Patient Satisfaction With Extended Release Tolterodine or Oxybutynin in Overactive Bladder

By Bolge, Susan C McDonnell, Diana D; Chen, Andrew; Wan, George J

Key words: Overactive bladder – Oxybutynin – Tolterodine – Treatment satisfaction ABSTRACT

Objective: to evaluate the effects of individual and condition characteristics on satisfaction with extended release tolterodine or oxybutynin in overactive bladder (OAB).

Methods: Data were from the 2005 National Health and Wellness Survey, an annual, nationally representative, self-administered, internet-based survey of 40000+ US adults (age 18+). Inclusion criteria for analysis were diagnosed OAB and using extended release tolterodine or oxybutynin but no other prescription medications for OAB. Satisfaction with extended release tolterodine or oxybutynin was rated on a five-point scale from 1 = not at all satisfied to 5 = extremely satisfied. Linear regression was used to evaluate independent effects demographics, patient perception of OAB, duration of use, requesting of medication, type of prescribing physician, medication compliance, and mental and physical health- related quality of life (Medical Outcomes Study, Eight-item Short- Form Health Survey; SF-8) on treatment satisfaction.

Results: There were 345 patients who met the inclusion criteria. Apparent predictors of medication satisfaction, in order of magnitude of effect, were: feelings that OAB is just an inconvenience (standardized beta = -0.28; p < 0.001); less impact of OAB on daily life (standardized beta = 0.24; p < 0.001); longer duration of use (standardized beta = 0.10; p = 0.052); overwhelming urges to urinate (standardized beta = 0.10; p = 0.061); younger age (standardized beta = -0.1 0; p = 0.054); and more frequent medication use (standardized beta = 0.09; p = 0.096).

Limitations: Data were cross-sectional and self-reported by patients via the internet.

Conclusions: Patient treatment satisfaction is affected by perceptions of OAB symptoms and impact, as well as consistent, long- term use of prescription treatments. Clinicians should reinforce to patients the importance of long-term compliance for successful treatment.

Introduction

Overactive bladder (OAB) is a chronic condition encompassing the symptoms of urinary frequency, urgency, and nocturia, caused by involuntary and unpredictable contractions of the detrusor muscle during the filling phase of the bladder1,2. People with OAB feel a very strong urge to pass urine before they leak urine3. To be considered OAB, the symptoms cannot be caused by metabolic problems such as diabetes mellitus, urinary tract infections, or neurological diseases. OAB is estimated to affect 17% of the US population, or about 33 million adults4. Prevalence among women is consistently found to be 1.5 to 2 times higher than prevalence among men in almost all studies5.

OAB, however, is more than a physiologic problem, as the associated emotional distress6 and economic burden7 is also a significant issue. Most OAB sufferers show reduction in their social functioning8. OAB can result in a need for compensatory and coping behaviors, social isolation, anxiety, low self-esteem, depression, and decreased life satisfaction9. OAB has also been linked to reduced work productivity2 and is the reason elderly people must abandon independent living and enter nursing homes in 10% of all institutionalizations10. The yearly direct medical costs for healthcare resource use in the US are estimated at $1.3-3 billion1.

The principal pharmacologic treatments used to improve the symptoms of OAB are based on muscarinic receptor antagonism3. In the United States (US), currently approved anti-muscarinics include two main products; extended-release oxybutynin chloride (Ditropan XL*)11,12 and extended-release tolterodine tartrate (Detrol LA[dagger])13,14, as well as several more recently approved treatments – trospium, solifenacin, and darifenacin15. The extended- release formulations of oxybutynin chloride and tolterodine tartrate11,13 provide longer lasting efficacy and improved tolerability than the immediate-release formulations16.

Satisfaction with treatment is one measure of patient-perceived outcomes. Patient satisfaction indicates whether the patient thought the treatment was worthwhile and whether they would choose the same treatment again. Measures of patient satisfaction thus provide an indication of treatment efficacy and preference17. Because OAB is a syndrome, its diagnosis and management are based almost entirely on patient reports of symptoms and their impact on daily functioning. Hence, the evaluation of treatment efficacy should be based – at least in part – on the subjective assessment of improvements in symptoms and their impact on function18.

