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Methodological framework to identify possible adverse drug reactions using population-based administrative data.

Sauer B, Nebeker J, Shen S, Rupper R, West S, Shinogle JA, Xu W, Lohr KN, Samore M - F1000Res (2014)

Bottom Line: Propensity-matched analysis of expected reactions revealed that AChEI treatment was associated with gastrointestinal episodes (Hazard Ratio [HR]: 2.02; 95%CI: 1.28-3.2), but not psychological episodes, respiratory disturbance, or death.AChEI exposure was not associated with an increase in hepatic episodes.Early findings, or signal detection, are considered hypothesis generating since confirmatory studies must be designed to determine if the signal represents a true drug safety problem.

View Article: PubMed Central - PubMed

Affiliation: Informatics, Decision Enhancement, and Surveillance (IDEAS) Center, VA Salt Lake City Health Care System, Salt Lake City, UT, UT 84148, USA.

ABSTRACT

Purpose: We present a framework for detecting possible adverse drug reactions (ADRs) using the Utah Medicaid administrative data. We examined four classes of ADRs associated with treatment of dementia by acetylcholinesterase inhibitors (AChEIs): known reactions (gastrointestinal, psychological disturbances), potential reactions (respiratory disturbance), novel reactions (hepatic, hematological disturbances), and death.

Methods: Our cohort design linked drug utilization data to medical claims from Utah Medicaid recipients. We restricted the analysis to 50 years-old and older beneficiaries diagnosed with dementia-related diseases. We compared patients treated with AChEI to patients untreated with anti-dementia medication therapy. We attempted to remove confounding by establishing propensity-score-matched cohorts for each outcome investigated; we then evaluated the effects of drug treatment by conditional multivariable Cox-proportional-hazard regression. Acute and transient effects were evaluated by a crossover design using conditional logistic regression.

Results: Propensity-matched analysis of expected reactions revealed that AChEI treatment was associated with gastrointestinal episodes (Hazard Ratio [HR]: 2.02; 95%CI: 1.28-3.2), but not psychological episodes, respiratory disturbance, or death. Among the unexpected reactions, the risk of hematological episodes was higher (HR: 2.32; 95%CI: 1.47-3.6) in patients exposed to AChEI. AChEI exposure was not associated with an increase in hepatic episodes. We also noted a trend, identified in the case-crossover design, toward increase odds of experiencing acute hematological events during AChEI exposure (Odds Ratio: 3.0; 95% CI: 0.97 - 9.3).

Conclusions: We observed an expected association between AChEIs treatment and gastrointestinal disturbances and detected a signal of possible hematological ADR after treatment with AChEIs in this pilot study. Using this analytic framework may raise awareness of potential ADEs and generate hypotheses for future investigations. Early findings, or signal detection, are considered hypothesis generating since confirmatory studies must be designed to determine if the signal represents a true drug safety problem.

No MeSH data available.


Related in: MedlinePlus

Treatment time-windows for cohort and case-crossover study.AChEI = Acetylcholinesterase inhibitors. Rx = Dispensed Prescription.
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f1: Treatment time-windows for cohort and case-crossover study.AChEI = Acetylcholinesterase inhibitors. Rx = Dispensed Prescription.

Mentions: Treatment Groups. We inferred patient AChEI use by reconstructing courses of AChEI therapy from pharmacy claims data. To achieve a greater homogeneity among users’ disease stage and risk of adverse reactions8, we restricted the AChEIs cohort to the first incident course of AChEI therapy, which was defined as their first course with at least a 180-day drug-free period. To ensure that patients were receiving medical care during the 180-day drug-free period and were not receiving the drug elsewhere, recipients’ had to be enrolled and to have at least one medical claim during the 180-day drug-free (baseline) period. We defined a course of AChEI therapy as beginning on the week the drug was first dispensed and ending on day 60 after a continuous gap in the drug supply of ≥ 60 days (Figure 1).


