Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p> Graphical abstract <p></p>

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Cost-effectiveness of procalcitonin-guided antibiotic duration for hospitalized patients with sepsis

  • Matt Stevenson,
  • Jessica E. Forsyth,
  • Anower Hossain,
  • Ranjit Lall,
  • Paul Dark,
  • Gordon Carlson,
  • Michael J. Naisbitt,
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  • Joanna Borzomato,
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  • Arra Mahiya,
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  • Zachary Thomas,
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  • Silvia Manes,
  • Jin-Xi Yuan,
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  • Jo Gresty,
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  • Aidan Butler,
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  • Sarah Ballinger,
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  • Amy Clark,
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  • Karen Ellis,
  • Christopher Sheridan,
  • Lisa Moody,
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  • Rachel Webster,
  • Samantha Harkett,
  • Sophia Beddows,
  • Caroline Dooley,
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  • Stephanie Goundry,
  • Elaine Spruce,
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  • Dhruv Parekh,
  • Natalie Walmsley,
  • Malikah Saba,
  • Rebecca Gill,
  • Esther Thomas,
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  • Mansoor Bangash,
  • Alistair Roy,
  • Anthony Rostron,
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  • Sarah Cornell,
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  • Jo Boxall,
  • Trina Burns,
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  • Jonathan Vernazza,
  • Maxwell Richardson,
  • Matthew Bickerton,
  • Andrew Camplejohn,
  • Roseanne Cope,
  • Julie Sheriff,
  • Simon Whiteley,
  • Max Ridley,
  • Richard Gould,
  • Sarah Perrin,
  • Elizabeth Wilby,
  • Susan Trott,
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  • Jodie Sedgwick,
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  • James McNamee,
  • Danny McAuley,
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  • Lynsey Reilly,
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  • Rachel Morrison,
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  • Amy Robinson,
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  • Chris Cockcroft,
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  • Jackie Todd,
  • Susan Kimachia,
  • Lisa Burgess,
  • Shereen Bano,
  • Thomas P. Hellyer,
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  • Stephen Hamilton,
  • Arti Gulati,
  • Benjamin Brown,
  • Stephanie Grieveson,
  • Tara Shrestha,
  • Ian Storey,
  • Fatima Simoes,
  • Verity Calder,
  • Carole Hays,
  • Maite Babio-Galan,
  • Deborah White,
  • Jennifer Collins,
  • Leigh Dunn,
  • Susan Taylor,
  • Luzgie Gavina,
  • Tessa Wilkinson,
  • Pamela Garcia,
  • Lauren Butler,
  • James Savage,
  • Jayne Harwood,
  • Sarah Cook,
  • Jonathan Shelton,
  • Ian Clement,
