Prostaglandin Analogues for the Treatment of Glaucoma and Ocular Hypertension a Systematic Review of Economic Evidence Michelle Orme and Annabel Boler

Prostaglandin Analogues for the Treatment of Glaucoma and Ocular Hypertension A Systematic Review of Economic Evidence Michelle Orme and Annabel Boler

Heron Evidence Development Ltd, Letchworth Garden City, UK

Supplementary Material

This supplementary material contains the search strategies and table referred to in the full version of this article, which can be found at http://www.adisonline.com/phe

1. Search Strategies

1.1 MEDLINE

#1. exp "GLAUCOMA,-OPEN-ANGLE"/ #2. exp "GLAUCOMA"/ #3. exp "OCULAR-HYPERTENSION"/ #4. (OPEN ANGLE adj5 GLAUCOMA).mp. [mp=ti, ot, ab, nm, hw] #5. ((OCULAR adj HYPERTENSION) or OHT).mp. [mp=ti, ot, ab, nm, hw] #6. (chronic adj3 simple adj3 glaucoma).mp. [mp=ti, ot, ab, nm, hw] #7. (wide adj3 angle adj3 glaucoma).mp. [mp=ti, ot, ab, nm, hw] #8. 1 or 2 or 3 or 4 or 5 or 6 or 7 #9. (Latanoprost$ or Xalatan$ or bimatoprost$ or Lumigan$ or travoprost$ or Travatan$ or unoprostone$ or Rescula$ or Xalacom$).mp. [mp=ti, ot, ab, nm, hw] #10. prostaglandin$.mp. [mp=ti, ot, ab, nm, hw] #11. Prostaglandins F, Synthetic/ #12. 9 or 10 or 11 #13. Economics/ #14. "costs and cost analysis"/ #15. Cost allocation/ #16. Cost-benefit analysis/ #17. Cost control/ #18. Cost savings/ #19. Cost of illness/ #20. Cost sharing/ #21. "deductibles and coinsurance"/ #22. Medical savings accounts/ #23. Health care costs/ #24. Direct service costs/ #25. Drug costs/ #26. Employer health costs/ #27. Hospital costs/ #28. Health expenditures/ #29. Capital expenditures/ #30. Value of life/ #31. exp economics, hospital/ #32. exp economics, medical/ #33. Economics, nursing/ #34. Economics, pharmaceutical/ #35. exp "fees and charges"/ #36. exp budgets/ #37. (low adj cost).mp. #38. (high adj cost).mp. #39. (health?care adj cost$).mp. #40. (fiscal or funding or financial or finance).tw. #41. (cost adj estimate$).mp. #42. (cost adj variable) #43. (cost adj effectiv$).mp. #44. (cost adj utilit$).mp. #45. (cost adj benef$).mp #46. (unit adj cost$).mp. #47. (economic$ or pharmacoeconomic$ or price$ or pricing).tw. #48. or/13-47 #49. 8 and 12 and 48

1.2 EMBASE

#1. exp "GLAUCOMA,-OPEN-ANGLE"/ #2. exp "GLAUCOMA"/ #3. exp "OCULAR-HYPERTENSION"/ #4. (OPEN ANGLE adj5 GLAUCOMA).mp. [mp=ti, ot, ab, nm, hw] #5. ((OCULAR adj HYPERTENSION) or OHT).mp. [mp=ti, ot, ab, nm, hw] #6. (chronic adj3 simple adj3 glaucoma).mp. [mp=ti, ot, ab, nm, hw] #7. (wide adj3 angle adj3 glaucoma).mp. [mp=ti, ot, ab, nm, hw] #8. or/1-7 #9. (Latanoprost$ or Xalatan$ or bimatoprost$ or Lumigan$ or travoprost$ or Travatan$ or unoprostone$ or Rescula$ or Xalacom$).mp. [mp=ti, ot, ab, nm, hw] #10. prostaglandin$.mp. [mp=ti, ot, ab, nm, hw] #11. Prostaglandins F, Synthetic/ #12. 9 or 10 or 11 #13. Socioeconomics/ #14. Cost benefit analysis/ #15. "Cost Effectiveness Analysis"/ #16. Cost of illness/ #17. Cost control/ #18. Economic aspect/ #19. Financial management/ #20. Health care cost/ #21. Health care financing/ #22. Health economics/ #23. Hospital cost/ #24. (fiscal or financial or finance or funding).tw. #25. Cost minimization analysis/ #26. (cost adj estimate$).mp. #27. (cost adj variable$).mp. #28. (unit adj cost$).mp. #29. (cost adj effectiv$).mp. #30. (cost adj utilit$).mp. #31. (cost adj benef$).mp. #32. or/13-31 #33. 8 and 14 and 32