Treatment satisfaction is one of a growing number of patient- reported outcomes (PROs), or reports coming from patients about a health condition or its treatment19. In clinical trials, incorporating PROs has become an increasingly common means of assessing treatment efficacy. A review by Brubaker et al.17 found that 30% of the new drugs approved by the US Food and Drug Administration (FDA) between 1997 and 2002 included PRO endpoints in their product labels, including all four urologie agents approved during this time. Khullar et al.15 also found that, of 56 randomized controlled trials of anti-muscarinics between 1966 and 2004, 25 (45%) included patient-reported outcomes. There is a growing recognition in the treatment of many symptomatic conditions18, that subjective assessments can provide valuable information on aspects of disease impact that are most bothersome to the patient and on treatment-related issues that may help optimize disease management.

There is little research, however, assessing patient satisfaction with OAB medication, and especially its contributing factors17. This study evaluates both individual and condition characteristics that affect satisfaction with treatment among a community-dwelling sample of people with OAB. As such, it responds to the call by Brubaker and Chappie18 to include assessments of PROs to gain a broader understanding of treatment-related outcomes.

Methods

Study design

Data were collected in June 2005 through a self-administered, internet-based questionnaire – the National Health and Wellness Survey (NHWS). The NHWS is an annual survey designed by a private survey research company (Consumer Health Sciences, Princeton, NJ) to assess the attitudes, behaviors, and treatment choices of healthcare consumers.

Respondents were a nationally representative sample of non- institutionalized adults (18 years of age and older) living in the US, identified through a web-based consumer panel. Participants included in this analysis met the following criteria: reported as being diagnosed with overactive bladder and using either extended- release oxybutynin or extended-release tolterodine but no other prescription product for overactive bladder. Newly approved medications were not included in the analysis due to their small sample sizes (trospium, n = 15; solifenacin, n = 23; darifenacin, n = 6) and the possibility that early adopters are not reflective of OAB sufferers who treat with prescription medication.

Study measures

Respondents were asked a series of (yes/no) questions about symptoms, including experiencing a sudden overwhelming urge to urinate, frequent urge to urinate, or involuntary loss of small amounts of urine (leakage), as well as urinating more than eight times per day or having to get up twice or more at night to urinate.

The impact of OAB was further evaluated by assessing feelings about OAB and its impact on daily activities. Both were measured on a four-point scale. The scale for feelings was as follows: 1 = it’s an inconvenience but I am in control of it; 2 = it’s an inconvenience but I can mostly manage it; 3 = I can mostly manage but sometimes it takes over; and 4 = my life seems to revolve around coping with my condition. The impact of OAB on daily activities was assessed by the following four-point scale: 1 = seriously interferes with my daily activities; 2 = makes it more difficult for me to do the things I want to do; 3 = has minimal impact on what I do day-to- day; and 4 = has no impact on my life. These two measures are reversed to enhance validity of responses and are highly correlated with each other (r = -0.53, p < 0.001). Respondents were also asked to evaluate whether they perceived their OAB symptoms as mild, moderate, or severe.

Treatment information was self-reported from a question asking respondents to choose their current OAB medications from a prompted list of currently available prescriptions. For each medication, they were asked whether they requested this specific drug from their doctor, the number of months they used the medication, and the number of days that medication had been used in the previous month. Respondents were also asked whether their prescribing doctor was a primary care physician or a specialist.

Medication compliance was assessed using the Morisky Medication Adherence Scale (MMAS). This patient-reported scale consists of four ‘yes/no’ questions: (1) Do you ever forget to take your medicine?; (2) Are you careless at times about taking your medicine?; (3) When you feel better do you sometimes stop taking your medicine?; and (4) Sometimes if you feel worse when you take the medicine, do you stop taking it? ‘Yes’ responses are summed to yield a five-point scale where 0 = compliant and 4 = non-compliant. This scale was originally validated within a hypertension sample, but it has since been implemented and found to be valid and reliable in other patient populations20. For each medication used, patients are asked, ‘How satisfied are you with medication name?’ Satisfaction with treatment was evaluated using a five-point Likert scale, from 1 (not at all satisfied) to 5 (extremely satisfied).

