A Monte Carlo simulation study comparing the up and down, biased-coin up and down and continual reassessment methods used to estimate an effective dose (ED95 or ED90) in anaesthesiology research
Background: Dose-finding studies in anaesthesiology aim to target the effective dose (ED) of an anaesthetic agent in a specific population. The common dose-finding designs used are the up and down method (UDM), the biased-coin up and down (BCD), and the continual reassessment method (CRM). Although...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | BJA Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772609623001041 |
| _version_ | 1827583618012151808 |
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| author | Jean-François Fils Panayota Kapessidou Philippe Van der Linden Emmanuel Guntz |
| author_facet | Jean-François Fils Panayota Kapessidou Philippe Van der Linden Emmanuel Guntz |
| author_sort | Jean-François Fils |
| collection | DOAJ |
| description | Background: Dose-finding studies in anaesthesiology aim to target the effective dose (ED) of an anaesthetic agent in a specific population. The common dose-finding designs used are the up and down method (UDM), the biased-coin up and down (BCD), and the continual reassessment method (CRM). Although the advantages of CRM over the UDM and BCD methods have been described in the statistical literature in terms of precision and direct estimation of ED, CRM may also offer attractive properties from an ethical point of view. Methods: Based on Monte Carlo simulations, this article aims to compare the three methods with regard to 1) their ability to find as close an estimate as possible for the ED95 or ED90 and 2) the total number of patients needed to treat and the number of failures. Results: In contrast to BCD and UDM, CRM does find an estimate for ED95 and ED90. UDM underestimates both ED95 and ED90. BCD is close to the targeted EDs when the starting dose does not exceed the ED of interest, otherwise it overestimates it. CRM with cohorts of two patients is closest to the ED of interest independently of the starting doses. CRM requires between 20 and 50 observations, UDM should include 90 patients, and BCD 100 or 60 observations. Lastly, CRM is associated with fewer failures, compared with BCD and UDM. Conclusions: Based on Monte Carlo simulations, our work suggests that the UDM is not an adequate dose-finding method because it underestimates the ED of interest. Compared with BCD, CRM offers the advantages of being more efficient, requires fewer patients to be included, and is associated with fewer failures. |
| first_indexed | 2024-03-08T23:09:21Z |
| format | Article |
| id | doaj.art-4e445daa88714109b6cbccfa9aed57a8 |
| institution | Directory Open Access Journal |
| issn | 2772-6096 |
| language | English |
| last_indexed | 2024-03-08T23:09:21Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | BJA Open |
| spelling | doaj.art-4e445daa88714109b6cbccfa9aed57a82023-12-15T07:27:28ZengElsevierBJA Open2772-60962023-12-018100225A Monte Carlo simulation study comparing the up and down, biased-coin up and down and continual reassessment methods used to estimate an effective dose (ED95 or ED90) in anaesthesiology researchJean-François Fils0Panayota Kapessidou1Philippe Van der Linden2Emmanuel Guntz3Ars Statistica, Nivelles, Belgium; Corresponding author.Department of Anesthesiology, University Hospital Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, BelgiumFaculty of Medicine, Campus Erasme, Free University of Brussels, Brussels, BelgiumDepartment of Anesthesiology, Hôpital Braine-l’Alleud Waterloo, Université Libre de Bruxelles (ULB), Braine-l’Alleud, BelgiumBackground: Dose-finding studies in anaesthesiology aim to target the effective dose (ED) of an anaesthetic agent in a specific population. The common dose-finding designs used are the up and down method (UDM), the biased-coin up and down (BCD), and the continual reassessment method (CRM). Although the advantages of CRM over the UDM and BCD methods have been described in the statistical literature in terms of precision and direct estimation of ED, CRM may also offer attractive properties from an ethical point of view. Methods: Based on Monte Carlo simulations, this article aims to compare the three methods with regard to 1) their ability to find as close an estimate as possible for the ED95 or ED90 and 2) the total number of patients needed to treat and the number of failures. Results: In contrast to BCD and UDM, CRM does find an estimate for ED95 and ED90. UDM underestimates both ED95 and ED90. BCD is close to the targeted EDs when the starting dose does not exceed the ED of interest, otherwise it overestimates it. CRM with cohorts of two patients is closest to the ED of interest independently of the starting doses. CRM requires between 20 and 50 observations, UDM should include 90 patients, and BCD 100 or 60 observations. Lastly, CRM is associated with fewer failures, compared with BCD and UDM. Conclusions: Based on Monte Carlo simulations, our work suggests that the UDM is not an adequate dose-finding method because it underestimates the ED of interest. Compared with BCD, CRM offers the advantages of being more efficient, requires fewer patients to be included, and is associated with fewer failures.http://www.sciencedirect.com/science/article/pii/S2772609623001041biased-coin up and downcontinual reassessment methoddose-findingeffective dose, up and downMonte Carlo simulations |
| spellingShingle | Jean-François Fils Panayota Kapessidou Philippe Van der Linden Emmanuel Guntz A Monte Carlo simulation study comparing the up and down, biased-coin up and down and continual reassessment methods used to estimate an effective dose (ED95 or ED90) in anaesthesiology research BJA Open biased-coin up and down continual reassessment method dose-finding effective dose, up and down Monte Carlo simulations |
| title | A Monte Carlo simulation study comparing the up and down, biased-coin up and down and continual reassessment methods used to estimate an effective dose (ED95 or ED90) in anaesthesiology research |
| title_full | A Monte Carlo simulation study comparing the up and down, biased-coin up and down and continual reassessment methods used to estimate an effective dose (ED95 or ED90) in anaesthesiology research |
| title_fullStr | A Monte Carlo simulation study comparing the up and down, biased-coin up and down and continual reassessment methods used to estimate an effective dose (ED95 or ED90) in anaesthesiology research |
| title_full_unstemmed | A Monte Carlo simulation study comparing the up and down, biased-coin up and down and continual reassessment methods used to estimate an effective dose (ED95 or ED90) in anaesthesiology research |
| title_short | A Monte Carlo simulation study comparing the up and down, biased-coin up and down and continual reassessment methods used to estimate an effective dose (ED95 or ED90) in anaesthesiology research |
| title_sort | monte carlo simulation study comparing the up and down biased coin up and down and continual reassessment methods used to estimate an effective dose ed95 or ed90 in anaesthesiology research |
| topic | biased-coin up and down continual reassessment method dose-finding effective dose, up and down Monte Carlo simulations |
| url | http://www.sciencedirect.com/science/article/pii/S2772609623001041 |
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