1.3 NHS EED

#1. (latanoprost or xalatan or bimatoprost or lumigan or travoprost or travatan or unoprostone or rescula or xalacom) #2. prostaglandin* #3. or/1-2 #4. glaucoma #5. glaucoma/ #6. (ocular next hypertension) #7. or/4-6 #8. 7 and 3

2. Review of Cost-Effectiveness Evidence

Table I. Summary of included economic studies evaluating the cost-effectiveness evidence for prostaglandin analogues in the management of glaucoma and ocular hypertension

Study Evaluation scope Evaluation framework Clinical outcomes Economic outcomes Key results Qualitative review (country) (disease, treatment (source) (source) and perspective)

Aballea et Glaucoma; 1st-line CEA; Markov model with Months of IOP control (RCR in Cost components [€] unclear and year of ICER LAT vs BB ranged Methodology: NR al.[1] a LAT or BB; 3rd-party Monte Carlo simulation; 2y Germany, Italy, Spain and UK) costs not stated (RCR in Germany, Italy, from €24.94 (95% CI Transparency: NR (Austria, payer timeframe Spain and UK; data for Austria, Belgium and 20.68, 30.11) per IOP- Sensitivity: NR Belgium, France generalised from this RCR) controlled month for Relevance: + France France to €272.84 (95% Overall score: NR Germany, CI 251.24, 297.17) for Italy, UK) Germany

Bernard et OHT or CEA; decision-analytical IOP-controlled days based on Cost components [€, 2002 values]: Total cost (3y): Methodology: + al.[2] OAG/treatment-naive model and Monte Carlo persistence data. Therapy medication, visits and surgery (2y European LAT €868.28 (SD Transparency: + (France) pts; 1st-line BB or simulation (10 000 pts per switch is assumed to imply RCR) 203.31), Sensitivity: ± LAT (0.005%) arm); 24mo and 36mo therapy failure (unpublished 2y Unit costs: Vidal, UNCANSS, PMSI BB €842.46 (SD 343.10) Relevance: + monotherapy, usual timeframe from start of RCR in UK, Italy, Germany and Incremental cost per day Overall score: + care for pts who monotherapy Spain) of IOP control of LAT vs switch therapy; 3rd- BB: €0.82 over 2y, €0.36 party payer direct over 3y costs (NHI)

Day et al.[3] OHT or OAG in CCA; RCR; 6mo timeframe Persistence [days on treatment] Cost components [$US, 2001 values]: At 6mo, BIM and BB- Methodology: ± (US) previously treated or from initiation of study and IOP (RCR from several glaucoma and other drugs, visits and treated pts had Transparency: − treatment-naive pts; monotherapy large glaucoma US practices) procedures, treatment of AEs – additional significantly higher IOPs Sensitivity: − LAT (0.005%) vs BIM visits and tests (RCR) (p < 0.0001) and lower Relevance: ± (0.03%) vs BB Drugs unit cost: AWP persistency (p < 0.0008) Overall score: − monotherapy; 3rd- Visits and procedures cost: Blue Cross and than LAT party payer direct Blue Shield insurer schedules Total cost (SD): costs LAT $US153.7 (46.7); BIM $US163.8 (51.2); BB $US119.3 (78.9)

Doyle et Glaucoma; BIM CEA; model not described; % of pts with target IOP levels Cost components [$US]: glaucoma drugs Incremental cost per Methodology: NR al.[4] a (US) (0.03%), combination 3mo timeframe <17mm Hg (3mo RCT) only (3mo RCT) additional treatment Transparency: NR product TIM Unit costs: AWP success with BIM Sensitivity: NR 0.5%/DOR 2%; Year of costs not stated $US214 Relevance: − pharmacy direct costs Overall score: NR (drugs only)

