Printer Friendly

Supplementary data: Cost-effectiveness of mirabegron compared to tolterodine ER 4 mg for overactive bladder in Canada.

References

(1.) Maman K, Aballea S, Nazir J, et al. Comparative efficacy and safety of medical treatments for the management of overactive bladder: A systematic literature review and mixed treatment comparison. Eur Urol 2014;65:755-65. http://dx.doi.org/10.1016/j.eururo.2013.11.010

(2.) Nitti VW, Khullar V, van Kerrebroeck P, et al. Mirabegron for the treatment of overactive bladder: A pre-specified pooled efficacy analysis and pooled safety analysis of three randomized, double-blind, placebo-controlled, phase 3 studies. Int J Clin Pract 2013;67:619-32. https://doi.org/10.1111/ijcp.12194

Sender Herschorn, MD (1); Jameel Nazir, MSc (2); Barbara Ramos, PhD (3); Zalmai Hakimi, PharmD (4)

(1) University of Toronto, Toronto, ON, Canada; (2) Astellas Pharma Europe Ltd, Chertsey, UK; (3) Astellas Pharma Canada, Markham, ON, Canada; (4) Astellas Pharma Europe B.V., Leiden, The Netherlands Published online April 11, 2017

Caption: Supplementary Fig. 1. Possible health state transitions in the model. Ln-1 indicates a lower level of OAB symptom severity, Ln+1 a higher level of severity, and Ln the same level of severity. AE: adverse event; OAB: overactive bladder.
Supplementary Table 1. Transition matrices for frequency of micturition
and incontinence episodes

A. Micturition, baseline to 1 month, mirabegron 50 mg
                                      Severity level at 1 month
           Mirabegron 50 mg    1      2      3      4      5

                            1  0.825  0.163  0.010  0.002  0.000
                            2  0.442  0.446  0.100  0.011  0.002
Severity level at baseline  3  0.184  0.392  0.321  0.078  0.025
                            4  0.066  0.213  0.358  0.240  0.123
                            5  0.036  0.078  0.152  0.233  0.501

B. Micturition, 1-2 months, mirabegron 50 mg
                                       Severity level at 2 months
Mirabegron 50 mg              1        2      3      4      5

                           1  0.784    0.194  0.018  0.004  0.001
                           2  0.367    0.463  0.145  0.021  0.004
Severity level at 1 month  3  0.125    0.332  0.380  0.124  0.039
                           4  0.036    0.147  0.346  0.313  0.158
                           5  0.017    0.046  0.126  0.259  0.551

C. Micturition, 2-3 months and subsequent months, mirabegron 50 mg
                                      Severity level at 3 months
Mirabegron 50 mg               1      2      3      4      5

                            1  0.759  0.216  0.020  0.003  0.001
                            2  0.334  0.485  0.158  0.019  0.004
Severity level at 2 months  3  0.110  0.337  0.400  0.108  0.045
                            4  0.032  0.149  0.365  0.273  0.181
                            5  0.014  0.045  0.127  0.216  0.599

D. Micturition, baseline-1 month, tolterodine ER 4 mg
                                      Severity level at 1 month
Tolterodine ER 4 mg            1      2      3      4      5

                            1  0.795  0.188  0.013  0.003  0.000
                            2  0.391  0.474  0.117  0.015  0.002
Severity level at baseline  3  0.148  0.378  0.342  0.103  0.029
                            4  0.048  0.186  0.347  0.290  0.128
                            5  0.025  0.066  0.141  0.270  0.498

E. Micturition, 1-2 months, tolterodine ER 4 mg
                                      Severity level at 2 months
Tolterodine ER 4 mg           1      2      3      4      5

                           1  0.749  0.222  0.022  0.006  0.001
                           2  0.318  0.481  0.167  0.030  0.005
Severity level at 1 month  3  0.097  0.309  0.392  0.159  0.043
                           4  0.026  0.124  0.325  0.366  0.159
                           5  0.012  0.038  0.115  0.296  0.539

