Overactive bladder (OAB) is a common

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1 REPORTS Economic Impact of Extended-release Tolterodine versus Immediate- and Extended-release Oxybutynin Among Commercially Insured Persons With Overactive Bladder Sujata Varadharajan, MS; Zhanna Jumadilova, MD, MBA; Prafulla Girase, MS; and Daniel A. Ollendorf, MPH Abstract Objective: To examine levels of persistence and compliance as well as the economic impact of extended-release tolterodine (tolterodine ER) versus immediate- and extended-release oxybutynin (oxybutynin IR or oxybutynin ER) among commerciallyinsured patients with overactive bladder (OAB). Methods: Patients with OAB who initiated tolterodine ER, oxybutynin IR, or oxybutynin ER between January 2001 and December 2002 were identified from the PharMetrics Patient-Centric database; the first medication used in this timeframe was used for treatment group assignment (ie, patients were only in 1 group). Exploratory assessment of persistency and compliance was conducted among all treated patients: subjects were matched 1:1 based on the estimated propensity score for tolterodine ER in remaining analyses. Measures included patient characteristics as well as levels of medication, outpatient and inpatient resource utilization, and costs. Primary comparisons were made descriptively; costs were evaluated using generalized linear models with a gamma distribution and log-link function. Results: Compliance did not differ between tolterodine ER (77.4%) and oxybutynin ER (74.3%), but was lower for oxybutynin IR (60.9%). Mean (± standard deviation) duration of therapy was higher for tolterodine ER (139 ± 132 days) versus oxybutynin ER (115 ± 122) and oxybutynin IR (60 ± 85). Totals of 7257 and 5936 matched pairs were available for tolterodine ER versus oxybutynin ER and oxybutynin IR comparisons, respectively. The mean age was 54 years in all groups; the majority was women. Utilization of outpatient and inpatient medical services was consistently lower among tolterodine ER patients in both comparisons. Total costs were slightly lower for tolterodine ER versus oxybutynin ER ($8303 ± $ vs $8862 ± $18 684) and oxybutynin IR ($9975 ± $ vs $ ± $22 602); differences were significant after multivariate adjustment. Conclusions: Use of tolterodine ER results in comparable compliance to oxybutynin ER and longer duration of use relative to either form of oxybutynin. In addition, tolterodine ER may be costeffective relative to oxybutynin IR or oxybutynin ER among commercially-insured persons with OAB. (Am J Manag Care. 2005;11:S140-S149) Overactive bladder (OAB) is a common and distressing medical condition resulting in symptoms that include urgency, with or without urinary frequency, and/or urgency incontinence. 1 It is estimated that 16% to 17% of Americans suffer from OAB. 2 In general, the symptoms of OAB can have a debilitating effect on an individual by disrupting quality of life (QOL), sleep patterns, and mental health. 3 Costs associated with OAB also are substantial. In 2000, the total direct and indirect cost of OAB in the United States was estimated at $12.02 billion, with $9.17 billion and $2.85 billion at the community and institution levels respectively. 4 Costs are expected to escalate even further as the prevalence of OAB in the United States increases because of the aging of the population. The goals of OAB treatment are to reduce symptomalogy and improve QOL. There are several treatment options available for this condition, including behavioral modification, pharmacotherapy, and surgical intervention, with the most common being behavioral therapy and pharmacotherapy. 5 Antimuscarinic agents have remained the mainstay of pharmacotherapy for OAB since the launch of oxybutynin in the 1970s. Although immediate-release oxybutynin (oxybutynin IR) has Ascend proved Media effective in relieving the symptoms of OAB, it is associated with many undesirable side effects, subsequently reducing patient adherence and compliance with time. 6 During the past several years, treatment for OAB has expanded to include newer agents that reduce major side effects DDAJMC (D) S140 THE AMERICAN JOURNAL OF MANAGED CARE JULY 2005

