Psychiatric adverse events in oseltamivir prophylaxis trials: Novel comparative analysis using data obtained from clinical study reports

Mark Jones, Susan E. Tett, Chris Del Mar

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Abstract

PURPOSE: Estimating the rate of adverse events (AEs) caused by a treatment in clinical trials typically involves comparing the proportions of patients experiencing AEs in intervention and control groups. However, potentially important information, including duration, recurrence, and intensity of events, is lost. In this study, we illustrate how the additional information can be obtained and incorporated into analyses of AEs.

METHODS: Data on psychiatric AEs were extracted from clinical study reports (CSRs) provided by the manufacturer of oseltamivir in 4 prophylaxis randomised trials in adults and adolescents. We analysed the incidence, recurrence, duration, and intensity of events, using logistic regression models where the outcome compared was proportion of days suffering from an event, and developed novel presentation techniques.

RESULTS: Psychiatric AEs were generally more frequent, longer, and more intense in the treatment than placebo arms. Logistic regression models confirm the apparent association overall (odds ratio [OR] 3.46, 95% confidence interval [CI] 1.28 to 9.32), particularly for events classified as severe (OR 34.5, 95% CI 3.66 to 325). However, the absolute difference in proportion of days suffering from severe psychiatric AEs between groups was small.

CONCLUSIONS: This example analysis shows evidence of a causal effect of oseltamivir on psychiatric AEs, not apparent in the published versions of the same trials and a Cochrane review which showed a nonsignificant 81% increased odds of experiencing a psychiatric event. This unique and important finding was dependent on obtaining previously unavailable data from clinical study reports and using novel analyses and presentation methods.

Original languageEnglish
Pages (from-to)1217-1222
Number of pages6
JournalPharmacoepidemiology and Drug Safety
Volume27
Issue number11
Early online date12 Sep 2018
DOIs
Publication statusPublished - 1 Nov 2018

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Oseltamivir
Psychiatry
Logistic Models
Odds Ratio
Confidence Intervals
Recurrence
Placebos
Clinical Studies
Comparative analysis
Adverse events
Clinical Trials
Control Groups
Incidence
Therapeutics

Cite this

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title = "Psychiatric adverse events in oseltamivir prophylaxis trials: Novel comparative analysis using data obtained from clinical study reports",
abstract = "PURPOSE: Estimating the rate of adverse events (AEs) caused by a treatment in clinical trials typically involves comparing the proportions of patients experiencing AEs in intervention and control groups. However, potentially important information, including duration, recurrence, and intensity of events, is lost. In this study, we illustrate how the additional information can be obtained and incorporated into analyses of AEs.METHODS: Data on psychiatric AEs were extracted from clinical study reports (CSRs) provided by the manufacturer of oseltamivir in 4 prophylaxis randomised trials in adults and adolescents. We analysed the incidence, recurrence, duration, and intensity of events, using logistic regression models where the outcome compared was proportion of days suffering from an event, and developed novel presentation techniques.RESULTS: Psychiatric AEs were generally more frequent, longer, and more intense in the treatment than placebo arms. Logistic regression models confirm the apparent association overall (odds ratio [OR] 3.46, 95{\%} confidence interval [CI] 1.28 to 9.32), particularly for events classified as severe (OR 34.5, 95{\%} CI 3.66 to 325). However, the absolute difference in proportion of days suffering from severe psychiatric AEs between groups was small.CONCLUSIONS: This example analysis shows evidence of a causal effect of oseltamivir on psychiatric AEs, not apparent in the published versions of the same trials and a Cochrane review which showed a nonsignificant 81{\%} increased odds of experiencing a psychiatric event. This unique and important finding was dependent on obtaining previously unavailable data from clinical study reports and using novel analyses and presentation methods.",
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Psychiatric adverse events in oseltamivir prophylaxis trials : Novel comparative analysis using data obtained from clinical study reports. / Jones, Mark; Tett, Susan E.; Del Mar, Chris.

In: Pharmacoepidemiology and Drug Safety, Vol. 27, No. 11, 01.11.2018, p. 1217-1222.

Research output: Contribution to journalArticleResearchpeer-review

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N2 - PURPOSE: Estimating the rate of adverse events (AEs) caused by a treatment in clinical trials typically involves comparing the proportions of patients experiencing AEs in intervention and control groups. However, potentially important information, including duration, recurrence, and intensity of events, is lost. In this study, we illustrate how the additional information can be obtained and incorporated into analyses of AEs.METHODS: Data on psychiatric AEs were extracted from clinical study reports (CSRs) provided by the manufacturer of oseltamivir in 4 prophylaxis randomised trials in adults and adolescents. We analysed the incidence, recurrence, duration, and intensity of events, using logistic regression models where the outcome compared was proportion of days suffering from an event, and developed novel presentation techniques.RESULTS: Psychiatric AEs were generally more frequent, longer, and more intense in the treatment than placebo arms. Logistic regression models confirm the apparent association overall (odds ratio [OR] 3.46, 95% confidence interval [CI] 1.28 to 9.32), particularly for events classified as severe (OR 34.5, 95% CI 3.66 to 325). However, the absolute difference in proportion of days suffering from severe psychiatric AEs between groups was small.CONCLUSIONS: This example analysis shows evidence of a causal effect of oseltamivir on psychiatric AEs, not apparent in the published versions of the same trials and a Cochrane review which showed a nonsignificant 81% increased odds of experiencing a psychiatric event. This unique and important finding was dependent on obtaining previously unavailable data from clinical study reports and using novel analyses and presentation methods.

AB - PURPOSE: Estimating the rate of adverse events (AEs) caused by a treatment in clinical trials typically involves comparing the proportions of patients experiencing AEs in intervention and control groups. However, potentially important information, including duration, recurrence, and intensity of events, is lost. In this study, we illustrate how the additional information can be obtained and incorporated into analyses of AEs.METHODS: Data on psychiatric AEs were extracted from clinical study reports (CSRs) provided by the manufacturer of oseltamivir in 4 prophylaxis randomised trials in adults and adolescents. We analysed the incidence, recurrence, duration, and intensity of events, using logistic regression models where the outcome compared was proportion of days suffering from an event, and developed novel presentation techniques.RESULTS: Psychiatric AEs were generally more frequent, longer, and more intense in the treatment than placebo arms. Logistic regression models confirm the apparent association overall (odds ratio [OR] 3.46, 95% confidence interval [CI] 1.28 to 9.32), particularly for events classified as severe (OR 34.5, 95% CI 3.66 to 325). However, the absolute difference in proportion of days suffering from severe psychiatric AEs between groups was small.CONCLUSIONS: This example analysis shows evidence of a causal effect of oseltamivir on psychiatric AEs, not apparent in the published versions of the same trials and a Cochrane review which showed a nonsignificant 81% increased odds of experiencing a psychiatric event. This unique and important finding was dependent on obtaining previously unavailable data from clinical study reports and using novel analyses and presentation methods.

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