Whole-of-Life Inclusion in Bayesian Adaptive Platform Clinical Trials

Anita J Campbell^{1

2

3}, Keerthi Anpalagan^{2

3}, Emma J Best^{4

5

6}, Philip N Britton^{7

8}, Amanda Gwee^{9

10

11}, James Hatcher^{12

13}, Brett J Manley^{14

15

16}, Julie Marsh^{2

17}, Rachel H Webb^{4

6

18}, Joshua S Davis^{19

20

21}, Robert K Mahar^{22

23

24}, Anna McGlothlin²⁵, Brendan McMullan^{26

27}, Michael Meyer^{28

29}, Jocelyn Mora³⁰, Srinivas Murthy³¹, Clare Nourse^{32

33}, Jesse Papenburg^{34

35}, Kevin L Schwartz^{36

37}, Oded Scheuerman^{38

39}, Thomas Snelling^{2

40}, Tobias Strunk^{3

41

42}, Michael Stark^{43

44}, Lesley Voss⁶, Steven Y C Tong^{30

45}, Asha C Bowen^{1

2}; Staphylococcus aureus Network Adaptive Platform Paediatric and Youth (SNAP-PY) working groupSNAP Global Trial Steering Committee

Collaborators, Affiliations

Collaborators

Staphylococcus aureus Network Adaptive Platform Paediatric and Youth (SNAP-PY) working groupSNAP Global Trial Steering Committee:
Zoe McQuilten, Steve Webb, David Paterson, George Heriot, Jason Roberts, Matthew Scarborough, David Lye, Genevieve Walls, Susan Morpeth, Tom Boyles, Marc Bonten, Marjolein P M Hensgens, Nick Daneman, Dafna Yahav, Anna L Goodman, Matthew Cheng, Catherine Cosgrove, Lynda Whiteway, Sebastian Van Hal, Todd C Lee, Roger J Lewis, Owen Robinson, Erica Hardy, Isabelle Malhamé

Affiliations

¹ Department of Infectious Diseases, Perth Children's Hospital, Perth, Western Australia, Australia.
² Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia.
³ School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
⁴ Department of Paediatrics, Child and Youth Health, The University of Auckland, Auckland, New Zealand.
⁵ The National Immunisation Advisory Centre, The University of Auckland, Auckland, New Zealand.
⁶ Department of Infectious Diseases, Starship Children's Hospital, Auckland, New Zealand.
⁷ Sydney Medical School and Sydney Infectious Diseases, University of Sydney, Sydney, New South Wales, Australia.
⁸ Department of Infectious Diseases and Microbiology, the Children's Hospital at Westmead, Sydney, New South Wales, Australia.
⁹ Department of General Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia.
¹⁰ Antimicrobials Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
¹¹ Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.
¹² Department of Microbiology, Great Ormond Street Hospital for Children, London, United Kingdom.
¹³ Infection, Immunity, and Inflammation Research Department, University College London, London, United Kingdom.
¹⁴ The Royal Women's Hospital, Melbourne, Victoria, Australia.
¹⁵ The Department of Obstetrics, Gynaecology and Newborn Health, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁶ Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
¹⁷ Centre for Child Health research, School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
¹⁸ Department of Paediatrics, Kidz First Children's 'Hospital, Auckland, New Zealand.
¹⁹ Menzies School of Health Research, Charles Darwin Hospital, Darwin, Northern Territory, Australia.
²⁰ John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia.
²¹ School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
²² Clinical Epidemiology and Biostatistics, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
²³ Centre for Epidemiology and Biostatistics Unit, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia.
²⁴ Centre for Data Science, Queensland University of Technology, Brisbane, Queensland, Australia.
²⁵ Berry Consultants, Austin, Texas.
²⁶ Department of Infectious Diseases, Sydney Children's Hospital, Randwick, Sydney, New South Wales, Australia.
²⁷ School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
²⁸ Neonatal Unit, Kidz First Middlemore Hospital Auckland, Auckland, New Zealand.
²⁹ Department of Paediatrics: Child and Youth Health University of Auckland, Auckland, Auckland, New Zealand.
³⁰ Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
³¹ Division of Critical Care, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
³² Queensland Children's Hospital, Brisbane, Queensland, Australia.
³³ Faculty of Medicine, University of Queensland, Queensland, Australia.
³⁴ Division of Pediatric Infectious Diseases, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
³⁵ Division of Microbiology, Department of Clinical Laboratory Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
³⁶ Division of Infectious Diseases, St Joseph's Health Centre - Unity Health Toronto, Toronto, Ontario, Canada.
³⁷ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
³⁸ Pediatrics B and Pediatric Infectious Diseases Unit, Schneider Children Medical Center Israel, Petach Tikva, Israel.
³⁹ Tel Aviv University, Tel Aviv, Israel.
⁴⁰ School of Public Health, University of Sydney, Sydney, New South Wales, Australia.
⁴¹ Neonatal Directorate Child and Adolescent Health Service, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia.
⁴² Telethon Kids Institute, Perth, Western Australia, Australia.
⁴³ The Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
⁴⁴ The Department of Neonatal Medicine, The Women's and Children's Hospital, Adelaide, South Australia, Australia.
⁴⁵ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

