- Email: [email protected]
Editorial Comment on: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Antimuscarinic Drugs for Overactive Bladder
european urology 54 (2008) 740–764
[51] Diokno AC, Appell RA, Sand PK, et al. Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial. Mayo Clin Proc 2003;78:687–95. [52] Homma Y, Paick JS, Lee JG, Kawabe K, Japanese, Korean Tolterodine Study Group. Clinical efficacy and tolerability of extended-release tolterodine and immediate-release oxybutynin in Japanese and Korean patients with an overactive bladder: a randomized, placebo-controlled trial. BJU Int 2003;92:741–7. [53] Giannitsas K, Perimenis P, Athanasopoulos A, Gyftopoulos K, Nikiforidis G, Barbalias G. Comparison of the efficacy of tolterodine and oxybutynin in different urodynamic severity grades of idiopathic detrusor overactivity. Eur Urol 2004;46:776–83. [54] Homma Y, Kawabe K. Health-related quality of life of Japanese patients with overactive bladder treated with extended-release tolterodine or immediate-release oxybutynin: a randomized, placebo-controlled trial. World J Urol 2004;22:251–6. [55] Madersbacher H, Halaska M, Voigt R, Alloussi S, Ho¨fner K. A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence. BJU Int 1999;84:646–51. [56] Halaska M, Ralph G, Wiedemann A, et al. Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. World J Urol 2003;20:392–9. [57] Junemann KP, Al-Shukri S. Efficacy and tolerability of trospium chloride and tolterodine in 234 patients with urgesyndrome: a double blind, placebo-controlled, multicentre clinical trial. Neurourol Urodynam 2000;488–90, abstract. [58] Ju¨nemann K-P, Halaska M, Rittstein T, et al. Propiverine versus tolterodine: efficacy and tolerability in patients with overactive bladder. Eur Urol 2005;48:478–82. [59] Chapple CR, Martinez-Garcia R, Selvaggi L, et al. A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating
Editorial Comment on: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Antimuscarinic Drugs for Overactive Bladder Rufus Cartwright Department of Urogynaecology, King’s College Hospital, London, UK [email protected] Previous meta-analyses and evidence-based guidelines concerning antimuscarinic medications for overactive bladder (OAB) have conflicting
[60]
[61]
[62]
[63]
[64]
[65]
[66] [67]
[68]
763
overactive bladder syndrome: results of the STAR trial. Eur Urol 2005;48:464–70. Chapple CR, Fianu-Jonsson A, Indig M, et al. Treatment outcomes in the STAR study: a subanalysis of solifenacin 5 mg and tolterodine ER 4 mg. Eur Urol 2007;52:1195– 1203. Thu¨roff JW, Bunke B, Ebner A, et al. Randomized, doubleblind, multicenter trial on treatment of frequency, urgency and incontinence related to detrusor hyperactivity: oxybutynin versus propantheline versus placebo. J Urol 1991;145:813–6. Leung HY, Yip SK, Cheon C, et al. A randomized controlled trial of tolterodine and oxybutynin on tolerability and clinical efficacy for treating Chinese women with an overactive bladder. BJU Int 2002;90:375–80. Altan-Yaycioglu R, Yaycioglu O, Aydin Akova Y, Guvel S, Ozkardes H. Ocular side-effects of tolterodine and oxybutynin, a single-blind prospective randomized trial. Br J Clin Pharmacol 2005;59:588–92. Davila GW, Daugherty CA, Sanders SW, Transdermal Oxybutynin Study Group. A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J Urol 2001;166:140–5. Dmochowski RR, Sand PK, Zinner NR, Gittelman MC, Davila GW, Sanders SW, Transdermal Oxybutynin Study Group. Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence. Urology 2003;62:237–42. Cartwright R, Cardozo L. Transdermal oxybutynin: sticking to the facts. Eur Urol 2007;51:907–14. Colli E, Parazzini F, Olivieri L, et al. Number of daytime micturitions and volume voided per micturition in the evaluation of efficacy of drugs for overactive bladder: findings from randomized clinical trials. Eur Urol 2007;52:525–30. Oxman AD, Guyatt GH. Validation of an index of the quality of review articles. J Clin Epidemiol 1991;44:1271–8.
recommendations with no consensus about appropriate first-line or second-line therapy [1–3]. With an increasing number of available agents and formulations licensed, the choice of antimuscarinic for patients with OAB has become complicated. The authors of this paper [4] have taken on the Herculean task of reviewing and analysing existing randomised controlled trials (RCTs) that might potentially help clinicians to make an evidencebased choice. So, is it a case of cleaning the Augean stables? The good news is clearly that existing RCTs are generally of high methodological quality.
