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Databases or Registries?Databases or Registries? Points to Consider Points to Consider
Mary Lou Skovron, DrPHMary Lou Skovron, DrPHGroup Director, Global EpidemiologyGroup Director, Global Epidemiology
Bristol-Myers SquibbBristol-Myers SquibbFDA/Industry Statistics WorkshopFDA/Industry Statistics Workshop
September 29, 2006September 29, 2006
OverviewOverview
Claims databasesClaims databases• TypesTypes• AdvantagesAdvantages• LimitationsLimitations
RegistriesRegistries• TypesTypes• AdvantagesAdvantages• LimitationsLimitations
ExamplesExamples ConclusionsConclusions
Claims DatabasesClaims Databases
Claims DatabasesClaims DatabasesTypesTypes
Open-Plan eg UHC, PharMetricsOpen-Plan eg UHC, PharMetrics• Pharmacy-basedPharmacy-based• Practice-basedPractice-based• Hospital-basedHospital-based
HMO, eg Kaiser-PermanenteHMO, eg Kaiser-Permanente Government eg Medicare, MedicaidGovernment eg Medicare, Medicaid
Claims Databases:Claims Databases:AdvantagesAdvantages
Already exist, accruing patient Already exist, accruing patient information…useful when a relatively information…useful when a relatively quick answer is neededquick answer is needed
Potentially large populations from Potentially large populations from which to draw treated patient and which to draw treated patient and comparison samples…statistical comparison samples…statistical power not usually an issuepower not usually an issue
May include subgroups not included May include subgroups not included in clinical trials…expand knowledgein clinical trials…expand knowledge
Claims Databases:Claims Databases:LimitationsLimitations
ICD-9 coding… potential for misclassification ICD-9 coding… potential for misclassification • Limited sensitivity/specificity Limited sensitivity/specificity • Coding affected by reimbursementCoding affected by reimbursement
Short ‘residence’ in the database Short ‘residence’ in the database Clinical, lab, imaging data not usually presentClinical, lab, imaging data not usually present Rare events in rare diseases require huge Rare events in rare diseases require huge
“electronic” populations to identify adequate “electronic” populations to identify adequate numbers treatednumbers treated
May not represent important sub-populationsMay not represent important sub-populations Surveillance bias and channeling biasSurveillance bias and channeling bias Inpatient drug exposures not usually recordedInpatient drug exposures not usually recorded
Claims Databases: Claims Databases: ApplicationApplication
Acute events (short-term events)Acute events (short-term events) Events that come to medical attention, eg Events that come to medical attention, eg
CVACVA Validated algorithm to identify indication Validated algorithm to identify indication
and event of interest OR medical record and event of interest OR medical record review to verify eventsreview to verify events
Statistical approaches for confounders (eg Statistical approaches for confounders (eg propensity scores, instrumental variables, propensity scores, instrumental variables, risk factor scores, multivariate analyses) risk factor scores, multivariate analyses)
RegistriesRegistries
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 time”population for a defined period of time”11
““A registry A registry per seper se is not a study. It is an is not a study. It is an organized collection of data in humans organized collection of data in humans within a particular disease group or other within a particular disease group or other special group…”special group…”22
1Arlett P, Moseley J, Seligman PJ p 119 in Pharmacoepidemiology Fourth Edition, Strom BL, ed 200522 CIOMS V Section II.h. CIOMS V Section II.h.
