reported a mortality benefit for HHD compared to in-center HD while a small, short-duration CCT found no difference. · Two registry studies reported no difference in cardiovascular mortality. · Limited data suggest that HHD patients may be more likely than in-center HD patients to switch dialysis modalities at some point during their treatment but no differences in rate of transplant or all-cause hospitalizations were observed. Results for quality of life and adverse events were mixed with some studies showing benefits of HHD and others showing no difference. · No studies suggested HHD was associated with harms. In-Home Hemodialysis (HHD) Compared to In-Center Hemodialysis (HD) Study Characteristics Seven registry studies, 8-14 2 RCTs, 15,16 and 3 CCTs17-19 reported mortality data for HHD and incenter HD programs. Another registry study reported hospitalization data. 20 Among the registry studies, 4 were from the US Renal Data System (USRDS), 8-10,20 two were from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, 11,12 one was from the UK (England and Wales),14 and one was completed in 3 countries – the US, Canada, and France, with the majority of patients from Canada. 13 Across the studies, registry enrollment occurred between 1986 and 2011; follow-up periods were up to 15 years. Sample sizes ranged from 1,72613 to 458,3299 with all but one study13 enrolling only incident HHD patients. Three studies 20 Home-based versus In-center Dialysis Evidence-based Synthesis Program included matched prevalent HD patients.8,13,20 HHD patients tended to be younger.9-13 Three studies reported a higher percentage of males in the HHD group,11-13 one reported the HHD patients were more likely non-white, 9 and 2 reported the HHD patients were more likely white or other race. 12,14 Additional information about patients included in the registries is presented in Appendix C, Table 1. Methods used for data analysis were similar in 4 of the studies – a Cox proportional hazards model and an intent-to-treat analysis with adjustment for patient demographics, and, in most studies, comorbid conditions and laboratory variables.8-10,13 One used a Cox proportional hazards model with an “as-treated” approach11 while another study used a marginal structural modeling (MSM) technique with an “as-treated” analysis. 12 Appendix C, Table 1 provides further details on the analysis approach used in each study. We also included data from 2 RCTs, one from Canada15 and one from New Zealand16 (Appendix C, Table 2). The study from Canada randomized patients to either 3 dialysis sessions per week (52% of the patients received in-center HD) or 5 to 6 dialysis sessions per week at home. The total sample size was 61 patients and follow-up was 6 months.15 The study from New Zealand was a cross-over RCT with 9 patients and 8 weeks per intervention period.16 The interventions were in-center HD for 3.5 to 4.5 hours per day, 3 times per week and HHD for 6 to 8 hours, 3 times per week. One CCT was a multinational study (US, Italy, France, and the UK),18 one was from the US,17 and one was from Canada. 19,21 The multi-national study enrolled 415 patients and both HD and HHD followed short, daily protocols. A total of 1,006 patient years of follow-up was reported.18 The US study enrolled 63 nocturnal (5 to 6 times per week) HHD patients and 121 matched conventional (3 times per week) HD patients. Patients were followed for up to 20 months.17 The study from Canada included a conventional in-center HD group (3.5 to 4.5 hours, 3 times per week), a nocturnal HHD group (6 to 8 hours, 5 to 6 times per week), and a daily HHD group (1.5 to 2.5 hours, 5 to 6 times per week). 19 Follow-up was 18 months. Additional study data are reported in Appendix C, Table 2. Mortality A summary of mortality outcomes is presented in Table 1. Five of 7 registry studies reported lower mortality overall in HHD patients with hazard ratios ranging from 0.48 to 0.88.8,10-13 In 2 studies, the benefit was also observed at follow-up intervals of one, 2, or more than 3 years.11,12 One study reporting a benefit included only NxStage System One users.8 The HHD group in this study completed 5 to 6 dialysis sessions per week. Although there was an overall benefit of HHD, the benefit was not observed at the 2 year follow-up assessment. 8 In another study, the HHD was “intensive” – sessions of at least 5.5 hours, 3 to 7 times per week.13 One study reported a higher mortality in the HHD group (HR 1.10 [95% CI 1.04, 1.17])9 and one study reported no difference (HR 1.06 [95% CI 0.55, 2.04]).14 Data are presented in Appendix C, Table 1. The 2 RCTs and 2 of the CCTs reported no difference in mortality between HD and HH (Appendix C, Table 2).15-17,19 The other CCT reported higher mortality in the HD group (HR 2.42 [95% CI 1.54, 2.79]).18 Findings from the RCTs and CCTs should be interpreted with caution given the small sample sizes and short follow-up periods. 21 Home-based versus In-center Dialysis Evidence-based Synthesis Program Three of the registry studies looked at the interaction of age and modality on mortality outcomes (Table 1 and Appendix C, Table 3). A study from Australia/New Zealand reported a significant interaction by age at dialysis inception (P = .03). The decrease in mortality risk associated with HHD was less