  • Samantha Burn,
  • Nathan Carroll,
  • Lauren Clark,
  • Lauren Ferguson,
  • Sam Foggett,
  • Alison Hague,
  • Tracy Handley,
  • Chelsea Hewison,
  • Samantha Kitchener,
  • Laura McEachan,
  • Nicole McEwen,
  • Ryan Perry,
  • Olivia Purdy,
  • Amie Thomson,
  • Stephanie Williams,
  • Madhu Balasubramaniam,
  • Rebecca Flanagan,
  • Emma McKenna,
  • Scott Latham,
  • Danielle Hollick,
  • Glykeria Pakou,
  • Helder Filipe,
  • Margaret McNeil,
  • Sara Mingo,
  • Catarina Veiga,
  • Poh Choo Teoh,
  • Amitaa Maharajh,
  • Mark De Neef,
  • Coral Cole,
  • Saida Solkar,
  • Oghenemega Okotete,
  • Mervyn Singer,
  • Chris Wilson,
  • David Brealey,
  • Niall MacCallum,
  • Ingrid Hass,
  • Georgia Bercades,
  • Deborah Smyth,
  • Gladys Martir,
  • Anna Reyes,
  • Maria Alexandra Zapata Martinez,
  • Laura Gallagher,
  • Hodan Omer,
  • Jonathan Bannard-Smith,
  • Deborah Paripoorani,
  • Charlotte Taylor,
  • Gregory Yates,
  • Katharine Wylie,
  • Sadiya Salah,
  • Fionn Quilty,
  • Timothy W. Felton,
  • Pete D. G. Alexander,
  • Luke Ward,
  • Joanne Rothwell,
  • Sherly George,
  • Hannah Currie,
  • Katharine Sellers,
  • Aditya Adhikarla,
  • Jayanthi Rajasekar,
  • Sarah Purvis,
  • Isha Garg,
  • Vijay Jagannathan,
  • Hillie Corr,
  • Magda Stefaniak,
  • Simon Sinclair,
  • Ceri Lynch,
  • Bethan Gibson,
  • Piroska Toth-Tarsoly,
  • Zolton Auer,
  • Daniel Law,
  • Jayparaska Singh,
  • Shaun Oram,
  • Arsalan Zaki,
  • Alan Dodd,
  • Bethan Deacon,
  • Lisa Roche,
  • Leannne Jones,
  • Justyna Smeaton,
  • Kevin Agravante,
  • Oladele Akinyoola,
  • Keri Turner,
  • Joanne Pugh,
  • Sam Evans,
  • Lisa Mellish,
  • Angharad Rees,
  • Geraint Lewis,
  • John Burke,
  • Nia Bromage,
  • Nicola Llewellyn,
  • Justine Evans,
  • Marlo Constantino,
  • Chinari P. K. Subudhi,
  • Celia Chu,
  • Katy Edwards,
  • Rashmi Gupta,
  • Carolyn Williams,
  • Lindiwe Mashangombe,
  • Misbah Javed,
  • Alistair Morris,
  • Julia Sampson,
  • Alexandra Gibbins,
  • Celia Peters,
  • Megan Meredith,
  • Alice Baddeley,
  • Anthony Baidoo,
  • Dan Harvey,
  • Alexandra McCoy,
  • Sophie Lubbock,
  • David Ford,
  • Amy Clark,
  • Laura Lloyd,
  • Mohammed Habib,
  • Gemma Clark,
  • Ian King,
  • Carla Goode,
  • Angela Sellick,
  • Shova Sharma,
  • Anita Assi,
  • Jennifer Dengate,
  • Matthew Grice,
  • Laura Brammer,
  • Chinyere Ajonu,
  • Samuel Redgate,
  • Wendy Smith,
  • Manjinder Khakh,
  • Hannah Howson-Wells,
  • Simon Atkin,
  • Max Casbon,
  • Frances Olsen,
  • Bhavin Mistry,
  • Victoria Mitchinson,
  • Aysha Talbot,
  • Jonathan Clayton,
  • Shondipon Laha,
  • Sushruth Madanapalli Raghunath,
  • Alex Jude Fonseca,
  • Alexandra Williams,
  • Sacha Connor,
  • Rebecca Allock,
  • Lisa Halsall,
  • Sean McMullen,
  • Jonathan C. Clayton,
  • Fiona Jutsum,
  • Laura Price,
  • Susie Pajak,
  • Hannah Gibson,
  • Mark Bates,
  • Karen Reid,
  • Alison Bland,
  • Alison Stephens,
  • Denise Donaldson,
  • Mandy Beekes,
  • Jo Stickley,
  • Colene Adams,
  • Amy Bowes,
  • Sanal Jose,
  • Nikolaos Manetas-Stavrakakis,
  • Rebecca Wilcox,
  • Rachel Rikunenko,
