We conduct a cost-effectiveness analysis of CKD screening test in SHC. Facing the scheduled revision of mandatory test items, we appraise two possible policy options compared with the status quo that 40% of insurers implement dipstick test to check proteinuria only and 60% implement dipstick test and serum Cr assay. Policy 1 is to mandate serum Cr assay in addition to the current dipstick test, so that 100% of insurers implement both dipstick test and serum Cr assay. Policy 2 is to mandate serum Cr assay and abandon dipstick test, so that 100% of insurers would stop providing dipstick test and switch to serum Cr assay. Our base-case analysis suggests that both policy options cost more and gain more. Estimated ICERs are ¥9,325,663/QALY (US $103,618/QALY) for policy 1 and ¥9,001,414/QALY (US $100,016/QALY) for policy 2.
To interpret these ICERs, there is no established value of social willingness to pay for one QALY gain in public health programmes such as mass screening in Japan, although some suggest ¥5 million/QALY (US $56 thousand/QALY) for an innovative medical intervention [37
]. We follow WHO recommendation in this study, which is three times GDP per capita [36
]. Its value is ¥11.5 million/QALY (US $128 thousand/QALY) gain in 2009 in Japan. Given this threshold, both policy 1 and policy 2 are judged as cost-effective. Therefore, mandating serum Cr assay in SHC can be justifiable as an efficient allocation of finite resources for health. Between policy 1 and policy 2, the ICER of policy 2 is slightly more favourable than that of policy 1, while 450 more patients out of 100,000 participants are screened by adopting policy 1. If secondary prevention of CKD is emphasised as a policy objective in addition to efficiency, policy 1 is an acceptable option as well as policy 2.
Our model estimators have a policy implication, although estimated ICERs do not directly depict any marginal change in society. The ICER of (a) dipstick test only compared with the do-nothing scenario, ¥1,139,399/QALY (US $12,660/QALY), is remarkably favourable. This implies that mass screening with dipstick test only is cost-effective compared with abolishment of mass screening for kidney diseases altogether. Therefore, continuing the current policy, i.e. mandatory dipstick test, could be justifiable as an efficient resource allocation.
This contrasts with the reported cost-ineffectiveness of annual mass screening for adults using dipstick test to check proteinuria in the USA [12
], although direct comparison cannot be made between the results of economic evaluations under different health systems. The difference could be attributable to the difference in the prevalence of proteinuria among screened population, with 5.450% being used in our model based on the Japan Tokutei-Kenshin CKD Cohort 2008, while 0.19% is assumed in the US study. Such epidemiological differences are known in terms of not only quantity but also in quality [7
]. The prevalence of glomerulonephritis, especially IgA nephropathy, is higher in Asian countries including Japan compared with Western countries [10
]. Also, the prevalence of renovascular disease such as ischaemic nephropathy, with which patients are often non-proteinuric until advanced stages of CKD, is lower in Asian countries [38
]. The inclusion of heart attack and stroke into our model, which are excluded in the US model [12
], may have also made the ICER more favourable.
