Corrected profile likelihood confidence interval for binomial paired incomplete data

Clinical trials often use paired binomial data as their clinical endpoint. The confidence interval is frequently used to estimate the treatment performance. Tang et al. (2009) have proposed exact and approximate unconditional methods for constructing a confidence interval in the presence of incomplete paired binary data. The approach proposed by Tang et al. can be overly conservative with large expected confidence interval width (ECIW) in some situations. We propose a profile likelihood‐based method with a Jeffreys' prior correction to construct the confidence interval. This approach generates confidence interval with a much better coverage probability and shorter ECIWs. The performances of the method along with the corrections are demonstrated through extensive simulation. Finally, three real world data sets are analyzed by all the methods. Statistical Analysis System (SAS) codes to execute the profile likelihood‐based methods are also presented. Copyright © 2013 John Wiley & Sons, Ltd.     

Smooth bootstrap-based confidence intervals for one binomial proportion and difference of two proportions

Constructing confidence intervals (CIs) for a binomial proportion and the difference between two binomial proportions is a fundamental and well-studied problem with respect to the analysis of binary data. In this note, we propose a new bootstrap procedure to estimate the CIs by resampling from a newly developed smooth quantile function in [11 Newcombe, R. G. 1998. Two-sided confidence intervals for the single proportion: Comparison of seven methods. Stat. Med., 17: 857–872. (doi:10.1002/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E)[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]] for discrete data. We perform a variety of simulation studies in order to illustrate the strong performance of our approach. The coverage probabilities of our CIs in the one-sample setting are superior than or comparable to other well-known approaches. The true utility of our new and novel approach is in the two-sample setting. For the difference of two proportions, our smooth bootstrap CIs provide better coverage probabilities almost uniformly over the interval (?1, 1), particularly in the tail region as compared than other published methods included in our simulation. We illustrate our methodology via an application to several different binary data sets.     

A note on new confidence intervals for the difference between two proportions based on an Edgeworth expansion

Zhou and Qin [2004. New intervals for the difference between two independent binomial proportions. J. Statist. Plann. Inference 123, 97–115; 2005. A new confidence interval for the difference between two binomial proportions of paired data. J. Statist. Plann. Inference 128, 527–542] “new confidence intervals” for the difference between two treatment proportions exhibit a severe lack of invariance property that is a compelling reason not to use them.     

Testing homogeneity of difference of two proportions for stratified correlated paired binary data

In ophthalmologic or otolaryngologic study, each subject may contribute paired organs measurements to the analysis. A number of statistical methods have been proposed on bilateral correlated data. In practice, it is important to detect confounding effect by treatment interaction, since ignoring confounding effect may lead to unreliable conclusion. Therefore, stratified data analysis can be considered to adjust the effect of confounder on statistical inference. In this article, we investigate and derive three test procedures for testing homogeneity of difference of two proportions for stratified correlated paired binary data in the basis of equal correlation model assumption. The performance of proposed test procedures is examined through Monte Carlo simulation. The simulation results show that the Score test is usually robust on type I error control with high power, and therefore is recommended among the three methods. One example from otolaryngologic study is given to illustrate the three test procedures.     

On confidence limits for the difference of two binomial parameters

In the present article we suggest two new methods for calculating approximate confidence limits for the differences of the two binomial parameters. Different methods for determining the confidence interval are compared.     

Approximate confidence intervals for a linear combination of binomial proportions: A new variant

We propose a new adjustment for constructing an improved version of the Wald interval for linear combinations of binomial proportions, which addresses the presence of extremal samples. A comparative simulation study was carried out to investigate the performance of this new variant with respect to the exact coverage probability, expected interval length, and mesial and distal noncoverage probabilities. Additionally, we discuss the application of a criterion for interpreting interval location in the case of small samples and/or in situations in which extremal observations exist. The confidence intervals obtained from the new variant performed better for some evaluation measures.     

A generalized score confidence interval for a binomial proportion

Constructing a confidence interval for a binomial proportion is one of the most basic problems in statistics. The score interval as well as the Wilson interval with some modified forms have been broadly investigated and suggested by many statisticians. In this paper, a generalized score interval CI_G(a) is proposed by replacing the coefficient 1/4 in the score interval with parameter a. Based on analyzing and comparing various confidence intervals, we recommend the generalized score interval CI_G(0.3) for the nominal confidence levels 0.90, 0.95 and 0.99, which improves the spike phenomenon of the score interval and behaves better and computes more easily than most of other approximate intervals such as the Agresti-Coull interval and the Jeffreys interval to estimate a binomial proportion.     

