Landmark Trials:Landmark Trials:Recommendations for Recommendations for

Interpretation and PresentationInterpretation and Presentation

Julianna Burzynski, PharmD, BCOP, BCPSJulianna Burzynski, PharmD, BCOP, BCPSHeme/Onc Clinical Pharmacy SpecialistHeme/Onc Clinical Pharmacy Specialist

11/29/07

Article CriteriaArticle Criteria

1.1. Significantly impacted our Significantly impacted our understanding as pharmacists and understanding as pharmacists and our approach to patient careour approach to patient care

2.2. If 2 articles are presented each must If 2 articles are presented each must be presented in less than 30 minutesbe presented in less than 30 minutes

3.3. Succinctly present and summarize Succinctly present and summarize • some have read the papersome have read the paper• some have some have notnot read paper read paper

Hierarchy of Evidence-Based Hierarchy of Evidence-Based Medicine (EBM) Resources Medicine (EBM) Resources

Presentation FormatPresentation Format

• Handout Handout

• PowerPoint Slides PowerPoint Slides

• The article aloneThe article alone• Guide audience thru materialGuide audience thru material• Identify page and paragraphIdentify page and paragraph

• Case based with a clinical questionCase based with a clinical question• e.g. Internal Medicine Clinical e.g. Internal Medicine Clinical

Decision Making Journal ClubDecision Making Journal Club

Article PresentationArticle Presentation

• Background / IntroductionBackground / Introduction

• Study RationaleStudy Rationale

• Objective / hypothesis / endpointsObjective / hypothesis / endpoints

• MethodsMethods

• Study ResultsStudy Results

• Author ConclusionsAuthor Conclusions

• Study Critique Study Critique

• Application to Clinical PracticeApplication to Clinical Practice

Background / IntroductionBackground / Introduction

1.1. Describe who this will impactDescribe who this will impact

2.2. Depict current standard of care Depict current standard of care • Reference and describe Reference and describe • Clinical trial that defines practiceClinical trial that defines practice• Evidence based guidelines or Evidence based guidelines or

position statement position statement • ASCO, ASH, NCCN, ASHPASCO, ASH, NCCN, ASHP

Study RationaleStudy Rationale

• Why was the study necessary?Why was the study necessary?

• Study ObjectiveStudy Objective1.1. HypothesisHypothesis2.2. Primary endpointPrimary endpoint3.3. Secondary endpointsSecondary endpoints

MethodsMethods

• InclusionInclusion• Are they appropriate / applicable?Are they appropriate / applicable?

• ExclusionExclusion• Are appropriate / applicable?Are appropriate / applicable?

• InterventionIntervention• Is it appropriate?Is it appropriate?• DoseDose• Duration of follow-upDuration of follow-up• Method of measurementMethod of measurement

• Is it supported by earlier studies Is it supported by earlier studies or literature?or literature?

StatisticsStatistics

• a priori power analysisa priori power analysis•risk you are willing to take risk you are willing to take

that you say there is no that you say there is no difference when one existsdifference when one exists

•risk you are willing to take risk you are willing to take

that difference is due to that difference is due to chancechance

anticipated differenceanticipated difference•Does this match with prior Does this match with prior

results?results?

Fire alarm analogy to statisticsFire alarm analogy to statistics

StatisticsStatistics

• Were the tests appropriate for the Were the tests appropriate for the type of data analyzedtype of data analyzed• Nominal, ordinal, continuousNominal, ordinal, continuous

• Parametric, non-parametricParametric, non-parametric

• SamplesSamples• Independent or related Independent or related • 2 or 2 or >> 3 3

• Number of confoundersNumber of confounders

Study ResultsStudy Results

• Describe who was includedDescribe who was included• N = XXN = XX• Number of patients screened, Number of patients screened,

enrolled, included in analysisenrolled, included in analysis• Lost to follow-up?Lost to follow-up?• Assessed in their assigned Assessed in their assigned

treatment group? treatment group?

• Primary endpointPrimary endpoint

• Secondary endpointsSecondary endpoints

Study ResultsStudy Results

• Were all results reported?Were all results reported?

• Were descriptive statistics Were descriptive statistics presented?presented?