PMID: 39158898
DOI: 10.1001/jamapediatrics.2024.2697

Whole-of-Life Inclusion in Bayesian Adaptive Platform Clinical Trials

Anita J Campbell et al. JAMA Pediatr. 2024.

. 2024 Oct 1;178(10):1066-1071.

doi: 10.1001/jamapediatrics.2024.2697.

Authors

Collaborators

Staphylococcus aureus Network Adaptive Platform Paediatric and Youth (SNAP-PY) working groupSNAP Global Trial Steering Committee:
Zoe McQuilten, Steve Webb, David Paterson, George Heriot, Jason Roberts, Matthew Scarborough, David Lye, Genevieve Walls, Susan Morpeth, Tom Boyles, Marc Bonten, Marjolein P M Hensgens, Nick Daneman, Dafna Yahav, Anna L Goodman, Matthew Cheng, Catherine Cosgrove, Lynda Whiteway, Sebastian Van Hal, Todd C Lee, Roger J Lewis, Owen Robinson, Erica Hardy, Isabelle Malhamé

Affiliations

¹ Department of Infectious Diseases, Perth Children's Hospital, Perth, Western Australia, Australia.
² Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia.
³ School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
⁴ Department of Paediatrics, Child and Youth Health, The University of Auckland, Auckland, New Zealand.
⁵ The National Immunisation Advisory Centre, The University of Auckland, Auckland, New Zealand.
⁶ Department of Infectious Diseases, Starship Children's Hospital, Auckland, New Zealand.
⁷ Sydney Medical School and Sydney Infectious Diseases, University of Sydney, Sydney, New South Wales, Australia.
⁸ Department of Infectious Diseases and Microbiology, the Children's Hospital at Westmead, Sydney, New South Wales, Australia.
⁹ Department of General Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia.
¹⁰ Antimicrobials Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
¹¹ Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.
¹² Department of Microbiology, Great Ormond Street Hospital for Children, London, United Kingdom.
¹³ Infection, Immunity, and Inflammation Research Department, University College London, London, United Kingdom.
¹⁴ The Royal Women's Hospital, Melbourne, Victoria, Australia.
¹⁵ The Department of Obstetrics, Gynaecology and Newborn Health, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁶ Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
¹⁷ Centre for Child Health research, School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
¹⁸ Department of Paediatrics, Kidz First Children's 'Hospital, Auckland, New Zealand.
¹⁹ Menzies School of Health Research, Charles Darwin Hospital, Darwin, Northern Territory, Australia.
²⁰ John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia.
²¹ School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
²² Clinical Epidemiology and Biostatistics, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
²³ Centre for Epidemiology and Biostatistics Unit, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia.
²⁴ Centre for Data Science, Queensland University of Technology, Brisbane, Queensland, Australia.
²⁵ Berry Consultants, Austin, Texas.
²⁶ Department of Infectious Diseases, Sydney Children's Hospital, Randwick, Sydney, New South Wales, Australia.
²⁷ School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
²⁸ Neonatal Unit, Kidz First Middlemore Hospital Auckland, Auckland, New Zealand.
²⁹ Department of Paediatrics: Child and Youth Health University of Auckland, Auckland, Auckland, New Zealand.
³⁰ Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
³¹ Division of Critical Care, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
³² Queensland Children's Hospital, Brisbane, Queensland, Australia.
³³ Faculty of Medicine, University of Queensland, Queensland, Australia.
³⁴ Division of Pediatric Infectious Diseases, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
³⁵ Division of Microbiology, Department of Clinical Laboratory Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
³⁶ Division of Infectious Diseases, St Joseph's Health Centre - Unity Health Toronto, Toronto, Ontario, Canada.
³⁷ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
³⁸ Pediatrics B and Pediatric Infectious Diseases Unit, Schneider Children Medical Center Israel, Petach Tikva, Israel.
³⁹ Tel Aviv University, Tel Aviv, Israel.
⁴⁰ School of Public Health, University of Sydney, Sydney, New South Wales, Australia.
⁴¹ Neonatal Directorate Child and Adolescent Health Service, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia.
⁴² Telethon Kids Institute, Perth, Western Australia, Australia.
⁴³ The Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
⁴⁴ The Department of Neonatal Medicine, The Women's and Children's Hospital, Adelaide, South Australia, Australia.
⁴⁵ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