  • Maria Houghton,
  • Andrew Donnelly,
  • Julie Summers,
  • Christopher Mowatt,
  • Katherine Richmond,
  • Rebecca Jones,
  • Tammy Davie,
  • Michael Barnsley,
  • Mick Pursglove,
  • James Pearce,
  • Philippa Lane,
  • Natasha Cole,
  • Megan Phillips,
  • Joanna Jasiewicz,
  • Sarah Hamad,
  • Jyoti Sharma,
  • Muhammad Adeeb,
  • Mohammad Qasim,
  • Lisa Barnsley,
  • Louise Walton,
  • Claire Wright,
  • Helen Kaura,
  • Cathy McCormack,
  • Dave Latham,
  • Emily Wynne,
  • Catherine McCormack,
  • Kathy Richmond,
  • Claire Gabriel,
  • Richard Lowsby,
  • Elijah Matovu,
  • Katherine Pagett,
  • Deborah Maren,
  • Tenifayo Adeyemo,
  • Hannah David,
  • Mark Quiambao,
  • Joanne Harold,
  • Sheron Clarke,
  • Valery Gurov,
  • Anthony Mkandhla,
  • Chris Duff,
  • Helen Duce,
  • Dumindu Karangoda,
  • Estefania Treus,
  • Leanne Howard,
  • Georgina Luck,
  • Alex Ross,
  • Mark Belsham,
  • Shatha Abu-Hijleh,
  • Christopher Thompson,
  • Minnie Gellamucho,
  • Jane Delaney,
  • Michelle Davies,
  • Elisa Sernicola,
  • Lucy Bailey,
  • Angelene Cope,
  • Claire Hudson,
  • Umar Mohyddin,
  • Jack Lee,
  • Ben Storey-Waters,
  • Faye Halliday,
  • George Mathew,
  • Sarah Birch,
  • Craig Denmade,
  • Sarah White,
  • Rosie Clare,
  • Ya-Wen J. Huang,
  • Dawn Herbert,
  • Lynn Rowbottom,
  • Madeleine McGrady,
  • Nazir I. Lone,
  • Timothy S. Walsh,
  • Maria Amamio,
  • Gillian Andrew,
  • Lucy Barclay,
  • Sophie Birch,
  • Kate Briton,
  • Lisa-Marie Butt,
  • Sarah Clark,
  • Jessica Crossan,
  • Katherine Doverman,
  • Michael Gillies,
  • David Griffith,
  • David Hope,
  • Kallirroi Kefala,
  • Ian Laurenson,
  • Nazir Lone,
  • Lucy Macdonald,
  • Craig Marshall,
  • Corrienne McCulloch,
  • Gregor McNeill,
  • Nicola Rea,
  • Scott Simpson,
  • Jo Singleton,
  • Joanne Thompson,
  • Elzbieta Czarniak,
  • Olga Lucia Moncayo Nieto,
  • Stephen Bonner,
  • Jeremy Henning,
  • Amy Thompson,
  • Jessica Jones,
  • Steven Liggett,
  • Craig Mower,
  • Sarah Bircham,
  • Bobette Kamangu,
  • Abiola Shoremekun,
  • Anitha Ratnakumar,
  • Keith Hugill,
  • Matt Thomas,
  • Paul Thomas,
  • Ruth Worner,
  • Borislava Borislavova,
  • Kati Hayes,
  • Beverley Faulkner,
  • Emma Gendall,
  • Elizabeth Goff,
  • Hayley Blackmore,
  • Mike Spivey,
  • Sarah Bean,
  • Karen Burt,
  • Anthea Patterson,
  • Lisa Vipond,
  • Matthew Martin,
  • Nick Vallotton,
  • Samuel Waterman,
  • Michael Kelsey,
  • Ana Zuriaga-Alvaro,
  • Loreta Mostoles,
  • Anezka Pratley,
  • Nabeel Amiruddin,
  • Helen Ashby,
  • Gemma Wood,
  • George Priestley,
  • Phil Antil,
  • Joseph Carter,
  • David Yates,
  • Rob Ferguson,
  • Harriet Carter,
  • Zoe Cinquina,
  • Belinder K. Ghuman,
  • Uzma Manazar,
  • Gillian Richards,
  • Hannah C. McNeil,
  • Keith K. Young,
  • Anthony C. Gordon,
  • Paul R. Mouncey,
  • Peter Wilson,
  • Dewi Williams,
  • Catherine Jardine,
  • Karen Craik,
  • Julia Anderson,
  • Laura Wild,
  • Stacey Cotterall,
  • Mandy Austin,
  • Mark Wilkinson,
  • Niall Harbison

摘要

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.

Graphical abstract