Title :

Statistical controversies in clinical research: should schedules of tumor size assessments be changed?

Author(s) :

Filleron, T. [Auteur]
Kouokam, W. [Auteur]
Gilhodes, J. [Auteur]
Duhamel, Alain [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Penel, Nicolas [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Joly, F. [Auteur]
Tresch-Bruneel, Emmanuelle [Auteur]
Kramar, Andrew [Auteur]
Houede, N. [Auteur]

Journal title :

Annals of oncology . official journal of the European Society for Medical Oncology

Abbreviated title :

Ann. Oncol.

Volume number :

27

Pages :

1981-1987

Publication date :

2016-11-01

ISSN :

0923-7534

English keyword(s) :

trial design
end point
time to progression
clinical trial
phase II

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Time to progression (TTP) is often used as a primary end point in phase II clinical trials. Since the actual date of nadir and progression is never known, most calculated TTP are overestimated. This study evaluates the ...
Show more >Time to progression (TTP) is often used as a primary end point in phase II clinical trials. Since the actual date of nadir and progression is never known, most calculated TTP are overestimated. This study evaluates the imprecision on the estimate of TTP under two hypothetical tumor kinetic settings and various assessment schedules. A two-component tumor growth model was used to account for treatment effect assuming exponential decay for tumor shrinkage and linear growth for progression. Evolution of tumor burden (TB) was modelized according to two scenarios using either a cytotoxic or a cytostatic agent and several assessment schedules. TB, nadir, progression and TTP were simulated for each visit schedule. For cytotoxic agents, our model predicted response at 1.5 weeks, a TB at nadir of 40.2 mm (starting from 100 mm) occurring at 6.7 weeks and true progression at 11.2 weeks with a TB of 48.2 mm. For cytostatic agents, our model predicted no response, a TB at nadir of 77 mm occurring at 9.2 weeks and true progression at 19.4 weeks with a TB of 92 mm. Depending on the assessment schedule, estimated TTP was increased from 0.8 to 36.8 weeks and from 0.6 to 28.6 weeks when compared with the true TTP and varied from 5.2% to 298% and from 1.66 to 109.58% when compared with the true TB at progression for cytotoxic and cytostatic agents, respectively. Our model further shows that for cytotoxic agents, evaluation of TB every 6 weeks is optimal to capture the true nadir, the time to nadir, the true progression and the true TTP, whereas for cytostatic agents, this evaluation is optimal every 10 weeks. Our results emphasize the importance to estimate the effects of tested drugs on tumor shrinkage before design any phase II clinical trials to choose optimal TB evaluation's timing.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Université de Lille

Collections :

• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Submission date :

2019-12-09T18:15:35Z