PMID- 33847541
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20240402
IS  - 1477-0334 (Electronic)
IS  - 0962-2802 (Print)
IS  - 0962-2802 (Linking)
VI  - 30
IP  - 6
DP  - 2021 Jun
TI  - A method for systematically ranking therapeutic drug candidates using multiple 
      uncertain screening criteria.
PG  - 1502-1522
LID - 10.1177/09622802211002861 [doi]
AB  - Multiple different screening tests for candidate leads in drug development may 
      often yield conflicting or ambiguous results, sometimes making the selection of 
      leads a nontrivial maximum-likelihood ranking problem. Here, we employ methods 
      from the field of multiple criteria decision making (MCDM) to the problem of 
      screening candidate antibody therapeutics. We employ the SMAA-TOPSIS method to 
      rank a large cohort of antibodies using up to eight weighted screening criteria, 
      in order to find lead candidate therapeutics for Alzheimer's disease, and 
      determine their robustness to both uncertainty in screening measurements, as well 
      as uncertainty in the user-defined weights of importance attributed to each 
      screening criterion. To choose lead candidates and measure the confidence in 
      their ranking, we propose two new quantities, the Retention Probability and the 
      Topness, as robust measures for ranking. This method may enable more systematic 
      screening of candidate therapeutics when it becomes difficult intuitively to 
      process multi-variate screening data that distinguishes candidates, so that 
      additional candidates may be exposed as potential leads, increasing the 
      likelihood of success in downstream clinical trials. The method properly 
      identifies true positives and true negatives from synthetic data, its predictions 
      correlate well with known clinically approved antibodies vs. those still in 
      trials, and it allows for ranking analyses using antibody developability profiles 
      in the literature. We provide a webserver where users can apply the method to 
      their own data: http://bjork.phas.ubc.ca.
FAU - Peng, Xubiao
AU  - Peng X
AD  - Department of Physics and Astronomy, University of British Columbia, Vancouver, 
      BC, Canada.
FAU - Gibbs, Ebrima
AU  - Gibbs E
AD  - Brain Research Center, Department of Medicine, University of British Columbia, 
      Vancouver, BC, Canada.
FAU - Silverman, Judith M
AU  - Silverman JM
AD  - Brain Research Center, Department of Medicine, University of British Columbia, 
      Vancouver, BC, Canada.
FAU - Cashman, Neil R
AU  - Cashman NR
AD  - Brain Research Center, Department of Medicine, University of British Columbia, 
      Vancouver, BC, Canada.
FAU - Plotkin, Steven S
AU  - Plotkin SS
AUID- ORCID: 0000-0001-8998-877X
AD  - Department of Physics and Astronomy, University of British Columbia, Vancouver, 
      BC, Canada.
AD  - Genome Science and Technology Program, University of British Columbia, Vancouver, 
      BC, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210413
PL  - England
TA  - Stat Methods Med Res
JT  - Statistical methods in medical research
JID - 9212457
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Humans
MH  - *Pharmaceutical Preparations
MH  - *Research Design
MH  - Uncertainty
PMC - PMC8189013
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - MCDM
OT  - SMAA-TOPSIS
OT  - drug development
OT  - lead optimization
OT  - ranking
COIS- Declaration of conflicting interests: The author(s) declared the following 
      potential conflicts of interest with respect to the research, authorship, and/or 
      publication of this article: SSP was the Chief Physics Officer of ProMIS 
      Neurosciences until October 2020. NRC is the Chief Scientific Officer of ProMIS 
      Neurosciences. XP has received consultation compensation from ProMIS. SSP, NRC, 
      and XP are inventors on several pending patent applications directed to 
      therapeutics for Alzheimer's disease and which describe immunogens, antibodies 
      and methods of their making as well as their use.
EDAT- 2021/04/14 06:00
MHDA- 2021/08/03 06:00
PMCR- 2021/06/09
CRDT- 2021/04/13 12:10
PHST- 2021/04/14 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2021/04/13 12:10 [entrez]
PHST- 2021/06/09 00:00 [pmc-release]
AID - 10.1177_09622802211002861 [pii]
AID - 10.1177/09622802211002861 [doi]
PST - ppublish
SO  - Stat Methods Med Res. 2021 Jun;30(6):1502-1522. doi: 10.1177/09622802211002861. 
      Epub 2021 Apr 13.