Economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): study protocol

• Main Authors: Katie Ross, Dimitra Fleming, John Marshall, Najib Ayas, François Lellouche, Justin Lys, Ryan Zarychanski, Timothy Karachi, Deborah J Cook, Marie-Claude Tremblay, Jeremy Grushka, Dan Deckelbaum, Kosar Khwaja, Tarek Razek, Donald Griesdale, John Muscedere, David Maslove, Roupen Hatzakorzian, Patrick Archambault, Feng Xie, François Lauzier, Heather Smith, David Williamson, Emmanuel Charbonney, John Granton, Alyson Takaoka, Kwadwo Kyeremanteng, Miranda Hunt, Ian Ball, Victoria McCredie, Michaël Chasse, Jennifer LY Tsang, Jordi Mancebo, Peter Dodek, Emilie Belley-Cote, Neala Hoad, Melissa Shears, Mark Soth, Tracy Campbell, Geeta Mehta, Daniel Chen, Shane English, Maureen Meade, John Kim, Jie Meng, Richard Johnston, Jennie Johnstone, Norman Dewhurst, Panagiota Giannakouros, Laura García, John Ma, Dev Jayaraman, Pierre Cardinal, Vincent Issac Lau, John C Marshall, John Basmaji, Deborah Cook, Erick Duan, France Clarke, Mary Copland, Marnie Jakab, Nicole Zytaruk, Christa Connolly, Denise Davis, Catherine Eaton, Tracy Gallinas, Jean Lee-Yoo, Connie Lukinuk, Leia Musielak, Nancy Pavunkovic, Joy Pelayo, Kaitlyn Phillips, Catherine Pracsovics, Julia Raimondo, Vida Stankus, Christine Wallace, Angela Wright, Crystal Young, Katrina Fimiani, Lori Hand, Harjot Jagdey, Lisa Klotz, Alexana Sabev, Nevena Savija, Deanne Cosentino, Diane Lourenco, Julie Misina, Gita Sobhi, Mashari Alghuroba, Alia Khaled, Lauren Locco, Tina Millen, Ryan Vaisler, Maya Biljan, Brittany Marriott, Jan Frieich, Jennifer Hodder, Imrana Khalid, Julie Lee, Yoon Lee, Pragma Roy, Kurtis Salway, Gyan Sandhu, Marlene Santos, Orla Smith, Melissa Wang, Ann Dowbenka, Ann Kosinski, Terri Norrie, Ranjit Parhar, Laura Parsons, Johanna Proceviat, Gitana Ramonas, Mae Yuen, Maria Agda, Victoria Alcuaz, Betty Jean Ashley, Kelsey Brewer, Janice Palmer, Glen Brown, Mara Pavan, Stephen Lapinsky, Laveena Munshi, Maedean Brown, Brittany Giacomino, Alan Kraguljac, Sumesh Shah, Erik Tamberg, Laura Vergeer, Doret Cheng, Gagan Grewal, Anew Han, Holly Leung, Ioanna Mantas, Hilary Roigues, Anew Wyllie, Alexis Turgeon, Danny Barriault, David Bellemare, Anick Boivin, Sarah-Judith Breton, Eve Cloutier, Marjorie Daigle, Charles Delisle-Thibeault, Stéphanie Grenier, Gabrielle Guilbault, Caroline Léger, Catherine Ouellet, Élisabeth Gagne, Julie Gaueau, Claire Grégoire, Véronique Labbé, Ariane Laprise-Rochette, Caroline Ouellet, Mélanie Samson, Marie-David Simoneau, Virginie Turcotte, Tuong-Vi Tran, Lauralyn McIntyre, Joe Pagilarello, Gianni D’Egidio, Mike Hartwick, Jonathon Hooper, Gwynne Jones, Dal Kubelik, Hilary Meggison, Sherissa Microys, Dave Neiliovitz, Guiseppe Pagliarello, Rakesh Patel, Jo Po, Peter Reardon, Erin Rosenberg, Aimee Sarti, Anew Seely, Shelley Acres, Brigette Gomes, Heather Langlois, Liane Leclair, Sydney Miezitis, Kaitlyn Montroy, Rebecca Porteous, Shawna Reddie, Amanda Van Beinum, Allyshia Van Tol, Irene Watpool, Wendy Aikens, Marianne Cox, Anne-Marie Dugal, Susan Fetzer, Kathy Fraser, Jennifer Kuhn, Rob MacLeod, Susanne Richard, Dawn Rose, Sherry Weir, Bill Henderson, Mypinder Sekhon, Denise Foster, Suzie Logie, Judy Yip, Margaret Herridge, s Alberto Goffi, Eyal Golan, Elizabeth Wilcox, Jaimie Archer, Paulina Farias, Brooke Fraser, Cheryl Geen-Smith, Barbara