Australian adults => 25 yrs of age. Australia, Australian Health sector

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1 CHAPTER 4-CKD GUIDELINE 4.1. THE INFLUENCE OF GFR, AGE, GENDER, ETHNICITY AND PROTEINURIA ON PATIENT OUTCOMES Q: At what level of GFR are patient outcomes significantly affected? Does this change with age? Gender? Ethnicity? Presence or absence of proteinuria? There were no health economics papers to review 4.2 WHO SHOULD BE TESTED FOR CKD? Q: In adults, who should be tested for CKD? Bibliographic reference Economic study type [1] Population, country & perspective Intervention Comparison(s) Howard, K., Salkeld,G., White,S., Chadban,S., Craig,J., McDonald,S., Perkovic,V., & Cass,A. The Cost- Effectiveness of Early Detection and Intervention to Prevent the Progression of Chronic Kidney Disease in Australia. Kidney Health Australia,Melbourne, 2006 Cost effective analysis, cost per life year saved and cost per qaly gained Australian adults => 25 yrs of age. Australia, Australian Health sector This study aims to provide a preliminary estimate of the incremental costs and effects of combining two approaches to reducing the impact of chronic kidney disease: (1) Screening and early detection of hypertension, diabetes (with or without microalbuminuria) and proteinuria in the Australian population aged 25 years and older; and (2) Better management of existing (known or unknown) patients with risk factors for CKD. The comparator for this study consists of current treatment practices for people with diabetes and/or hypertension and protein. Chronic kidney disease: evidence tables DRAFT Page 1 of 17

2 Source of effectiveness data [2] Method of eliciting health valuations (if applicable) Cost components included Separate trials estimating the size of effect of screening and treatment for independent risk factors, that is, hypertension, diabetes and proteinuria. Further studies provided evidence on the chance of progression from a state of having an elevated risk factor through to CKD and ESKD. Modelling disease progression was predicated on knowing the current prevalence of disease risk factors. The AusDiab study, a population-based cross sectional survey of national diabetes mellitus prevalence and associated risk factors in people aged >= 25 years, conducted in , provided the estimate of risk factor prevalence The outcomes and management of CKD, and consequently the costs incurred, are not easily isolated from other chronic diseases. Cardiovascular disease in particular is both a cause and a consequence of CKD. This report has included only those health sector costs which are directly attributable to CKD. Indirect costs, such as lost Chronic kidney disease: evidence tables DRAFT Page 2 of 17

3 Currency and cost year productivity, have been excluded from this analysis. Costs of drugs, services and resources used are covered for conventional and intensive glucose and hypertension control, ACEi regimens and costs of ESKD. Australian Dollar Chronic kidney disease: evidence tables DRAFT Page 3 of 17

4 Results cost per patient per alternative Chronic kidney disease: evidence tables DRAFT Page 4 of 17

5 Results effectiveness per patient per alternative Chronic kidney disease: evidence tables DRAFT Page 5 of 17

6 Chronic kidney disease: evidence tables DRAFT Page 6 of 17

7 Chronic kidney disease: evidence tables DRAFT Page 7 of 17

8 Results incremental costeffectiveness Screening for proteinuria and addition of an ACE inhibitor in all known diabetics and known and new patients with proteinuria The Figures above provide indicative estimates of possible cost effectiveness of screening for proteinuria, with addition of an ACEi for all known diabetic patients and for all (known + screen detected) patients with proteinuria (with and without diabetes; with and without hypertension), for the health outcomes of life years saved (LYS) and Quality Adjusted Life Years Saved (QALYS) Sensitivity analysis around the screening interval has also been conducted. The base case screening interval is screening from years; the upper age limit has been increased to 79 years in sensitivity analyses. The mean incremental cost-effectiveness estimates are $3,398/LYS and $4,269/QALY for screening up to age 69. For screening to age 79, the mean cost effectiveness estimates are $4,604/LYS and $5,740/QALY. Chronic kidney disease: evidence tables DRAFT Page 8 of 17