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Table I. Summary of included economic studies evaluating the cost-effectiveness evidence for prostaglandin analogues in the management of glaucoma and ocular hypertension

Study Evaluation scope Evaluation framework Clinical outcomes Economic outcomes Key results Qualitative review (country) (disease, treatment (source) (source) and perspective)

Evans et Glaucoma; BIM CEA; model; timeframe: % of pts with target IOP Cost components [€]: medication and visits Average expected costs: Methodology: − al.[5] a (0.03%)orTIM costs over 12mo, <17mm Hg for all measurements (unclear) €485 (BIM) vs €471 Transparency: NR (country 0.5%/DOR 2%; 3rd- effectiveness over 3mo throughout day (RCT with 3mo Year of costs not stated (TIM/DOR) Sensitivity: NR unclear) party payer direct follow-up) Cost per pt reaching IOP Relevance: − costs target at 3mo = €139 Overall score: NR (BIM) vs €190 (TIM/DOR)

Fiscella et Glaucoma; BB, CAI, CA; cost identification study; NA Total no. of drops per bottle measured to Daily costs: Methodology: − al.[6] (US) BRI, PAs; pharmacy timeframe not specified calculate daily cost (AWP; $US, 2002 BB $US0.38–1.08, Transparency: + direct costs (drugs values) CAI $US1.05–1.33, Sensitivity: − only) PAs $US0.90–1.25, Relevance: − BRI $US1.29 Overall score: −

Gosden et POAG; 1st-line LAT, CEA; decision-analytical Days of IOP control estimated Cost components [£, 2003 values]: For a cohort of 1000 pts, Methodology: NR al.[7] a (UK) BB, TRA or BIM; NHS model over 1y by assuming switching therapy consultations, drug usage and glaucoma LAT results in 10 397, Transparency: NR direct costs implies failure to control IOP for surgery (expert opinion) 14 341 and 17 142 more Sensitivity: NR half the time on treatment days of IOP control vs Relevance: + (persistency data[8]) BB, TRA and BIM, Overall score: NR respectively Treatment costs (vs LAT): £29 597 more with TRA; £36 650 more with BIM

Halpern et OAG or OHT in Black CCA; extrapolation IOP and VFD scores (combined Estimated effects of VFD change on cost Mean additional annual Methodology: − al.[9] (US) subjects; TRA model/unclear; 12mo six published algorithms linking [inflated to $US, 2000 values] of cost: Transparency: − (0.004%), timeframe IOP and VFD progression with hospitalisation and outpatient care LAT vs TRA 0.004%, Sensitivity: − TRA (0.0015%), data from a subgroup of 132 (hospitalisations: Morse et al.,[11] 1996 $US170 (SD 69, range Relevance: − LAT (0.005%), Black pts included in a trial of National Health Interview Survey,[12] 70–263); Overall score: − TIM (0.5%); 3rd-party 596 pts[10]) Medicare cost schedule 1995) TIM vs TRA 0.004%, payer direct costs Outpatient costs: estimated from guidelines $US247 (SD 112, range (Medicare) – Preferred Practice Patterns of the AAO 66–365) 1996

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Table I. Summary of included economic studies evaluating the cost-effectiveness evidence for prostaglandin analogues in the management of glaucoma and ocular hypertension

Study Evaluation scope Evaluation framework Clinical outcomes Economic outcomes Key results Qualitative review (country) (disease, treatment (source) (source) and perspective)

Ikeda et OAG or OHT; PAs, CA; cost identification study; NA Total no. of drops per bottle measured to Daily cost [$US]: Methodology: − al.[13] BB,EPI/PIL,CAIs; timeframe: not specified calculate daily cost [$US, 2000 values; LAT $US0.44, UNO: Transparency: + (Japan) pharmacy direct cost exchange rate: ¥107 = $US1] $US0.68, Sensitivity: − (drugs only) (Government controlled standard price – TIM: ranged from Relevance: − Japan) $US0.43 for Timoptol Overall score: − XE®b 0.25% to $US1.04 for Rysmon-TG® 0.5%; EPI/PIL $US0.10

