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Relevantie van observationeel onderzoek in de klinische praktijk

Relevantie van observationeel onderzoek in de klinische praktijk. Themabijeenkomst “observationeel onderzoek” 20 september 2005. Ne derlandse C oöperatieve S tudie naar de A dequaatheid van D ialyse. Presentatie. NECOSAD Mogelijkheden observationeel onderzoek; voorbeelden:

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Relevantie van observationeel onderzoek in de klinische praktijk

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  1. Relevantie van observationeel onderzoek in de klinische praktijk Themabijeenkomst “observationeel onderzoek” 20 september 2005

  2. Nederlandse Coöperatieve Studienaar de Adequaatheidvan Dialyse

  3. Presentatie • NECOSAD • Mogelijkheden observationeel onderzoek; voorbeelden: - HD versus PD - Vroege versus late start - Dialysedosis PD • Conclusies

  4. NECOSAD • Initiatief van de Dialyse Groep Nederland (DGN) • Eerste ideeën 1991 • 1993 - 1995 NECOSAD-1 (pilot-studie) • 1997 - 2003 NECOSAD-2 Uitgevoerd in 38 dialysecentra Gefinancierd door de Nierstichting en de Ziekenfondsraad

  5. Raad van Toezicht Prof. dr. G. K. van der Hem Prof. dr H. A. Koomans Prof. dr. K. M. L. Leunissen Dr. R. van Leusen Projectleiding Dr. E. W. Boeschoten Dr. F. W. Dekker Prof. dr. R. T. Krediet Onderzoeksverpleegkundigen NECOSAD NECOSAD – verpleegkundigen in de centra Begeleidingscommissie Dr. A. J. Apperloo, Dr. J. N. M. Barendrecht, Dr. R. J. Birnie, Dr. M. Boekhout, Dr. W. H. Boer, Dr. E. F. H. van Bommel, Prof. Dr. H. R. Büller, F. Th. de Charro, Dr. C. J. Doorenbos, Dr. W. T. van Dorp, Dr. A. van Es, Dr. W. J. Fagel, Dr. G. W. Feith, Dr. C. F. M. Franssen, Dr. L. A. M. Frenken, Dr. J. A. C. A . van Geelen, Dr. P. G. G. Gerlag, Drs. J. P. M. C. Gorgels, Dr. W. Grave, Dr. R. M. Huisman, Dr. K. J. Jager, Dr. K. Jie, Drs. W. A.. H. Koning-Mulder, Dr. M. I. Koolen, Dr. T. K. Kremer Hovinga, Drs. A. T. J. Lavrijssen, Dr. A. W. Mulder, Dr. K. J. Parlevliet, Dr. J. L. C. M. van Saase, Drs. M. J. M. Schonk, Dr. M. M. J. Schuurmans, Prof. Dr. J. G. P. Tijssen, Dr. R. M. Valentijn, Dr. GH Vastenburg, Dr. C. A. Verburgh, Dr. V. M. C. Verstappen, Dr. H. H. Vincent, Dr. P. Vos. Organisatie NECOSAD

  6. Doelstellingen NECOSAD • Analyse van de factoren die de uitkomst van de dialysebehandeling in Nederland bepalen • Toetsen en ontwikkelen van richtlijnen voor een optimale behandeling • Bijdragen aan de kwaliteit van de behandeling door terugkoppeling van centrumgebonden resultaten en het ontwikkelen van benchmarks

  7. Studieopzet van NECOSAD • Prospectieve observationele multi-center cohort studie bij incidente volwassen dialysepatiënten. • Binnen dit cohort gerandomiseerde trial HD versus PD

  8. Gegevensverzameling • 4 - 0 weken voor de start: demografie, poliklinische voorbereiding, starttherapie (+ reden), primaire nierziekte, co-morbiditeit, rookgewoonten, lengte, gewicht, RR, medicijngebruik, albumine, ureum, creatinine, GFR, kwaliteit van leven • 0, 3, 6, 12, 18…..maanden dialysemodaliteit, therapiewisselingen, registratie op wachtlijst NTx, gewicht, RR, voedingstoestand, medicijngebruik, opnames, lab., dialysedosis, rGFR, Karnofsky-index, KvL.

  9. DatabasePer 01-05-03 ondergebracht bij Hans Mak Instituut

  10. Ingevroren materiaal • Op elk meetmoment afname van spijtmateriaal (serum, urine en dialysaat) • Vanaf 2000 werden ook bloedmonsters voor genotypering ingevroren

  11. Inclusion NECOSAD - 2

  12. Baseline Characteristics Necosad-2

  13. Presentatie • NECOSAD • Mogelijkheden observationeel onderzoek; voorbeelden: - HD versus PD - Vroege versus late start - Dialysedosis PD • Conclusies

  14. Survival in HD and PD • Several studies show small and opposing differences between HD and PD for survival and for quality of life • Variability - due to methodological differences such as type of statistical models, case-mix and follow-up? - or due to an absence of a true difference between HD and PD ?

