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

2. Why?

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

5. 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

6. 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

7. Key recommendations Antimuscarinic drugs Mirabegron

8. 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”

9. Who takes the best history? Prim Care Sec Care Patient Q KHQ Stress only 25 15 7 2 Mixed 15 32 41 45 OAB 2 0 0 1 Not Classified 7 - - -

10. History taking More detailed history may be more accurate

11. e-PAQ

13. 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

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

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

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

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

18. 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

19. 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

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

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

22. Oxybutynin IR 0.390.550.431.020.430.540.570.490.870.380.600.480.49 (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 1.401.092.611.111.391.461.262.240.991.531.231.26 (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) 0.701.06 Oxybutynin ER 0.781.870.790.991.040.901.600.711.090.880.90 (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) 0.931.381.31 Tolterodine IR 2.401.021.281.341.152.050.911.401.131.16 (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) 0.741.111.060.81 Propiverine IR 0.420.530.560.480.860.380.590.470.48 (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) 0.500.750.710.540.67 Tolterodine ER 1.261.321.142.020.891.381.121.14 (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) 0.580.870.830.630.791.17 Propiverine ER 1.050.901.610.711.100.890.91 (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) 0.600.890.850.650.801.201.02 Fesoterodine 0.861.540.681.050.850.86 (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) 0.721.081.020.780.971.441.231.20 Trospium 1.790.791.220.981.00 (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) 0.620.920.870.670.831.231.051.030.85 Oxybutynin TD 0.440.680.550.56 (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) 0.801.191.130.861.071.591.361.331.111.30 Darifenacin 1.551.251.27 (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) 0.800.990.940.720.891.331.131.110.921.080.83 Trospium ER 0.810.82 (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) 0.630.940.890.680.841.251.071.050.871.020.790.95Oxybutynin 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) 0.340.510.480.370.460.680.580.570.470.550.430.510.54Placebo (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)

23. 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

24. 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 16,842 537,462 £ 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 2,045 111,263 £ 598,112 Propiverine IR 15mg1 2,566 154,896 £ 497,881 Propiverine ER1 1,240 36,446 £ 318,248 Trospium ER1 13,308 652,283 £ 2,790,039 Trospium ER1 7,171 199,423 £ 1,641,647

25. DrugCostQALYs ICER (1 st line) ICER (2 nd line) No treatment£416,000740.00 Oxybutynin IR£560,164765.03£5,760 Tolterodine IR£583,781760.16Dominated Propiverine IR£592,050764.05Dominated Oxybutynin ER£651,233758.67Dominated£12,601 Trospium£681,989758.06Dominateddominated Darifenacin£694,991758.67Dominateddominated Trospium ER£706,168761.93Dominated£16,855 Tolterodine ER£709,659761.07Dominateddominated Fesoterodine£743,784757.80Dominateddominated Solifenacin£740,666759.47Dominateddominated Oxybutynin TD£738,980760.66Dominateddominated Table 6.14. 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).

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

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

28. 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.”

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