A note on effective sample size for constructing confidence intervals for the difference of two proportions

Proportion differences are often used to estimate and test treatment effects in clinical trials with binary outcomes. In order to adjust for other covariates or intra-subject correlation among repeated measures, logistic regression or longitudinal data analysis models such as generalized estimating equation or generalized linear mixed models may be used for the analyses. However, these analysis models are often based on the logit link which results in parameter estimates and comparisons in the log-odds ratio scale rather than in the proportion difference scale. A two-step method is proposed in the literature to approximate the calculation of confidence intervals for the proportion difference using a concept of effective sample sizes. However, the performance of this two-step method has not been investigated in their paper. On this note, we examine the properties of the two-step method and propose an adjustment to the effective sample size formula based on Bayesian information theory. Simulations are conducted to evaluate the performance and to show that the modified effective sample size improves the coverage property of the confidence intervals.     

New large-sample confidence intervals for a linear combination of binomial proportions

In this paper, we consider the problem wherein one desires to estimate a linear combination of binomial probabilities from k>2$k>2$ independent populations. In particular, we create a new family of asymptotic confidence intervals, extending the approach taken by Beal [1987. Asymptotic confidence intervals for the difference between two binomial parameters for use with small samples. Biometrics 73, 941–950] in the two-sample case. One of our new intervals is shown to perform very well when compared to the best available intervals documented in Price and Bonett [2004. An improved confidence interval for a linear function of binomial proportions. Comput. Statist. Data Anal. 45, 449–456]. Furthermore, our interval estimation approach is quite general and could be extended to handle more complicated parametric functions and even to other discrete probability models in stratified settings. We illustrate our new intervals using two real data examples, one from an ecology study and one from a multicenter clinical trial.     

Bayesian estimation of the difference between two proportions

This paper is concerned with the problem of allocating a fixed number of trials between two independent binomial populations with unknown success probabilities θ₁ and θ₂, in order to estimate θ₁ - θ₂ with squared error loss. Introducing independent beta priors on θ₁ and θ₂, a heuristic allocation procedure is introduced and compared both with the optimal and with the best fixed allocation procedure. Numerical and asymptotic results of these comparisons are given and seem to indicate that there are situations when the best fixed allocation procedure performs almost as well as the optimal procedure.     

One-way analysis of proportions for misclassified binomial data

We consider data with a nominal grouping variable and a binary response variable. The grouping variable is measured without error, but the response variable is measured using a fallible device subject to misclassification. To achieve model identifiability, we use the double-sampling scheme which requires obtaining a subsample of the original data or another independent sample. This sample is then classified by both the fallible device and another infallible device regarding the response variable. We propose two Wald tests for testing the association between the two variables and illustrate the test using traffic data. The Type-I error rate and power of the tests are examined using simulations and a modified Wald test is recommended.     

Sequential risk-efficient estimation for the ratio of two binomial proportions

A risk-efficient sequential point estimator is considered for the ratio of two independent binomial proportions based on maximum likelihood estimation under squared error loss and cost proportional to the observations. It is assumed that the cost per observation is constant. First-order asymptotic expansions are obtained for large-sample properties of the proposed procedure. Performance of the procedure is studied through the criteria of risk efficiency and regret analysis. Monte Carlo simulation is carried out to obtain the expected sample size that minimizes the risk and to examine its finite sample behavior. An example is provided to illustrate its use.     

Simultaneous confidence interval construction for many-to-one comparisons of proportion differences based on correlated paired data

In some medical researches such as ophthalmological, orthopaedic and otolaryngologic studies, it is often of interest to compare multiple groups with a control using data collected from paired organs of patients. The major difficulty in performing the data analysis is to adjust the multiplicity between the comparison of multiple groups, and the correlation within the same patient''s paired organs. In this article, we construct asymptotic simultaneous confidence intervals (SCIs) for many-to-one comparisons of proportion differences adjusting for multiplicity and the correlation. The coverage probabilities and widths of the proposed CIs are evaluated by Monte Carlo simulation studies. The methods are illustrated by a real data example.     

