Transcript Databases or Registries? Points to Consider

Databases or Registries?
Points to Consider
Mary Lou Skovron, DrPH
Group Director, Global Epidemiology
Bristol-Myers Squibb
FDA/Industry Statistics Workshop
September 29, 2006
Overview
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Claims databases
• Types
• Advantages
• Limitations
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Registries
• Types
• Advantages
• Limitations
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Examples
Conclusions
Claims Databases
Claims Databases
Types
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Open-Plan eg UHC, PharMetrics
• Pharmacy-based
• Practice-based
• Hospital-based
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HMO, eg Kaiser-Permanente
Government eg Medicare, Medicaid
Claims Databases:
Advantages
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Already exist, accruing patient
information…useful when a relatively
quick answer is needed
Potentially large populations from
which to draw treated patient and
comparison samples…statistical
power not usually an issue
May include subgroups not included
in clinical trials…expand knowledge
Claims Databases:
Limitations
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ICD-9 coding… potential for misclassification
• Limited sensitivity/specificity
• Coding affected by reimbursement
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Short ‘residence’ in the database
Clinical, lab, imaging data not usually present
Rare events in rare diseases require huge
“electronic” populations to identify adequate
numbers treated
May not represent important sub-populations
Surveillance bias and channeling bias
Inpatient drug exposures not usually recorded
Claims Databases:
Application
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Acute events (short-term events)
Events that come to medical attention, eg
CVA
Validated algorithm to identify indication
and event of interest OR medical record
review to verify events
Statistical approaches for confounders (eg
propensity scores, instrumental variables,
risk factor scores, multivariate analyses)
Registries
Registries
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“A systematic collection of defined events
or product exposures in a defined patient
population for a defined period of time”1
“A registry per se is not a study. It is an
organized collection of data in humans
within a particular disease group or other
special group…”2
1Arlett
P, Moseley J, Seligman PJ p 119 in
Pharmacoepidemiology Fourth Edition, Strom BL, ed 2005
2 CIOMS V Section II.h.
Registries:
Types
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Drug/Device Registry: Includes
subjects receiving the drug or device
regardless of indication
Disease Registry: Includes patients
with the disease regardless of drug
or device exposure
Registries:
Strengths
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Richer data than in electronic databases:
Patient SES, history, treatment, clinical
data can be collected
Define encounter frequency and follow-up
duration
Event ascertainment does not depend on
ICD-9 coding
Can address additional questions in the
data
Registries:
Limitations
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Accrual can be slow if insufficient
sites engaged
Generalizability must be established
Practical limits on number of patients
followed
Registries:
Application
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Long-term outcomes
Rare diseases
Potential confounders important
Multiple objectives
Usefulness of Registries
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Characteristics of patients in the
target population for the new drug
Clinical course of the disease
Treatment patterns, health care
utilization
Frequency of adverse events
Registry Lifecycle
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Early: Describe patient demographics,
clinical characteristics, practice patterns
(usually cross-sectional analyses);
incidence of AEs with short lag times
Intermediate: Analyze relationships pf
patient characteristics, treatment with
outcomes; incidence of less common
AEs, AEs with longer lag times; assess
risk factors for AE incidence
Advanced: Evaluate changes in practice
patterns; impact on outcomes and AE
incidence; assess rare AE incidence
Registry Quality
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DeCIDE Network currently
developing a reference document on
developing, conducting and
evaluating registries
Sponsored by AHRQ
Document in draft, Outline available
on the web
Report currently in draft
Examples
Example:
Cox-2 Inhibitors and Cardiac
Events
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Cox-2 use frequent in population
Primary care drug
Cardiac events not rare in target
population
Short-term (< 2 years) events
Clinical history important
One Solution
Cox-2 Inhibitors and Cardiac
Events
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Claims database analysis1
• Advantages:
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Data already accrued when study need identified
Large population
• Limitation offset
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Multivariate regression to control confounding
Verified cardiac events by chart review
• Remaining limitations
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Under-represented > 65 yo
1Velentgas
P et al 2006
Key Feature of the Solution
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Numbers readily available:
• Exposure: ~ 425,000 eligible subjects
available for study
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at least one dispensing of the 5 study medications
during preceding 18-month period
first dispensing after minimum of six months without
any of the medications
• Endpoint: ~ 725 confirmed MI/ACS
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Verification of endpoints
• Medial record review applying accepted criteria
Example:
Thrombolytics And Bleeding
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Important focus: subpopulations eg
ethnicity, gender, age
Short-term event
Benefit and risk
Hospital-based treatment
Solution
Thrombolytics and Bleeding
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Registry approach: National Registry of
Myocardial Infarctions
Salient strengths:
• Clinical and lab data ascertained
• Data from medical records
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Limitation Offset
• Validated completeness against another data source
• Large number of hospitals to assure adequate
subpopulations
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Remaining limitations
• Short-term data cannot answer long-term questions
Key Feature of the Solution
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Large number of hospitals participate order to
gather data on~200,000 MIs per year
Rich patient, clinical, treatment and outcome
information
Answered the question about safety in subgroups
under-represented in the clinical trials
In its > 10 year lifecycle has contributed to broad
understanding and improvement of medical
practice
External investigators can propose research;
external advisory group reviews and approves all
research
Example: Safety of Orencia®, a
New Biological for RA
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Short-term (infections) and longerterm (NHL and other malignancies)
events
Low general population prevalence of
RA candidates for biologics treatment
RA a specialty-treated disorder
Proactive approach
Solution: Complementary
Approaches
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Claims database study in UHC data
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Event validation
Large pool of potential comparators
Population treatment patterns
Infections, other possible short-term events
Registry building on the independently conducted
National databank for Rheumatic Diseases
• Large pool of participating rheumatologists
• 5,000 Orencia® initiators comparison to >=15,000
initiators/switchers of other treatments
• Patient self-report and event verification
• Enrollment and retention enhancements
• Short and long-term events
Key Features of the Solution
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External scientific advisory group
• Individual protocols
• Statistical analysis plans
• Interpretation of results including
approaches to integration
Conclusions
Conclusions
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One size does not fit all: evaluate
options
Registries: a useful alternative to
electronic databases
Consider complementary approaches
Useful References
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Strom BL, ed;
Pharmacoepidemiology 4th Edition;
UK; John Wiley and Sons Ltd;2005
AHRQ DeCIDE Network upcoming
publication
• http://effectivehealthcare.ahrq.gov/decide/
Thank You