Economic evaluation of genetic screening for Lynch syndrome in Germany

Abstract

Purpose: Lynch syndrome (LS) screening among patients with newly diagnosed colorectal cancer can decrease mortality in their affected first-degree relatives. In Germany, it is not yet clinical practice and the cost-effectiveness of different testing strategies is unknown. Methods:We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the German Statutory Health Insurance system. A total of 22 testing strategies considering family-history assessment, analysis of tumor samples (i.e., immunohistochemistry (IHC), microsatellite instability, and BRAF mutation testing) and genetic sequencing were analyzed. Life-years gained in relatives by closedmeshed colonoscopy and aspirin prophylaxis were estimated by Markov models. Uncertainty was assessed deterministically and probabilistically.Results: On average, detected mutation carriers gained 0.52 lifeyears (undiscounted: 1.34) by increased prevention. Most strategies were dominated, with three exceptions: family assessment by the Bethesda criteria followed by IHC and BRAF testing and genetic sequencing; IHC and BRAF testing and genetic sequencing; and direct sequencing of all index patients. Their incremental cost-effectiveness was €77,268, €253,258, and €4,188,036 per life-year gained, respectively. Conclusion:The results were less favorable than those of previous models. Chemoprevention appears to provide comparably low additional benefit and improves cost-effectiveness only slightly.

Which Lynch syndrome screening programs could be implemented in the “real world”? A systematic review of economic evaluations

“…26,31,32,39 Most economic models used were based on a decision analysis, [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]42,43 while a Markov model was applied in 11 studies. 28,29,[32][33][34][35]38,39,42,43 The most frequently used discount rate for costs and benefits was 3%. 26,27,[30][31][32][33][34][35][38][39][40][41][42]44 The ICER thresholds stated in the studies were in the range 50,000-100,000 for US dollar-based economic models 27,[30][31][32][33]…”

“…29,35,37,[40][41][42]44 Although to different degrees, most studies gave details of the modeling and parameters used. [26][27][28][30][31][32][33][34][35][36][37][38][39]42,43 The time horizon of the analysis was not always clearly defined, although it could be deduced from the model. 29,31,40,41,44 Sensitivity analysis was performed in all economic evaluations: [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] six studies used only univariate analysis, 25,28,31,...…”

“…29,31,40,41,44 Sensitivity analysis was performed in all economic evaluations: [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] six studies used only univariate analysis, 25,28,31,39,41,44 while nine studies performed probabilistic sensitivity analysis. 26,27,33,34,36,38,40,42,43 Furthermore, most studies reported the range over which variables varied. [25][26][27][28][29][30][33][34][35][37]…”

“…[25][26][27][28][29][30][33][34][35][37][38][39][40][41][42][43][44] All economic evaluations provided an incremental analysis. [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Influential parameters and basic assumptions…”

“…43 Several studies reported percentages greater than 99% for both sensitivity and specificity of MMR genes sequencing 30,[38][39][40]43,44 (Supplementary Table S5), but a lower sensitivity was assumed by Ramsey (87%), 26,27 Dinh (90%), 31 and Snowsill (90%). 37 The sensitivity ranges of microsatellite instability (MSI) and immunohistochemistry (IHC) tests were respectively 76-91% 26,27,30,33,34,[37][38][39]42 and 77-92%, [30][31][32][33][34][37][38][39][40]42,43 whereas specificity ranges were 79-93% for MSI [26][27][28]30,33,34,[37][38][39]42 tests and 70-91% for IHC tests. [30][31][32][33][34][37]…”