were addressed. Quality of existing systematic reviews was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) criteria. 6 DATA SYNTHESIS Due to differences in study methodology, data could not be pooled. For Key Questions 1 and 2, we summarize the results by outcome. For Key Question 3, we summarize findings for health care system, provider, and patient factors. For Key Question 4, we summarize costs of HHD versus in-center HD and PD versus in-center HD. 16 Home-based versus In-center Dialysis Evidence-based Synthesis Program RATING THE BODY OF EVIDENCE We rated strength of evidence for our main outcome (mortality) as reported in the registry studies for the comparisons of HHD to HD and PD to HD. The rating is based on risk of bias of individual studies and consistency, precision, and directness of the overall evidence as described by Owens et al. 7 PEER REVIEW A draft version of this report was reviewed by clinical content experts as well as clinical leadership. Their comments and our responses are presented in Appendix B and the report was modified as needed. 17 Home-based versus In-center Dialysis Evidence-based Synthesis Program RESULTS The majority of studies identified compared in-center hemodialysis (HD) to peritoneal dialysis (PD). Relatively few studies compared in-home hemodialysis (HHD) to HD or PD. LITERATURE FLOW Details of the literature search and study selection process are presented in Figure 1. For Key Questions 1 and 2, we identified 32 registry studies (16 from the US, 4 from Canada, 3 from Australia/New Zealand, 7 from Europe or the UK, and 2 multi-national) that compared PD to HD. Seven registry studies (4 from the US, 2 from Australia/New Zealand, one from the UK, and one multinational study) provided data for the comparison of HHD to HD. Two registry studies (one from the US and one from the UK) also compared HHD to PD. We also identified 3 RCTS. One study from Canada and one from New Zealand compared HHD to HD; one study from the Netherlands compared PD to HD. We identified 3 CCTs (one from the US, one from Canada and one multinational study) that compared HHD to HD and 2 clinical cohort studies (one from the US and one from the Netherlands) that compared PD to HD. To further address other Key Question 1 and 2 outcomes (hospitalization, quality of life, cognitive, depression, and adverse events) we report findings from systematic reviews, RCTs, CCTs, longitudinal studies, and cross-sectional studies. There were 15 articles from Europe or the UK, 5 from the US, 4 from Canada, and one from Australia/New Zealand; the systematic reviews were multinational. For Key Question 3, we included 49 articles, 16 from the US, 17 from Canada, one from the US and Canada, 12 from Europe/UK, 2 from Australia/New Zealand, and one multinational. Most of the studies addressed either patient factors associated with selection of a dialysis modality or factors associated with technique survival for PD. We identified 15 studies that reported cost outcomes (Key Question 4) comparing either PD to HD or HHD to HD. There were 2 studies from the US, 6 from Canada, 6 from Europe/UK, and one from Australia/New Zealand. 18 Home-based versus In-center Dialysis Evidence-based Synthesis Program Figure 1. Literature Flow Chart Search results: 2169 references Full text review: 331 references Included: 130 references 114 studies (reported in 127 articles) 3 systematic reviews Excluded: 232 references · No outcomes of interest 42 · Not related to Key Questions 26 · Country not included 40 · Sample size 49 · Length of follow-up 13 · No comparator 22 · Study design 40 Key Questions 1 and 2: 32 registry studies (reported in 34 articles) 22 other studies (reported in 29 articles) 3 systematic reviews Key Question 3: 45 studies (reported in 49 articles) Key Question 4: 15 studies Excluded: 1838 references Hand searching: 31 references 19 Home-based versus In-center Dialysis Evidence-based Synthesis Program KEY QUESTION 1. What are the benefits and harms (ie, all-cause mortality, cardiovascular events, hospitalizations, depression, cognitive impairment, quality of life, conversion to a different type of dialysis, complications related to vascular access, complications of dialysis) of in-home compared to in-center hemodialysis? Summary of Findings · Evidence is generally of high risk of bias regarding the comparative effectiveness of HHD versus in-center HD. We found few randomized or controlled clinical trials or prospective clinical cohort studies comparing in HHD and in-center HD. Available clinical trials were small in size, had short follow-up durations, and focused on intermediate outcomes rather than mortality outcomes. · Strength of evidence for mortality was low based on high risk of bias associated with the registry studies. Results from registry studies should be interpreted with caution due to likely residual confounding. · Of 7 registry studies included, 5 suggest that HHD is associated with improved overall survival compared to in-center HD. One registry study found a benefit for individuals receiving in-center HD over HHD while another found no difference. Two small RCTs of short follow-up duration reported no difference in mortality between in-center versus inhome modalities. A multinational CCT with 415 patients and 1006 patient-years of follow-up