Ultrasound from About using Ultrasound from JAMA, but can’t remember the JAMA, but can’t remember the

findings. findings.

Primary ResourcePrimary Resource: : A medical student comes into your A medical student comes into your

library looking for an article on library looking for an article on Plantar Fascitis.Plantar Fascitis.

You decide to send her to MedLine,

Via PubMED’s CQ To Refresh her Memory…..

http://pubmed.gov

A researcher is looking for a way to quickly identify evidence from all sources on TB resistance.

Tell him to try SumSearch http://sumsearch.uthscsa.edu

Meta-Search Engines

Synthesized Resources:Synthesized Resources:

eMedicineeMedicine UpToDateUpToDate FIRSTConsultFIRSTConsult othersothers

Evidence Based Review Vary with “User Friendliness”

Clinical ScenarioClinical Scenario

One of your “regulars” comes in. One One of your “regulars” comes in. One of his patients is a healthy, active 76 of his patients is a healthy, active 76 year old male comes in for a “check year old male comes in for a “check up”. up”.

What Health Maintenance What Health Maintenance interventions are indicatedinterventions are indicatedfor this person?for this person?

Synthesized ResourcesSynthesized Resources

Expert in the field; Provide the reader with:Expert in the field; Provide the reader with:EBM ReviewEBM Review

Consultant’s AdviceConsultant’s AdviceSimple Search InterfaceSimple Search Interface

Web, Desktop, CDROM, Pocket PCWeb, Desktop, CDROM, Pocket PC

-Web, PDA, Desktop-Updated Every 4 Mon-EASY to use

-Comprehensive-Current-Convenient

UpToDateUpToDate: : Comprehensive Comprehensive andand Current Current

ComprehensiveComprehensive Nearly 3,000 Expert Physician AuthorsNearly 3,000 Expert Physician Authors 6,000 topics, 60,000 pages, 100,000+ 6,000 topics, 60,000 pages, 100,000+

abstractsabstracts 10,000 pictures, 150+ movies10,000 pictures, 150+ movies Drug DatabaseDrug Database CME credits—Credit for Your WorkCME credits—Credit for Your Work Patient InformationPatient Information

CurrentCurrent Completely updated every four monthsCompletely updated every four months

Cranberry JuiceCranberry Juice

Earlier, we asked “Where do you look to Earlier, we asked “Where do you look to determine if Cranberry Juice Prevent A determine if Cranberry Juice Prevent A UTI?”UTI?”

What do YOU think?What do YOU think?

10 minute Break10 minute Break

Attendee CasesAttendee Cases

Epi Review:Epi Review:Scandinavian Lipid StudyScandinavian Lipid Study

Which would Which would you you take for 5 Years?take for 5 Years?Drug A – Drug B – Drug CDrug A – Drug B – Drug C

Patients taking Drug A had Patients taking Drug A had 33%33% fewer Myocardial fewer Myocardial Infarctions than those taking placeboInfarctions than those taking placebo

19%19% of patients taking Drug B had MI’s vs. 28 of patients taking Drug B had MI’s vs. 28%% on on placeboplacebo

11 people had to take Drug C before one MI was 11 people had to take Drug C before one MI was preventedprevented

Randomised trial of cholesterol lowering Randomised trial of cholesterol lowering in 4444 patients with coronary heart in 4444 patients with coronary heart

disease: the Scandinavian Simvastatin disease: the Scandinavian Simvastatin Survival Study (4S)Survival Study (4S)

4444 patients with angina pectoris or previous myocardial infarction and 4444 patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet were serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet were

randomised to double-blind treatment with simvastatin or placebo. Over randomised to double-blind treatment with simvastatin or placebo. Over the 5.4 years median follow-up period, simvastatin produced mean the 5.4 years median follow-up period, simvastatin produced mean changes in total cholesterol, low-density-lipoprotein cholesterol, and changes in total cholesterol, low-density-lipoprotein cholesterol, and

high-density-lipoprotein cholesterol of -25%, -35%, and +8%, high-density-lipoprotein cholesterol of -25%, -35%, and +8%, respectively, with few adverse effects. 256 patients (12%) in the respectively, with few adverse effects. 256 patients (12%) in the

placebo group died, compared with 182 (8%) in the simvastatin group. placebo group died, compared with 182 (8%) in the simvastatin group. The relative risk of death in the simvastatin group was 0.70 (95% CI The relative risk of death in the simvastatin group was 0.70 (95% CI

