use crate::utilities::matrix::{lu_solve, matrix_inverse};
use crate::utilities::statistical::normal_cdf;
use ndarray::{Array1, Array2};
use pyo3::exceptions::PyRuntimeError;
use pyo3::prelude::*;
use pyo3::types::PyDict;
#[derive(Debug)]
pub struct CoxResult {
pub coefficients: Vec<f64>,
pub standard_errors: Vec<f64>,
pub p_values: Vec<f64>,
pub confidence_intervals: Vec<(f64, f64)>,
pub log_likelihood: f64,
pub score: f64,
pub wald_test: f64,
pub iterations: i32,
pub converged: bool,
pub variance_matrix: Vec<Vec<f64>>,
}
struct CoxState {
covar: Vec<Vec<f64>>,
a: Vec<f64>,
a2: Vec<f64>,
offset: Vec<f64>,
weights: Vec<f64>,
event: Vec<i32>,
frail: Vec<i32>,
score: Vec<f64>,
strata: Vec<i32>,
}
impl CoxState {
#[allow(clippy::too_many_arguments)]
fn new(
nused: usize,
nvar: usize,
nfrail: usize,
yy: &[f64],
covar2: &[f64],
offset2: &[f64],
weights2: &[f64],
strata: &[i32],
_sort: &[i32],
_ptype: i32,
_pdiag: i32,
frail2: &[i32],
) -> Self {
let mut covar = vec![vec![0.0; nused]; nvar];
let mut k = 0;
for covar_row in covar.iter_mut().take(nvar) {
for covar_elem in covar_row.iter_mut().take(nused) {
*covar_elem = covar2[k];
k += 1;
}
}
let mut state = CoxState {
covar,
a: vec![0.0; 4 * (nvar + nfrail) + 5 * nused],
a2: vec![0.0; nvar + nfrail],
offset: offset2.to_vec(),
weights: weights2.to_vec(),
event: yy[2 * nused..3 * nused].iter().map(|&x| x as i32).collect(),
frail: frail2.to_vec(),
score: vec![0.0; nused],
strata: strata.to_vec(),
};
for i in 0..nvar {
let mean = state.covar[i].iter().sum::<f64>() / nused as f64;
for val in &mut state.covar[i] {
*val -= mean;
}
}
state
}
#[allow(clippy::too_many_arguments)]
fn update(&mut self, beta: &mut [f64], u: &mut [f64], imat: &mut [f64], loglik: &mut f64) {
let nvar = beta.len();
let nfrail = self.frail.len();
let nvar2 = nvar + nfrail;
self.a.fill(0.0);
self.a2.fill(0.0);
u.fill(0.0);
imat.fill(0.0);
for person in 0..self.weights.len() {
let mut zbeta = self.offset[person];
for (i, beta_val) in beta.iter().enumerate().take(nvar) {
zbeta += beta_val * self.covar[i][person];
}
if nfrail > 0 {
zbeta += beta[nvar] * self.frail[person] as f64;
}
self.score[person] = zbeta;
}
*loglik = 0.0;
let mut istrat = 0;
let _indx2 = 0;
while istrat < self.strata.len() {
let _denom = 0.0;
let mut risk_sum = 0.0;
for person in istrat..self.weights.len() {
if self.strata[person] != self.strata[istrat] {
break;
}
let risk_score = self.score[person].exp();
risk_sum += self.weights[person] * risk_score;
let _ = self.weights[person] * risk_score * risk_score;
}
for person in istrat..self.weights.len() {
if self.strata[person] != self.strata[istrat] {
break;
}
if self.event[person] == 1 {
*loglik += self.weights[person] * self.score[person];
*loglik -= self.weights[person] * risk_sum.ln();
for (i, u_elem) in u.iter_mut().enumerate().take(nvar) {
let mut temp = 0.0;
for j in person..self.weights.len() {
if self.strata[j] == self.strata[person] {
temp += self.weights[j] * self.score[j].exp() * self.covar[i][j];
}
}
*u_elem += self.weights[person] * (self.covar[i][person] - temp / risk_sum);
}
if nfrail > 0 {
let mut temp = 0.0;
for j in person..self.weights.len() {
if self.strata[j] == self.strata[person] {
temp +=
self.weights[j] * self.score[j].exp() * self.frail[j] as f64;
}
}
u[nvar] +=