2 Economic Impact of Extended-release Tolterodine versus Immediate- and Extended-release Oxybutynin and thereby improve adherence to therapy. Newer extended-release antimuscarinics, such as tolterodine, and the extended-release form of oxybutynin (oxybutynin ER) have demonstrated improved efficacy, convenience, and a tolerability profile better than their immediate-release counterparts by offering once-daily dosing and diminished side effects. 6-8 Several trial-based studies have been conducted in the past that compare efficacy, costs, and adherence in oxybutynin IR and immediate-release tolterodine (tolterodine IR) relative to their extended-release forms. 9,10 The results of another recent analysis of data that evaluated extended-release tolterodine (tolterodine ER) and controlledrelease oxybutynin by using a 4-way crossover design indicated that tolterodine ER was as effective as the controlled-release oxybutynin but with a better tolerability profile. 11 Although there are numerous clinical studies that focus primarily on the cost and efficacy of immediate-release forms or the extended-release versions of oxybutynin and tolterodine separately, to date there has been no large-scale retrospective study that comprehensively assesses relevant outcomes associated with tolterodine ER in comparison to both oxybutynin IR and oxybutynin ER. Additionally, the availability of various treatment options and the potential cost implications associated with these alternatives give rise to the need for comparisons from a typical US clinical practice perspective (ie, nonclinical trial population and setting). The present study examines adherence to OAB pharmacotherapy as well as the impact of tolterodine ER versus oxybutynin IR and oxybutynin ER on the levels of resource utilization and cost in a large commercially-insured population with OAB. Methods Data Source. Data were obtained from the PharMetrics Patient-Centric database, which is comprised of fully adjudicated medical and pharmaceutical claims for more than 46 million unique patients from 82 health plans across the United States. The database includes both inpatient and outpatient diagnoses (in International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] format) and procedures (in Current Procedural Terminology 4 and Health Care Common Procedural Coding System formats) as well as both standard and mail order prescription records. Data on prescription records include the National Drug Code as well as days supplied and quantity dispensed. Both health plan paid and charged amounts are available for all services rendered as well as dates of service for all claims. Additional data elements include demographic variables (ie, age, sex, geographic region), plan type (eg, health maintenance organization [HMO], preferred provider organization [PPO]), payor type (eg, commercial, self-insured), provider specialty, and plan enrollment dates. Sample Selection. All patients diagnosed with OAB (ICD-9-CM 596.5X [excluding , ], 788.3X, , ) and at least 1 pharmacy claim for any of the medications of interest (ie, tolterodine ER, oxybutynin ER, oxybutynin IR) between January 1, 2001, and December 31, 2002, were initially selected for inclusion in the study sample. The date of first medication use served as the patient s index date. Preindex and follow-up periods of 12 months duration each were created in relation to the index date. Claims for these patients were then accumulated spanning the period of January 1, 2000, to December 31, Patients not continuously eligible for drug and health benefits during their entire preindex and follow-up periods were excluded. Patients who had evidence of using an OAB drug of interest during the pre-index period were also excluded. In addition, patients participating in plans without pharmacy benefits were excluded, as were patients aged 65 years or older who were not enrolled in a Medicare risk plan (ie, an agreement by which a commercial health plan agrees to assume full financial risk for the coverage of a Medicare beneficiary); the latter exclusion was implemented to ensure that elderly patients had complete reporting of medical and pharmaceutical utilization. All patients treated with tolterodine ER, oxybutynin ER, or oxybutynin IR who had valid information on pharmacy claims were selected for the persistency and compli- VOL. 11, NO. 4, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S141