Registries:Registries:TypesTypes
Drug/Device Registry: Includes Drug/Device Registry: Includes subjects receiving the drug or device subjects receiving the drug or device regardless of indicationregardless of indication
Disease Registry: Includes patients Disease Registry: Includes patients with the disease regardless of drug with the disease regardless of drug or device exposureor device exposure
Registries:Registries:StrengthsStrengths
Richer data than in electronic databases: Richer data than in electronic databases: Patient SES, history, treatment, clinical Patient SES, history, treatment, clinical data can be collecteddata can be collected
Define encounter frequency and follow-up Define encounter frequency and follow-up durationduration
Event ascertainment does not depend on Event ascertainment does not depend on ICD-9 codingICD-9 coding
Can address additional questions in the Can address additional questions in the datadata
Registries:Registries:LimitationsLimitations
Accrual can be slow if insufficient Accrual can be slow if insufficient sites engagedsites engaged
Generalizability must be establishedGeneralizability must be established Practical limits on number of patients Practical limits on number of patients
followedfollowed
Registries:Registries:ApplicationApplication
Long-term outcomesLong-term outcomes Rare diseasesRare diseases Potential confounders importantPotential confounders important Multiple objectivesMultiple objectives
Usefulness of RegistriesUsefulness of Registries
Characteristics of patients in the Characteristics of patients in the target population for the new drugtarget population for the new drug
Clinical course of the diseaseClinical course of the disease Treatment patterns, health care Treatment patterns, health care
utilizationutilization Frequency of adverse eventsFrequency of adverse events
Registry LifecycleRegistry Lifecycle Early: Describe patient demographics, Early: Describe patient demographics,
clinical characteristics, practice patterns clinical characteristics, practice patterns (usually cross-sectional analyses); (usually cross-sectional analyses); incidence of AEs with short lag timesincidence of AEs with short lag times
Intermediate: Analyze relationships pf Intermediate: Analyze relationships pf patient characteristics, treatment with patient characteristics, treatment with outcomes; outcomes; incidence of less common incidence of less common AEs, AEs with longer lag times; assess AEs, AEs with longer lag times; assess risk factors for AE incidencerisk factors for AE incidence
Advanced: Evaluate changes in practice Advanced: Evaluate changes in practice patterns; impact on outcomes and patterns; impact on outcomes and AE AE incidence; assess rare AE incidenceincidence; assess rare AE incidence
Registry QualityRegistry Quality
DeCIDE Network currently DeCIDE Network currently developing a reference document on developing a reference document on developing, conducting and developing, conducting and evaluating registriesevaluating registries
Sponsored by AHRQSponsored by AHRQ Document in draft, Outline available Document in draft, Outline available
on the webon the web Report currently in draftReport currently in draft
ExamplesExamples
Example:Example:Cox-2 Inhibitors and Cardiac Cox-2 Inhibitors and Cardiac
EventsEvents Cox-2 use frequent in populationCox-2 use frequent in population Primary care drugPrimary care drug Cardiac events not rare in target Cardiac events not rare in target
populationpopulation Short-term (< 2 years) eventsShort-term (< 2 years) events Clinical history importantClinical history important
One SolutionOne SolutionCox-2 Inhibitors and Cardiac Cox-2 Inhibitors and Cardiac
EventsEvents Claims database analysisClaims database analysis11
• Advantages: Advantages: Data already accrued when study need identifiedData already accrued when study need identified Large populationLarge population
• Limitation offsetLimitation offset Multivariate regression to control confoundingMultivariate regression to control confounding Verified cardiac events by chart review Verified cardiac events by chart review
• Remaining limitationsRemaining limitations Under-represented > 65 yoUnder-represented > 65 yo
1Velentgas P et al 2006
Key Feature of the SolutionKey Feature of the Solution
Numbers readily available: Numbers readily available: • Exposure: ~ 425,000 eligible subjects available Exposure: ~ 425,000 eligible subjects available
for studyfor study at least one dispensing of the 5 study medications at least one dispensing of the 5 study medications
during preceding 18-month periodduring preceding 18-month period first dispensing after minimum of six months without first dispensing after minimum of six months without
any of the medications any of the medications
