2007May221 Journal Club for Analysis of Complex Datasets Frost FJ, Petersen H, Tollestrup K, Skipper...
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Transcript of 2007May221 Journal Club for Analysis of Complex Datasets Frost FJ, Petersen H, Tollestrup K, Skipper...
![Page 1: 2007May221 Journal Club for Analysis of Complex Datasets Frost FJ, Petersen H, Tollestrup K, Skipper B. Influenza and COPD mortality protection as pleiotropic,](https://reader033.fdocuments.in/reader033/viewer/2022052706/5a4d1ada7f8b9ab05997441f/html5/thumbnails/1.jpg)
2007May22 1
Journal Club for Analysis of Complex Datasets
Frost FJ, Petersen H, Tollestrup K, Skipper B. Influenza and COPD mortality protection as pleiotropic, dose-
dependent effects of statins.Chest 2007; 131: 1006-1012.
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2007May22 2
Acknowledgement
• Carlos Grijalva, MD, MPHDepartment of Preventive Medicine
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2007May22 3
Background
• Data on antiinflammatory & immunomodulatory effects of statins suggest they may reduce mortality risks from influenza & COPD.
• 2 observational studies suggest statins may protect community-acquired pneumonia & COPD.– Mortenson EM, et al. Respir Res 2005; 6: 82.– Mancini GB, et al. J Am Coll Cardiol 2006; 47: 2554.
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2007May22 4
Purpose
• Objective: compare influenza & COPD mortality risks for low-dose & moderate-dose statins users & nonusers.
• Design: matched cohort study & 2 case-control studies.
• Data: Lovelace Patient Database.– Deidentified, longitudinal db of health-care
encounter data comprising several HMO’s.• Time period: 92Jan01 – 03Dec31.
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2007May22 5
Matched cohort• E+: 90+ cumulative days statin exposure prior to
death or disenrollment (N=19,058).– Further classified as low daily dose (<4 mg/d) or
moderate dose (4+ mg/d).– Mean mg/d for 3-month – 1-yr period after statin initiation.
• E-: 3 HMO members w/o hx of statin therapy matched to each E+ based on gender, birth yr, & HMO enrollment period (N=57,174).– Enrollment period matching permitted observation of
events for both groups during closely comparable time periods.
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2007May22 6
Outcomes• Pneumonia or influenza death.• Unspecified pneumonia & influenza deaths.• COPD deaths.
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2007May22 7
Analysis
• Logistic & proportional hazards reg.• Adjusted for:
– Duration of enrollment before initiation of statin therapy (phase 1).
– Phase 1 Charlson comorbidity index.– # of different med’s taken during phase 1.– Receiving 3+ influenza vaccinations after
statin therapy initiation (phase 2).
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2007May22 8
Case-control studies• E+ had more CV comorbidities than E-.
– Adjustment for these could have inadvertently affected other outcomes.
• Pneumonia/influenza study:– D+: Hospital discharge of deceased & pneumonia or
influenza.– D-: Surviving patients w/ 1+ in/outpatient visits for
pneumonia or influenza.• COPD study:
– D+: Hospital discharge of deceased & COPD.– D-: Surviving COPD patients w/ 2+ in/outpatient visits.
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2007May22 9
Analysis• Logistic reg.• Adjusted for:
– Sex.– Birth year.– Duration of phase 2 enrollment.
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2007May22 10
Results: matched cohortlogistic regression
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2007May22 11
Results: matched cohortproportional hazards
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2007May22 12
Results: case-control study
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2007May22 13
Concerns
• Observational study.– Adjusted for few covariates.– Unmeasured confounders?– Confounding by indication.
• “…unlikely explanation since it would affect both low- and moderate-dose statin users.”
– Large cohort (N>75,000).– Propensity scores?– Sensitivity analysis?
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2007May22 14
Concerns (2)
• Motivation for case-control studies unclear.– Results similar to cohort study is not a validation of
results.• “Since the reductions were observed in both the cohort
and case-control studies, it is unlikely they could be due to artifacts of either study design or the analysis.”
– Cases & controls sampled from same db as matched cohort.
• Case-control studies had 2x’s events as matched cohort.
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2007May22 15
Concerns (3)
• Logistic reg analysis of survival data.– Ignores censoring.– Cannot account for time-dependent
covariates.• Immortal-time bias: Ayumi!
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2007May22 16