  15. Design & Aim • A randomized controlled trial (RCT) within a prospective cohort • Compare survival and quality of life between Hemodialysis and Peritoneal dialysis patients

  16. Study design • Patients without medical, social or logistic objections were invited • Patients were educated about HD and PD • Informed consent • Patients were randomized by telephone service: HD or PD • Patients were treated according to usual local care

  17. Study design • Primary outcome: QALY in first 2 years • QALY: quality of the time spent on dialysis • Patients evaluated their own quality with EuroQol

  18. Best imaginable state 100 80 60 40 20 Worst imaginable state 0 EuroQol

  19. Example: QALY-scores after 2-yrs. 80.0 55.0 † 20.6

  20. Study design • Difference of 10 QALY-points clinical relevant • Calculated sample size: 100 patients 50 HD patients 50 PD patients

  21. Trial profile

  22. Trial profile

  23. Mean (SD) QALY-scores after 2 yrs.i.t.t. HD patients: 59.1 (11.7) PD patients: 54.0 (18.9) Difference HD and PD: 5.1 (p = 0.41) Difference after adjustment: 2.1 (p = 0.63) (adjusted for: age, comorbidity, primary kidney disease)

  24. Deceased after 5-year follow-up Years 0 1 2 3 4 5 Total HD - 1 2 2 4 - 9 (50%) PD - 1 1 1 1 1 5 (25%)

  25. Survival (i.t.t.)

  26. Hazard ratio’s after 5 years follow-up i.t.t.

  27. Number changed modality after 5-yr follow-up Years 0 1 2 3 4 5 Total HD - 2 0 0 0 - 2 (11%) PD - 5 1 1 0 0 7 (35%)

  28. Conclusions from the RCT HD versus PD • In terms of QALY scores HD and PD are equivalent • Better survival on PD compared to HD over the first 5 years in i.t.t. analysis • Incident dialysis patients may benefit from starting on PD

  29. Termorshuizen et al. Hemodialysis and peritoneal dialysis: comparison of adjusted mortality rates according to the duration of dialysis: analysis of the NECOSAD 2 study. JASN 2003;14:2851-2860 Design & Aim • Prospective cohort study of patients new on dialysis treatment • Compare mortality rates between HD and PD patients

  30. Patient characteristics – 3 months * p<0.05 HD vs PD

  31. Patient characteristics (cont’d) * p<0.05 HD vs PD

  32. Unadjusted death rates and RR of deathHD – PD cohort study

  33. Multivariate analysis HD compared with PDAdjusted for: ( age, gender, comorbidity, prim kidney dis, SGA, Hb, Alb, renal Kt/v baseline)

  34. Conclusions from the prospective cohort study • During the first 2 years lower mortality rates in PD patients < 60 yr • After 2 years tendency towards greater relative mortality rates for PD patients, especially in PD patients > 60 yr • Indication of a survival benefit of long-term PD patients after switching to HD

  35. From: Lysacht M et al. ASAIO Trans, 1991

  36. Significant risk factors for the decline of GFR during the 1st year on dialysis relative risk effect on index GFR (mL/min) HD vs PD 1.2 -1.5 Diastolic BP (10 mm Hg ) 1.07 -0.4 Proteinuria (g/day) 1.07 -0.5 From: Jansen MAM et al. Kidney Int, 2002

  37. Dialysis related mechanisms responsible for the decline in rGFR(adjusted for baseline GFR, age, sex, PKD, comorbidity) ß p HD: hypotensive episodes - 0.95 0.004 PD: dehydration - 1.94 0.003 Jansen et al KI 2002;62:1042-1053

  38. Presentatie • NECOSAD • Mogelijkheden observationeel onderzoek; voorbeelden: - HD versus PD - Vroege versus late start - Dialysedosis PD • Conclusies

  39. Lancet 2001:358:1046-50

  40. NECOSAD analysisKorevaar et al Lancet 2001;358:1046-1050 • Consecutive new ESRD patients > 18 yrs in 29 dialysis centres • Exclusion of patients without predialysis care and with malignancies • GFR 0-4 weeks before start dialysis • Timely start defined according to DOQ1

  41. Initiation guideline DOQIAm J Kidney Dis 1997 • Timely initiation 1. renal Kt/Vurea  2.0/week 2. Renal Kt/Vurea < 2.0, but BMI  20 kg/m² and nPNA  0.8/kg/day • Late initiation: all other patients

  42. Patient characteristics at start late (n=94) timely (n=159) age (yrs) 56 57 male (%) 65 60 BMI (kg/m²) 25 25 GFR (ml/min/1.73 m³) 4.9 7.1* Kt/Vurea (per week) 1.0 1.5* % HD 40 38 * = p < 0.05

  43. Comparison between timely and late starters • Timely starters have a 2.5 month longer survival on dialysis after 3 years, but • Timely starters begin dialysis 4.1 to 8.3 months earlier in the time course of their disease • No effect of an early start of dialysis on survival

  44. Comparison between timely and late starters • No effect of a timely start of dialysis on survival • Effect on quality of life?

  45. Korevaar et al Am J Kidney Dis 2002;39:108-115

  46. ConclusionsEarly start of dialysis • NKF-DOQI targets on the start of dialysis were not evidence based • An earlier start of chronic dialysis in patients with end-stage renal disease than currently applied in developed countries is not warranted

  47. Presentatie • NECOSAD • Mogelijkheden observationeel onderzoek; voorbeelden: - HD versus PD - Vroege versus late start - Dialysedosis PD • Conclusies

  48. Ademex study(Paniagua R. et al. J Am Soc Nephrol, 2002) • 965 Mexican patients with peritoneal creatinine clearance < 60 L/week/1.73 m2. • Control: 4 x 2L CAPD treated: pCCr > 60 L/week/1.73 m2. • No differences in baseline characteristics. • Minimum follow-up: 2 years.

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