• Endpoint: ~ 725 confirmed MI/ACSEndpoint: ~ 725 confirmed MI/ACS Verification of endpointsVerification of endpoints
• Medial record review applying accepted criteriaMedial record review applying accepted criteria
Example:Example:Thrombolytics And BleedingThrombolytics And Bleeding
Important focus: subpopulations eg Important focus: subpopulations eg ethnicity, gender, ageethnicity, gender, age
Short-term eventShort-term event Benefit and riskBenefit and risk Hospital-based treatmentHospital-based treatment
SolutionSolutionThrombolytics and BleedingThrombolytics and Bleeding
Registry approach: National Registry of Registry approach: National Registry of Myocardial InfarctionsMyocardial Infarctions
Salient strengths:Salient strengths:• Clinical and lab data ascertainedClinical and lab data ascertained• Data from medical recordsData from medical records
Limitation OffsetLimitation Offset• Validated completeness against another data sourceValidated completeness against another data source• Large number of hospitals to assure adequate Large number of hospitals to assure adequate
subpopulationssubpopulations Remaining limitationsRemaining limitations
• Short-term data cannot answer long-term questionsShort-term data cannot answer long-term questions
Key Feature of the SolutionKey Feature of the Solution Large number of hospitals participate order to Large number of hospitals participate order to
gather data on~200,000 MIs per yeargather data on~200,000 MIs per year Rich patient, clinical, treatment and outcome Rich patient, clinical, treatment and outcome
informationinformation Answered the question about safety in subgroups Answered the question about safety in subgroups
under-represented in the clinical trialsunder-represented in the clinical trials In its > 10 year lifecycle has contributed to broad In its > 10 year lifecycle has contributed to broad
understanding and improvement of medical understanding and improvement of medical practicepractice
External investigators can propose research; External investigators can propose research; external advisory group reviews and approves all external advisory group reviews and approves all researchresearch
Example: Safety of OrenciaExample: Safety of Orencia®®, a , a New Biological for RANew Biological for RA
Short-term (infections) and longer-Short-term (infections) and longer-term (NHL and other malignancies) term (NHL and other malignancies) eventsevents
Low general population prevalence of Low general population prevalence of RA candidates for biologics RA candidates for biologics treatmenttreatment
RA a specialty-treated disorderRA a specialty-treated disorder Proactive approachProactive approach
Solution: Complementary Solution: Complementary ApproachesApproaches
Claims database study in UHC data Claims database study in UHC data • Event validationEvent validation• Large pool of potential comparatorsLarge pool of potential comparators• Population treatment patternsPopulation treatment patterns• Infections, other possible short-term eventsInfections, other possible short-term events
Registry building on the independently conducted Registry building on the independently conducted National databank for Rheumatic Diseases National databank for Rheumatic Diseases • Large pool of participating rheumatologistsLarge pool of participating rheumatologists• 5,000 Orencia® initiators comparison to >=15,000 5,000 Orencia® initiators comparison to >=15,000
initiators/switchers of other treatmentsinitiators/switchers of other treatments• Patient self-report and event verificationPatient self-report and event verification• Enrollment and retention enhancementsEnrollment and retention enhancements• Short and long-term eventsShort and long-term events
Key Features of the SolutionKey Features of the Solution
External scientific advisory groupExternal scientific advisory group• Individual protocolsIndividual protocols• Statistical analysis plansStatistical analysis plans• Interpretation of results including Interpretation of results including
approaches to integrationapproaches to integration
ConclusionsConclusions
ConclusionsConclusions
One size does not fit all: evaluate One size does not fit all: evaluate optionsoptions
Registries: a useful alternative to Registries: a useful alternative to electronic databaseselectronic databases
Consider complementary approachesConsider complementary approaches
Useful ReferencesUseful References
Strom BL, ed; Pharmacoepidemiology Strom BL, ed; Pharmacoepidemiology 44thth Edition; UK; John Wiley and Sons Edition; UK; John Wiley and Sons Ltd;2005Ltd;2005
AHRQ DeCIDE Network upcoming AHRQ DeCIDE Network upcoming publicationpublication• http://effectivehealthcare.ahrq.gov/decide/http://effectivehealthcare.ahrq.gov/decide/
Thank YouThank You