3 REPORTS ance analyses. Matched pairs of patients were created to compare outcomes, resource utilization, and costs in comparable groups. To control for potential differences between treatment groups, propensity scores were calculated using multivariate logistic regression and a stepwise selection procedure. A propensity score represents a specific patient s fitted probability (ie, propensity) of receiving a given treatment option and is calculated by summing coefficient values for a list of potential confounding variables. Use of these scores confers the advantage of having a single estimate available to control for multiple differences between treatment groups in a matched-pairs analytic design. 18 Demographic and clinical characteristics as well as pre-index variables were introduced as covariates into the model using stepwise logistic regression techniques; those achieving significance at a level of P <.05 were retained. The outcome of interest was the propensity for, or likelihood of, treatment with tolterodine ER. Separate propensity scores were created for each set of pair-wise comparisons. Thus, patients treated with tolterodine ER were matched on a 1:1 basis to patients treated with oxybutynin ER and oxybutynin IR, and matching was conducted based on a difference of ± 0.01 in this probability. Measures. The primary measures of interest for this study included persistence and compliance as well as resource utilization and costs of OAB-related and unrelated services, which were all measured over 12 months of follow-up. A number of demographic and clinical characteristics, including age, sex, health plan type (eg, HMO, PPO), geographic region, presence of selected pretreatment comorbidities (ie, Alzheimer s disease, chronic obstructive pulmonary disease, congestive heart failure, diabetes, hypertension, ischemic heart disease, multi-infarct dementia, multiple sclerosis, Parkinson s disease, prostate hyperplasia, stroke, urinary retention, urticaria), and comorbidity score (ie, Charlson Index with Deyo modification), 19 were tracked for each treatment group. Among patients receiving an OAB drug of interest, persistence and compliance were measured. Persistence was calculated based on the time (in days) from therapy initiation until the first discontinuation. First discontinuation was defined as a gap in therapy exceeding 2 times the therapy days supplied on the previous prescription. Compliance was expressed as a ratio of the number of therapy days supplied divided by the persistence measure described above. Persistence was also calculated on a monthly basis over a 12-month follow-up period from therapy initiation. Each patient s persistence duration was recorded as a data point in the correct range (ie, months 1-12) for when therapy was discontinued. OAB-related and -unrelated resource utilization and costs were assessed during the follow-up period and included pharmaceutical claims indicated for OAB as well as all other pharmacy claims and medical claims (office management, emergency room, other outpatient, inpatient) related and unrelated to OAB. Where relevant, medical claims were defined as OAB-related versus all others based on the presence of an OAB diagnosis. Costs were estimated based on health plan payments for medications and services rendered and net of patient responsibility (ie, copayment, coinsurance, and/or deductible). Costs were updated as necessary using the medical care component of the US Consumer Price Index. Non- OAB related claims also were tallied and were categorized in similar fashion (ie, pharmacy, outpatient/emergency room, inpatient). Analyses. Differences in patient characteristics, as well as costs during follow-up, were assessed using inferential statistics (ie, chi-square tests for categorical variables and Wilcoxon rank-sum tests for continuous variables); P <.05 was deemed to be statistically significant. Generalized linear models were also used to compare total healthcare costs between the matched patient subgroups. Independent variables in the base models included age, sex, health plan type, geographic region, treating physician specialty, pre-index comorbidities, and pre-index Charlson Comorbidity score. All analyses S142 THE AMERICAN JOURNAL OF MANAGED CARE JULY 2005

