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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

Dementia diagnosis and AChEI drug treatment in the eligible study population.Note: Groups highlighted in blue met the inclusion criteria for this study and were the primary comparison.
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f3: Dementia diagnosis and AChEI drug treatment in the eligible study population.Note: Groups highlighted in blue met the inclusion criteria for this study and were the primary comparison.

Mentions: Of the 29,046 eligible patients in the study populations, 4,109 had a medical claim with a dementia diagnosis between 1/01/2003 and 12/31/2005. The AChEI-treated cohort consisted of 976 total users and 332 users with incident courses; of the latter, 224 were started on donepezil, 59 on rivastigmine, and 49 on galantamine. Because the numbers of incident users of specific AChEIs were small, we did not assess potential ADRs for individual drugs. In the AChEI-treated group the median duration of incident courses was 33.4 weeks with an interquartile range (IQR) from 15 to 68.5 weeks. The median proportion of weeks for which the AChEI-treated group was estimated to have access to the medication at least 1 day during the week was 100%, with an IQR of 95%–100%. The untreated cohort consisted of 2,968 patients who were diagnosed with dementia but did not receive medication to treat the disorder during the study period (Figure 3).


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)

Dementia diagnosis and AChEI drug treatment in the eligible study population.Note: Groups highlighted in blue met the inclusion criteria for this study and were the primary comparison.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Dementia diagnosis and AChEI drug treatment in the eligible study population.Note: Groups highlighted in blue met the inclusion criteria for this study and were the primary comparison.
Mentions: Of the 29,046 eligible patients in the study populations, 4,109 had a medical claim with a dementia diagnosis between 1/01/2003 and 12/31/2005. The AChEI-treated cohort consisted of 976 total users and 332 users with incident courses; of the latter, 224 were started on donepezil, 59 on rivastigmine, and 49 on galantamine. Because the numbers of incident users of specific AChEIs were small, we did not assess potential ADRs for individual drugs. In the AChEI-treated group the median duration of incident courses was 33.4 weeks with an interquartile range (IQR) from 15 to 68.5 weeks. The median proportion of weeks for which the AChEI-treated group was estimated to have access to the medication at least 1 day during the week was 100%, with an IQR of 95%–100%. The untreated cohort consisted of 2,968 patients who were diagnosed with dementia but did not receive medication to treat the disorder during the study period (Figure 3).

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