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

Session: 

Oral session: Statistical methods (1)

Date: 

Monday 17 September 2018 - 11:50 to 12:00

Location: 

Fintry Auditorium

All authors in correct order:

Jones M1, Tett S1, Del Mar C2
1 University of Queensland, Australia
2 Bond University, Australia
Presenting author and contact person

Presenting author:

Mark Jones

Contact person:

Mark Jones
Abstract text
Background: Estimating the rate of adverse events (AEs) caused by a treatment in systematic reviews of clinical trials typically involves extracting data from publications and comparing the proportions of patients experiencing AEs in intervention and control groups. However potentially important information, including duration, recurrence, and intensity of events, is not usually available and not included in the analysis.
Objectives: We aim to illustrate how additional important information on AEs can be obtained from clinical study reports (CSRs) and incorporated into meta-analyses.

Methods: Data on psychiatric AEs were extracted from CSRs provided by the manufacturer of oseltamivir in four 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 patient days suffering from an event, and developed novel presentation techniques.

Results: Psychiatric adverse events 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). Analysing the intensity of the AEs showed little difference between groups (OR 1.15, 95% CI 0.29 to 4.52) for mild AEs, but a non-significant increase for moderate AEs (OR 4.90, 95% CI 0.75 to 32.1), and a large, significant increase for severe AEs (OR 34.5, 95% CI 3.66 to 325). However the absolute difference in proportion of patient days suffering from severe psychiatric adverse events 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 statistically non-significant 81% increased odds of experiencing a psychiatric event. The unique and important finding was dependent on obtaining previously unavailable data from CSRs and using novel analyses and presentation methods.

Patient or healthcare consumer involvement: Patient/consumer partners were not involved in this research.

Relevance to patients and consumers: 

Evidence is mounting that the medications we take are often less effective and less safe than is currently reported based on existing systematic reviews and other publicly available information. Using full information on adverse events available from clinical study reports in systematic reviews has the potential to make significant improvements in publicly available information on the safety of medications. This may lead to patients and doctors being able to make more informed choices of what may be a suitable medication for the patient’s medical condition. Patient/consumer partners did not help us with this statement.