Health-related quality of life (HRQOL) was measured using the Medical Outcomes Study, Eight-item Short-Form Health Survey (SF- 8)21. The SF-8 is a widely used, validated HRQOL measure designed to assess physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health within the previous month. The resulting physical and mental component summary scores are normative for the US population, with a mean of 50 and standard deviation of 10; higher scores indicate better physical or mental HRQOL21. In a meta-analysis, Khullar et al.15 concluded that the SF measures were highly recommended (i.e., there were published data of questionnaire validity, reliability, and responsiveness) for use among people with OAB.

Demographics, including age, gender, race/ethnicity, and education, were reported directly by respondents.

Analyses

The assessment of patient-reported satisfaction with OAB medication was first examined at the bivariate level using Chi- square for categorical variables and ANOVA to compare mean scores for continuous variables. All statistical tests were two-tailed at an alpha level of 0.05.

To fully understand predictors of medication satisfaction, a linear regression model was used to evaluate the independent effects of all possible predictors. Potential predictors included demographics (age, gender, race/ ethnicity, and education), patient perception of OAB (severity, symptoms, feelings about OAB, and impact of OAB on daily life), duration of use (months using product and days used product in the past month), whether the respondent requested the medication, whether the prescribing physician was a specialist, MMAS score, and mental and physical HRQOL. As this analysis was exploratory in nature, we focused on all predictors where p < 0.10. A best-fit model was then used to evaluate the effects of those variables where p < 0.10 in the full model. Within the best-fit model, we focused only on predictors where p < 0.05.

Results

Figure 1 summarizes the inclusion criteria and final sample. The 2005 NHWS had 41 184 respondents, of whom 4741 (12%) self-reported experiencing overactive bladder and/or urinary incontinence; 50% of these (n = 2353) reported that their OAB had been diagnosed by a healthcare professional. Of those diagnosed, 785 (33%) were using a prescription medication to treat their overactive bladder, 42 of whom (5%) reported more than one medication and were therefore excluded from the analysis. Of the remaining 743 medication users, 345 were using extended-release oxybutynin or tolterodine and therefore constituted the final sample. This represents 46% of the single medication users, 44% of the users of any prescription medication for overactive bladder, 1 5% of those diagnosed with and 7% of those who self-reported OAB, and 1% of the total survey sample.

Table 1 describes the sample and evaluates medication satisfaction by the variables specified above. Of the 345 respondents in the final sample, 87% were women and 91% were white. The mean age was 57.7 years (standard deviation +- 12.5) and 30% had completed college. Respondents’ mean (+- standard deviation) mental and physical HRQOL were low (46.1 +- 11.7 and 39.5 +- 11.1,respectively).

Figure 1. Inclusion criteria and sample size. Dx’d = diagnosed; NHWS = National Health and Wellness Survey; OAB = overactive bladder; Rx = prescription treatment

Regarding their OAB medication, 1 9% of respondents had requested that medication from their doctor, 72% of which were general practitioners. Patients had been using their regimen for about 2.5 years (33.2 months +- 30.0), and used it an average of 27 days per month (+- 8.0). Respondents reported high compliance with taking their OAB medication, scoring close to the maximum of zero on the Morisky Medication Adherence Scale (0.5 +- 0.9).

Most respondents (58%) perceived their OAB severity to be moderate. Leakage was the most commonly reported symptom (70%), followed by sudden overwhelming (63%) and/or frequent (62%) urge to urinate. About one-third of the sample described feeling inconvenienced by OAB but in control (32%) or mostly managing (35%) their condition. OAB did affect their daily activities, but relatively minimally. About half (47%) reported that OAB had a minor impact on their daily activities, while an additional third (32%) were slightly more inconvenienced, where OAB made it difficult to do things they wanted to do. OAB seriously interfered with the daily activities for 6% of respondents.

