Matt Stevenson, Jessica M. Forsyth, Anower Hossain, Ranjit Lall, Paul Dark, ADAPT-Sepsis collaborators, Gordon Carlson, Michael J. Naisbitt, Dominic Kay, Sharon Barber, Jane Parez, Stephanie Lee, Reece Doonan, Lisa Swindells, Jessica Pendlebury, Jessica Holden, Jacob Hadfeild, Jay Naisbitt, Andrew Claxton, Emma Parkin, Daniel Horner, Anila Sukumarian, Benedict Gyamerah, A. S. Duncombe, Chris Taylor, Wadhi Habeichi, Joanna Borzomato, Paul Ferris, Justin Roberts, Jonathan Clayton, John Macdonald, Redmond P. Tully, Andrew Drummond, Joy Dearden, Michelle Mulcahy, Carrole Blessen, Angiy Vian-Michael, Grainne O’Connor, Jonathan Scargill, Sarah Winnard, Jonathan C. Clayton, Ingeborg D. Welters, Karen Williams, David Shaw, Victoria Waugh, Julie Patrick-Heselton, Carol Paisley, Suzannah Phillips, Emily Johnson, Jaime Fernandez Roman, Maria Lopez Martinez, Arra Mahiya, Daniel Watkin, Zachary Thomas, Andrew Davison, Sofia Farina, Maria Norris, Silvia Manes, Jin-Xi Yuan, Josh Colfar, Caitlin Lythgoe, Ibrahim Almafreji, Lisa Bailey, Robert J. Parker, Ian Turner-Bone, Laura Wilding, Michaela Lloyd, Harriet Murrant, Leanne Smith, Ben Morton, Dylan Middleton, William McCaig, Amie Hughes, Lucy Fuller, Gavin Perkins, Jo Gresty, Ellie Reeves, Teresa Melody, Helen R. Taylor, Sara Bawa, Celinamma Maliaykal, William McIver, Mohamed Mooradun, Tayyibah Mohamed, Heather Willis, Aidan Butler, Amy Hooper, Adam Boulton, Lucie Linhartova, Rachel Smith, Daniel Park, Anna Dennis, Joyce Yeung, Hozefa Ebrahim, Neil Crooks, Sarah Milton-White, Sarah Ballinger, Natalie Carling, Julia Sampson, Chloe Norman
BACKGROUND: Procalcitonin (PCT)-guided antibiotic duration for critically ill adults with sepsis may be clinically effective and safe. However, cost-effectiveness analyses using clinical trial data for this precision medicine approach in critical care are lacking. This economic evaluation investigates the cost-effectiveness of a daily PCT-guided protocol to guide the duration of antibiotic treatment in adult patients with sepsis. METHODS: Two analyses were conducted, the first estimating the cost per quality-adjusted life year (QALY) of the ADAPT-Sepsis study, which recruited 2760 patients randomized to a daily PCT-guided protocol, a daily C-reactive protein-guided protocol and standard care. The second analysis used meta-analyzed results from ADAPT-Sepsis and other PCT-guided treatment studies and employed a lifetime horizon. Key outcomes were the incremental costs and QALYs gained from using the daily PCT-guided protocol approach compared with standard care. Other outcome measures included changes in days of antibiotics, days of hospital stay, days of intensive care unit stay, the percentage of deaths and the number of PCT tests performed. RESULTS: Cost-effectiveness results were driven by the assumed impact of PCT testing on mortality although the confidence/credible intervals for ADAPT-Sepsis and the meta-analyzed data both included no effect. Within ADAPT-Sepsis, the use of PCT tests cost €427 more per patient and was associated with a small QALY loss (0.001), which suggests the daily PCT-guided protocol is dominated. Using meta-analyzed data, the daily PCT-guided protocol was assumed to cost €330 more per patient but was associated with 0.139 more QALYs, resulting in a cost per QALY gained of €2384. If only antibiotic use and PCT tests were assumed to differ then PCT testing is estimated to cost no more than €110 per patient with QALYs equal in both arms regardless of whether ADAPT-Sepsis or meta-analyzed data were used. CONCLUSIONS: This economic analysis has shown that a PCT-guided protocol to guide the duration of antibiotic treatment could be cost-effective. Where only differences in antibiotic use and PCT testing are assumed, the increased costs per patient are modest which may be seen as worthwhile to safely improve antibiotic stewardship for critically ill adult patients with sepsis.