Kosky, Anea Matte, Christina Pugliese, Priscila Robles, Lia Stenyk, Cristian Urrea, Karolina Walczak, Kyung Ae, Jane Ascroft, Fatima Haji, Rajvinder Kaur, Jane Lui, Sophia Mateo, Nga Pham, Tam Pham, Matthew Suen, Jennifer Teng, Gordon Wood, Daniel Ovakim, Fiona Auld, Gayle Camey, Ralph Fleming, Jennifer Good, Mandeep Manhas, Karin Boyd, Jane Dheere, Priscilia Robles, Muhammad Walid, Jill Westlund, Yoan Lamarche, Soazig Leguillan, Karim Serri, Colin Verdant, Yanick Beaulieu, Patrick Bellemare, Philippe Bernard, Marc Giasson, Véronique Brunette, Alexanos Cavayas, Émilie Lévesque, Halina Labikova, Julia Lainer Palacios, Marie-Ève Langlois, Virginie Williams, Thuy Anh Nguyen, Valérie Phaneuf, Frédérick D’Aragon, Charles St-Arnaud, Hector Quiroz, Virginie Bolduc, Elaine Carbonneau, Joannie Marchand, Marie-Hélène Masse, Sylvie Cloutier, Marianne Guay, Line Morin, Jessie Nicolson, Isabelle Paquette, Patricia Roy, France Théberge, Arnold S Kristof, Peter Goldberg, Sheldon Magder, Jason Shahin, Salman Qureshi, Josie Campisi, Vasilica Botan, Anissa Capilnean, Alyssa Corey, Annick Gagné, Jasmine Mian, Kathleen Normandin, Ash Gursahaney, David Hornstein, Robert Salasidis, Patrizia Zanelli, Norine Alam, Tonia Doerksen, Ariane Lessard, Gilbert Matte, Marie-France Robert, Martin Girard, Pierre Aslanian, Sylvain Belisle, François-Martin Carrier, Ané Denault, Jean-Gilles Guimond, Antoine Halwagi, Paul Hébert, Christopher Kolan, Nicholas Robillard, Fatna Benettaib, Dounia Boumahni, Casey Bourdeau Caporuscio, Marie-Ève Cantin, Virginy Côté-Gravel, Ali Ghamraoui, Martine Lebrasseur, Lancelot Legene Courville, Stéphanie Lorio, Maria Trinidad Maid, Nicole Poitras, Romain Rigal, Maya Salame, Valérie Tran, Katie Bacon, Nathalie Boueau, Cecilia Carvajal, Lyne Gauthier, Julie Genon, Karine Jean, Louise Laforest, Antonietta Lembo, Sothun Lim, Jennifer Morrissette, France Pagé, Lucie Pelletier, Marie-Christine Roigue, Jim Kutsiogiannis, Raiyan Chowdhury, Jon Davidow, Curt Johnston, Kim Macala, Sam Marcushamer, Darren Markland, Doug Matheson, Damian Paton-Gay, David Zygun, Nadine Grant, Tayne Hewer, Pat Thompson, Maggie Ge, Janny Hall, Sharon Matenchuk, Osama Loubani, Rick Hall, Robert Green, Diana Gillis, Lisa Julien, Laura Lee Magennis, Tamara Mitterer, Joanna Arsenault, Kim Bruce-Payne, Patti Gallant, Gord Boyd, Christine D’Arsigny, John Over, Jason Erb, Chris Parker, Stephanie Sibley, Tracy Boyd, Ilinca Georgescu, Danielle Muscedere, Cathy Baker, Jennifer Engel, Jennifer Fleming, Lisa Roderick, Shelley Silk, Marcy Spencer, Michelle Tryon, Marcus Blouw, Kendiss Olafson, Bojan Paunovic, Oliver Gutieror, Nicole Marten, Sherri Lynn Wingfield, Marnie Boyle, Halyna Ferens, Debbie Hrabi, Beata Kozak, Chantal MacDonald, Julie Muise, Eileen Campbell, Susie Imerovski, Athena Ovsenek, Rebecca Rondinelli, Teresa Longfield, Amy Moyer, Faith Norris, Janice Sumpton, Karina Teterycz, Brenda Reeve, Karen Bento, Megan Davis, Will Dechert, Krista Gallo, Barbara Longo, Courtney Mullen, Elysia Skrzypek, Laurenne Wierenga, Wesam Abuzaiter, Lynda Amorim, Rosemarie Bauer, Rachel Damota, Thoa Ho, Nicole Macdougall, Mary Thornewell, Lara Pe, Jennifer Visocchi, Auey Bhairo, Halyna Ferenes, Debra Kubin, Dawn-Lee McLaughlin, Maria Valente, Steve Reynolds, Suzette Willems, Tina Sekhon, Sebastien Trop, Alexana Binnie, Ronald Heslegrave, Kim