Persistent User Bias in Case-Crossover Studies in Pharmacoepidemiology

Jesper Hallas, Anton Pottegård, Shirley Wang, Sebastian Schneeweiss, Joshua J Gagne

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Studying the effect of chronic medication exposure by means of a case-crossover design may result in an upward-biased odds ratio. In this study, our aim was to assess the occurrence of this bias and to evaluate whether it is remedied by including a control group (the case-time-control design). Using Danish data resources from 1995-2012, we conducted case-crossover and case-time-control analyses for 3 medications (statins, insulin, and thyroxine) in relation to 3 outcomes (retinal detachment, wrist fracture, and ischemic stroke), all with assumed null associations. Controls were matched on age, sex, and index date, and exposure over the preceding 12 months was ascertained. For retinal detachment, the case-crossover odds ratio was 1.60 (95% confidence interval (CI): 1.42, 1.80) for statins, 1.40 (95% CI: 1.02, 1.92) for thyroxine, and 1.53 (95% CI: 1.04, 2.24) for insulin. Estimates for the retinal detachment controls were similar, leading to near-null case-time-control estimates for all 3 medication classes. For wrist fracture and stroke, the odds ratios were higher for cases than for controls, and case-time-control odds ratios were consistently above unity, thus implying significant residual bias. In case-crossover studies of medications, contamination by persistent users confers a moderate bias upward, which is partly remedied by using a control group. The optimal strategy for dealing with this problem is currently unknown.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Epidemiology
Vol/bind184
Udgave nummer10
Sider (fra-til)761-769
ISSN0002-9262
DOI
StatusUdgivet - 2016

Fingeraftryk

Pharmacoepidemiology
Cross-Over Studies
Retinal Detachment
Odds Ratio
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Confidence Intervals
Wrist
Insulin
Control Groups

Citer dette

Hallas, Jesper ; Pottegård, Anton ; Wang, Shirley ; Schneeweiss, Sebastian ; Gagne, Joshua J. / Persistent User Bias in Case-Crossover Studies in Pharmacoepidemiology. I: American Journal of Epidemiology. 2016 ; Bind 184, Nr. 10. s. 761-769.
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abstract = "Studying the effect of chronic medication exposure by means of a case-crossover design may result in an upward-biased odds ratio. In this study, our aim was to assess the occurrence of this bias and to evaluate whether it is remedied by including a control group (the case-time-control design). Using Danish data resources from 1995-2012, we conducted case-crossover and case-time-control analyses for 3 medications (statins, insulin, and thyroxine) in relation to 3 outcomes (retinal detachment, wrist fracture, and ischemic stroke), all with assumed null associations. Controls were matched on age, sex, and index date, and exposure over the preceding 12 months was ascertained. For retinal detachment, the case-crossover odds ratio was 1.60 (95{\%} confidence interval (CI): 1.42, 1.80) for statins, 1.40 (95{\%} CI: 1.02, 1.92) for thyroxine, and 1.53 (95{\%} CI: 1.04, 2.24) for insulin. Estimates for the retinal detachment controls were similar, leading to near-null case-time-control estimates for all 3 medication classes. For wrist fracture and stroke, the odds ratios were higher for cases than for controls, and case-time-control odds ratios were consistently above unity, thus implying significant residual bias. In case-crossover studies of medications, contamination by persistent users confers a moderate bias upward, which is partly remedied by using a control group. The optimal strategy for dealing with this problem is currently unknown.",
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Persistent User Bias in Case-Crossover Studies in Pharmacoepidemiology. / Hallas, Jesper; Pottegård, Anton; Wang, Shirley; Schneeweiss, Sebastian; Gagne, Joshua J.

I: American Journal of Epidemiology, Bind 184, Nr. 10, 2016, s. 761-769.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Persistent User Bias in Case-Crossover Studies in Pharmacoepidemiology

AU - Hallas, Jesper

AU - Pottegård, Anton

AU - Wang, Shirley

AU - Schneeweiss, Sebastian

AU - Gagne, Joshua J

N1 - © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2016

Y1 - 2016

N2 - Studying the effect of chronic medication exposure by means of a case-crossover design may result in an upward-biased odds ratio. In this study, our aim was to assess the occurrence of this bias and to evaluate whether it is remedied by including a control group (the case-time-control design). Using Danish data resources from 1995-2012, we conducted case-crossover and case-time-control analyses for 3 medications (statins, insulin, and thyroxine) in relation to 3 outcomes (retinal detachment, wrist fracture, and ischemic stroke), all with assumed null associations. Controls were matched on age, sex, and index date, and exposure over the preceding 12 months was ascertained. For retinal detachment, the case-crossover odds ratio was 1.60 (95% confidence interval (CI): 1.42, 1.80) for statins, 1.40 (95% CI: 1.02, 1.92) for thyroxine, and 1.53 (95% CI: 1.04, 2.24) for insulin. Estimates for the retinal detachment controls were similar, leading to near-null case-time-control estimates for all 3 medication classes. For wrist fracture and stroke, the odds ratios were higher for cases than for controls, and case-time-control odds ratios were consistently above unity, thus implying significant residual bias. In case-crossover studies of medications, contamination by persistent users confers a moderate bias upward, which is partly remedied by using a control group. The optimal strategy for dealing with this problem is currently unknown.

AB - Studying the effect of chronic medication exposure by means of a case-crossover design may result in an upward-biased odds ratio. In this study, our aim was to assess the occurrence of this bias and to evaluate whether it is remedied by including a control group (the case-time-control design). Using Danish data resources from 1995-2012, we conducted case-crossover and case-time-control analyses for 3 medications (statins, insulin, and thyroxine) in relation to 3 outcomes (retinal detachment, wrist fracture, and ischemic stroke), all with assumed null associations. Controls were matched on age, sex, and index date, and exposure over the preceding 12 months was ascertained. For retinal detachment, the case-crossover odds ratio was 1.60 (95% confidence interval (CI): 1.42, 1.80) for statins, 1.40 (95% CI: 1.02, 1.92) for thyroxine, and 1.53 (95% CI: 1.04, 2.24) for insulin. Estimates for the retinal detachment controls were similar, leading to near-null case-time-control estimates for all 3 medication classes. For wrist fracture and stroke, the odds ratios were higher for cases than for controls, and case-time-control odds ratios were consistently above unity, thus implying significant residual bias. In case-crossover studies of medications, contamination by persistent users confers a moderate bias upward, which is partly remedied by using a control group. The optimal strategy for dealing with this problem is currently unknown.

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DO - 10.1093/aje/kww079

M3 - Journal article

C2 - 27780801

VL - 184

SP - 761

EP - 769

JO - American Journal of Epidemiology

JF - American Journal of Epidemiology

SN - 0002-9262

IS - 10

ER -