1Objectives: The economic burden of mu ltimo rbid ity is considerable. This review analyzed the methods of cost-of-2 illness (COI) studies and summarized the economic outcomes of mu ltimo rbidity.
3Methods: A systematic review (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016) was performed, which was registered with Prospero, reported according 4 to PRISMA, and used a quality checklist adapted for COI studies . The inclusion criteria were peer-reviewed COI 5 studies on multimo rbidity, whereas the exclusion criterion was studies focusing on an index d isease. Ext racted data 6 included the definition, measure, and prevalence of mult imorb idity; the number of included hea lth conditions; the 7 age of study population; the variables used in the COI methodology; the percentage of mu ltimorb idity vs. total costs; 8 and the average costs per capita.
9Results: Among the 26 included articles, 14 defined mult imorbid ity as a simple coun t of 2 or mo re conditions.
10Methodologies used to derive the costs were markedly d ifferent. Given different healthcare systems, OOP pay ments 11 of mult imorbid ity varied across countries. In the 17 and 12 studies with cut-offs of ≥2 and ≥3 condit ions,
12respectively, the ratios of multimo rbid ity to non-mult imorbid ity costs ranged from 2-16 and 2-10. A mong the 10 13 studies that provided cost breakdowns, studies with and without a societal perspective attributed the largest 14 percentage of mult imorb idity costs to social care and inpatient care/med icine, respectively.
15Conclusion: Multimorbid ity was associated with considerable economic burden . Synthesising the cost of 16 mu ltimo rbidity was challenging due to mu ltip le definitions of mult imorb idity and heterogeneity in COI methods.
17Count method was most popular to define mu ltimo rbid ity. There is consistent evidence that multimo rbidity was 18 associated with higher costs.