F. Micturition, 2-3 months and subsequent months, tolterodine ER 4 mg
                                      Severity level at 3 months
Tolterodine ER 4 mg            1      2      3      4      5

                            1  0.722  0.246  0.026  0.005  0.001
                            2  0.287  0.501  0.180  0.026  0.005
Severity level at 2 months  3  0.085  0.314  0.412  0.139  0.050
                            4  0.023  0.128  0.345  0.322  0.183
                            5  0.004  0.021  0.092  0.264  0.619
G. Micturition, no treatment
                                      Severity level at (n+1) months
No treatment                   1      2      3      4      5

                            1  0.063  0.296  0.262  0.187  0.193
                            2  0.063  0.296  0.262  0.187  0.193
Severity level at n months  3  0.063  0.296  0.262  0.187  0.193
                            4  0.063  0.296  0.262  0.187  0.193
                            5  0.063  0.296  0.262  0.187  0.193

H. Incontinence, baseline-1 month, mirabegron 50 mg
                                      Severity level at 1 month
Mirabegron 50 mg               1      2      3      4      5

                            1  0.838  0.136  0.014  0.005  0.006
                            2  0.420  0.444  0.085  0.032  0.018
Severity level at baseline  3  0.302  0.393  0.158  0.104  0.043
                            4  0.133  0.315  0.187  0.213  0.151
                            5  0.077  0.119  0.149  0.152  0.503

I. Incontinence, 1-2 months, mirabegron 50 mg
                                      Severity level at 2 months
Mirabegron 50 mg              1      2      3      4      5

                           1  0.843  0.124  0.018  0.006  0.009
                           2  0.422  0.404  0.109  0.039  0.025
Severity level at 1 month  3  0.290  0.341  0.193  0.120  0.056
                           4  0.119  0.255  0.212  0.229  0.186
                           5  0.062  0.086  0.152  0.146  0.555

J. Incontinence, 2 to 3 months and subsequent months, mirabegron 50 mg
                                      Severity level at 3 months
Mirabegron 50 mg               1      2      3      4      5

                            1  0.807  0.158  0.018  0.007  0.010
                            2  0.368  0.469  0.096  0.039  0.027
Severity level at 2 months  3  0.253  0.397  0.170  0.121  0.059
                            4  0.102  0.293  0.185  0.227  0.193
                            5  0.053  0.098  0.132  0.144  0.574

K. Incontinence, baseline-1 month, tolterodine ER 4 mg
                                      Severity level at 1 month
Tolterodine ER 4 mg            1      2      3      4      5

                            1  0.852  0.120  0.015  0.005  0.008
                            2  0.443  0.408  0.093  0.032  0.024
Severity level at baseline  3  0.315  0.357  0.170  0.102  0.055
                            4  0.135  0.278  0.195  0.203  0.190
                            5  0.070  0.094  0.140  0.129  0.567

L. Incontinence, 1-2 months, tolterodine ER 4 mg
                                      Severity level at 2 months
Tolterodine ER 4 mg           1      2      3      4      5

                           1  0.855  0.109  0.019  0.006  0.011
                           2  0.442  0.368  0.118  0.038  0.033
Severity level at 1 month  3  0.299  0.307  0.205  0.117  0.072
                           4  0.118  0.220  0.218  0.214  0.230
                           5  0.055  0.067  0.140  0.122  0.616

M. Incontinence, 2-3 months and subsequent months, tolterodine ER 4 mg
                                      Severity level at 3 months
Tolterodine ER 4 mg            1      2      3      4      5

                            1  0.822  0.140  0.019  0.007  0.013
                            2  0.389  0.432  0.105  0.039  0.035
Severity level at 2 months  3  0.263  0.360  0.183  0.118  0.077
                            4  0.102  0.254  0.191  0.213  0.240
                            5  0.036  0.053  0.120  0.112  0.679

