PharmacoEconomics

, Volume 19, Issue 5, pp 497–512

Cost Effectiveness of Ramipril in Patients with Non-Diabetic Nephropathy and Hypertension

Economic Evaluation of Ramipril Efficacy In Nephropathy (REIN) Study for Germany from the Perspective of Statutory Health Insurance
  • Peter K. Schädlich
  • Josef Georg Brecht
  • Massimo Brunetti
  • Eva Pagano
  • Badrudin Rangoonwala
  • Eduard Huppertz
Original Research Article

Abstract

Background: In the Ramipril Efficacy In Nephropathy (REIN) trial, ramipril significantly lowered the rate of reaching the combined end-point of doubling of baseline serum creatinine levels or end-stage renal failure (ESRF).

Objective: To determine the additional cost per patient-year of chronic (long term) dialysis avoided (PYCDA) when the ACE inhibitor, ramipril, was added to conventional treatment of patients with non-diabetic nephropathy and hypertension.

Study perspective: Statutory Health Insurance (SHI) provider in Germany.

Design and setting: Data from the REIN Study were used in a cost-effectiveness analysis (CEA). A modelling approach was used, which was based on secondary analysis of published data, and costs were those incurred by the SHI provider (i.e. SHI expenses). In the base-case analysis, average case-related SHI expenses were applied and PYCDA were quantified using the cumulative incidence of ESRF as observed in the REIN trial.

Main outcome measures and results: The incremental cost-effectiveness ratios (ICERs) of ramipril varied between about − 76 700 deutschmarks (DM) and -DM81 900 per PYCDA(DM1 ≈ 0.55 US dollars; 1999 values), according to the treatment periods of 1 year and 3 years, respectively. In the sensitivity analysis, the robustness of the model and its results were shown when the extent of influence of different model variables on the base-case results was investigated. First, probabilities of ESRF and PYCDA were estimated according to the Weibull method. Second, the influence of the model variables on the target variable was quantified using a deterministic model. Third, the dependency of the target variable (ICER) on random variables was described in a simulation. The cost for chronic dialysis had by far the greatest impact on the target variable, which was 28 times greater than the impact of clinical effectiveness of ramipril, i.e. the number of PYCDA. There were net savings per PYCDA with ramipril treatment after 1, 2 and 3 years: 95% of the 10 000 simulation steps resulted in savings of between DM69 500 and DM94 600 per PYCDA after 3 years.

Conclusions: Results from this evaluation show that ramipril offers enormous savings from the perspective of the SHI provider (third-party payer) in Germany when added to the conventional treatment of patients with non-diabetic nephropathy and hypertension.

