“URINARY INCONTINENCE IN WOMEN 2013” NICE guidelines implementation in Primary Care Tony Smith Urogynaecologist St Mary’s HospitalAnson Medical CentreManchester

Why?

Relevance of NICE to GPs NICE provides the evidence base for Quality and Outcomes Framework (QOF)

Relevance of NICE to GPs NICE provides the evidence base for Quality and Outcomes Framework (QOF) NICE pathways define appropriate transfer of care from GP to specialist care

Relevance of NICE to GPs NICE provides the evidence base for Quality and Outcomes Framework (QOF) NICE pathways define appropriate transfer of care from GP to specialist care NICE quality standards should form the basis for assessing the quality of the new GP commissioners

Key recommendations Antimuscarinic drugs Mirabegron

NICE Key recommendations “At the initial assessment, the woman’s UI should be categorised as stress UI, mixed UI, or urge UI / OAB. Initial treatment should be started on this basis. In mixed UI, treatment should be directed towards the predominant symptom.” “expert opinion concludes that symptomatic categorisation of UI based on reports from the woman and history taking is sufficiently reliable to inform initial, non-invasive treatment decisions”

Who takes the best history? Prim Care Sec Care Patient Q KHQ Stress only Mixed OAB Not Classified

History taking More detailed history may be more accurate

e-PAQ

EPAQ Comprehensive, validated questionnaire Provides a database of patient details Outcome analysis Potential for online use Referral from primary to secondary care Care integration triage

NICE Key recommendations Management of OAB Lifestyle advice / behavioural therapy Pelvic floor physiotherapy Drug therapies PTNS Botox SNS

NICE Guideline 2006 Drug therapies 1 st IR oxybutinin (if training ineffective) 2 nd solifenacin, tolterodine, darifenacin etc or transdermal oxybutinin

NICE Guideline 2013 Problems with the literature on anti-muscarinic drugs Most studies compare drug to placebo

NICE Guideline 2013 Problems with the literature on anti-muscarinic drugs Most studies compare drug to placebo Outcome measures vary with different trials

NICE Guideline 2013 Problems with the literature on anti-muscarinic drugs Most studies compare drug to placebo Outcome measures vary with different trials Head to head comparison difficult

NICE Guideline 2013 Problems with the literature on anti-muscarinic drugs Most studies compare drug to placebo Outcome measures vary with different trials Head to head comparison difficult Compliance in trials vs real life

NICE Guideline 2013 Network Metanalysis of drugs Drug A vs placebo Drug B vs placebo Drug C vs placebo

NICE Guideline 2013 Network Metanalysis of drugs Robust outcome measures Similar regimes Adverse event / compliance Incontinence Higher dose 12 weeks

Oxybutynin IR (0.25,0.61)(0.33,0.89)(0.27,0.65)(0.52,1.97)(0.28,0.66)(0.23,1.31)(0.36,0.88)(0.26,0.91)(0.28,2.86)(0.22,0.69)(0.31,1.17)(0.26,0.89)(0.32,0.75) 0.67 Solifenacin (0.31,1.40)(0.95,2.06)(0.84,1.41)(1.23,5.53)(0.90,1.36)(0.66,3.07)(1.17,1.82)(0.76,2.07)(0.77,6.88)(0.64,1.53)(0.88,2.67)(0.76,1.99)(1.05,1.51) Oxybutynin ER (0.30,1.60)(0.71,1.57)(0.54,1.13)(0.85,4.09)(0.56,1.12)(0.45,2.35)(0.72,1.52)(0.50,1.61)(0.53,5.13)(0.42,1.20)(0.58,2.07)(0.50,1.56)(0.63,1.29) Tolterodine IR (0.50,1.72)(0.65,3.12)(0.57,3.17)(1.13,5.07)(0.80,1.29)(0.60,2.88)(1.04,1.73)(0.69,1.93)(0.70,6.35)(0.58,1.43)(0.80,2.48)(0.69,1.86)(0.93,1.45) Propiverine IR (0.24,2.32)(0.48,2.64)(0.42,2.67)(0.25,2.52)(0.20,0.89)(0.19,1.56)(0.27,1.18)(0.20,1.14)(0.17,0.87)(0.24,1.45)(0.20,1.12)(0.23,1.00)(0.60,2.76) Tolterodine ER (0.24,1.04)(0.66,0.86)(0.49,1.03)(0.24,1.16)(0.28,1.54)(0.60,2.76)(1.12,1.55)(0.70,1.84)(0.70,6.16)(0.59,1.35)(0.81,2.38)(0.70,1.77)(1.00,1.30) Propiverine ER (0.26,1.32)(0.60,1.28)(0.49,1.40)(0.26,1.45)(0.31,1.92)(0.82,1.69)(0.48,2.20)(0.36,2.12)(0.44,5.95)(0.30,1.63)(0.43,2.68)(0.36,2.08)(0.41,1.87) Fesoterodine (0.28,1.24)(0.77,1.04)(0.58,1.24)(0.29,1.38)(0.34,1.84)(1.09,1.31)(0.71,1.47)(0.53,1.40)(0.53,4.69)(0.45,1.04)(0.61,1.81)(0.53,1.35)(0.75,0.99) Trospium (0.29,1.78)(0.63,1.88)(0.53,1.97)(0.30,1.97)(0.35,2.59)(0.85,2.49)(0.66,2.34)(0.71,2.09)(0.57,5.94)(0.43,1.45)(0.61,2.46)(0.52,1.87)(0.63,1.59) Oxybutynin TD (0.20,1.93)(0.40,2.22)(0.35,2.27)(0.21,2.10)(0.25,2.72)(0.54,2.95)(0.43,2.68)(0.45,2.47)(0.32,2.37)(0.14,1.35)(0.20,2.20)(0.17,1.72)(0.19,1.61) Darifenacin (0.32,2.00)(0.69,2.12)(0.59,2.21)(0.33,2.20)(0.39,2.87)(0.93,2.81)(0.72,2.61)(0.78,2.36)(0.52,2.37)(0.47,3.49)(0.80,2.96)(0.69,2.26)(0.86,1.88) Trospium ER (0.32,2.00)(0.75,1.31)(0.60,1.48)(0.31,1.57)(0.37,2.09)(1.02,1.72)(0.74,1.72)(0.85,1.44)(0.51,1.64)(0.44,2.55)(0.45,1.48)(0.41,1.59)(0.49,1.39) Oxybutynin TG1.02 (0.27,1.41)(0.65,1.36)(0.53,1.49)(0.28,1.56)(0.34,2.06)(0.88,1.80)(0.66,1.75)(0.74,1.50)(0.46,1.63)(0.40,2.50)(0.41,1.47)(0.62,1.44)(0.65,1.59) Placebo (0.16,0.70)(0.44,0.58)(0.33,0.70)(0.17,0.78)(0.19,1.04)(0.61,0.75)(0.41,0.82)(0.51,0.63)(0.27,0.79)(0.23,1.26)(0.24,0.72)(0.40,0.65)(0.38,0.76)

