EBMWhocares?

MarcBlockman

June2017

AdilemmaYouareveryill…

Early Trial in K-L

Whichdoctordoyouwant?

WilliamOsler,1900 Smartyoungdoctor

Whichdoctordoyouwant?

Wise&experiencedsmartyoungdoctor

ThePrognosisofIgnoranceisPoor

Worsewith“durationinpractice”

MystudentsaredismayedwhenIsaytothem“Halfofwhatyouaretaughtasmedicalstudentswillin10yearshavebeenshowntobewrong.Andthetroubleis,noneofyourteachersknowswhichhalf.”

(DrSydneyBurwell,DeanofHarvardMedicalSchool)

TheSlipperySlope

Years since Med School graduation

Knowledgeof best current HTNcare

Shin,etal:CMAJ;1993:969-976

r= -0.54

P= <0.001

Whydowereadarticles?

• Browsing• Forinformation• Forresearch• Forreview• Apaperfromsomeoneweknow

• Forgoingtosleep!

DoWeRead?

• Self-reportedreadingtimeperweek.(Universitysetting)– Medicalstudents 60min.– Interns none– Seniorresidents 10min.– Fellows 45min.

DoWeRead?

UniversityofVirginia• Mailingtoprimarycarephysicians

– 50%hadnotreadamedicaljournalarticleinthelastyear.

– Themostcommonlysitedsourceofinformationwaspharmaceuticalrepresentatives.

JASPA*(Journalassociatedscoreofpersonalangst)

J:AreyouambivalentaboutrenewingyourJOURNAL subscriptions?A:DoyoufeelANGER towardsprolificauthors?S:DoyoueverusejournalstohelpyouSLEEP?P:AreyousurroundedbyPILESofPERIODICALS?A:DoyoufeelANXIOUSwhenjournalsarrive?

* Modified from: BMJ 1995;311:1666-1668

0 (?liar) 1-3 (normal range) >3 (sick; at risk for polythenia gravis and related conditions)

AnnofIntMed137(4),2002

Whatisevidence-basedmedicine?

“Evidence-basedmedicineistheintegrationofbestresearchevidencewithclinicalexpertise andpatientvalues”

- Dave Sackett

PatientConcerns

Clinical Expertise

Best research evidence

EBM

EvidenceBasedMedicine

• Forimportantquestionswithseriousmortality/morbidity,needstrongerevidencesuchasRCTs

• IfRCTsnotpossible,needtobecautious&vigilantaboutTreatmentsonlybasedonobservation/associationortheory

The Hierarchy of Evidence

1. Systematic reviews & meta-analyses

2. Randomised controlled trials

3. Cohort studies

4. Case-control studies

5. Cross sectional surveys

6. Case reports

7. Expert opinion

8. Anecdotal

WashingtonMonument

A Year of MEDLINEindexed journals

555 feet

MedicalPublishing

Annually:• 22,000journals• 19,000newbooksMEDLINE:• 5,000journals• 6.5Millionreferences• 500,000newentriesyearly

Words used by 41 doctors to describe their information supply

• Impossible Impossible Impossible Impossible Impossible Impossible

• Overwhelming Overwhelming Overwhelming Overwhelming Overwhelming Overwhelming

• Difficult Difficult Difficult Difficult

• Daunting Daunting Daunting• Pissed off• Choked• Depressed• Despairing• Worrisome• Saturation

• Vast• Help• Exhausted• Frustrated• Time consuming• Dreadful• Awesome• Struggle• Mindboggling• Unrealistic• Stress• Challenging

Challenging Challenging• Excited• Vital importance

AParadigmShiftforPhysicians

• FromMemoryRepositories• To InformationManagers

• From “HowdoIkeepupwithnewdevelopmentsinmedicine?”

• To “WhatdevelopmentsinmedicinedoIneedtokeepupwith?”

ThrombolytictherapyinMI

21

5

101

1 2

8

7

8

12

4

3

1

1

2

8

7

2

1

1

12

8

1

5

15

6

NotM

entio

ned

Routine

Experim

ental

Rare/N

ever

Specific

MMMM

MM

Textbook/ReviewRecommendations

OddsRatio(LogScale)

0.5 1.0 2.0

FavoursTreatment FavoursControl

RCTs Pts

123

265

3149

431671793

102544112651153311173929225452

P<.01

235767

27612530634633657143210595422051

67475316547185

7048154

P<.001

P<.00001

CumulativeYear

1965

1970

1980

1985

1990

AntmanEM,etal.JAMA,268:240-8,1992

Lagtimefromtimeof“knowing”totimeofimplementation

• 13yrsforthrombolytictherapy.

• 10yrsforcorticosteroidstospeedfetallungmaturity.

Ourtextbooksare out-of-date

• FailtorecommendRxuptotenyears afterit’sbeenshowntobeefficacious.

• Continuetorecommendtherapyuptotenyears afterit’sbeenshowntobeuseless.

Investinevidencedatabases• ACPJournalClub

http://www.acponline.org/journals/acpjc/jcmenu.htm

• BestEvidencewww.acponline.org/• CochraneLibrary• UpToDate• MEDLINE• Harrison’sOnline• Medscape

www.medscape.com/Home/Topics/homepages.html• MDConsultwww.mdconsult.com

The Evidence Pyramid

Validity/Strength of Inference

Time Spent in C

ritical Appraisal

Levels of Evidence

Criticalappraisal-WhatPushesUs…?