Methodological framework to identify possible adverse drug reactions using population-based administrative data.

Sauer B, Nebeker J, Shen S, Rupper R, West S, Shinogle JA, Xu W, Lohr KN, Samore M - F1000Res (2014)

Treatment time-windows for cohort and case-crossover study.AChEI = Acetylcholinesterase inhibitors. Rx = Dispensed Prescription.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4490782&req=5

f1: Treatment time-windows for cohort and case-crossover study.AChEI = Acetylcholinesterase inhibitors. Rx = Dispensed Prescription.
Mentions: Treatment Groups. We inferred patient AChEI use by reconstructing courses of AChEI therapy from pharmacy claims data. To achieve a greater homogeneity among users’ disease stage and risk of adverse reactions8, we restricted the AChEIs cohort to the first incident course of AChEI therapy, which was defined as their first course with at least a 180-day drug-free period. To ensure that patients were receiving medical care during the 180-day drug-free period and were not receiving the drug elsewhere, recipients’ had to be enrolled and to have at least one medical claim during the 180-day drug-free (baseline) period. We defined a course of AChEI therapy as beginning on the week the drug was first dispensed and ending on day 60 after a continuous gap in the drug supply of ≥ 60 days (Figure 1).

Bottom Line: Propensity-matched analysis of expected reactions revealed that AChEI treatment was associated with gastrointestinal episodes (Hazard Ratio [HR]: 2.02; 95%CI: 1.28-3.2), but not psychological episodes, respiratory disturbance, or death.AChEI exposure was not associated with an increase in hepatic episodes.Early findings, or signal detection, are considered hypothesis generating since confirmatory studies must be designed to determine if the signal represents a true drug safety problem.

View Article: PubMed Central - PubMed

Affiliation: Informatics, Decision Enhancement, and Surveillance (IDEAS) Center, VA Salt Lake City Health Care System, Salt Lake City, UT, UT 84148, USA.

ABSTRACT

Purpose: We present a framework for detecting possible adverse drug reactions (ADRs) using the Utah Medicaid administrative data. We examined four classes of ADRs associated with treatment of dementia by acetylcholinesterase inhibitors (AChEIs): known reactions (gastrointestinal, psychological disturbances), potential reactions (respiratory disturbance), novel reactions (hepatic, hematological disturbances), and death.

Methods: Our cohort design linked drug utilization data to medical claims from Utah Medicaid recipients. We restricted the analysis to 50 years-old and older beneficiaries diagnosed with dementia-related diseases. We compared patients treated with AChEI to patients untreated with anti-dementia medication therapy. We attempted to remove confounding by establishing propensity-score-matched cohorts for each outcome investigated; we then evaluated the effects of drug treatment by conditional multivariable Cox-proportional-hazard regression. Acute and transient effects were evaluated by a crossover design using conditional logistic regression.

Results: Propensity-matched analysis of expected reactions revealed that AChEI treatment was associated with gastrointestinal episodes (Hazard Ratio [HR]: 2.02; 95%CI: 1.28-3.2), but not psychological episodes, respiratory disturbance, or death. Among the unexpected reactions, the risk of hematological episodes was higher (HR: 2.32; 95%CI: 1.47-3.6) in patients exposed to AChEI. AChEI exposure was not associated with an increase in hepatic episodes. We also noted a trend, identified in the case-crossover design, toward increase odds of experiencing acute hematological events during AChEI exposure (Odds Ratio: 3.0; 95% CI: 0.97 - 9.3).

Conclusions: We observed an expected association between AChEIs treatment and gastrointestinal disturbances and detected a signal of possible hematological ADR after treatment with AChEIs in this pilot study. Using this analytic framework may raise awareness of potential ADEs and generate hypotheses for future investigations. Early findings, or signal detection, are considered hypothesis generating since confirmatory studies must be designed to determine if the signal represents a true drug safety problem.

No MeSH data available.


Related in: MedlinePlus