Status: Finalised
First registered on:
01/10/2014
Last updated on:
03/08/2017
1. Study identification
EU PAS Register NumberEUPAS7584
Official titleHepatic Outcomes Among Adults Taking Duloxetine in
Study title acronymF1J-MC-B037
Study typeObservational study
Brief description of the studyWe conducted a retrospective matched cohort study to
evaluate the association of clinically significant hepatic
injury and exposure to duloxetine, with specific
definitional and methodological enhancements to focus
on potential drug-related associations. The primary
study objective was to estimate the absolute and relative
incidence of clinically significant hepatic events
(hepatic-related death, liver failure, other clinically
significant liver injury, hepatic-related death and liver
failure combined, all clinically significant hepatic injury
categories combined) among patients with depression
who initiated duloxetine relative to each of 3 propensity
score-matched comparison cohorts: patients with
depression who initiated venlafaxine, patients with
depression who initiated SSRIs, and patients with a
diagnosis of depression who did not receive treatment.
Secondary objectives addressed a range of potential
alternative explanations for the observed results (e.g.,
residual confounding).
Was this study requested by a regulator?Yes: EMA
Is the study required by a Risk Management Plan (RMP)?
EU RMP category 3 (required)
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsOptum
Department/Research groupEpidemiology
Organisation/affiliationOptum
Details of (Primary) lead investigator
Title Dr
Last name Li
First name Hu
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
United States
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed01/04/201007/12/2012
Start date of data collection01/04/201007/12/2012
Start date of data analysis
Date of interim report, if expected
Date of final study report01/05/201320/09/2013
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesEli Lilly and Company100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Li
First name Hu
Address line 1Eli Lilly and Company
Address line 2Lilly Corporate Center
Address line 3
CityIndianapolis
Postcode46285
CountryUnited States
Phone number (incl. country code)1-3176559951
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Li
First name Hu
Address line 1Eli Lilly and Company
Address line 2Lilly Corporate Center
Address line 3
CityIndianapolis
Postcode46285
CountryUnited States
Phone number (incl. country code)1-3176559951
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)N06AX21 (duloxetine)
7. Medical conditions to be studied
Medical condition(s)Yes
Drug-induced liver injury
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects30844
Additional information
From 01 August 2004 through 30 September 2010, a
total of 30,844 duloxetine initiators
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources not registered with ENCePP
Optumum Insight, United States
Sources of data
Administrative database, e.g. claims database
11. Scope of the study
What is the scope of the study?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
to estimate the absolute and relative incidence of clinically significant
hepatic events among patients with depression who initiated duloxetine relative to each of 3 propensity score-matched comparison cohorts.
Are there primary outcomes?Yes
Clinically significant hepatic injury (hepatic-related death, liver
failure, other clinically significant hepatic injury,
hepatic-related death or liver failure combined, and all
clinically significant hepatic categories combined).
Are there secondary outcomes?Yes
non-serious asymptomatic hepatic enzyme elevation
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
Duration of follow-up:
Follow-up was restricted to 3 specified exposure
windows: time from cohort entry through 15 days
following discontinuation of treatment; time from
cohort entry through 30 days following discontinuation
of treatment; and time restricted to the 1st 90 days
following cohort entry.
15. Data analysis plan
Please provide a brief summary of the analysis method
We matched duloxetine initiators to each of the 3 comparator cohorts (venlafaxine, SSRI, untreated) using a multivariable technique (propensity score analysis and matching) that can achieve a high degree of balance between comparison groups. Incidence rates were calculated as the number of cases divided by the relevant person-time. We also estimated 95% confidenceintervals (CIs) of the IRs for the duloxetine initiator and comparator cohorts. Rate ratios (RR) and associated 95% CIs were estimated for duloxetine initiators compared with each of the 3 propensity score-matched comparator cohorts.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
Not submitted
18. Study Results
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
None
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