9 Screening for proteinuria and addition of an ACE inhibitor in known and new patients with proteinuria The Table above provides indicative estimates of possible cost effectiveness of screening for proteinuria, with addition of an ACEi for all (known + screen detected) patients with proteinuria (with and without diabetes; with and without hypertension), for the health outcomes of life years saved (LYS) and Quality Adjusted Life Years Saved (QALYS) Sensitivity analysis around the screening interval has also been conducted. The base case screening interval is screening from years; the upper age limit has been increased to 79 years in sensitivity analyses. The mean incremental cost-effectiveness estimates are $2,854/LYS and $3,577/QALY for screening up to age 69. For screening to age 79, the mean cost effectiveness estimates are $4,146/LYS and $5,152/QALY. Results-uncertainty Time horizon & Sensitivity analysis and monte carlo simulations carried out 5% per annum, model ran for 46 years Chronic kidney disease: evidence tables DRAFT Page 9 of 17

10 discount rate Source of funding Comments Overall study quality (++,+,-) Kidney health Australia The authors do highlight that thecost effectiveness analysis is based on very limited data on the effectiveness of screening. There are no trials that look at this intervention in the relevant patient group: proteinuria with no diabetes and no hypertension and point out that there is a need for randomized trial evidence of ACEi in proteinuric patients with minimal other comorbidities such as diabetes or hypertension. The results presented in this Report should therefore be taken as exploratory only. The results suggest some benefit under optimistic assumption ++ Bibliographic reference Economic study type [1] Population, country & perspective Intervention Comparison(s) Boulware L.E, Jaar B.G, Tarver-Carr M.E, Brancati F.L, Powe N.R. Screening for Proteinuria in US Adults A Cost-Effectiveness Analysis JAMA, Dec 17, 2003 VOl 290, No 23 A cost effectiveness analysis based on a Markov Decision analytic model, Cost per QALY adjusted Life Yr United States, Societal perspective. US Adults aged 50 yrs(with demographic characteristics similar to persons in the 3 rd National Health and Nutrition Examination Survey[NHANES III] 52 % Female, 80% non-hispanic white, 11 % non-hispanic Black, 5% Mexican American) All person screened annually till 75 yrs, development of ESRD or death A strategy of annual screening for proteinuria and subsequent treatment with ACE/ARB therapy with a strategy of routine clinical practice for persons with neither hypertension nor diabetes and for persons with hypertension and for persons with type 2 diabetes (many of whom had hypertension) THE SCREENING STRATEGY: consisted of Urine dipstick test to detect proteinuria (i.e. 1+ result on a colorimetric urine dipstick test for gross proteinuria) during an annual visit with a primary care physician. Positive dipstick followed up by second visit to reassess urine protein levels using quantitative random (albumin to creatinine ratio) or timed urine specimens in addition to measurement of Chronic kidney disease: evidence tables DRAFT Page 10 of 17

11 serum creatinine level and estimation of GFR using recommended equations Positive quantitative results would lead to either treatment with ACE/ARB by primary care physician for those with normal renal function Or referral to nephrologist followed up with ACE/ARB for persons with GFR<90ml/min per 1.73 m2 + dipstick & - quantitative urine protein tests = false positive /non persistent proteinuria, did not proceed further, routine screening next yr Source of effectiveness data [2] THE NO SCREENING STRATEGY: No dipstick testing and natural progression of kidney disease with an annual opportunity for incidental testing/symptom development and disease detection Various studies, cohort and clinical, whose level of evidence was based on hierarchy of research design based on US Preventative Services Task Force were used and for subgroups in which insufficient evidence was available conservative Assumptions made by study researches NHANES III Sensitivity analysis, % COHORT Base Case, % In favour of screening Against Screening Prevalence of Proteinuria by clinical history Neither hypertension nor diabetes Hypertension Diabetes Incidence of Proteinuria by clinical history published literature Neither hypertension nor diabetes Hypertension Diabetes Chronic kidney disease: evidence tables DRAFT Page 11 of 17