N. Incontinence, no treatment
                                      Severity level at (n+1) months
No treatment                   1      2      3      4      5

                            1  0.299  0.187  0.163  0.105  0.247
                            2  0.299  0.187  0.163  0.105  0.247
Severity level at n months  3  0.299  0.187  0.163  0.105  0.247
                            4  0.299  0.187  0.163  0.105  0.247
                            5  0.299  0.187  0.163  0.105  0.247

Supplementary Table 2. Key assumptions of model
Assumptions

Variations in health state utilities over time could only be explained
by variations in frequency of OAB symptoms (frequency of micturition
and incontinence) and AEs. Urgency had no independent effect in health
state utilities.
For AEs leading to discontinuation, utilities were reduced from the
midpoint of the one month cycle during which the AE occurred. Most
patients discontinued treatment at the end of the cycle (i.e., two
weeks later) and the AE resolved immediately, but a small number of
patients could choose to continue treatment despite having AEs.
The average number of micturitions and incontinence episodes within
each severity level was the same for both treatments and are
constant overtime.
Discontinuation of treatment could be due to AEs or other reasons. The
probability of discontinuation for other reasons was independent of the
severity of symptoms, as patients could discontinue for lack of
efficacy or because their symptoms had resolved. The rate of
discontinuation for other reasons was the same for both treatments.
Patients did not receive further drug treatment after stopping
mirabegron or tolterodine ER 4 mg, i.e., they were assigned to
'no treatment.' Patients who stopped treatment could reinitiate
treatment at a later cycle.
The distribution of patients by level of symptom severity after
treatment discontinuation was identical to the distribution
at baseline.
Other than dry mouth and constipation, there was no significant
difference in the probabilities of AEs between mirabegron and
tolterodine ER4mg.1
The probability of symptom improvement was greatest in the first month
following treatment initiation, then decreased progressively and was
assumed constant after three months (i.e., the probabilities of
transition between severity levels were the same in the fourth and
subsequent months as those in the third month).
No cost was incurred for primary care visits for prescription renewals,
as these were made during routine visits and occurred independently
of treatment.
Primary care and specialist visits occurred when a new treatment was
started (i.e., at initial entry into the model) or restarted.
The number of pads per day was derived for each health state and was
independent of treatment for a given level of severity.
Productivity costs related to absenteeism were dependent upon
incontinence severity and were independent of treatment for a given
level of severity. Employment rate and annual salary were calculated
based on age distribution in the ARIES study.2
Patients took one tablet per day of mirabegron or tolterodine ER 4 mg,
for each day of every month until discontinuation. The analyses did
not account for drug wastage or partial compliance.
Patients took 50 mg mirabegron or 4 mg tolterodine ER once daily; the
dose or formulation did not change over time.
The probability of reinitiating drug treatment among patients who
previously discontinued was 5.61% (50% annually). All patients were
re-initiated with the same treatment that was discontinued if the
discontinuation was due to well-managed symptoms or remission of
symptoms.
The monthly probability of treatment discontinuation among patients
with AEs was 90%.

AE: adverse events; ER: extended release; OAB: overactive bladder.
COPYRIGHT 2017 Canadian Urological Association
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2017 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:ORIGINAL RESEARCH
Author:Herschorn, Sender; Nazir, Jameel; Ramos, Barbara; Hakimi, Zalmai
Publication:Canadian Urological Association Journal (CUAJ)
Date:Mar 1, 2017
Words:1848
Previous Article:Supplementary data: Prospective evaluation of anxiety, pain, and embarrassment associated with cystoscopy and urodynamic testing in clinical practice.
Next Article:Impact of smartphone digital photography, email, and media communication on emergency room visits post-hypospadias repair.
Topics:

Terms of use | Privacy policy | Copyright © 2020 Farlex, Inc. | Feedback | For webmasters