Department seminar by Haolun Shi, Simon Fraser UniversityExport this event to calendar

Tuesday, February 4, 2020 — 10:00 AM EST

Bayesian Utility-Based Toxicity Probability Interval Design for Dose Finding in Phase I/II Trials


Molecularly targeted agents and immunotherapy have revolutionized modern cancer treatment. Unlike chemotherapy, the maximum tolerated dose of the targeted therapies may not pose significant clinical benefit over the lower doses. By simultaneously considering both binary toxicity and efficacy endpoints, phase I/II trials can identify a better dose for subsequent phase II trials than traditional phase I trials in terms of efficacy-toxicity tradeoff.  Existing phase I/II dose-finding methods are model-based or need to pre-specify many design parameters, which makes them difficult to implement in practice. To strengthen and simplify the current practice of phase I/II trials, we propose a utility-based toxicity probability interval (uTPI) design for finding the optimal biological dose (OBD) where binary toxicity and efficacy endpoints are observed. The uTPI design is model-assisted in nature, simply modeling the utility outcomes observed at the current dose level based on a quasibinomial likelihood. Toxicity probability intervals are used to screen out overly toxic dose levels, and then the dose escalation/de-escalation decisions are made adaptively by comparing the posterior utility distributions of the adjacent levels of the current dose. The uTPI design is flexible in accommodating various utility functions while only needs minimum design parameters. A prominent feature of the uTPI design is that it has a simple decision structure such that a concise dose-assignment decision table can be calculated before the start of trial and be used throughout the trial, which greatly simplifies practical implementation of the design. Extensive simulation studies demonstrate that the proposed uTPI design yields desirable as well as robust performance under various scenarios. This talk is based on the joint work with Ruitao Lin and Ying Yuan at MD Anderson Cancer Center.
 

Location 
M3 - Mathematics 3
Room 3127
200 University Avenue West

Waterloo, ON N2L 3G1
Canada

S M T W T F S
29
30
31
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
1
2
  1. 2022 (2)
    1. August (1)
    2. April (1)
  2. 2021 (78)
    1. December (4)
    2. November (10)
    3. October (7)
    4. September (5)
    5. July (4)
    6. June (3)
    7. May (6)
    8. April (8)
    9. March (13)
    10. February (7)
    11. January (12)
  3. 2020 (71)
    1. December (2)
    2. November (13)
    3. October (16)
    4. September (7)
    5. August (5)
    6. July (3)
    7. June (2)
    8. May (1)
    9. March (4)
    10. February (4)
    11. January (14)
  4. 2019 (65)
  5. 2018 (44)
  6. 2017 (55)
  7. 2016 (44)
  8. 2015 (37)
  9. 2014 (44)
  10. 2013 (46)
  11. 2012 (44)