Noninferiority Margin Size and Acceptance of Trial Results: Contingent Valuation Survey of Clinician Preferences for Noninferior Mortality

Sandra Pong¹, Robert A Fowler^{2

3

4}, Nicholas Mitsakakis^{5

6}, Srinivas Murthy^{7

8}, Jeffrey M Pernica⁹, Elaine Gilfoyle¹⁰, Asha Bowen^{11

12}, Patricia Fontela^{13

14}, Winnie Seto^{1

4

15}, Michelle Science¹⁶, James S Hutchison¹⁰, Philippe Jouvet^{17

18}, Asgar Rishu¹⁹, Nick Daneman²⁰

Affiliations

¹ Department of Pharmacy, The Hospital for Sick Children, Toronto, ON, Canada.
² Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto ON, Canada.
³ Tory Trauma Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁴ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁵ Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
⁶ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁷ Department of Pediatrics, Division of Critical Care, University of British Columbia, Vancouver, BC, Canada.
⁸ Research Institute, BC Children's Hospital, Vancouver, BC, Canada.
⁹ Division of Infectious Diseases, McMaster University, Hamilton, ON, Canada.
¹⁰ Department of Critical Care Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
¹¹ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia Perth Children's Hospital, Nedlands, WA, Australia.
¹² Department of Infectious Diseases, Perth Children's Hospital, Nedlands, WA, Australia.
¹³ Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.
¹⁴ Department of Pediatrics, McGill University, Montreal, QC, Canada.
¹⁵ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
¹⁶ Division of Infectious Diseases, Department of Paediatric Medicine, The Hospital for Children, Toronto, ON, Canada.
¹⁷ Pediatric Intensive Care Unit, Sainte-Justine Hospital University Center, Montreal, QC, Canada.
¹⁸ Department of Pediatrics, Université de Montréal, Montreal, QC, Canada.
¹⁹ Critical Care Research Unit, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁰ Division of Infectious Diseases, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

PMID: 35583116
PMCID: PMC9277322
DOI: 10.1177/0272989X221099493

Noninferiority Margin Size and Acceptance of Trial Results: Contingent Valuation Survey of Clinician Preferences for Noninferior Mortality

Sandra Pong et al. Med Decis Making. 2022 Aug.

. 2022 Aug;42(6):832-836.

doi: 10.1177/0272989X221099493. Epub 2022 May 18.

Authors

Affiliations

¹ Department of Pharmacy, The Hospital for Sick Children, Toronto, ON, Canada.
² Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto ON, Canada.
³ Tory Trauma Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁴ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁵ Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
⁶ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁷ Department of Pediatrics, Division of Critical Care, University of British Columbia, Vancouver, BC, Canada.
⁸ Research Institute, BC Children's Hospital, Vancouver, BC, Canada.
⁹ Division of Infectious Diseases, McMaster University, Hamilton, ON, Canada.
¹⁰ Department of Critical Care Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
¹¹ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia Perth Children's Hospital, Nedlands, WA, Australia.
¹² Department of Infectious Diseases, Perth Children's Hospital, Nedlands, WA, Australia.
¹³ Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.
¹⁴ Department of Pediatrics, McGill University, Montreal, QC, Canada.
¹⁵ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
¹⁶ Division of Infectious Diseases, Department of Paediatric Medicine, The Hospital for Children, Toronto, ON, Canada.
¹⁷ Pediatric Intensive Care Unit, Sainte-Justine Hospital University Center, Montreal, QC, Canada.
¹⁸ Department of Pediatrics, Université de Montréal, Montreal, QC, Canada.
¹⁹ Critical Care Research Unit, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁰ Division of Infectious Diseases, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

PMID: 35583116
PMCID: PMC9277322
DOI: 10.1177/0272989X221099493

Abstract

Objectives: We used modified contingent valuation methodology to determine how noninferiority margin sizes influence clinicians' willingness to accept clinical trial results that compare mortality in critically ill children.

Methods: We surveyed pediatric infectious diseases and critical care clinicians in Canada, Australia, and New Zealand and randomized respondents to review 1 of 9 mock abstracts describing a noninferiority trial of bacteremic critically ill children assigned to 7 or 14 d of antibiotics. Each scenario showed higher mortality in the 7-d group but met noninferiority criterion. We explored how noninferiority margins and baseline mortality rates influenced respondent acceptance of results.

Results: There were 106 survey respondents: 65 (61%) critical care clinicians, 28 (26%) infectious diseases physicians, and 13 (12%) pharmacists. When noninferiority margins were 5% and 10%, 73% (24/33) and 79% (27/33) respondents would accept shorter treatment, compared with 44% (17/39) when the margin was 20% (P = 0.003). Logistic regression adjusted for baseline mortality showed 5% and 10% noninferiority margins were more likely to be associated with acceptance of shorter treatment compared with 20% margins (odds ratio [OR] 3.5, 95% confidence interval [CI]: 1.3-9.6, P = 0.013; OR 5.1, 95% CI: 1.8-14.6, P = 0.002). Baseline mortality was not a significant predictor of acceptance of shorter treatment.

Conclusions: Clinicians are more likely to accept shorter treatment when noninferiority margins are ≤10%. However, nearly half of respondents who reviewed abstracts with 20% margins were still willing to accept shorter treatment. This is a novel application of contingent valuation methodology to elicit acceptance of research results among end users of the medical literature.

Highlights: Clinicians are more likely to accept shorter treatment durations based on noninferior mortality results when the noninferiority margin is 5% or 10% than if the margin is 20%.However, nearly half of clinicians would still accept shorter-duration treatment as noninferior with margins of 20%.Baseline mortality does not independently predict acceptance of shorter-duration treatment.Contingent valuation is a novel approach to elicit the acceptance of research design parameters from the perspective of endusers of the medical literature.

Keywords: antimicrobials; contingent valuation; duration of therapy; evidence uptake; mortality; noninferiority margin.

PubMed Disclaimer

Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was not funded. Sandra Pong is supported by a SickKids Clinician-Scientist Training Program Scholarship from The Hospital for Sick Children.

Figures

**Figure 1**
Subgroups of respondents accepting shorter-duration treatment in each noninferiority margin level.

See this image and copyright information in PMC

References

1. Piaggio G, Elbourne DR, Altman DG, et al.. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA. 2006;295:1152–60. - PubMed
1. Mauri L, D’Agostino RB. Challenges in the design and interpretation of non-inferiority trials. N Engl J Med. 2017;377:1357–67. - PubMed
1. Pong S, Urner M, Fowler RA, et al.. Testing for non-inferior mortality: a systematic review of non-inferiority margin sizes and trial characteristics. BMJ Open. 2021;11:e044480. - PMC - PubMed
1. Arrow K, Solow R, Portney P, et al.. Report of the NOAA Panel on Contingent Valuation. Washington (DC): National Oceanic and Atmospheric Administration; 1993.
1. O’Brien B, Gafni A. When do the “dollars” make sense? Towards a conceptual framework for contingent valuation studies in health care. Med Decis Making. 1996;16:288–99. - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Miscellaneous
- NCI CPTAC Assay Portal

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

Noninferiority Margin Size and Acceptance of Trial Results: Contingent Valuation Survey of Clinician Preferences for Noninferior Mortality

Affiliations

Noninferiority Margin Size and Acceptance of Trial Results: Contingent Valuation Survey of Clinician Preferences for Noninferior Mortality

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Miscellaneous