Use of the case-crossover design to study prolonged drug exposures and insidious outcomes.
OBJECTIVE
The case-crossover design was originally intended to study brief exposures with immediate and transient effects, and acute outcomes with abrupt onsets. We investigated whether case-crossover methods can be used to study prolonged exposures and insidious outcomes.


METHODS
We conducted a case-crossover study of 8220 patients aged > or = 65 years enrolled in several health benefits programs in New Jersey during the period between 1991 and 1995. All had episodes of central nervous system (CNS) adverse events (e.g., delirium). Drug exposures were assessed during case time periods and control time periods lasting 1, 2, 3, or 4 months. Exposures included 3 active regimens with established deleterious CNS effects (corticosteroids, digoxin, and opiates) and 2 inactive regimens without such effects (multivitamins and statins).


RESULTS
In conditional logistic regression models, significantly elevated risks were observed for all three active drugs, regardless of which time windows were used. The magnitude of these risks generally increased with longer time windows. No significantly increased risks were observed for the 2 inactive drugs, regardless of the window duration.


CONCLUSIONS
These results suggest that with lengthened exposure assessment windows, case-crossover methods may be useful for studying exposures with prolonged effects and outcomes with insidious onsets.
Wang
Philip S
PS
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. pwang@rics.bwh.harvard.edu
Schneeweiss
Sebastian
S
Glynn
Robert J
RJ
Mogun
Helen
H
Avorn
Jerry
J
D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D002493:Central Nervous System Diseases / Q000139:chemically induced*; D015897:Comorbidity; D018592:Cross-Over Studies; D004077:Digoxin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D009294:Narcotics / Q000009:adverse effects*; D009515:New Jersey; D018570:Risk Assessment; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D000889:Anti-Arrhythmia Agents; D009294:Narcotics; D004077:Digoxin