764
european urology 54 (2008) 740–764
It is lamentable, however, that even within the limited scope of the objective outcomes considered in this review, many trials are still reporting data in a format that is not amenable to meta-analysis. This difficulty in comparing and assimilating data from different trials is compounded by the wide variety of outcome measures employed, some of which are of limited relevance to patients. The increased regulation in the European Union puts large, multicentre drug trials out of the reach of all but the most organised and determined bodies. As the authors note, most available antimuscarinic data are, therefore, from industry-led trials. There may be a conflict between so-called ‘‘experimercials’’ [5], aiming to increase market share, and the needs of clinicians in providing targeted interventions. The key question, which remains largely unanswered for this class of medication, regards long-term subjective efficacy for different subgroups of OAB patients. As efficacious pharmaceutical agents from different classes are developed and as different modalities of treatment become established, it is to be hoped that long-term, head-to-head studies will help define the roles of different antimuscarinic medications and formulations more clearly.
References [1] Hay-Smith J, Herbison P, Ellis G, Morris A. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database of Systematic Reviews;2005. Abstract CD005429. [2] Chapple C, Khullar V, Gabriel Z, Dooley JA. The effects of antimuscarinic treatments in overactive bladder: a systematic review and meta-analysis. Eur Urol 2005; 48:5–26. [3] National Institute for Health and Clinical Excellence. Urinary incontinence: the management of urinary incontinence in women [clinical guideline]. Available at: http:// guidance.nice.org.uk/CG40. Accessed June 2008. [4] Novara G, Galfano A, Secco S, et al. A systematic review and meta-analysis of randomized controlled trials with antimuscarinic drugs for overactive bladder. Eur Urol 2008;54:740–64. [5] Brownlee S. Medicine. In: Blum D, Knudson M, Henig RM, editors. A Field Guide for Science Writers: The Official Guide of the National Association of Science Writers. 2nd ed. New York, NY: Oxford University Press; 2006. p. 155–61.
DOI: 10.1016/j.eururo.2008.06.081 DOI of original article: 10.1016/j.eururo.2008.06.080
[51] Diokno AC, Appell RA, Sand PK, et al. Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial. Mayo Clin Proc 2003;78:687–95. [52] Homma Y, Paick JS, Lee JG, Kawabe K, Japanese, Korean Tolterodine Study Group. Clinical efficacy and tolerability of extended-release tolterodine and immediate-release oxybutynin in Japanese and Korean patients with an overactive bladder: a randomized, placebo-controlled trial. BJU Int 2003;92:741–7. [53] Giannitsas K, Perimenis P, Athanasopoulos A, Gyftopoulos K, Nikiforidis G, Barbalias G. Comparison of the efficacy of tolterodine and oxybutynin in different urodynamic severity grades of idiopathic detrusor overactivity. Eur Urol 2004;46:776–83. [54] Homma Y, Kawabe K. Health-related quality of life of Japanese patients with overactive bladder treated with extended-release tolterodine or immediate-release oxybutynin: a randomized, placebo-controlled trial. World J Urol 2004;22:251–6. [55] Madersbacher H, Halaska M, Voigt R, Alloussi S, Ho¨fner K. A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence. BJU Int 1999;84:646–51. [56] Halaska M, Ralph G, Wiedemann A, et al. Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. World J Urol 2003;20:392–9. [57] Junemann KP, Al-Shukri S. Efficacy and tolerability of trospium chloride and tolterodine in 234 patients with urgesyndrome: a double blind, placebo-controlled, multicentre clinical trial. Neurourol Urodynam 2000;488–90, abstract. [58] Ju¨nemann K-P, Halaska M, Rittstein T, et al. Propiverine versus tolterodine: efficacy and tolerability in patients with overactive bladder. Eur Urol 2005;48:478–82. [59] Chapple CR, Martinez-Garcia R, Selvaggi L, et al. A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating
Editorial Comment on: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Antimuscarinic Drugs for Overactive Bladder Rufus Cartwright Department of Urogynaecology, King’s College Hospital, London, UK [email protected] Previous meta-analyses and evidence-based guidelines concerning antimuscarinic medications for overactive bladder (OAB) have conflicting
[60]
[61]
[62]
[63]
[64]
[65]
[66] [67]
[68]
763