PMID: 39158898
DOI: 10.1001/jamapediatrics.2024.2697

Erratum in

Error in Byline and End Matter.
[No authors listed] [No authors listed] JAMA Pediatr. 2024 Oct 1;178(10):1086. doi: 10.1001/jamapediatrics.2024.4237. JAMA Pediatr. 2024. PMID: 39373737 No abstract available.

Abstract

Importance: There is a recognized unmet need for clinical trials to provide evidence-informed care for infants, children and adolescents. This Special Communication outlines the capacity of 3 distinct trial design strategies, sequential, parallel, and a unified adult-pediatric bayesian adaptive design, to incorporate children into clinical trials and transform this current state of evidence inequity. A unified adult-pediatric whole-of-life clinical trial is demonstrated through the Staphylococcus aureus Network Adaptive Platform (SNAP) trial.

Observations: Bayesian methods provide a framework for synthesizing data in the form of a probability model that can be used in the design and analysis of a clinical trial. Three trial design strategies are compared: (1) a sequential adult-pediatric bayesian approach that involves a separate, deferred pediatric trial that incorporates existing adult trial data into the analysis model to potentially reduce the pediatric trial sample size; (2) a parallel adult-pediatric bayesian trial whereby separate pediatric enrollment occurs in a parallel trial, running alongside an adult randomized clinical trial; and (3) a unified adult-pediatric bayesian adaptive design that supports the enrollment of both children and adults simultaneously in a whole-of-life bayesian adaptive randomized clinical trial. The SNAP trial whole-of-life design uses a bayesian hierarchical model that allows information sharing (also known as borrowing) between trial age groups by linking intervention effects of children and adults, thereby improving inference in both groups.

Conclusion and relevance: Bayesian hierarchical models may provide more precision for estimates of safety and efficacy of treatments in trials with heterogenous populations compared to traditional methods of analysis. They facilitate the inclusion of children in clinical trials and a shift from children deemed therapeutic orphans to the vision of no child left behind in clinical trials to ensure evidence for clinical practice exists across the life course. The SNAP trial provides an example of a bayesian adaptive whole-of-life inclusion design that enhances trial population inclusivity and diversity overall, as well as generalizability and translation of findings into clinical practice.

PubMed Disclaimer

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Ovid Technologies, Inc.
- Silverchair Information Systems

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Whole-of-Life Inclusion in Bayesian Adaptive Platform Clinical Trials

Collaborators

Affiliations

Whole-of-Life Inclusion in Bayesian Adaptive Platform Clinical Trials

Authors

Collaborators

Affiliations

Erratum in

Abstract

MeSH terms

LinkOut - more resources

Full Text Sources