4 Economic Impact of Extended-release Tolterodine versus Immediate- and Extended-release Oxybutynin were conducted using Statistical Analysis Software ([SAS], SAS Institute, Cary, NC), Version 8.2. Results A total of patients with a diagnosis of OAB or a claim for any of the OAB drugs were initially identified in the PharMetrics database during the timeframe of interest. After applying the exclusion criteria, patients remained available for study and had evidence of using 1 of the drugs of interest (16 198, 8320, and 8549 for tolterodine ER, oxybutynin ER, and oxybutynin IR, respectively) (Table 1). A total of patients had valid data for the persistency and compliance analyses. Totals of 7257 and 5936 matched pairs were available for the tolterodine ER versus oxybutynin ER and tolterodine ER versus oxybutynin IR comparisons, respectively. The relatively low match rate for the tolterodine ER/oxybutynin IR comparison was likely the result of severity differences between the overall cohorts, because oxybutynin IR patients were younger and had lower levels of comorbidity relative to tolterodine ER patients before matching (data not shown). Nonmatched Comparisons Compliance and Persistence. In general, patients receiving medication for OAB were relatively compliant but not persistent (data not shown). The average compliance rate was 74% for the overall group; compliance was highest among tolterodine ER patients (77.4%), whereas oxybutynin ER and oxybutynin IR patients had lower compliance rates of 74.3% and 61%, respectively. However, overall persistency on these medications was low; three quarters of treated patients discontinued therapy within 6 months. On average, patients were persistent on therapy for 113 days (standard deviation [SD] = 124). Again, mean (± SD) persistence was highest among the patients receiving tolterodine ER and lowest among patients receiving oxybutynin IR (139 [± 132] days vs 115 [± 122] vs 60 [± 85] days for tolterodine ER, oxybutynin ER, and oxybutynin IR, respectively). In addition, differences in persistence were Table 1. Attrition of Study Sample by Reason Reason for attrition Total number of patients with a diagnosis of OAB or claim for tolterodine ER, oxybutynin ER, or oxybutynin IR in database between January 1, 2001, and December 31, 2002 Exclusions: Not continuously enrolled 12 months before index date Not continuously enrolled 12 months after index date No treatment with OAB drugs of interest Patient had OAB drug usage in pre-period 7639 Miscellaneous data quality 72 Total exclusions Total patients before matching Total patients in sample before matching: OAB drugs of interest (index drug) Tolterodine ER Oxybutynin ER 8320 Oxybutynin IR 8549 Tolterodine ER versus oxybutynin ER: Propensity match rate 59.2% Total number of matched pairs 7257 Tolterodine ER versus oxybutynin IR: Propensity match rate 48% Total number of matched pairs 5936 OAB indicates overactive bladder; ER, extended release; IR, immediate release. significantly (all P <.0001) in favor of tolterodine ER at months 1, 2, 3, and 12 for both comparisons to oxybutynin ER and oxybutynin IR (data not shown). Matched Pairs Comparisons Demographic and Clinical Characteristics. There were no substantive differences in the demographic and clinical characteristics in the tolterodine ER versus oxybutynin ER and the tolterodine ER versus oxybutynin IR treatment cohorts (Table 2). The average age within both groups was 54 years; 19% of the patients were men in the tolterodine ER versus oxybutynin ER group, whereas 28% were men in the tolterodine ER N VOL. 11, NO. 4, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S143

5 REPORTS Table 2. Demographic/Clinical Characteristics Among Matched Patients in Study Sample Tolterodine ER vs Oxybutynin ER and Tolterodine ER vs Oxybutynin IR Tolterodine ER Oxybutynin ER Tolterodine ER Oxybutynin IR Characteristic (n = 7257) (n = 7257) P value (n = 5936) (n = 5936) P value Age Mean SD Minimum Median Maximum Sex, men 19.5% 19.2% % 28%.4634 Plan type HMO 47% 46.1% % 59.7%.7303 PPO 35.3% 35.9% 23.7% 22.8% POS 12.1% 12.3% 12.7% 12.9% Indemnity 3.8% 3.9% 3.1% 2.9% Other 1.8% 1.8% 1.4% 1.6% Geographic region Northwest 19.7% 20.3% % 14.2%.091 Midwest 42.1% 42.5% 46.7% 46.7% South 31.1% 30% 22.5% 24.1% West 7.1% 7.2% 16.2% 14.9% Treating physician specialty Family practice/general practice 10% 9.9% % 11.7%.6579 Internal medicine 6.5% 6.4% 6.8% 6.4% Obstetrician/gynecologist 6.6% 6.7% 5% 5.2% Urologist 20.5% 21.5% 23.6% 23.1% Other 12.2% 12.2% 13% 13.2% Unknown 44.1% 43.3% 39.3% 40.4% Pre-index comorbidities Alzheimer s disease 0.3% 0.3% % 0.4%.0843 Chronic obstructive pulmonary 5.4% 5.1% % 5.9%.1618 disease Congestive heart failure 2.2% 2.5% % 2.8%.4125 Diabetes mellitus 11.1% 11.9% % 11.9%.5358 Hypertension 31.1% 30.7% % 31.8%.8593 Ischemic heart disease 7.6% 7.5% % 8.1%.6406 Multi-infarct dementia 0.3% 0.4% % 0.5%.8944 Multiple sclerosis 2.4% 2.5% % 2.9%.7454 Parkinson s disease 0.7% 0.8% % 0.7%.4074 Prostate hyperplasia 6.4% 6.4% % 7.9%.7094 Stroke 1.6% 1.6% % 2.1%.6552 Urinary retention 3.6% 4.2% % 4.4%.9643 Uticaria 0.9% 1.1% % 1%.2942 Pre-index Charlson Comorbidity Index Mean SD Minimum Median Maximum ER indicates extended release; IR, immediate release; SD, standard deviation; HMO, health maintenance organization; PPO, preferred provider organization; POS, point of service. S144 THE AMERICAN JOURNAL OF MANAGED CARE JULY 2005