References

  1. 1.
    Remuzzi G, Ruggenenti P, Benigni A. Understanding the nature of renal disease progression. Kidney Int 1997; 51: 2–15PubMedCrossRefGoogle Scholar
  2. 2.
    Kobrin S, Aradhye S. Preventing progression and complications of renal disease. Hosp Med 1997; 33 (11): 11–12, 17–18, 20, 29–31, 35–36, 39–40Google Scholar
  3. 3.
    Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease: the role of haemodynamically mediated glomerular injury in the pathogenesis of progressive gomerular sclerosis. N Engl J Med 1982; 307: 652–9PubMedCrossRefGoogle Scholar
  4. 4.
    Hostetter TH, Olson JL, Rennke HG, et al. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol 1981; 241: F85–93PubMedGoogle Scholar
  5. 5.
    Bailey RR. Nephrotic syndrome. In: Speight T, Sutherland J, editors. New ethicals disease index. 4th ed. Auckland (NZ): Adis International Limited, 1995: 661–2Google Scholar
  6. 6.
    Songer TJ. The economic costs of NIDDM. Diabetes Metab Rev 1992; 8: 389–404PubMedCrossRefGoogle Scholar
  7. 7.
    Federal Statistical Office. Chronic renal failure. In: Health Report for Germany. Stuttgartt: Metzler-Poeschel, 1998: 254–8Google Scholar
  8. 8.
    Pastan S, Bailey J. Dialysis therapy. N Engl J Med 1998; 338: 1428–37PubMedCrossRefGoogle Scholar
  9. 9.
    Frei U, Schober-Halstenberg HJ. Annual Report of the German Renal Registry 1998. QuaSi-Niere Task ForceGroup for quality assurance in renal replacement therapy. Nephrol Dial Transplant 1999; 14: 1085–90PubMedCrossRefGoogle Scholar
  10. 10.
    Klahr S. Prevention of progression of nephropathy. Nephrol Dial Transplant 1997; 12 Suppl. 2: 63–6PubMedGoogle Scholar
  11. 11.
    Klang MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med 1996; 334: 13–8CrossRefGoogle Scholar
  12. 12.
    Valderrábano F, Gómez-Campderá F, Jones EH. Hypertension as cause of end-stage renal disease: lessons learnt from international registries. Kidney Int 1998; 68 Suppl.: S60–6CrossRefGoogle Scholar
  13. 13.
    Mogensen CE. Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy. BMJ 1982; 285: 685–9PubMedCrossRefGoogle Scholar
  14. 14.
    Parving HH, Andersen AR, Smidt UM, et al. Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1983; I: 1175–9CrossRefGoogle Scholar
  15. 15.
    Parving HH, Hommel E, Smidt UM. Protection of kidney function and decrease in albuminuria by captopril in insulin dependent diabetics with nephropathy. BMJ 1988; 297: 1086–91PubMedCrossRefGoogle Scholar
  16. 16.
    Bjorck S, Mulec H, Johnsen SA, et al. Renal protective effect of enalapril in diabetic nephropathy. BMJ 1992; 304: 339–43PubMedCrossRefGoogle Scholar
  17. 17.
    Lewis JB, Berl T, Bain RP, et al. Effect of intensive blood pressure control on the course of type 1 diabetic nephropathy. Collaborative Study Group. Am J Kidney Dis 1999; 34: 809–17PubMedCrossRefGoogle Scholar
  18. 18.
    Gruppo Italiano di Studi Epidemiologici in Nephrologia (GISEN). A long-term, randomized clinical trial to evaluate the effects of ramipril on the evaluation of renal function in chronic nephropathies. J Nephrol 1991; 3: 193–202Google Scholar
  19. 19.
    GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997; 349: 1857–63CrossRefGoogle Scholar
  20. 20.
    Le Pen C, Petitjean P, Lévy P, et al. Economic evaluation of the contribution of captopril in the treatment of diabetic nephropathy: a cost-benefit approach. Nephrologie 1996; 17: 321–6PubMedGoogle Scholar
  21. 21.
    Szucs T, Ritz E, Standl E. Die Wirtschaftlichkeit von Captopril. Eine Analyse an Patienten mit diabetischer Nephropathie in Deutschland. Münch med Wschr 1994; 136: 581–5Google Scholar
  22. 22.
    Garrattini L, Brunetti M, Salvioni F, et al. Economic evaluation of ACE inhibitor treatment of nephropathy in patients with insulin-dependent diabetes mellitus in Italy. Pharmacoeconomics 1997; 12: 67–75CrossRefGoogle Scholar
  23. 23.
    Hendry BM, Viberti GC, Hummel S, et al. Modelling and costing the consequences of using an ACE inhibitor to slow the progression of renal failure in type I diabetic patients. Q J Med 1997; 90: 277–82CrossRefGoogle Scholar
  24. 24.
    van Hout BA, Simeon GP, McDonnell J, et al. Economic evaluation of benazepril in chronic renal insufficiency. Kidney Int 1997; 63 Suppl.: S159–62Google Scholar
  25. 25.
    Brecht JG, Jenke A, Köhler ME, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Pharmakologie und Therapie zur Durchführung und Bewertung pharmakoökonomischer Studien. Klin Pharmakol akt 1995; 6 (1): 4–11Google Scholar
  26. 26.
    Glaeske G, von Stillfried D. Pharmakoökonomie als Entscheidungshilfe in der Arzneimittelversorgung: Perspektiven aus Sicht der GKV. Ersatzkasse 1995; 75: 298–307Google Scholar
  27. 27.
    Ruggenenti P, Perna A, Mosconi L, et al. Patient data of stratum 2 in the randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Bergamo: Ospedali Riuniti di Bergamo and Mario Negri Institute for Pharmacological Research, 1996. (Data on file)Google Scholar
  28. 28.
    Große Deutsche Spezialitäten-Taxe, Lauer®-Taxe mit Apotheken-Ein- und Verkaufspreisen. Fürth: Pharma Daig + Lauer, 1999 Okt 15Google Scholar
  29. 29.
    Gesetz zur Stärkung der Solidarität in der gesetzlichen Krankenversicherung, 1998Google Scholar
  30. 30.