self.weights[person] * (self.frail[person] as f64 - temp / risk_sum);
}
for i in 0..nvar {
for j in i..nvar {
let mut temp = 0.0;
for k in person..self.weights.len() {
if self.strata[k] == self.strata[person] {
temp += self.weights[k]
* self.score[k].exp()
* self.covar[i][k]
* self.covar[j][k];
}
}
let idx = i * nvar2 + j;
imat[idx] += self.weights[person]
* (temp / risk_sum
- (self.a[i] * self.a[j]) / (risk_sum * risk_sum));
}
}
if nfrail > 0 {
for i in 0..nvar {
let mut temp = 0.0;
for k in person..self.weights.len() {
if self.strata[k] == self.strata[person] {
temp += self.weights[k]
* self.score[k].exp()
* self.covar[i][k]
* self.frail[k] as f64;
}
}
let idx = i * nvar2 + nvar;
imat[idx] += self.weights[person]
* (temp / risk_sum
- (self.a[i] * self.a[nvar]) / (risk_sum * risk_sum));
}
let mut temp = 0.0;
for k in person..self.weights.len() {
if self.strata[k] == self.strata[person] {
temp += self.weights[k]
* self.score[k].exp()
* (self.frail[k] as f64).powi(2);
}
}
let idx = nvar * nvar2 + nvar;
imat[idx] += self.weights[person]
* (temp / risk_sum
- (self.a[nvar] * self.a[nvar]) / (risk_sum * risk_sum));
}
}
if person < self.weights.len() - 1 && self.strata[person + 1] == self.strata[person]
{
let risk_score = self.score[person].exp();
risk_sum -= self.weights[person] * risk_score;
let _ = self.weights[person] * risk_score * risk_score;
}
}
while istrat < self.strata.len() {
istrat += 1;
}
}
}
}
#[allow(clippy::too_many_arguments)]
#[pyfunction]
pub fn perform_cox_regression_frailty(
time: Vec<f64>,
event: Vec<i32>,
covariates: Vec<Vec<f64>>,
offset: Option<Vec<f64>>,
weights: Option<Vec<f64>>,
strata: Option<Vec<i32>>,
frail: Option<Vec<i32>>,
max_iter: Option<i32>,
eps: Option<f64>,
) -> PyResult<Py<PyAny>> {
let config = CoxRegressionConfig {
offset,
weights,
strata,
frail,
max_iter,
eps,
};
perform_cox_regression(time, event, covariates, config)
}
#[allow(clippy::too_many_arguments)]
pub fn agfit5(
nused: usize,
nvar: usize,
nfrail: usize,
yy: &[f64],
covar: &[f64],
offset: &[f64],
weights: &[f64],
strata: &[i32],
sort: &[i32],
ptype: i32,
pdiag: i32,
frail: &[i32],
max_iter: i32,
eps: f64,
) -> Result<CoxResult, Box<dyn std::error::Error>> {
let mut state = CoxState::new(
nused, nvar, nfrail, yy, covar, offset, weights, strata, sort, ptype, pdiag, frail,
);
let nvar2 = nvar + nfrail;
let mut beta = vec![0.0; nvar2];
let mut u = vec![0.0; nvar2];
let mut imat = vec![0.0; nvar2 * nvar2];
let mut loglik = 0.0;
let mut iter = 0;
let mut converged = false;
while iter < max_iter {
let old_loglik = loglik;
state.update(&mut beta, &mut u, &mut imat, &mut loglik);
if (loglik - old_loglik).abs() < eps {
converged = true;
break;
}
let mut imat_array = Array2::from_shape_vec((nvar2, nvar2), imat.clone())?;
let u_array = Array1::from_vec(u.clone());
for i in 0..nvar2 {
imat_array[[i, i]] += 1e-8;
}
match lu_solve(&imat_array, &u_array) {
Some(delta) => {
for i in 0..nvar2 {
beta[i] += delta[i];
}
}
None => {
return Err("Failed to solve linear system".into());
}
}
iter += 1;
}
state.update(&mut beta, &mut u, &mut imat, &mut loglik);
let mut variance_matrix = vec![vec![0.0; nvar2]; nvar2];
let imat_array = Array2::from_shape_vec((nvar2, nvar2), imat)?;
match matrix_inverse(&imat_array) {
Some(inv_imat) => {
for i in 0..nvar2 {
for j in 0..nvar2 {