In bivariate analyses, 32% (n = 111) of respondents reported being extremely satisfied with their OAB medication; only 4% (n = 13) were not at all satisfied. Age, gender, race, and education were not significantly associated with satisfaction. Satisfied respondents were more likely to have used their medication closer to every day and reported more adherent attitudes on the MMAS than those who were less satisfied (p < 0.001 for both).

OAB severity, feelings, and impact were all negatively correlated with satisfaction – i.e., people who were more satisfied were less likely to report that their OAB was severe (p = 0.036), that their life revolved around coping with OAB (p < 0.001), and that OAB seriously interfered with their daily activities (p < 0.001). Not surprisingly, satisfied respondents generally reported fewer symptoms than those who were not satisfied. These differences were significant for nocturia (p = 0.005).

Table 1. Sample description and bivariate analysis of satisfaction with extended release prescription OAB medication

Table 1. Sample description and bivariate analysis of satisfaction with extended release prescription OAB medication

Table 1. Sample description and bivariate analysis of satisfaction with extended release prescription OAB medication

Medication satisfaction did not differ by age, gender, education, physical or mental well-being, requesting medication, length of time using medication, or type of prescriber.

To assess the independent effects of each variable on medication satisfaction, variables were next entered into a multivariate linear regression model. The complete model is summarized in Table 2.

Controlling for all other characteristics, respondents were more likely to be satisfied with their medications if OAB had less impact on their lives (standardized beta = 0.24; p < 0.001) and they felt OAB was just an inconvenience, compared to something around which their lives revolved (standardized beta = -0.28; p < 0.001). The following were not significant in the original model but did have p < 0.10: duration of use (standardized beta = 0.10; p = 0.052), more frequent medication use (standardized beta = 0.09; p = 0.096), overwhelming urges to urinate (standardized beta = 0.10; p = 0.061), and younger age (standardized beta = -0.10; p = 0.054).

Table 3 summarizes the best-fit model. Age, duration and frequency of medication use, feelings about OAB, and impact of OAB remain significant predictors of medication satisfaction in the best- fit model.

Discussion

Most people in this community-based sample of OAB sufferers reported being satisfied with their OAB medications. Satisfaction with treatment was higher among those for whom OAB interfered as little as possible with their normal daily activities. Those who were satisfied also tended to be more long term and consistent users of medication. Given the magnitude of this disorder and the importance of disease impact and compliance to satisfaction, primary care physicians should be encouraged to set realistic treatment goals and expectations that take into account patients’ needs and preferences22.

From the patient’s viewpoint, subjective psychosocial measures may better reflect the success of treatment23. The results from this study, therefore, add to the growing recognition that research using a combination of objective and subjective assessments produces a more complete view of the OAB experience24. As Fairclough25 aptly states, ‘While we can measure a biological response, we may not be able to determine whedier that response makes a noticeable difference to the patient’. Treatment plans must be tailored to meet individual goals and, as supported by the results of this study, based on the patient’s perceived impact of the condition. An integral step in achieving this goal is the development of a patient- physician partnership that promotes the clarification and negotiation of realistic expectations22.

Table 2. Multivariate analysis of satisfaction with extended release prescription medication for overactive bladder (complete model)

Table 3. Multivariate analysis of satisfaction with extended release prescription medication for overactive bladder (best-fit model)

In this community-based study, 12% of respondents (of both genders and across all ages) reported experiencing overactive bladder. This is lower than the 19% prevalence found in the similarly sampled National Overactive Bladder Evaluation (NOBLE) program26, based on telephone survey responses. Treatment seeking in the current study was similarly infrequent, as found in past studies: 50% of those who self-reported OAB symptoms had not been physician diagnosed, similar to rates found in reviews by Minassian et al. (43%)27 and Epstein and Goldberg (60%)4.

