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Confidence Interval After Trial Termination for Phase 2/3 Seamless Design

Source: R/RcppExports.R
getCI_seamless.Rd

Obtains the p-value, point estimate, and confidence interval after the end of a phase 2/3 seamless trial.

Usage

getCI_seamless(
  M = NA_integer_,
  r = 1,
  corr_known = TRUE,
  L = NA_integer_,
  zL = NA_real_,
  IMax = NA_real_,
  informationRates = NA_real_,
  efficacyStopping = NA_integer_,
  criticalValues = NA_real_,
  alpha = 0.025,
  typeAlphaSpending = "sfOF",
  parameterAlphaSpending = NA_real_,
  spendingTime = NA_real_
)

Arguments

M

Number of active treatment arms in Phase 2.

r

Randomization ratio of each active arm to the common control in Phase 2.

corr_known

Logical. If TRUE, the correlation between Wald statistics in Phase 2 is derived from the randomization ratio \(r\) as \(r / (r + 1)\). If FALSE, a conservative correlation of 0 is assumed.

L

The termination look in Phase 3.

zL

The z-test statistic at the termination look.

IMax

Maximum information for any active arm versus the common control.

informationRates

The information rates up to look L.

efficacyStopping

Indicators of whether efficacy stopping is allowed at each stage up to look L. Defaults to TRUE if left unspecified.

criticalValues

The upper boundaries on the max z-test statistic scale for Phase 2 and the z-test statistics for the selected arm in Phase 3 up to look L. If missing, boundaries will be computed based on the specified alpha spending function.

alpha

The significance level. Defaults to 0.025.

typeAlphaSpending

The type of alpha spending for the trial. One of the following: "OF" for O'Brien-Fleming boundaries, "P" for Pocock boundaries, "WT" for Wang & Tsiatis boundaries, "sfOF" for O'Brien-Fleming type spending function, "sfP" for Pocock type spending function, "sfKD" for Kim & DeMets spending function, "sfHSD" for Hwang, Shi & DeCani spending function, and "none" for no early efficacy stopping. Defaults to "sfOF".

parameterAlphaSpending

The parameter value for the alpha spending. Corresponds to \(\Delta\) for "WT", \(\rho\) for "sfKD", and \(\gamma\) for "sfHSD".

spendingTime

The error spending time up to look L. Defaults to missing, in which case, it is the same as informationRates.

Value

A data frame with the following components:

  • pvalue: p-value for rejecting the null hypothesis.

  • thetahat: Point estimate of the parameter.

  • cilevel: Confidence interval level.

  • lower: Lower bound of confidence interval.

  • upper: Upper bound of confidence interval.

Details

If typeAlphaSpending is "OF", "P", "WT", or "none", then informationRates, efficacyStopping, and spendingTime must be of full length \(K + 1\), and informationRates and spendingTime must end with 1.

References

Ping Gao, Yingqiu Li. Adaptive two-stage seamless sequential design for clinical trials. Journal of Biopharmaceutical Statistics, 2025, 35(4), 565-587.

Author

Kaifeng Lu, kaifenglu@gmail.com

Examples

getCI_seamless(
  L = 2, zL = 2.075,
  M = 2, r = 1, corr_known = FALSE,
  IMax = 300 / 4, informationRates = c(1/3, 2/3, 1),
  alpha = 0.025, typeAlphaSpending = "sfOF")
#>       pvalue  thetahat cilevel       lower     upper
#> 1 0.03423737 0.2005519    0.95 -0.01534503 0.4651547