• Relative risk or odds ratioRelative risk or odds ratio

• Confidence intervalConfidence interval

• Relative and absolute risk reductionRelative and absolute risk reduction

• Number needed to treat or harmNumber needed to treat or harm

Author ConclusionsAuthor Conclusions

• Their application to practiceTheir application to practice

General ConsiderationsGeneral Considerations

• Conflict of interestConflict of interest

• Informed consent / IRB approvalInformed consent / IRB approval

• Funding sourceFunding source

• Journal reputationJournal reputation• Peer - reviewedPeer - reviewed

• ValidityValidity

• BiasBias

• Confounding variableConfounding variable

ValidityValidity

• Does the study measure what it was Does the study measure what it was intended to measure?intended to measure?

• Does it represent an unbiased Does it represent an unbiased estimate of underlying truth?estimate of underlying truth?

• Internal ValidityInternal Validity• ReproducibleReproducible

• External ValidityExternal Validity• GeneralizableGeneralizable

BiasBias

• AllocationAllocation

• ChannelingChanneling

• ClassificationClassification

• ComplianceCompliance

• DetectionDetection

• InformationInformation

• InterviewerInterviewer

• MeasurementMeasurement

• ObserverObserver

• RecallRecall

• SelectionSelection

• A systematic tendency to produce an outcome that differs from the underlying truth

Confounding VariableConfounding Variable

• Related to the outcome of interestRelated to the outcome of interest• May May the likelihood of the outcome the likelihood of the outcome

• Unequally distributed in groupsUnequally distributed in groups• Not usually a concern in RCTNot usually a concern in RCT

Application to Clinical PracticeApplication to Clinical Practice

• Describe how this changes or fits in Describe how this changes or fits in to current clinical practiceto current clinical practice

• Make a recommendation for or Make a recommendation for or against treatment of the patient against treatment of the patient population studied based on your population studied based on your reviewreview

ResourcesResources

• Dr. GuyattDr. Guyatt

• Plummer Library Plummer Library • RR• 118.6118.6• .U83.U83• 2002x2002x

3 Questions to Ask3 Questions to Ask

1.1. Are the results valid?Are the results valid?

2.2. What are the results?What are the results?

3.3. How can I apply the results to How can I apply the results to patient care?patient care?

Gyatt, G, Rennie D (ed). Users’ Guides to the Medical Literature. Chicago: American Medical Association. 2002.

3 Questions to Ask3 Questions to Ask

1.1. Are the results valid?Are the results valid?

• Did the groups begin w/ similar Did the groups begin w/ similar prognosis/risk factorsprognosis/risk factors

• Were they randomized?Were they randomized?• Was it blinded or masked?Was it blinded or masked?• Were they analyzed as ITT?Were they analyzed as ITT?• Was follow-up complete?Was follow-up complete?

3 Questions to Ask3 Questions to Ask

2.2. What are the results? What are the results?

• How large was the treatment How large was the treatment effect?effect?

• How precise was the estimate of How precise was the estimate of treatment effect?treatment effect?

3 Questions to Ask3 Questions to Ask

3.3. How can I apply the results to How can I apply the results to patient care?patient care?

• Were the study patients similar to Were the study patients similar to mine?mine?

• Were all clinically important Were all clinically important outcomes considered?outcomes considered?

• Are the likely treatment benefits Are the likely treatment benefits worth the potential harm & costs?worth the potential harm & costs?

Internet Resources for EBMInternet Resources for EBM

• U of TorontoU of Toronto

• BMJBMJ

• U of Utah U of Utah

Study DesignStudy DesignPICOPICO

• PParticipantsarticipants• How were patients selected?How were patients selected?

• EExposurexposure• Intervention definitionIntervention definition• How / when / by whom administeredHow / when / by whom administered

• CComparisonomparison• Control intervention definitionControl intervention definition• How / when / by whom administeredHow / when / by whom administered

• OOutcomeutcome• Definition of 1Definition of 1°° & 2 & 2°° outcome outcome• How / when / by whom assessed?How / when / by whom assessed?

ResourcesResources

• Dr. GehlbachDr. Gehlbach

• Plummer LibraryPlummer Library• RR• 118.6118.6• .G43.G43• 20062006