Limitations of this analysis include its reliance on self- reported data. Because responses were not verified by physicians or clinical records, we cannot be assured of the accuracy of self- reported symptom, treatment, or personal information. Additionally, items that require recall by respondents such as number of days on which a medication was used in the past month have an even greater risk of inaccuracy. Secondly, respondents were recruited from a panel of registered internet survey participants that we cannot be assured entirely represent the general US population, especially the segment that either does not have access to or does not regularly use the internet. This may in part explain why the sample is more educated than the general population with 30% of the sample having a college degree as compared to 25% of the adult population based on the March 2005 Current Population Survey of the US Census Bureau. However, in March 2004, Nielson/NetRatings estimated that 75% of US homes equipped with a telephone line were connected to the internet. Based on the US Census 2003 American Community Survey, more than 4 million American households (about 3%) lack telephone service. Therefore, it is reasonable to infer that a fairly large number of Americans at the lowest socioeconomic groups or residing in rural areas, as well as people who are not proficient or interested in the internet, were excluded from this study28,29.

Related to recruiting, another limitation is that this was an observational study, with conclusions based on cross-sectional assessments of people’s satisfaction at a single point in time. We have no information about (and no basis to evaluate) those who discontinued medications before the survey. Because satisfaction is highly correlated with adherence to a medication regimen30, patients who are dissatisfied are more likely to discontinue medications. Therefore, over time the dissatisfied are consistently removed from the population of medication users, enriching the remaining population with satisfied patients. Also, there are likely to be unmeasured (and therefore unadjusted) differences between those who were and were not satisfied that could potentially explain the variation in reported levels of satisfaction.

Satisfaction was measured on a five-point Likert scale and not using a validated instrument. Therefore, individual patients may have defined satisfaction differently. Further studies are needed that begin to differentiate specific components of satisfaction – the aspect(s) of the medications that most appeal to users and best distinguish them from each other and from non-pharmaceutical methods. Although these medications have been around for many years, few studies have specifically assessed patient satisfaction; this study hopes to encourage further research in this area3.

Because of the positive associations found between treatment satisfaction and compliance, physicians should consider patient satisfaction when discussing OAB medications. In this vein, further research is also needed to increase long-term compliance2. When pursuing this goal, trials should include patients’ perception of change in symptoms and satisfaction as primary study outcomes3.

Conclusion

Among community-based OAB sufferers, satisfaction with OAB medication is influenced by perceptions of OAB symptoms and impact. Psychological and social issues are important in urology because they affect not only the patient’s willingness to seek out therapy, but also their ability to benefit from it3′. With proper evaluation and treatment, the majority of people with overactive bladder can be helped or cured27. To further this aim, healthcare professionals should set expectations for patients and monitor their satisfaction with the prescribed treatment regimen.

Satisfaction among OAB sufferers also is associated with consistent and long-term treatment. For this reason, clinicians should take the time to further educate patients about treatment and reinforce the need for long-term compliance which is the key to successful management of this chronic condition.

Acknowledgments

Declaration of interest: This study was funded by Ortho Women’s Health & Urology, a Division of Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ, USA.

* Ditropan XL is a trade name of Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ, USA

[dagger] Detrol LA is a trade name of Pfizer, Inc., New York, NY, USA

References

1. Norton P, Brubaker L. Urinary incontinence in women. Lancet 2006;367:57-67

2. McGhan WF. Cost effectiveness and quality of life considerations in the treatment of patients with overactive bladder. Am J Manag Care 2001;7:S62-75

3. Hay-Smith J, Herbison P, Ellis G, Morris A. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database Syst Rev 2005;20:CD005429

4. Epstein LB, Goldberg RP. The overactive bladder and quality of life. Int J Fertil Womens Med 2005;50:30-6

5. Davila GW, Neimark M. The overactive bladder: prevalence and effects on quality of life. Clin Obstet Gynecol 2002;45:173-81

6. Bradway C. UI among older women: measurement of the effect on health-related quality of life. J Gerontol Nurs 2003;29: 13-9

7. Hampel C, Artibani W, Espuna Pons M, Haab F, et al. Understanding the burden of stress UI in Europe: a qualitative review of the literature. Eur Urol 2004;46:15-27

8. Lenderking WR, Nackley JF, Anderson RB, Testa MA. A review of the quality-of-life aspects of urinary urge incontinence. Pharmacoeconomics 1996;9:11-23

9. Criner JA. UI in a vulnerable population: older women. Semin Perioper Nurs 2001;10:33-7

10. Morrison A, Levy R. Fraction of nursing home admissions attributable to urinary incontinence. Value Health 2006;9: 272-4