6 Economic Impact of Extended-release Tolterodine versus Immediate- and Extended-release Oxybutynin Table 3. Resource Utilization During 12-month Follow-up Period Among Matched Patients in Study Sample Tolterodine ER vs Oxybutynin ER and Tolterodine ER vs Oxybutynin IR Tolterodine ER Oxybutynin ER Tolterodine ER Oxybutynin IR (n = 7257) (n = 7257) (n = 5936) (n = 5936) Treatments, medications, and services Mean SD Mean SD P value Mean SD Mean SD P value Pharmacy claims OAB medications < <.0001 Other sympathomimetic urinary medications Other pharmacy services OAB-related Outpatient claims: Outpatient management Outpatient emergency department Laboratory/diagnostic tests Outpatient ancillary Inpatient claims: Inpatient hospitalizations Days in hospital All other Outpatient claims: Outpatient management Outpatient emergency department Laboratory/diagnostic tests < <.0001 Outpatient ancillary <.0001 Inpatient claims: Inpatient hospitalizations Days in hospital ER indicates extended release; IR, immediate release; SD, standard deviation; OAB, overactive bladder. versus oxybutynin IR matched group. Approximately 21% to 23% of patients in both groups were seen by a urologist. The most common comorbidities between both groups were hypertension (~31%-32%), diabetes (~11%- 12%), and ischemic heart disease (~8%). Importantly, there were no observed differences in multiple sclerosis or Parkinson s disease prevalence between the matched groups; the prevalence of corresponding neurogenic bladder was therefore also likely to be similar. Resource Utilization and Cost. Information on healthcare utilization is presented in Table 3 for each of the comparisons of interest. After initiation of therapy, tolterodine ER and oxybutynin ER patients averaged 4 to 5 prescriptions per patient for index therapy (4.79 vs 4.33, respectively), whereas oxybutynin IR users received significantly fewer prescriptions (3.10 per patient) during this period (P <.0001). In addition, although tolterodine ER patients had significantly higher numbers of prescriptions (P <.05) for sympathomimetics, the numbers of claims for all other medications did not differ; also, tolterodine ER patients had a significantly lower utiliza- VOL. 11, NO. 4, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S145

7 REPORTS Table 4. Healthcare Costs* During 12-month Follow-up Period Among Matched Patients in Study Sample Tolterodine ER vs Oxybutynin ER and Tolterodine ER vs Oxybutynin IR Tolterodine ER Oxybutynin ER Tolterodine ER Oxybutynin IR (n = 7257) (n = 7257) (n = 5936) (n = 5936) Treatments, medications, and services Mean ($) SD ($) Mean ($) SD ($) P value Mean ($) SD ($) Mean ($) SD ($) P value Pharmacy claims OAB medications < <.0001 Other sympathomimetic urinary medications Other pharmacy services <.0001 Total pharmacy-related <.0001 healthcare costs OAB-related Outpatient claims: Outpatient management Outpatient emergency department Laboratory/diagnostic tests Outpatient ancillary Inpatient claims: Inpatient hospitalizations Total OAB-related healthcare costs All other Outpatient claims: Outpatient management <.0001 Outpatient emergency department Laboratory/diagnostic tests <.0001 Outpatient ancillary <.0001 Inpatient claims: Inpatient hospitalizations Total all other healthcare costs <.0001 Total healthcare costs *Costs expressed in 2004 US dollars. ER indicates extended release; IR, immediate release; SD, standard release; OAB, overactive bladder. tion (P <.01) of selected OAB-related services compared with the oxybutynin ER group. In comparison, tolterodine ER users in the tolterodine ER/oxybutynin IR cohort required a higher number of all medication types (P <.05) compared with the oxybutynin IR group. Use of OAB-related medical services was higher in oxybutynin IR users (P <.05), because most utilization was manifested in outpatient ancillary claims. All other services were also higher among the oxybutynin IR users; this was noticeable across most inpatient and outpatient services (P <.05). Within the all other category, the most common coded diagnoses of interest were related to urinary tract infections, pelvic and/or genital pain, and other nonspecific S146 THE AMERICAN JOURNAL OF MANAGED CARE JULY 2005