overactive bladder syndrome: results of the STAR trial. Eur Urol 2005;48:464–70. Chapple CR, Fianu-Jonsson A, Indig M, et al. Treatment outcomes in the STAR study: a subanalysis of solifenacin 5 mg and tolterodine ER 4 mg. Eur Urol 2007;52:1195– 1203. Thu¨roff JW, Bunke B, Ebner A, et al. Randomized, doubleblind, multicenter trial on treatment of frequency, urgency and incontinence related to detrusor hyperactivity: oxybutynin versus propantheline versus placebo. J Urol 1991;145:813–6. Leung HY, Yip SK, Cheon C, et al. A randomized controlled trial of tolterodine and oxybutynin on tolerability and clinical efficacy for treating Chinese women with an overactive bladder. BJU Int 2002;90:375–80. Altan-Yaycioglu R, Yaycioglu O, Aydin Akova Y, Guvel S, Ozkardes H. Ocular side-effects of tolterodine and oxybutynin, a single-blind prospective randomized trial. Br J Clin Pharmacol 2005;59:588–92. Davila GW, Daugherty CA, Sanders SW, Transdermal Oxybutynin Study Group. A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J Urol 2001;166:140–5. Dmochowski RR, Sand PK, Zinner NR, Gittelman MC, Davila GW, Sanders SW, Transdermal Oxybutynin Study Group. Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence. Urology 2003;62:237–42. Cartwright R, Cardozo L. Transdermal oxybutynin: sticking to the facts. Eur Urol 2007;51:907–14. Colli E, Parazzini F, Olivieri L, et al. Number of daytime micturitions and volume voided per micturition in the evaluation of efficacy of drugs for overactive bladder: findings from randomized clinical trials. Eur Urol 2007;52:525–30. Oxman AD, Guyatt GH. Validation of an index of the quality of review articles. J Clin Epidemiol 1991;44:1271–8.
recommendations with no consensus about appropriate first-line or second-line therapy [1–3]. With an increasing number of available agents and formulations licensed, the choice of antimuscarinic for patients with OAB has become complicated. The authors of this paper [4] have taken on the Herculean task of reviewing and analysing existing randomised controlled trials (RCTs) that might potentially help clinicians to make an evidencebased choice. So, is it a case of cleaning the Augean stables? The good news is clearly that existing RCTs are generally of high methodological quality.
764
european urology 54 (2008) 740–764
It is lamentable, however, that even within the limited scope of the objective outcomes considered in this review, many trials are still reporting data in a format that is not amenable to meta-analysis. This difficulty in comparing and assimilating data from different trials is compounded by the wide variety of outcome measures employed, some of which are of limited relevance to patients. The increased regulation in the European Union puts large, multicentre drug trials out of the reach of all but the most organised and determined bodies. As the authors note, most available antimuscarinic data are, therefore, from industry-led trials. There may be a conflict between so-called ‘‘experimercials’’ [5], aiming to increase market share, and the needs of clinicians in providing targeted interventions. The key question, which remains largely unanswered for this class of medication, regards long-term subjective efficacy for different subgroups of OAB patients. As efficacious pharmaceutical agents from different classes are developed and as different modalities of treatment become established, it is to be hoped that long-term, head-to-head studies will help define the roles of different antimuscarinic medications and formulations more clearly.
References [1] Hay-Smith J, Herbison P, Ellis G, Morris A. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database of Systematic Reviews;2005. Abstract CD005429. [2] Chapple C, Khullar V, Gabriel Z, Dooley JA. The effects of antimuscarinic treatments in overactive bladder: a systematic review and meta-analysis. Eur Urol 2005; 48:5–26. [3] National Institute for Health and Clinical Excellence. Urinary incontinence: the management of urinary incontinence in women [clinical guideline]. Available at: http:// guidance.nice.org.uk/CG40. Accessed June 2008. [4] Novara G, Galfano A, Secco S, et al. A systematic review and meta-analysis of randomized controlled trials with antimuscarinic drugs for overactive bladder. Eur Urol 2008;54:740–64. [5] Brownlee S. Medicine. In: Blum D, Knudson M, Henig RM, editors. A Field Guide for Science Writers: The Official Guide of the National Association of Science Writers. 2nd ed. New York, NY: Oxford University Press; 2006. p. 155–61.
DOI: 10.1016/j.eururo.2008.06.081 DOI of original article: 10.1016/j.eururo.2008.06.080