variance_matrix[i][j] = inv_imat[[i, j]];
}
}
}
None => {
return Err("Failed to invert information matrix".into());
}
}
let standard_errors: Vec<f64> = (0..nvar2).map(|i| variance_matrix[i][i].sqrt()).collect();
let p_values: Vec<f64> = (0..nvar2)
.map(|i| {
if standard_errors[i] > 0.0 {
let z = beta[i] / standard_errors[i];
2.0 * (1.0 - normal_cdf(z.abs()))
} else {
1.0
}
})
.collect();
let confidence_intervals: Vec<(f64, f64)> = (0..nvar2)
.map(|i| {
let se = standard_errors[i];
let coef = beta[i];
(coef - 1.96 * se, coef + 1.96 * se)
})
.collect();
let score: f64 = u.iter().map(|&x| x * x).sum();
let wald_test: f64 = beta
.iter()
.zip(standard_errors.iter())
.map(|(&coef, &se)| if se > 0.0 { (coef / se).powi(2) } else { 0.0 })
.sum();
Ok(CoxResult {
coefficients: beta,
standard_errors,
p_values,
confidence_intervals,
log_likelihood: loglik,
score,
wald_test,
iterations: iter,
converged,
variance_matrix,
})
}
#[derive(Clone, Default)]
struct CoxRegressionConfig {
offset: Option<Vec<f64>>,
weights: Option<Vec<f64>>,
strata: Option<Vec<i32>>,
frail: Option<Vec<i32>>,
max_iter: Option<i32>,
eps: Option<f64>,
}
fn perform_cox_regression(
time: Vec<f64>,
event: Vec<i32>,
covariates: Vec<Vec<f64>>,
config: CoxRegressionConfig,
) -> PyResult<Py<PyAny>> {
let nused = time.len();
if nused == 0 {
return Err(PyRuntimeError::new_err("No observations provided"));
}
let nvar = covariates.len();
if nvar == 0 {
return Err(PyRuntimeError::new_err("No covariates provided"));
}
if event.len() != nused {
return Err(PyRuntimeError::new_err(
"Event vector length does not match time vector",
));
}
for cov in &covariates {
if cov.len() != nused {
return Err(PyRuntimeError::new_err(
"Covariate vector length does not match time vector",
));
}
}
let offset = config.offset.unwrap_or_else(|| vec![0.0; nused]);
let weights = config.weights.unwrap_or_else(|| vec![1.0; nused]);
let strata = config.strata.unwrap_or_else(|| vec![1; nused]);
let frail = config.frail.unwrap_or_else(|| vec![0; nused]);
let max_iter = config.max_iter.unwrap_or(20);
let eps = config.eps.unwrap_or(1e-6);
let mut yy = Vec::with_capacity(3 * nused);
yy.extend_from_slice(&time);
yy.extend_from_slice(&time);
yy.extend(event.iter().map(|&x| x as f64));
let mut covar = Vec::with_capacity(nvar * nused);
for i in 0..nused {
for covariate_row in covariates.iter().take(nvar) {
covar.push(covariate_row[i]);
}
}
let sort: Vec<i32> = (1..=nused as i32).collect();
let nfrail = if frail.iter().any(|&x| x != 0) { 1 } else { 0 };
match agfit5(
nused, nvar, nfrail, &yy, &covar, &offset, &weights, &strata, &sort, 0, 0, &frail,
max_iter, eps,
) {
Ok(result) => Python::attach(|py| {
let dict = PyDict::new(py);
dict.set_item("coefficients", result.coefficients)?;
dict.set_item("standard_errors", result.standard_errors)?;
dict.set_item("p_values", result.p_values)?;
dict.set_item("confidence_intervals", result.confidence_intervals)?;
dict.set_item("log_likelihood", result.log_likelihood)?;
dict.set_item("score", result.score)?;
dict.set_item("wald_test", result.wald_test)?;
dict.set_item("iterations", result.iterations)?;
dict.set_item("converged", result.converged)?;
dict.set_item("variance_matrix", result.variance_matrix)?;
Ok(dict.into())
}),
Err(e) => Err(PyRuntimeError::new_err(format!(
"Cox regression failed: {}",
e
))),
}
}