8 Economic Impact of Extended-release Tolterodine versus Immediate- and Extended-release Oxybutynin urinary symptoms. Other prevalent conditions included those commonly found in this population demographic (eg, hypertension, lipid disorders, arthritis and arthropathies, diabetes). Annual total pharmacy-related costs after initiation of index therapy were similar between the tolterodine ER and the oxybutynin ER groups (Table 4). However, total OAB-related costs were significantly lower for tolterodine ER users (P =.0018) versus those in the oxybutynin ER group ($188 [$1224] vs $279 [$1783] for tolterodine ER and oxybutynin ER, respectively), primarily because of differences in the costs of hospitalization and ancillary services. Additionally, total all other costs were significantly higher (approximately $400 on average) for the oxybutynin ER group than for the tolterodine ER group ($5575 [$17 532] vs $5993 [$16 875] for tolterodine ER and oxybutynin ER respectively; P =.0014), primarily because of higher use of outpatient and ancillary services. This increased trend of higher outpatient and inpatient costs across all services in the oxybutynin ER group was responsible for triggering an increase of ~7% in grand total healthcare costs compared with the tolterodine ER group ($8862 [$18 684] vs $8303 [$18 802]; P =.0109). With respect to pharmacy costs, average annual costs of tolterodine ER were much higher than for oxybutynin ER ($358 [$341] vs $56 [$139]; P <.0001). Patients using tolterodine ER also had significantly higher other pharmacy related costs compared with oxybutynin IR users ($2791 [$4997] vs $2204 [$3944]; P <.0001). However, there was a statistical trend toward lower OABrelated medical costs among tolterodine ER patients ($215 [$1470] vs $272 [$2433] for oxybutynin IR; P =.0591). Despite higher pharmacy costs, total healthcare costs were nominally lower (albeit nonsignificantly) among tolterodine ER users ($9975 [$24 860] vs $ [$22 602]; P =.3612), primarily because of reductions in the costs of hospitalization and ancillary services. Multivariate Analyses of Cost Results of multivariate analyses of grand total costs for the tolterodine ER versus oxybutynin ER cohort indicate that patients in the oxybutynin ER group had significantly (P =.0032) higher total costs compared with tolterodine ER. In this analysis, men and younger patients were associated with reduced drug costs, whereas patients treated by a urologist were linked with significantly higher total costs. The presence of any of the pre-index comorbidities was also associated with increased costs. Total costs were significantly lower for the tolterodine ER group compared with the oxybutynin IR group (P <.0001). Women in this comparison also contributed to lower total costs. Age, plan type, geography, and most pre-index comorbidities were also important factors in determining overall costs. Discussion In an effort to better understand the economic outcomes among patients receiving tolterodine ER in comparison to both oxybutynin ER and oxybutynin IR in a large, commercially-insured cohort, a retrospective analysis of pharmacy and medical claims for patients diagnosed with OAB was undertaken. The study spanned the period January 1, 2000, to December 31, 2003, and focused attention on resource utilization, costs, compliance, and persistency. Of those patients receiving OAB pharmacotherapy, tolterodine ER patients had significantly lower pharmacy utilization and used fewer outpatient and inpatient services compared with either oxybutynin cohort. In addition, patients receiving tolterodine ER incurred lower overall healthcare costs, suggesting that its use may be a cost-minimizing alternative for the management of OAB relative to oxybutynin. Although compliance and persistence was relatively poor across treatment groups, our findings suggest that patients appear to be somewhat more compliant and remain on therapy longer with tolterodine ER; thus, even with increased drug exposure (and corresponding cost), tolterodine appears to retain a positive pharmacoeconomic profile relative to oxybutynin. We note several limitations of our analysis. First, we cannot rule out the possibility that differences in associated treatment VOL. 11, NO. 4, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S147