11. Goldenberg MM. An extended-release formulation of oxybutynin chloride for the treatment of overactive urinary bladder. Clin Ther 1999;21:634-42

12. Comer AM, Goa KL. Extended-release oxybutynin. Drugs Aging 2000;16:149-55

13. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, et al.; Tolterodine Study Group. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology 2001;57:414-21

14. Clemett D, Jarvis B. Tolterodine: a review of its use in the treatment of overactive bladder. Drugs Aging 2001;18:277-304

15. Khullar V, Chapple C, Gabriel Z, Dooley JA. The effects of antimuscarinics on health-related quality of life in overactive bladder: a systematic review and meta-analysis. Urology 2006;68:38- 48

16. Dmochowski RR, Appell RA. Advancements in pharmacologic management of the overactive bladder. Urology 2000;56:41-9

17. Brubaker L, Chappie C, Coyne KS, Kopp Z. Patient-reported outcomes in overactive bladder: importance for determining clinical effectiveness of treatment. Urology 2006;68:3-8

18. Brubaker L, Chapple C. Introduction. Urology 2006;68:1-2

19. Office of New Drugs and Office of Medical Policy: guidance for industry patient-reported outcome measures: use in medical product development to support labeling claims. Rockville, MD: Center for Drug Evaluation and Research (CDER), 2006

20. Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care 1986;24:67-74

21. Ware JE, Kosinski M, Dewey JE1 Gandek B. A manual for users of the SF-8 Health Survey. Lincoln, RI: QualityMetric Incorporated, 2001

22. Marschall-Kehrel D, Roberts RG, Brubaker L. Patient-reported outcomes in overactive bladder: the influence of perception of condition and expectation for treatment benefit. Urology 2006;68:29- 37

23. Hajjar RR. Psychosocial impact of UI in the elderly population. Clin Geriate Med 2004;20:553-64, viii

24. Abrams P, Artibani W, Gajewski JB, Hussain I. Assessment of treatment outcomes in patients with overactive bladder: importance of objective and subjective measures. Urology 2006;68:17-28

25. Fairclough DL. Patient reported outcomes as endpoints in medical research. Stat Methods Med Res 2004;13:115-38

26. Coyne KS, Zhou Z, Thompson C, Versi E. The impact on health- related quality of life of stress, urge and mixed UI. BJU Int 2003;92:731-5

27. Minassian VA, Drutz HP, Al-Badr A. UI as a worldwide problem. Int J Gynaecol Obstet 2003;82:327-38

28. Best SJ, Krueger B, Hubbard C, Smith A. An assessment of the generalizability of internet surveys. Soc Sci Comput Rev 2001;19:131- 45

29. Wyatt, JC. When to use web-based surveys. J Am Med Inform Assoc 2000;7:426-30

30. Shikiar R, Rentz AM. Satisfaction with medication: an overview of conceptual, mediodologic, and regulatory issues. Value Health 2004;4:204-15

31. Umlauf MG, Goode S, Burgio KL. Psychosocial issues in geriatric urology: problems in treatment and treatment seeking. Urol Clin North Am 1996;23:127-36

CrossRef links are available in the online published version of this paper: http://www.cmrojournal.com

Paper CMRO-3982_3, Accepted for publication: 18 May 2007

Published Online: 03 July 2007

doi:10.1185/030079907X210598

Susan C. Bolge(a), Diana D. McDonnell(a), Andrew Chen(b) and George J. Wan(b)

a Consumer Health Sciences, Princeton, NJ, USA

b Ortho Women’s Health & Urology, Raritan, NJ, USA

Address for correspondence: Susan C. Bolge, Consumer Health Sciences, 116 Village Blvd., Suite 200, Princeton, NJ 08540, USA. Tel.: +1 609 924 4455; Fax: + 1 609 924 7794; susan.bolge@chsinternational.com

Copyright Librapharm Aug 2007

(c) 2007 Current Medical Research and Opinion. Provided by ProQuest Information and Learning. All rights Reserved.