Kobelt et POAG or OHT initially CA; Markov model; State transitions [1st-line Cost components [DM, 1997 values]: drugs, Expected 1y Methodology: ± al.[14] treated with BB; 2nd- timeframe 12mo from treatment, 2nd-line treatment, visits,tests,ALT,TRAB charge/cost: Transparency: − (Germany) line LAT or DOR; 3rd- initiation of 2nd-line combination therapy, TRAB, Costs valued independently from resource LAT DM497/746; DOR Sensitivity: + party payer direct laser surgery, post-surgery and use; charges calculated using a standard DM451/745 Relevance: − medical costs (GKV) post ALT {1st-line} calculated charge for each input using the no. of points Overall score: ± from % of pts controlled {IOP determined for every resource and service in <22mm Hg or ≥15% reduction the EBM (observational study) from baseline} during 3mo between visits; (DOR,[15] LAT[16-19] assumed for 2nd-line treatment [both taken as monotherapy or in combination with TIM]). Treatment effect based on trial data[15-19] but as this includes treatment-naive pts, effects were reduced to reflect difficulty in controlling 1st-line failures. The scaling factor was chosen arbitrarily

Kobelt and POAG or OHT initially Same as Kobelt et al.[14] Same as Kobelt et al.[14] (in Resource use: as per Kobelt et al.[14] Average 12mo cost per Methodology: ± Jonsson[20] treated with BB; 2nd- addition, assumption for BRI;[21] Pt co-payments or prescription charges pt: Transparency: − (UK, France) line LAT, DOR, combination efficacy PIL/TIM[19] included as appropriate (France: tariffs from Standard therapy Sensitivity: + BRI, TIM/PIL or and standard therapy efficacy Social Security; UK: NHS reference costs FF2389, £380 Relevance: − standard therapy, (BB taken from RCRs from an and public prices for drugs). Year of costs LAT FF2087, £307 Overall score: ± monotherapy then observational study) unclear DOR FF2305, £324 switch to alternative); TIM/PIL FF2305, £NA 50% of LAT was given BRI FF NA, £325. as combination therapy; direct medical costs to the health system Continued next page

Table I. Summary of included economic studies evaluating the cost-effectiveness evidence for prostaglandin analogues in the management of glaucoma and ocular hypertension

Study Evaluation scope Evaluation framework Clinical outcomes Economic outcomes Key results Qualitative review (country) (disease, treatment (source) (source) and perspective)

Le Pen et Advanced glaucoma; CEA/CUA; Markov model % of pts developing new VFD; Cost components [€, 2005 values]: Incremental utility of Methodology: ± al.[22] (UK, TRA, LAT, TIM; 3rd- (1mo cycles); 5y timeframe utility (a discriminant function glaucoma drugs, visits, laser treatment, TRA vs LAT or TIM = Transparency: − Austria, party and pt direct obtained from a 5y cohort study surgery, tests (France: survey of 88 0.0046 and 0.0209 Sensitivity: − France, costs of 72 pts with advanced ophthalmologists; UK: GPRD; other QALYs, respectively Relevance: ± Germany, glaucoma,[23] used to predict countries: expert panel) Incremental cost-utility Overall score: − The probability of new VFD. The Unit costs: national sources ratio [per QALY] for Netherlands) average and variance in daily TRA: IOP variables in the function Austria: LAT dominated, were from a 12mo clinical trial;[10] TIM: €43 503 [compliance variable omitted France: LAT: €23 948, from calculation]) TIM: €32 116 Germany: LAT dominated, TIM: €43 296 The Netherlands: LAT dominated, TIM €26 742 UK: LAT dominated, TIM €23 828

Malone et Treatment-naive OAG CEA; RCR; timeframe not Absolute and % change in IOP; Cost [$US] components and year of costs Average cost per day Methodology: NR al.[24] a (US) pts; 1st-line LAT, BRI stated (data extracted from medical not stated (as for clinical outcomes) (SD): Transparency: NR or BB; provider direct database at one US centre) BRI $US0.29 (0.39), Sensitivity: NR costs LAT $US0.30 (0.42), Relevance: + BB $US0.05 (0.09) Overall score: NR Cost per day per % reduction in IOP: BRI $US7.15, LAT $US7.58, BB $US8.42 ICER vs BB: BRI $US3.23, LAT $US5.05