9 REPORTS costs for services may be a result of selection biases inherent in a retrospective database study. However, to control for differences between treatment cohorts, propensitymatched pairs were created and appropriate multivariate adjustments were employed in statistical testing procedures. Although unobserved differences may remain in these populations, they would likely only affect the magnitude (rather than the direction) of our findings. Second, for patients 65 years of age and older, our sample was restricted to include only patients who were enrolled in a Medicare risk plan. These patients who are enrolled in a managed Medicare program may differ in certain respects from the overall US elderly population (eg, demographics, severity of disease). In addition, this analysis was limited to direct costs only, because indirect costs are not measurable through medical claims data. As is the case with any long-term disorder, indirect costs may represent a substantial burden in the management of OAB. However, because the demographic and clinical characteristics of the 3 treatment groups were similar in many respects, one would expect total cost differences to persist even if indirect costs were included. Because the data source employed was retrospective claims data, there was not sufficient detail to determine the contributing factors to lower costs and better adherence in the tolterodine ER group. Lower rates of OAB-related conditions, such as urinary tract infections and fractures, have been suggested for pharmacologically treated compared to untreated patients. 20 The conduct of new prospective economic studies with sufficient detail on major individual cost drivers would greatly add to the evidence on this topic. Despite these limitations, our study has important implications. Our findings suggest that initiation of therapy with tolterodine ER has tangible economic advantages compared with oxybutynin ER or oxybutynin IR among commercially-insured persons with OAB. In addition, adherence to therapy is an important marker of the success of pharmacotherapy in controlling symptoms. As therapies for OAB continue to evolve, prospective studies that evaluate clinical and economic outcomes among patients receiving newer therapies for OAB are recommended to confirm our findings. REFERENCES 1. Getsios D, Caro JJ, Ishak KJ, et al. Oxybutynin extended release and tolterodine immediate release. Clin Drug Invest. 2004;24: Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20: Gross A, Gates C. Transdermal oxybutynin in overactive bladder. Hospital Pharmacist. 2004;11: Hu TW, Wagner TH, Bentkover JD, et al. Estimated economic costs of overactive bladder in the United States. Urology. 2003;61: Ginsberg DA. Overactive bladder: past, present and future. Available at: urologytimes/article/articledetail.jspid= Accessed January 19, Lai HH, Tim BB, Rodney AA. Selecting a medical therapy for overactive bladder. Rev Urol. 2002;4(suppl 4):S28-S Chancellor MB. New frontiers in the treatment of overactive bladder and incontinence. Rev Urol. 2002;4(suppl 4):S50-S MacDiarmid S. New antimuscarinic therapy for the treatment of mixed incontinence. Rev Urol. 2003;5(suppl 8):S18-S Birns J, Lukkari E, Malone-Lee JG. A randomized controlled trial comparing the efficacy of controlledrelease oxybutynin tablets (10 mg once daily) with conventional oxybutynin tablets (5 mg twice daily) in patients whose symptoms were stabilized on 5 mg twice daily oxybutynin. BJU Int. 2000;85: Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine Study Group. Tolterodine oncedaily: superior efficacy and tolerability in the treatment of overactive bladder. Urology. 2001;57: Noe L, Becker R, Williamson T, Chen D. A pharmacoeconomic model comparing two long-acting treatments for overactive bladder. J Manag Care Pharm. 2002;8: Abrams P, Freeman R, Anderstrom C, Mattiasson A. Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Br J Urol. 1998;81: Appell RA. Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis. Urology. 1997;(50 suppl 6A):90-96;discussion Malone-Lee J, Shaffu B, Anand C, Powell C. Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial. J Urol. 2001;165: Millard R, Tuttle J, Moore K, et al. Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity. J Urol. 1999;161: Rentzhog L, Stanton SL, Cardozo L, Nelson E, Fall M, Abrams P. Efficacy and safety of tolterodine in patients with detrusor instability: a dose-ranging study. Br J Urol. 1998;81: S148 THE AMERICAN JOURNAL OF MANAGED CARE JULY 2005

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