density_threshold_integrand

Wrapper around density_threshold_both for use with cubature integration.

internal

Implements statistical methods for exploratory subgroup identification
in clinical trials with survival endpoints. Provides tools for identifying
patient subgroups with differential treatment effects using machine learning
approaches including Generalized Random Forests (GRF), LASSO regularization,
and exhaustive combinatorial search algorithms. Features bootstrap bias
correction using infinitesimal jackknife methods to address selection bias
in post-hoc analyses. Designed for clinical researchers conducting exploratory
subgroup analyses in randomized controlled trials, particularly for
multi-regional clinical trials (MRCT) requiring regional consistency
evaluation. Supports both accelerated failure time (AFT) and Cox proportional
hazards models with comprehensive diagnostic and visualization tools.
Methods are described in León et al. (2024) <doi:10.1002/sim.10163>.

Larry Leon

forestsearch

Exploratory Subgroup Identification in Clinical Trials with
Survival Endpoints

density_threshold_integrand function

<dl><dt>x</dt>
<dd>Numeric vector of length 2. Log hazard ratio estimates from
the two split-halves.</dd>
<dt>theta</dt>
<dd>Numeric. True hazard ratio in the subgroup.</dd>
<dt>prop_cens</dt>
<dd>Numeric. Proportion censored (0-1). Default: 0.3</dd>
<dt>n_sg</dt>
<dd>Integer. Subgroup sample size.</dd>
<dt>k_avg</dt>
<dd>Numeric. Threshold for average log(HR) across splits.
Typically log(hr.threshold).</dd>
<dt>k_ind</dt>
<dd>Numeric. Threshold for individual split log(HR).
Typically log(hr.consistency).</dd></dl>

Arguments

Vectorized Density for Integration — density_threshold_integrand

<dl>

<dt>x</dt>
<dd>Numeric vector of length 2. Log hazard ratio estimates from
the two split-halves.</dd>


<dt>theta</dt>
<dd>Numeric. True hazard ratio in the subgroup.</dd>


<dt>prop_cens</dt>
<dd>Numeric. Proportion censored (0-1). Default: 0.3</dd>


<dt>n_sg</dt>
<dd>Integer. Subgroup sample size.</dd>


<dt>k_avg</dt>
<dd>Numeric. Threshold for average log(HR) across splits.
Typically log(hr.threshold).</dd>


<dt>k_ind</dt>
<dd>Numeric. Threshold for individual split log(HR).
Typically log(hr.consistency).</dd>

</dl>

density_threshold_integrand: Vectorized Density for Integration

Description

Usage

Value

Arguments