Mick et al.[25] Indication not CA; cost identification study; NA Total no. of drops per bottle measured to Daily cost: BIM Methodology: − (US) specified; BIM 2.5mL, timeframe: not specified calculate daily cost $US0.579, Transparency: + LAT 2.5mL, TRA Unit costs [$US, 2002 values]: average of LAT $US0.632, TRA Sensitivity: − 2.5mL, UNO 5mL; 100 pharmacy costs, across US $US0.601, Relevance: − pharmacy direct UNO $US0.490 Overall score: − medical cost (drug only)

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Table I. Summary of included economic studies evaluating the cost-effectiveness evidence for prostaglandin analogues in the management of glaucoma and ocular hypertension

Study Evaluation scope Evaluation framework Clinical outcomes Economic outcomes Key results Qualitative review (country) (disease, treatment (source) (source) and perspective)

Poulsen et Previously treated CEA; decision-analytical Pts achieving target IOP [target Cost components [€] included and year of Pts achieving target Methodology: NR al.[26] a glaucoma or OHT pts; model; 12mo timeframe from not stated] (multinational RCT of costs not stated (as for clinical outcomes) IOP: BIM 36%, LAT 22% Transparency: NR (Austria and 2nd-line LAT 2nd-line therapy initiation 269 adult pts with inadequate Cost per pt achieving Sensitivity: NR Finland) (0.005%) or BIM IOP control) IOP target: Relevance: − 0.03%; societal Austria: BIM €2279, LAT Overall score: NR perspective €3917 Finland: BIM €2317, LAT €3998

Reardon et Treatment-naive; 1st- CEA; decision-analytical Success defined as persistence Cost [$US] components included and year of Success rates: BIM Methodology: NR al.[27] a (US) lineBIM2.5or5mL, model; costs measured over on therapy [continuous time on costs not stated (as for clinical outcomes) (2.5mL), 25%; BIM Transparency: NR LAT 2.5mL, TRA 12mo, success measured at initial therapy for at least 180d] (5mL), 30%; LAT, 36%; Sensitivity: NR 2.5mL; 3rd-party 180d (retrospective cohort analysis TRA, 25% Relevance: ± payer direct costs from managed care database) 1y treatment costs: BIM Overall score: NR (2.5mL), $US791; BIM (5mL), $US958; LAT, $US742; TRA, $US707 Cost per success: BIM (2.5mL), $US3126; BIM (5mL), $US3183; LAT, $US2078; TRA, $US2862 Lowest additional cost per additional treatment success: LAT, $US318

Roberts et Glaucoma; BIM or CEA; Markov model with Number of mo pts spent at IOP Cost components [€]: drugs and physician Months with IOP <17mm Methodology: NR al.[28] a LAT; healthcare Monte Carlo simulations; <17mm Hg (published clinical visits (unknown) Hg: BIM 9.7, LAT 9.3 Transparency: NR (France) system direct costs 12mo timeframe trials) Year of costs not stated (p < 0.05) Sensitivity: NR Annual physician visits: Relevance: − BIM 5.14, LAT 5.48 Overall score: NR (p < 0.001) Monthly cost per pt with IOP <17mm Hg: BIM €41.96, LAT €44.60

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Table I. Summary of included economic studies evaluating the cost-effectiveness evidence for prostaglandin analogues in the management of glaucoma and ocular hypertension

Study Evaluation scope Evaluation framework Clinical outcomes Economic outcomes Key results Qualitative review (country) (disease, treatment (source) (source) and perspective)

Rouland and Glaucoma or OHT pts CEA; decision analytical Mean IOP reduction 12mo after Cost components [€, 2001 values]: Incremental cost per Methodology: ± Le Pen[29] for whom previous model with bootstrapping; inclusion in naturalistic glaucoma medication, visits, procedures and 1mm Hg of IOP control Transparency: − (France) treatment has failed; timeframe: 12mo from prospective study (naturalistic, surgery (as for clinical outcomes) gained: LAT vs BB €102 Sensitivity: + 2nd-line LAT initiation of 2nd-line therapy prospective study conducted in (95% CI 32, 516) Relevance: ± monotherapy, French ophthalmology centres) Daily cost (per eye) Overall score: − LAT/TIM dual therapy, given that pt persists combinations without with 2nd-line for 1y: LAT LAT, other 2nd-line; €0.65 (95% CI 0.64, 3rd-party payer direct 0.66); BB €0.36 (95% CI costs (NHI) 0.34, 0.38); LAT/TIM €0.88 (95% CI 0.81, 0.95) Combination not including LAT €0.75 (95% CI 0.69, 0.80).

