Pharmacoepidemiologic AssessmentPharmacoepidemiologic Assessment

Judy A. Staffa, PhD, RPhJudy A. Staffa, PhD, RPh

Epidemiology Team LeaderEpidemiology Team Leader

Division of Surveillance, Research & Division of Surveillance, Research & Communication SupportCommunication Support

Office of Drug Safety, CDEROffice of Drug Safety, CDER

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When and why are pharmacoepidemiologic When and why are pharmacoepidemiologic studies recommended?studies recommended?

• To further characterize potential safety To further characterize potential safety signals from controlled clinical trialssignals from controlled clinical trials– chronic exposureschronic exposures– patients with co-morbid conditionspatients with co-morbid conditions

• To further evaluate and quantify a safety To further evaluate and quantify a safety signal identified after approvalsignal identified after approval– incidence rate vs. reporting rateincidence rate vs. reporting rate

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Pharmacoepidemiologic Study DesignPharmacoepidemiologic Study Design

• Cohort Cohort • Case-controlCase-control• Nested case-controlNested case-control• Hybrid designsHybrid designs

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Minimum Requirements for a Good Minimum Requirements for a Good Pharmacoepidemiologic Study ProtocolPharmacoepidemiologic Study Protocol

• Clearly specified study objectivesClearly specified study objectives• Critical review of the literatureCritical review of the literature• Detailed research methodsDetailed research methods– Study populationStudy population– Data sourcesData sources– Projected study sizeProjected study size– Methods for data Methods for data

collection/management/analysiscollection/management/analysis

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Studies using Automated Data: Studies using Automated Data: Factors affecting Choice of DatabaseFactors affecting Choice of Database

• Demographics of patientsDemographics of patients• Turnover rate/mobility Turnover rate/mobility • Plan coverage of study medicationsPlan coverage of study medications• Size of population available for studySize of population available for study• Availability of outcomes of interestAvailability of outcomes of interest• Coding of outcomes of interestCoding of outcomes of interest• Access to medical recordsAccess to medical records

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RegistriesRegistries

• A systematic collection of defined events A systematic collection of defined events or product exposures in a defined patient or product exposures in a defined patient population for a defined period of timepopulation for a defined period of time

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Good Registry ProtocolsGood Registry Protocols

• ObjectivesObjectives• Literature reviewLiterature review• Detailed research methodsDetailed research methods– Patient recruitment and follow upPatient recruitment and follow up– Projected sample sizeProjected sample size– Methods for data collection, management and Methods for data collection, management and

analysisanalysis

• Carefully designed data collection formsCarefully designed data collection forms• Validation of findingsValidation of findings

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SurveysSurveys

• Further evaluate safety signalsFurther evaluate safety signals• Assess knowledge of labeled eventsAssess knowledge of labeled events• Assess product useAssess product use• Assess compliance with risk management Assess compliance with risk management

programsprograms11

• Address proprietary name confusionAddress proprietary name confusion

1Concept Paper: Risk Management Programs

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Good Survey ProtocolsGood Survey Protocols

• ObjectivesObjectives• Detailed research methodsDetailed research methods– Patient or provider recruitment and follow upPatient or provider recruitment and follow up– Projected sample sizeProjected sample size– Methods for data collection, management and Methods for data collection, management and

analysisanalysis

• Carefully designed survey instrumentsCarefully designed survey instruments• Validation of findingsValidation of findings

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Reporting Safety Signals to FDAReporting Safety Signals to FDA

• Submit a synthesis of all available safety Submit a synthesis of all available safety informationinformation

• Provide an assessment of the risk/benefit Provide an assessment of the risk/benefit profile of the product profile of the product

• Propose steps to further investigate Propose steps to further investigate through additional studiesthrough additional studies

• Propose risk management programs as Propose risk management programs as appropriateappropriate11

1Concept Paper: Risk Management Programs

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FDA’s Assessment of Safety SignalsFDA’s Assessment of Safety Signals

• Magnitude of the signalMagnitude of the signal• Precision of the signalPrecision of the signal• Consistency of findings across available data Consistency of findings across available data

sourcessources• Biological plausibilityBiological plausibility• Seriousness of the eventSeriousness of the event• Degree of benefit Degree of benefit • Availability of other therapiesAvailability of other therapies• Mitigate events occurring in population(s) Mitigate events occurring in population(s)

through risk management programsthrough risk management programs11

1Concept Paper: Risk Management Programs

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Questions for Public CommentQuestions for Public Comment

Under what circumstances would a registry Under what circumstances would a registry be useful as a surveillance tool and when be useful as a surveillance tool and when

would it cease to be useful?would it cease to be useful?

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Questions for Public CommentQuestions for Public Comment

Under what circumstances would active Under what circumstances would active surveillance strategies prove useful to surveillance strategies prove useful to

identify as yet unreported adverse events?identify as yet unreported adverse events?

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Questions for Public CommentQuestions for Public Comment

Under what circumstances would additional Under what circumstances would additional pharmacoepidemiologic studies be useful?pharmacoepidemiologic studies be useful?