    Sozialgesetzbuch, Fünftes Buch, 1993 mit §§ 31 und 39 über Zuzahlungen von in der GKV Versicherten bei Arznei- und Verbandmitteln sowie bei Krankenhausbehandlung sowie § 130 über den Rabatt in Höhe von fünf Prozent auf den Arzneimittelabgabepreis, den die gesetzlichen Krankenkassen von den Apotheken erhaltenGoogle Scholar
  31. 31.
    Frei U, Schober-Halstenberg HJ. Nierenersatztherapie in Deutschland. Bericht über Dialysebehandlung und Nierentransplantation in Deutschland 1996. Berlin: Projektgeschäftsstelle QuaSi-Niere, Jul 1998Google Scholar
  32. 32.
    Nebel M. Behandlungskosten der verschiedenen Nierenersatzverfahren. Präsentation beim Satelliten-Symposium ‘Wird Dialyse unbezahlbar — Netzwerkstrategien zur Verbesserung der Frühdiagnostik von Nierenerkrankungen’ der 105. Tagung der Deutschen Gesellschaft für Innere Medizin — Internistenkongress; 1999 Apr 10–14; WiesbadenGoogle Scholar
  33. 33.
    Verordnung zur Regelung der Krankenhauspflegesätze (Bundespflegesatzverordnung — BPflV) vom 26. September 1994, zuletzt geändert durch die Fünfte Verordnung zur Änderung der Bundespflegesatzverordnung vom 9. Dezember 1997, mit Anlage 1: Fallpauschalen-KatalogGoogle Scholar
  34. 34.
    Goergen H, Riedel RR, Vetter H. Sonderentgelte und Fallpauschalen. Köln: Deutscher Ärzte-Verlag, 1997: 29Google Scholar
  35. 35.
    Valderrábano F, Jones EHP, Mallick NP. Report of management of renal failure in Europe, XXIV, 1993. Nephrol Dial Transplant 1995; 10 Suppl. 5: 1–25PubMedCrossRefGoogle Scholar
  36. 36.
    Greiner W. Ökonomische Evaluationen von Gesundheitsleistungen. (Gesundheitsökonomische Beiträge, Band 31). In: Gäfgen G, Oberender P, editors. Baden-Baden: Nomos Verlagsgesellschaft, 1999: 240Google Scholar
  37. 37.
    Drummond MF, Stoddart GL, Torrance GW. Methods for the economic evaluation of healthcare programmes. Oxford: Oxford University Press, 1987Google Scholar
  38. 38.
    Coyle D, Tolley K. Discounting of health benefits in the pharmacoeconomic analysis of drug therapies: an issue for debate? Pharmacoeconomics 1992; 2: 153–62PubMedCrossRefGoogle Scholar
  39. 39.
    Weibull W. A statistical theory of the strength of materials. Ing Vetenkaps Akad Handl 1939; 151: 1–45Google Scholar
  40. 40.
    Bronstein IN, Semendjajew KA. Taschenbuch der Mathematik. 25, durchgesehene Auflage. Stuttgart: Teubner, 1991Google Scholar
  41. 41.
    Schädlich PK, Brecht JG. The cost effectiveness of acamprosate in the treatment of alcoholism in Germany: economic evaluation of the Prevention of Relapse with Acamprosate in the Management ofAlcoholism (PRAMA) study. Pharmacoeconomics 1998; 13 (6): 719–30PubMedCrossRefGoogle Scholar
  42. 42.
    Schädlich PK, Huppertz E, Brecht JG. Cost-effectiveness analysis of ramipril in heart failure after myocardial infarction: economic evaluation of the Acute Infarction Ramipril Efficacy (AIRE) study for Germany from the perspective of Statutory Health Insurance. Pharmacoeconomics 1998; 14 (6): 654–69Google Scholar
  43. 43.
    Schädlich PK, Brecht JG. Economic evaluation of specific immunotherapy versus symptomatic treatment of allergic rhinitis in Germany. Pharmacoeconomics 2000; 17 (1): 37–52PubMedCrossRefGoogle Scholar
  44. 44.
    Kleijnen JPC, editor. Statistical techniques in simulation. Part I, II. New York (NY): Marcel Dekker, 1975Google Scholar
  45. 45.
    Jöckel K-H. Eigenschaften und effektive Anwendung von Monte-Carlo-tests [dissertation]. Dortmund: University of Dortmund, 1982Google Scholar
  46. 46.
    Hartung J, Elpelt B, Klösener KH. Statistik: Lehr- und Handbuch der angewandten Statistik. 3. Auflage. München: Oldenbourg, 1985Google Scholar
  47. 47.
    Langley PC. The future of pharmacoeconomics: a commentary. Clin Ther 1997; 19: 762–9PubMedCrossRefGoogle Scholar
  48. 48.
    Evans C. The use of consensus methods and expert panels in pharmacoeconomic studies: practical applications and methodological shortcomings. Pharmacoeconomics 1997; 12 (2 Pt 1): 121–9PubMedCrossRefGoogle Scholar
  49. 49.
    Kasiske BL, Kalil RSN, Ma JZ, et al. Effects of antihypertensive therapy on the kidney in patients with diabetes: a meta regression analysis. Ann Intern Med 1993; 118: 129–38PubMedGoogle Scholar
  50. 50.
    Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency (AIPRI) Study Group. N Engl J Med 1996; 334: 939–45PubMedCrossRefGoogle Scholar
  51. 51.
    Ruggenenti P, Perna A, Gherardi G, et al. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Lancet 1998; 352: 1252–6PubMedCrossRefGoogle Scholar
  52. 52.
    Salvetti A, Mattei P, Sudano I. Renal protection and antihypertensive drugs: current status. Drugs 1999; 57: 665–93PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Peter K. Schädlich
    • 1
  • Josef Georg Brecht
    • 1
  • Massimo Brunetti
    • 2
  • Eva Pagano
    • 3
  • Badrudin Rangoonwala
    • 4
  • Eduard Huppertz
    • 5
  1. 1.Bureau ItzehoeInForMed GmbH - Outcomes Research & Health EconomicsItzhoeGermany
  2. 2.Centro per la Valuazione della Efficacia della Assistenza Sanitaria (CEVEAS)ModenaItaly
  3. 3.Progetto Sperimentazione GestazionaleAzienda Ospedaliera San Giovanni BattistaTorinoItaly
  4. 4.Hofheim/TaunusGermany
  5. 5.Aventis Pharma Deutschland GmbHBad Soden/TaunusGermany

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