Sharman, Zaynab Panchbhaya, Rakhi Goel, Kim Kozluk, Julianne Labelle, Hina Marsonia, Cecillia Scott, Dave Nagpal, Tracey Bentall, Jessica Sturt-Smith, Michelle Alexander, Tammy Ellis, Mindy Muylaert, Cindy Paczkowski, Wendy Sligl, Sean Bagshaw, Nadia Baig, Lorena McCoshen, Katrina Alexanopoulos, Sherri Bain, Michelle Brandt, Cathy Constable, Kari Douglas, Shaleen Maharaj, Sabrina Travers, Tom Stelfox, Philippe Couillard, Christopher Doig, Ken Parhar, Joshua Booth, Cassidy Codan, Stacy Ruddell, Candice Cameron, Rhonda Edison, Anne Martin, Breanna Mina, Dan Niven, Luc Berthiaume, Jonathan Gaudet, Gina Fleming, Mercedes Carmargo, Beverly Hoekstra, Rita Caporuscio, Rachel Kressner Falvo, Carmelina Maxwell, Karmen Plantic, François Marquis, Han Tin Wang, Francis Toupin, Stephane Ahern, Brian Laufer, Marc Brosseau, Pauline Dul, Johanne Harvey, Lotthida Inthanavong, Danae Tassy, Helen Assayag, Maude Bachand, Marysa Betournay, Karine Daoust, Kristine Goyette, Marceline Quach, Paul Hosek, Bill Plaxton, Catherine Armstrong, Rhonda Barber, William Dechert, Janelle Ellis, Kayla Fisk, Melissa Gabnouri, Emilie Gordon, Rebecca Haegens, Lisa Halford, Brooklynn Hillis, Rebecca Jesso, Jenn McLaren, Elliot McMillan, Mariska Pelkmans, Matthew Rekman, Sylvia Sinkovitis, Monica Truong, Michelle White, Noah Bates, Susan Bryden-Cromwell, Lisa Cha, Colleen Cameron, Aminah Deen, Sheri DiGiovanni, Anders Foss, Esther Lee, Heidi MacGregor, Esther Galbraith, Robyn McArthur, Julie McGregor, Keith Miller, Sharon Morris, Shelley Parker, Candice Smith, Joanna Stoglow, Jennifer Tung, Melissa Vos, Neill Adhikari, Ane Amaral, Ane Carlos, Brian Cuthbertson, Rob Fowler, Damon Scales, Navjot Kaur, Nicole Marinoff, Adic Perez, Jane Wang, Katrina Hatzifilalithis, John Iazzetta, Chrys Kolos, Ingrid Quinton, Paul Lysecki, Joseph Berlingieri, Sameer Shaikh, Steven Skitch, Hala Basheer, Kathy Bruder, Jane Cheng, Kaiser Qureshi, Celeste Thibault, Ying Tung Sia, Mathieu Simon, Pierre-Alexane Bouchard, Patricia Lizotte, Nathalie Chateauvert, Thérèse Grenier, Jean-François Bellemare, Simon Bordeleau, Christine Ouin, Benoît Duhaime, Ann Laberge, Philippe Lachance, Mélanie Constantin, Estel Deblois, Maude Dionne, Lise Lavoie, Isabelle Michel, Alexane Pépin, Sanine Poulin, Sarah Anctil, Amélie Chouinard, Louis-Étienne Marchand, Robin Roy, Roigo Cartin-Ceba, Richard Oeckler, Brenda Anderson, Lavonne Liedl, Laurie Meade, Sueanne Weist, Anna Bartoo, Debbie Bauer, Vince Brickley, Shaun Bridges, Greg Brunn, Jennifer Eickstaedt, Jill Randolph, Sandy Showalter, Melissa Wendling, Robert Taylor, Margaret Cytron, Kim Fowler, Katie Krause, Jackie O’Brien, Marianne Tow, Kaitlin Stassi, Abdulaziz Al-Dawood, Haytham Tlayjeh, Alaaeldien Ghanem, Ahmad Hassanien, Mohamed Hegazy, Ashraf El Sharkawi, Felwa Bin Humaid, Hala Alanizi, Nadyah Alanizy, Njoud Al Bogami, Mohammed Muhaidib, Jawaher Gramish, Randa Alsomali, Nora Devera, Marjane Villafranca
• Format: Article
• Language: English
• Published: BMJ Publishing Group 2020-06-01
• Series: BMJ Open
• Online Access: https://bmjopen.bmj.com/content/10/6/e036047.full

Introduction Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysis The objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and dissemination Study approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration number NCT01782755; Pre-results.