0.58-0.85, p = 0.0003). The 6-year probabilities of survival in the 0.58-0.85, p = 0.0003). The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6% and 91.3%, respectively. placebo and simvastatin groups were 87.6% and 91.3%, respectively. There were 189 coronary deaths in the placebo group and 111 in the There were 189 coronary deaths in the placebo group and 111 in the

simvastatin group (relative risk 0.58, 95% CI 0.46-0.73), while simvastatin group (relative risk 0.58, 95% CI 0.46-0.73), while noncardiovascular causes accounted for 49 and 46 deaths, noncardiovascular causes accounted for 49 and 46 deaths,

respectively. 622 patients (28%) in the placebo group and 431 (19%) in respectively. 622 patients (28%) in the placebo group and 431 (19%) in the simvastatin group had one or more major coronary events. The the simvastatin group had one or more major coronary events. The

relative risk was 0.66 (95% CI 0.59-0.75, p < 0.00001), and the relative risk was 0.66 (95% CI 0.59-0.75, p < 0.00001), and the respective probabilities of escaping such events were 70.5% and respective probabilities of escaping such events were 70.5% and

79.6%. 79.6%.

Scandinavian Lipid StudyScandinavian Lipid Study

Which would Which would you you take for 5 Years?take for 5 Years?

Relative Risk ReductionRelative Risk Reduction: Patients taking Drug : Patients taking Drug A had A had 33%33% fewer Myocardial Infarctions than fewer Myocardial Infarctions than those taking placebothose taking placebo

Absolute/Attributable RiskAbsolute/Attributable Risk: : 19%19% of patients of patients taking Drug B had MI’s vs. 28taking Drug B had MI’s vs. 28%% on placebo on placebo

Number Needed to Treat:Number Needed to Treat: 1111 people had to people had to take Drug C for 5 years before one MI was take Drug C for 5 years before one MI was preventedprevented

Let’s look at the numbersLet’s look at the numbers Absolute Risk MI on Simvistatin 19%; Placebo 28%Absolute Risk MI on Simvistatin 19%; Placebo 28%

• Absolute Risk ReductionAbsolute Risk Reduction = = 28% - 19% = 9%28% - 19% = 9%

• Number Needed to Treat Number Needed to Treat = =

• NNTNNT = 100 / (28% - 19% = 9%) = = 100 / (28% - 19% = 9%) = 1111

• Relative Risk ReductionRelative Risk Reduction = =

(28-19)/28 = 33%(28-19)/28 = 33%

““Zocor reduces Heart Attacks by Zocor reduces Heart Attacks by 33%!!!”33%!!!”

NewspapersNewspapers RadioRadio TelevisionTelevision InternetInternet Medical JournalsMedical Journals

33% is a Relative Risk Reduction

What is a What is a Good NNTGood NNT??B-Blocker in CHF decrease all cause B-Blocker in CHF decrease all cause Mortality:38Mortality:38Riboflavin 400 mg/day Prevent Migraine Riboflavin 400 mg/day Prevent Migraine

Attacks NNT=2.8 & Days with HA NNT=2.3Attacks NNT=2.8 & Days with HA NNT=2.3

Calcium (1200/d) for PMS NNT=5 (48-30%)Calcium (1200/d) for PMS NNT=5 (48-30%)NNS—Colon CA 1300, Breast CA 2400NNS—Colon CA 1300, Breast CA 2400

Bottom Line: It is a Value Judgment- Yours & Your Patients

““Fosomax Reduces Hip Fractures”Fosomax Reduces Hip Fractures”