12 Symptoms leading to testing (by level of GFR, ml/min per 1.73 m2 per year) [Represents rates of testing due to patient complaints of symptoms or incidental office based testing for proteinuria] >= < Base Case, % Sensitivity analysis, % In favour of screening Screening Test Characteristics Sensitivity (1+ proteinuria) Specificity (1+ proteinuria) Against Screening Base Case, % Sensitivity analysis, % In favour of Against screening Screening Potential benefit of screening in all subgroups RR reduction in progression Chronic kidney disease: evidence tables DRAFT Page 12 of 17

13 toward ESRD afforded by ACEi/ARB RR reduction in all-cause mortality afforded by ACEi/ARB Base Case, % Sensitivity analysis, % In favour of Against screening Screening Number Utilities for Health states, GFR in ml/min per 1.73 m2 >= 90 with proteinuria (with or without proteinuria) <15 (with or without proteinuria) Chronic kidney disease: evidence tables DRAFT Page 13 of 17

14 Clinical History and Kidney Function Annual Decline in GFR, ml/min per 1.73m2 Base case Against In favour of Screening screening Neither Hypertension nor Diabetes No proteinuria >= 90 to to <15 1.0* Proteinuria >= 90 to * to < Hypertension No proteinuria >= 90 to * to < Proteinuria >= 90 to * to < Diabetes No proteinuria >= 90 to to < Proteinuria >= 90 to to < * Assumptions Chronic kidney disease: evidence tables DRAFT Page 14 of 17

15 Method of eliciting health valuations (if applicable) Cost components included Sensitivity analysis, $ Cost component Base case, $ screening Initial generalist physician visit Follow up generalist physician visit In favour of screening Test ( urine dipstick) Initial specialist physician evaluation by clinical history Neither hypertension nor diabetes Hypertension Diabetes Follow up specialist fees Physician Testing Annual cost of therapy ACEi ARB ESRD (weighted average cost of HD, PD and Tx) Against Screening Discount rate 3% 1 5% Currency and cost year US$ 2002 Chronic kidney disease: evidence tables DRAFT Page 15 of 17

16 Results cost per patient per alternative Results effectiveness per patient per alternative Results incremental costeffectiveness [Authors considered C-E ratios of less than $ per QALY highly favourable towards screening] Cost-effectiveness of Annual Dipstick Testing for Proteinuria Clinical history &Screening Strategy Cost of Strategy in 2002 US$ Incremental cost,$ Effectiveness of Strategy (QALY) Incremental Effectiveness (QALY) C-E ratio, $ per QALY saved Neither Hypertension nor Diabetes Screening No Screening Hypertension Screening No screening Results-uncertainty Age screening Begins, y Clinical History Cost-effectiveness Ratio, $ per QALY saved No Hypertension or Diabetes Hypertension way SA, multi-way SA, Monte Carlo simulations undertaken. Age when screening begins: For persons with neither hypertension nor diabetes, the C-E ratio of annual screening versus no screening was unfavourable until age 60 yrs. For those with hypertension, ann. Screening beginning at 30 yrs resulted in highly favourable ratios when compared to no screening and remained so at older ages. Chronic kidney disease: evidence tables DRAFT Page 16 of 17

17 Frequency of Screening: For 50 yrs old with neither hypertension nor diabetes, screening less frequently resulted in more favourable C-E ratios.(5-10 yr intervals). Similar results were achieved with screening older persons at different intervals. For patients with hypertension screening less frequently resulted in improved C-E in all age groups. (decreased cost of screening but accompanied by 5- to 70% decrease in QALYs saved in each group) The C-E of screening people with hypertension remained highly favourable for all variables biased against screening at their extremes. Monte-carlo simulation in which all parameters were varied simultaneously over their distributions, supported the base case results. Time horizon & discount rate 3% Source of funding Comments Overall study quality (++,+,-) ++ Charitable, public/private This study concludes that selective annual testing focusing on high risk groups is highly cost effective. For persons with neither hypertension nor diabetes, annual screening starting at age 60 yrs or older is moderately C-E. For persons with hypertension, annual screening from ages 30 to 70 is highly cost effective. [1] Including primary clinical effectiveness outcome measure used in the economic analysis [2] e.g. RCT, decision analysis, etc. [3] public, private, charitable, public/private Chronic kidney disease: evidence tables DRAFT Page 17 of 17