rand.stg2: Stage 2 Adaptive Randomization

In iAdapt: Two-Stage Adaptive Dose-Finding Clinical Trial Design

Description

Function rand.stg2() fits a linear regression for the continuous efficacy outcomes, computes the randomization probabilities/dose and allocates the next patient to a dose that is considered acceptably safe and has the most promising efficacy. Dose safety is still monitored using LR and doses that become unacceptable are discarded (never re-visited).

Usage

rand.stg2(
  dose,
  dose.tox,
  p1,
  p2,
  K,
  coh.size,
  m,
  v,
  N,
  stop.rule = 9,
  cohort = 1,
  samedose = TRUE,
  nbb = 100
)

Arguments

dose	number of doses to be tested (scalar)
dose.tox	vector of true toxicities for each dose. Values range from 0 - 1.
p1	toxicity under null (unsafe DLT rate). Values range from 0 - 1.
p2	toxicity under alternative (safe DLT rate). Values range from 0 - 1; p1 > p2
K	threshold for LR. Takes integer values: 1,2,...(recommended K=2)
coh.size	cohort size (number of patients) per dose (Stage 1)
m	vector of mean efficacies per dose. Values range from 0 - 100. (e.g, T cell persistence - values b/w 5 and 80 per cent)
v	vector of efficacy variances per dose. Values range from 0 - 1. (e.g., 0.01)
N	total sample size for stages 1&2
stop.rule	if only dose 1 safe, allocate up to 9 (default) patients at dose 1 to collect more info
cohort	cohort size (number of patients) per dose (Stage 2). Default is 1.
samedose	designates whether the next patient is allocated to the same dose as the previous patient. Default is TRUE. Function adjusts accordingly.
nbb	binomial parameter (default = 100 cells per patient)

Value

List of the following objects:

• Y.final - vector of all efficacy outcomes (Ys) corresponding to dose assignments (Stages 1&2)

• d.final - vector of all dose assignments(Stages 1&2)

If dose allocation stops early, put NAs in d.final and y.final until it reaches the total sample size.

Examples

# Number of pre-specified dose levels
dose <- 5
# Vector of true toxicities associated with each dose
dose.tox <- c(0.05, 0.10, 0.20, 0.35, 0.45)       
# Acceptable (p_yes) and unacceptable (p_no) DLT rates used for establishing safety
p_no <- 0.40                                     
p_yes <- 0.15    

# Likelihood-ratio (LR) threshold
K <- 2                                          

# Cohort size used in stage 1
coh.size <- 3 

# Vector of true mean efficacies per dose (here mean percent persistence per dose)
m <- c(5, 15, 40, 65, 80)   # MUST BE THE SAME LENGTH AS dose.tox                  

# Efficacy(equal) variance per dose
v <- rep(0.01, 5) 

# Total sample size (stages 1&2)                            
N <- 25                                        

# Stopping rule: if dose 1 is the only safe dose, allocate up to 9 pts.
stop.rule <- 9 

rand.stg2(dose, dose.tox, p_no, p_yes, K, coh.size, m, v, N, stop.rule = stop.rule, 
cohort = 1, samedose = TRUE, nbb = 100) 

iAdapt documentation built on Aug. 6, 2021, 9:08 a.m.