Soto and De OAG; LAT, TIM, BIM, CEA; decision-analytical % of pts achieving target IOP Cost components [€] included and year of Cost per pt: TIM €368, Methodology: NR Miguel[30] a TRA; direct costs model over 6mo timeframe [≤18mmHg]at6mo costs not stated (clinical trials and local LAT €379, BIM €377, Transparency: NR (Spain) (NHS) (published clinical trials) expert panel with unit costs from Spanish TRA €383 Sensitivity: NR NHS/national database and official sources) Cost per successfully Relevance: NR treated pt: TIM €1 116, Overall score: NR LAT €702, BIM €785, TRA €912 Incremental cost per additional pt reaching IOP control: LAT vs TIM €54, BIM €40, TRA €−32

Soto and De Glaucoma; 2nd-line CEA; decision-analytical % of pts achieving good IOP Cost components [€] included and year of % of pts with good IOP Methodology: NR Miguel[31] a fixed combination model over 3mo control [≥25% drop in IOP] costs not stated (assumed as for Soto and control: LAT/TIM 80%, Transparency: NR (Spain) LAT/TIM or DOR/TIM; (clinical trial) De Miguel[30]) DOR/TIM 65% Sensitivity: NR NHS (p < 0.01) Relevance: − Cost/treatment success: Overall score: NR LAT/TIM €719, DOR/TIM €840 ICER: LAT/TIM vs DOR/TIM €196 for each additional pt achieving optimal control

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Table I. Summary of included economic studies evaluating the cost-effectiveness evidence for prostaglandin analogues in the management of glaucoma and ocular hypertension

Study Evaluation scope Evaluation framework Clinical outcomes Economic outcomes Key results Qualitative review (country) (disease, treatment (source) (source) and perspective)

Stewart et OHT or POAG CCA; RCR; timeframe: up to Therapeutic success, defined as Cost components [$US]: glaucoma drugs, Cost analyses [pre vs Methodology: − al.[32] (US) previously treated with 6mo before and 12mo after pt taking only study treatment visits and procedures (as for clinical post enrolment (SD)] per Transparency: ± BB therapy; LAT switch from BB monotherapy and ≥2mmHgdropinIOP.A outcomes) person per month: Sensitivity: − 0.005% monotherapy, <2mm Hg drop in IOP, an Year of costs not stated LAT $US66.71 (99.80) Relevance: − BB/BRI, BB/LAT adverse event causing vs $US53.63 (11.95); Overall score: − 0.005%; 3rd-party discontinuation and requirement cost difference payer direct costs of additional therapy defined as $US−13.08 (101.08) therapeutic failure; perfect LAT/BB: $US53.98 compliance of medication was (19.12) vs $US83.19 assumed(RCRfromlargeUS (79.29); ophthalmology practices) cost difference $US29.21 (81.52) BRI/BB: $US75.67 (92.45) vs $US106.20 (134.59); cost difference $US30.53 (134.43)

Vetrugno et Glaucoma or OHT; CA; Markov model; 4y NA Cost components [€] included and year of 4y cost: BIM €3 372 Methodology: NR al.[33] a (Italy) BIM 0.03% or filtration timeframe costs not stated (clinical trial and expert Filtration surgery €4 284 Transparency: NR surgery; national statements with unit costs taken from an Sensitivity: NR healthcare sector Italian tariffs review) Relevance: − Overall score: NR

Vold et al.[34] Glaucoma; BB, PAs, CA; prescription claims file NA Cost components [$US, 1998–2000 values]: Average annual cost: Methodology: ± (US) CAIs, AA; pharmacy analysis; 1y timeframe glaucoma drugs only; (3y prescription claims Cosopt® $US470; Transparency: + direct costs (drugs data with unit costs as total selling price to Betoptic-S® $US370; Sensitivity: − only) pharmacy) Xalatan® $US352; Relevance: − Trusopt® $US287; Overall score: − Agan® $US273; generic LEV $US138; Optipranolol® $US135; generic TIM $US133