Toward• curiosity• Provecolleagueswrong• Keepscomingup• Riskofpatientharm• Wanttodobetter• Anxiety• Avoidlitigation• Internetinformed

patient

AwayTimeWealreadyknowtheanswerFatigueAccessInferioritycomplex-anxiety-

afraidofadmittingknowledgegaps

CynicalLazinessLackofsupportPreviousfailureatsearchingLackofresourcesNooneelsedoesitFearofchange

ReviewtheWorldLiteratureFortnightly**"KillasFewPatientsasPossible"- OscarLondon

0

500000

1000000

1500000

2000000

2500000

Biomedical MEDLINE Trials Diagnostic?

Med

ical

Arti

cles

per

Yea

r

5,000?per day

1,500 per day

95 per day

MedicalArticlesP

erYear

IskeepinguptodateMissionImpossible?

Bluegreenblog 2006

1990:Sackett’s“JustinTime”learningAnEBMApproachtoEducation

• Evidencecartonwardrounds- 1995• Lookedup2-3questionsperpatient• Took15-90secondstofind• Changeabout1/3decisions• Roundstooklonger!

Dave Sackett

Copingwiththeoverload:threepossiblethingsyoumighttry

A. Read an evidence-basedabstraction journal(and cancel other journals)

B. Keep a logbook of yourown clinical questions

C. Run a case-discussion journalclub with your practice

PROCESS• 120+journalsscanned

– 60,000articles• Isitvalid?(<5%)NNtoRead20+

– Intervention:RCT– Prognosis:inceptioncohort– Etc

• Isitrelevant?– 6-12GPs&specialistsasked:

Relevant?Newsworthy?

• <0.5%selectedNNtoread200

www.evidence-basedmedicine.com

Filtered knowledgeHow much is valid AND relevant?

RunajournalclubExample Questions• Are antidepressants safe in adolescents?• Is atenolol OK for hypertension?• Should all diabetics take aspirin?• Do probiotics prevent AB diarrhoea?• Does ‘bibliotherapy’ help depression?• What is the impact of Tamiflu on flu?• Are combined inhalers better in

asthma?• Pelvic floor exercises for ED?

The meta-analyses clearly indicate that bibliotherapy in unipolar depression is an effectivetreatment modality which is no less effective than individual or group therapy.

Of course this conclusion is mentioned with caution, since it is based on a limited number of studies in which the bibliotherapy, as well as the other forms of therapy, differ considerably from each other.

There are also differences in the target populations and the contact with therapists.Furthermore, the studies in the meta-analyses are methodologically solid but concern onlysmall experimental groups with non-clinical populations. By recruiting through mass media, itis possible that a group of patients is reached that cannot be reached by traditional forms oftherapy, but that can be motivated for bibliotherapy and benefit by it. Perhaps bibliotherapy canprevent worsening of the depression and be used as a preventive instrument.

An important danger in meta-analysis is that only studies in which relevant and significant effects are found are published. Particularly when small samples are used, this means that a study is published only when the effects are large. This could mean that the effect sizes found are not a random selection from the total group of possible effect sizes.

J Behav. Thet & Exp. Psychiat. Voh 28, No. 2, pp. 139-147. 1997.

Whicharebiased?WhichOK?

1. Allpositivestudies2. Allstudieswithmorethan100patients3. AllstudiespublishedinBMJ,Lancet,JAMA

orNEJM4. Allstudiesregisteredstudies

PublicationBias:Solution

• Alltrialsregisteredatinception,• TheNationalClinicalTrialsRegistry:CancerTrials• NationalInstitutesofHealthInventoryofClinicalTrialsandStudies

• InternationalRegistryofPerinatalTrials

• Meta-RegistryoftrialRegistries– www.controlled-trials.com

Beware poolingtheresults

Applyingtotheindividual

• Whatdotheresultsmeanonaverage?

• Whatdotheymeanforthisindividual?

AlternativeApproachestoMedicine

DoesCMEWork?

• DavisDA,etal.Changingphysicianperformance.Asystematicreviewoftheeffectofcontinuingmedicaleducationstrategies.JAMA1995;274:700-1.

• SibleyJC,Arandomizedtrialofcontinuingmedicaleducation.NEngl JMed1982;306:511-5.

• Conclusion–TraditionalCMEinaniceplacewithpleasantafterlecturediversionsis,unfortunately,completelyineffectiveinchangingourbehavior.

Anotherreasontoread!

RapidCriticalAppraisal

It’speer-reviewed,thereforeitmustbeOK?

Why do I have to bother?Can’t I trust the editors?

Percent of articles meeting quality criteria

NEJM 12.6Ann Int Med 7.6JAMA 7.2Lancet 6.2BMJ 4.4Arch Int Med 2.4

The Hierarchy of Evidence

1. Systematic reviews & meta-analyses

2. Randomised controlled trials

3. Cohort studies

4. Case-control studies

5. Cross sectional surveys

6. Case reports

7. Expert opinion

8. Anecdotal

FAQ:HowLong…?• Proficient?Quickly• Mastery? Lifetime

• Humanexpertisetakes>10,000hours,>10years

→Deliberatepractice

Isbedresteverhelpful?Asystematicreviewoftrials*

*Allen, Glasziou, Del Mar. Lancet, 1999

• 10trialsofbedrest afterspinalpuncture– nochangeinheadachewith bedrest– Increaseinbackpain

• ProtocolsinUKneurologyunits- 80%stillrecommendbedrestafterLP

SerpellM,BMJ1998;316:1709–10

• …evidenceofharmavailablefor17yearspreceding...

“Doingtherightthingiseasy.Knowingwhatitis,ismoredifficult.”

HarryTruman