Alendronate vs Standard TherapyAlendronate vs Standard Therapy >65 Yr., with Hx of >65 Yr., with Hx of osteoporosis & at least 1 vertebral fracture x 4 yearsosteoporosis & at least 1 vertebral fracture x 4 years

Hip Fx In Alendronate = 1.1 %Hip Fx In Alendronate = 1.1 %

Hip Fx In PlaceboHip Fx In Placebo = 2.2% = 2.2%

RRR = (Incidence P – Incidence I) / Incidence PRRR = (Incidence P – Incidence I) / Incidence P RRR = (2.2-1.1) / 1 = 0.51 or RRR = (2.2-1.1) / 1 = 0.51 or 51%51%

NNT = 100 / (Incidence P – Incidence I) = 100/1.1NNT = 100 / (Incidence P – Incidence I) = 100/1.1 NNT = 91 x 4 Years to Prevent 1 Hip FractureNNT = 91 x 4 Years to Prevent 1 Hip Fracture

RRR is NOT same as Relative RiskRRR is NOT same as Relative Risk

Bottom LineBottom LineIf < 1.0, it reduces risk-the smaller the number,If < 1.0, it reduces risk-the smaller the number,

the greater the risk reduction. the greater the risk reduction.

If > 1.0, it increases the risk-the greater the If > 1.0, it increases the risk-the greater the number, the greater the risk increase. number, the greater the risk increase.

Relative Risk:Number of times more or less than 1 an

event will happen in one group when compared to another

How do you explain RR to How do you explain RR to Patients?Patients?

““Not wearing a seat belt when involved in motor vehicle Not wearing a seat belt when involved in motor vehicle

accidents resulted in a RR of death of 3.5”accidents resulted in a RR of death of 3.5”

Their Risk of death was more than 3 times the risk

than if they had been wearing seat Belts

“Tea Drinkers had a RR of 0.6 of dying from CAD”

Tea Drinkers had a Risk of Dying from CAD only 2/3 Of those that did not

Framingham: “ASA Causes Cancer

Bias: Bias: any data that can lead to conclusions that any data that can lead to conclusions that

are different from the truthare different from the truth

Selection BiasSelection Bias: Who gets in & who gets reported: Who gets in & who gets reported

0

1

2

3

4

Per

cen

t

Treatment

% of Patients with Atrial Fibrillation who had a CVA

No Tx

ASA

Coumadin

0102030405060708090

100

Perc

ent

Treatment

Patients with A. Fibrillation

No CVA

CoumadinNo TxASA

Publication BiasPublication BiasOnly Publish what “works”Only Publish what “works”

RCT of using 400 IU/day of Vitamin E to prevent RCT of using 400 IU/day of Vitamin E to prevent Coronary Artery DiseaseCoronary Artery Disease. .

InterventionIntervention PlaceboPlacebo

MIMI 4.24.2 3.9 3.9 p=0.4 p=0.4

No benefit to supplementing diet with Vitamin No benefit to supplementing diet with Vitamin E in the prevention of CADE in the prevention of CAD

Lead Article May 8, 2002 JAMA

2 IQ Tests: WAIS & BPP<1 month 99.42-3 months 101.74-6 months 102.37-9 months 106.0>9 months 104.0

P=0.003 all F tests

Information Bias: data collection results in misleading results

Wall Street Journal, N Y Times, Washington Post“Breastfeeding Increases I.Q.”

Comparator BiasComparator BiasComparing new treatment to no treatment, Comparing new treatment to no treatment,

rather than the current standard of carerather than the current standard of care

““Azithromycin is superior to placebo in the Azithromycin is superior to placebo in the treatment of Acute Sinusitis” treatment of Acute Sinusitis”

That is nice, but is it superior to Amoxicillin That is nice, but is it superior to Amoxicillin or Bactrim? Don’t know; they didn’t do (or or Bactrim? Don’t know; they didn’t do (or won’t publish) that study.won’t publish) that study.