Walt et Glaucoma; BIM (after CEA; model not described; % of pts achieving target IOP of Cost components [$US] included and year of 2mo cost per pt Methodology: NR al.[35] a (US) switch from LAT 2mo timeframe 17mm Hg (2mo naturalistic trial) costs not stated; (not stated) achieving target: BIM Transparency: − combination), LAT $US279; LAT Sensitivity: NR combination; combination $US 784 Relevance: − pharmacy direct costs ICER: BIM dominated all Overall score: NR (assumed) LAT combinations

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Table I. Summary of included economic studies evaluating the cost-effectiveness evidence for prostaglandin analogues in the management of glaucoma and ocular hypertension

Study Evaluation scope Evaluation framework Clinical outcomes Economic outcomes Key results Qualitative review (country) (disease, treatment (source) (source) and perspective)

Walt and OHT or glaucoma/ CEA; decision analytical % of pts achieving target IOP Cost components [$US]: drugs, scheduled Weighted average Methodology: − Lee[36] (US) treatment-naive pts model; timeframe: 12mo measured at 12pm at end of visits (assumed that pts reaching target IOP expected annual cost: Transparency: ± with an IOP 22– from initiation of treatment period. First follow-up at 3mo continue 1st-line monotherapy for BIM $US1181; LAT Sensitivity: − 34mm Hg in at least monotherapy at 3mo and if target IOP further 9mo. Assumed that pts failing 1st-line $US1224 Relevance: − one eye; 1st-line BIM achieved, it was assumed target receive adjunctive therapy [% weightings Average incremental Overall score: − (0.03%)orLAT maintained to model endpoint based on market data]. Timing of visits and cost per pts achieving (0.005%) (RCTs with 3mo[37] and 6mo[38] addition of adjunctive therapy from expert target IOP for BIM vs monotherapy; 3rd- follow-up) opinion[39] LAT: $US−188 party payer direct Cost of drugs AWP; $US, 2003 values) (weighted by % for costs each target IOP, and ranged from −68 to −237, depending on target)

Walt et Glaucoma; LAT, TRA CA; retrospective analysis of NA Cost components [$US, 2003 values]: Mean days between Methodology: NR al.[40] a (US) or BIM; pharmacy retail pharmacy database; glaucoma drugs only (pharmacy retail refills: LAT 47; TRA 53; Transparency: NR direct costs (drug 1y timeframe database [mean no. of days between claims BIM 52 Sensitivity: NR only) and refills]) Mean refills per year: Relevance: − LAT 7.8; TRA 6.9; BIM Overall score: NR 7.0 Mean cost per pt: TRA $US11; BIM $US434.70; LAT $US455.36 a Presented as an abstract. b The use of trade names is for product identification purposes only and does not imply endorsement.

AA = α-adrenoceptor agonists; AAO = American Academy of Ophthalmology; AE = adverse event; ALT = argon laser trabeculoplasty; AWP = average wholesale price; BB = β-adrenoceptor antagonist; BIM = bimatoprost; BRI = brimonidine; CA = cost analysis; CAI = carbonic anhydrase inhibitor; CCA = cost-consequence analysis; CEA = cost-effectiveness analysis; CUA = cost-utility analysis; DM = deutschmark; DOR = dorzolamide; EBM = einheitlicher Bewertungs-Maßstab; EPI = epinephrine (adrenaline); FF = French francs; GKV = gesetzliche Krankenversicherung; GPRD = General Practice Research database; IOP = intraocular pressure; LAT = latanoprost; LEV = levobunolol; NA = not applicable; NHI = national health insurance; NHS = National Health Service; NR = not reviewed; OAG = open- angle glaucoma; OHT = ocular hypertension; PA = prostaglandin analogue; PIL = pilocarpine; PMSI = Programme de Medicalisation des Systemes d’Information; POAG = primary open-angle glaucoma; pt(s) = patient(s); RCR = retrospective patient chart review; RCT = randomised controlled trial; SD = standard deviation; TIM = timolol; TRA = travoprost; TRAB = trabeculoplasty; UNCANSS = Union nationale des caisses de sécurité sociale, UNO = unoprostone; VFD = visual field defect; + indicates adequate; ± indicates neutral; − indicates inadequate.

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