Post-authorization Safety Study: Evaluation of Neoplasm Events in Users of Mirabegron and Other Treatments for Overactive Bladder in the CPRD

Date of Approval: 
2016-12-16 00:00:00
Lay Summary: 
Mirabegron is used to treat overactive bladder, a condition in which a person may have a strong and/or frequent urge to urinate or in which he or she may involuntarily leak urine. A few studies conducted while mirabegron was being developed have raised concern that this drug may be associated with an increase in abnormal tissue growth and tumours, both cancerous and non-cancerous. The objective of this research is to evaluate, in real-world practice in the United Kingdom, if there is an association between mirabegron use and cancer. In this study, we will calculate and compare the occurrence of ten common cancers among new users of mirabegron and new users of several other medications commonly used to treat overactive bladder.
Technical Summary: 
This will be a cohort study comparing the incidence of commonly occurring malignant neoplasms among new users of mirabegron and new users of any comparator antimuscarinic medication, as a group, used in the treatment of overactive bladder (OAB). Incidence rates for sex-specific composite cancer endpoints will be calculated as follows: - Males: prostate, lung and bronchus, colon and rectum, melanoma of skin, urinary bladder, non-Hodgkin's lymphoma, kidney and renal pelvis, and pancreas. - Females: breast, lung and bronchus, colon and rectum, melanoma of skin, urinary bladder, non-Hodgkin's lymphoma, kidney and renal pelvis, corpus uteri, and pancreas. In addition, the incidence of the 10 individual cancers included in the composite endpoints will be estimated within each of the two exposure cohorts. We will compare cancer incidence between mirabegron follow-up time and antimuscarinic follow-up time. For this comparison of neoplasm endpoints, potential confounders will be addressed and the outcomes will be modelled, accounting for differences in follow-up time between the cohorts. Adjustment for potential confounders will be performed by matching on PS to balance cohorts with respect to factors present at or before the time of cohort entry. We will express results as estimated hazard ratios (HRs) of each study outcome comparing mirabegron to the reference antimuscarinic medications.
Health Outcomes to be Measured: 
The primary aims of the CPRD study are:. - To estimate and compare the incidence of sex-specific composite cancer endpoints (1 for men and 1 for women) among new users of mirabegron and new users of any comparator antimuscarinic medication (as a group) used in the treatment of OAB, stratified into categories of cancers that occur up to 1 year following the start of treatment, and those that occur more than 1 year following the start of treatment. . - To restrict the above analysis to patients aged 65 years and older.. - To estimate and compare the incidence of the 10 individual sex-specific cancers included in the composite cancer endpoints among new users of mirabegron and new users of any comparator antimuscarinic medication, stratified into categories of cancers that occur up to 1 year following the start of treatment, and those that occur more than 1 year following the start of treatment. . For the primary objectives, sensitivity analyses to examine protopathic bias will be conducted by estimating and comparing incidence in post-treatment initiation intervals of 0 to < 6 months, 6 to < 12 months, 12 to < 24 months, and 24 months or more. Several secondary aims will be evaluated for the sex-specific composite outcomes. Specifically, we will:. - Estimate and compare the sex-specific composite outcomes while:. - Stratifying by new user status (i.e., naive new users vs non-naive new users).. - Excluding immunocompromised patients.. - Censoring person-time when a patient switches from antimuscarinic treatment to mirabegron.. - Estimate and compare the effect of cumulative exposure in tertiles of mirabegron cumulative dose relative to tertiles of antimuscarinic cumulative dose and within mirabegron exposure across tertiles of mirabegron cumulative dose.
Application Number: 
16_220
Collaborators: 

Alejandro Arana Navarro - Chief Investigator - RTI Health Solutions
Alejandro Arana Navarro - Corresponding Applicant - RTI Health Solutions
Andrea Margulis - Collaborator - RTI Health Solutions
Billy Franks - Collaborator - Astellas Pharmaceuticals
Christine Bui - Collaborator - RTI Health Solutions
David Martinez - Collaborator - RTI Health Solutions
James Kaye - Collaborator - RTI Health Solutions
Jamie Robinson - Collaborator - Astellas Pharmaceuticals
Jennifer Bartsch - Collaborator - RTI Health Solutions
Jianmin Wang - Collaborator - RTI Health Solutions
Kenneth Rothman - Collaborator - RTI Health Solutions
Kwame Appenteng - Collaborator - Astellas Pharmaceuticals
Lisa McQuay - Collaborator - RTI Health Solutions
Maria Reynolds - Collaborator - RTI Health Solutions
Milbhor D'Silva - Collaborator - Astellas Pharmaceuticals
Ryan Ziemiecki - Collaborator - RTI Health Solutions
Stefan de Vogel - Collaborator - Astellas Pharmaceuticals
Susana Perez-Gutthann - Collaborator - RTI Health Solutions
Willem Jan Atsma - Collaborator - Astellas Pharmaceuticals

Linkages: 
HES Admitted Patient Care;HES Admitted Patient Care;NCRAS Cancer Registration Data;NCRAS Cancer Registration Data;ONS Death Registration Data;ONS Death Registration Data;Patient Level Index of Multiple Deprivation