NICE Guideline 2013 Anti-muscarinic drugs Conclusions Incontinent /dry only robust outcome All drugs are of similar efficacy Compliance varies from 20% to 35% at 12 months Cost

Antimuscarinic prescriptions dispensed, quantity and cost (one month data) (National prescribing data, March 2013) 31/06/2012doseitems Drug name and doseper daydispensedQuantityNet ingredient cost Solifenacin 5mg & 10mg1 156,797 4,964,855 £ 50,312,131 Darifenacin 7.5 & 15mg1 1,586 50,000 £ 373,229 Fesoterodine 4mg & 8mg1 16, ,462 £ 4,948,605 Oxybutynin IR - generic - 2.5, 3 & 5 mg1 84,460 4,673,778 £ 3,506,906 Oxybutynin ER 5mg & 10mg1 34,980 1,438,950 £ 9,314,160 Tolterodine IR 1 & 2mg1 23,912 1,213,075 £ 6,504,092 Tolterodine ER 4mg1 2, ,263 £ 598,112 Propiverine IR 15mg1 2, ,896 £ 497,881 Propiverine ER1 1,240 36,446 £ 318,248 Trospium ER1 13, ,283 £ 2,790,039 Trospium ER1 7, ,423 £ 1,641,647

DrugCostQALYs ICER (1 st line) ICER (2 nd line) No treatment£416, Oxybutynin IR£560, £5,760 Tolterodine IR£583, Dominated Propiverine IR£592, Dominated Oxybutynin ER£651, Dominated£12,601 Trospium£681, Dominateddominated Darifenacin£694, Dominateddominated Trospium ER£706, Dominated£16,855 Tolterodine ER£709, Dominateddominated Fesoterodine£743, Dominateddominated Solifenacin£740, Dominateddominated Oxybutynin TD£738, Dominateddominated Table Incremental cost effectiveness ratios (ICERs) for first-line treatment with antimuscarinic drugs for OAB with additional costs of primary and secondary care included. One year analysis (n=1000 women).

Anti-muscarinic drugs Is the additional cost of the better tolerated drugs worth paying for?

Mirabegron Betmiga B adrenergic agonist First in class Similar efficacy to tolterodine Adverse events

Mirabegron Betmiga B adrenergic agonist First in class Similar efficacy to tolterodine Adverse events “treatment-emergent adverse events (TEAEs) were similar between the mirabegron 50 mg (26.2%) and tolterodine groups (27.6%), the incidence of treatment related serious adverse events (SAEs) was 1.2% in the mirabegron 50 mg group and 0.6% in the tolterodine group and the incidence of treatment-related TEAEs leading to study drug discontinuation was 4.3% in the mirabegron 50 mg group and 3.8% in the tolterodine group.”

NICE guidelines for urinary incontinence in primary care Conclusions Pathways and standards are important Commissioning Treatment choices are difficult GP input to NICE GDG