There is a report of cost-ineffectiveness of population-based screening for CKD with serum Cr assay from Canada [39
]. This Canadian model can be compared with our model estimators of (b) serum Cr only compared with the do-nothing scenario. Their health outcomes gain or incremental effectiveness is 0.0044 QALY, which is smaller than ours, 0.04801 QALY, while their incremental cost is C $463 (US $441, using US $1 = C $1.05), which is also smaller than ours, ¥390,002 (US $4,333). These differences probably reflect the difference in the prevalence of CKD between Canada and Japan. Regarding the efficiency of screening programme, our model estimator of ICER, ¥8,122,492/QALY (US $90,250/QALY), is slightly more favourable than that of Canada, C $104,900/QALY (US $99,905/QALY). However, the contradictory conclusion regarding cost-effectiveness is not due to this difference but rather the threshold taken. The Canadian study adopts lower value such as C $20,000 to C $50,000/QALY (US $19,048 to US $47,619/QALY) following local practice [40
Our sensitivity analysis suggests instability of the results in only three variables, so our findings are robust to a certain extent. The most sensitive variable is the effectiveness of CKD treatment delaying progression to ESRD: 42.1% reduction is adopted in our economic model according to the unique clinical evidence from Japan, whose agent is angiotensin-converting enzyme inhibitor. It is marginally larger than comparative values reported from Western countries. Reductions in the rate of GFR decline are 35.9% by Agodoa et al. [41
], 39.8% by The GISEN Group [42
] and 22.5% by Ruggenenti et al. [43
]. However, we think our assumption of base-case value is reasonable in two accounts: in light of the indication of angiotensin receptor blockers [17
], whose use is more tolerated than angiotensin-converting enzyme inhibitors [44
], and the higher prevalence of glomerulonephritis including IgA nephropathy, being a primary renal disease for ESRD, in Japan [10
], for which the effect of early treatment such as renin–angiotensin system (RAS) inhibition, an immunosuppression, reduces risk of ESRD by 60% [45
In regards to the other sensitive variables, we think the prognosis of non-proteinuric stage 5 CKD without treatment does not greatly undermine our findings of base-case analysis, since the value is calculated from extended follow-up of an established database [18
]. Uncertainty of the base-case value should be much less than the analysed ±50%. On the other hand, the cost of treatment for stage 5 CKD relates to one of the weaknesses of this study, as discussed in the following.
There are weaknesses in this study. The most significant one is that our economic model depicts the prognosis of CKD by initial renal function stratum. This approach is taken because of the limitation of epidemiological data, and it has little difficulty in estimating outcomes in terms of survival. However, it becomes problematic when it comes to costing. For example, a patient initially screened as stage 1 CKD stays at (1) screened and/or examined before transiting to the following health states such as (2) ESRD. This means that a patient skips over stage 2 CKD to 5 CKD before progressing to ESRD. To estimate the cost for this health state, the diversity of patients in terms of progression of the CKD stages should be taken into account. Our expert committee has developed treatment models to understand this problem. This type of uncertainty is larger in stage 1 CKD and smaller in stage 5 CKD, but the cost of stages 1–4 CKD are not found to be so sensitive in our sensitivity analysis. Also, we think that uncertainty of the cost of stage 5 CKD, the second most sensitive variable, is less than the analysed ±50%, and our findings based on the base-case analysis are plausible. The problem also affects quality of life adjustment, which tends to produce larger QALY outcomes.
Other weaknesses include our assumption of 100% adherence to treatment and so on. However, the most significant strength of this study is that our economic model depends totally on evidence from Japan only, which could justify our simplification in modelling on data availability basis. There is an opportunity for further refinement of our economic model, because a large-scale field trial evaluating the effect of multifactorial treatment including lifestyle modification for early-stage CKD [46
] is ongoing in Japan, which will enable us to model progression of CKD with more rigorous clinical evidence [47
In conclusion, we, the Japanese Society of Nephrology Task Force for the Validation of Urine Examination as a Universal Screening, recommend to mandate use of serum Cr assay in addition to the current dipstick test in the next revision of SHC, from the viewpoint of value for money and the importance of secondary prevention (Table ). We think that continuation of current policy, in which dipstick test only is mandatory, is still a sensible policy option. Development of adequate Specific Counselling Guidance for screened participants is also recommended.
Recommendation of the Japanese Society of Nephrology Task Force for the validation of urine examination as a universal screening
Whereas the primary objective of this study is to appraise policy options in Japanese context, it also demonstrates that good value for money can be expected from mass screening with dipstick test to check proteinuria in population with high prevalence; that is, a population strategy could be adopted for control of CKD. However, caution is needed when extrapolating this conclusion, since the scope of costing of our economic model does not cover the initial cost of launching mass screening. The model here is based on currently running SHC. The practice of annual mass screening for adults in Japan is quite exceptional, while such universal programmes are rarely found in other countries [48