A Bayesian non‐inferiority test for two independent binomial proportions

In drug development, non‐inferiority tests are often employed to determine the difference between two independent binomial proportions. Many test statistics for non‐inferiority are based on the frequentist framework. However, research on non‐inferiority in the Bayesian framework is limited. In this paper, we suggest a new Bayesian index τ = P(π₁ > π₂ ? Δ₀ | X₁,X₂), where X₁ and X₂ denote binomial random variables for trials n₁ and n₂, and parameters π₁ and π₂, respectively, and the non‐inferiority margin is Δ₀ > 0. We show two calculation methods for τ, an approximate method that uses normal approximation and an exact method that uses an exact posterior PDF. We compare the approximate probability with the exact probability for τ. Finally, we present the results of actual clinical trials to show the utility of index τ. Copyright © 2013 John Wiley & Sons, Ltd.     

Evaluation of alternative confidence intervals to address non-inferiority through the stratified difference between proportions

The confidence interval (CI) for the difference between two proportions has been an important and active research topic, especially in the context of non-inferiority hypothesis testing. Issues concerning the Type 1 error rate, power, coverage rate and aberrations have been extensively studied for non-stratified cases. However, stratified confidence intervals are frequently used in non-inferiority trials and similar settings. In this paper, several methods for stratified confidence intervals for the difference between two proportions, including existing methods and novel extensions from unstratified CIs, are evaluated across different scenarios. When sparsity across the strata is not a concern, adding imputed observations to the stratification analysis can strengthen Type-1 error control without substantial loss of power. When sparseness of data is a concern, most of the evaluated methods fail to control Type-1 error; the modified stratified t-test CI is an exception. We recommend the modified stratified t-test CI as the most useful and flexible method across the respective scenarios; the modified stratified Wald CI may be useful in settings where sparsity is unlikely. These findings substantially contribute to the application of stratified CIs for non-inferiority testing of differences between two proportions.     

Confidence interval estimation of the difference between paired AUCs based on combined biomarkers

In many diagnostic studies, multiple diagnostic tests are performed on each subject or multiple disease markers are available. Commonly, the information should be combined to improve the diagnostic accuracy. We consider the problem of comparing the discriminatory abilities between two groups of biomarkers. Specifically, this article focuses on confidence interval estimation of the difference between paired AUCs based on optimally combined markers under the assumption of multivariate normality. Simulation studies demonstrate that the proposed generalized variable approach provides confidence intervals with satisfying coverage probabilities at finite sample sizes. The proposed method can also easily provide P-values for hypothesis testing. Application to analysis of a subset of data from a study on coronary heart disease illustrates the utility of the method in practice.     

Confidence regions for two proportions from independent negative binomial distributions

The negative binomial distribution offers an alternative view to the binomial distribution for modeling count data. This alternative view is particularly useful when the probability of success is very small, because, unlike the fixed sampling scheme of the binomial distribution, the inverse sampling approach allows one to collect enough data in order to adequately estimate the proportion of success. However, despite work that has been done on the joint estimation of two binomial proportions from independent samples, there is little, if any, similar work for negative binomial proportions. In this paper, we construct and investigate three confidence regions for two negative binomial proportions based on three statistics: the Wald (W), score (S) and likelihood ratio (LR) statistics. For large-to-moderate sample sizes, this paper finds that all three regions have good coverage properties, with comparable average areas for large sample sizes but with the S method producing the smaller regions for moderate sample sizes. In the small sample case, the LR method has good coverage properties, but often at the expense of comparatively larger areas. Finally, we apply these three regions to some real data for the joint estimation of liver damage rates in patients taking one of two drugs.     

Confidence intervals for the difference between independent binomial proportions: comparison using a graphical approach and moving averages

This paper uses graphical methods to illustrate and compare the coverage properties of a number of methods for calculating confidence intervals for the difference between two independent binomial proportions. We investigate both small‐sample and large‐sample properties of both two‐sided and one‐sided coverage, with an emphasis on asymptotic methods. In terms of aligning the smoothed coverage probability surface with the nominal confidence level, we find that the score‐based methods on the whole have the best two‐sided coverage, although they have slight deficiencies for confidence levels of 90% or lower. For an easily taught, hand‐calculated method, the Brown‐Li ‘Jeffreys’ method appears to perform reasonably well, and in most situations, it has better one‐sided coverage than the widely recommended alternatives. In general, we find that the one‐sided properties of many of the available methods are surprisingly poor. In fact, almost none of the existing asymptotic methods achieve equal coverage on both sides of the interval, even with large sample sizes, and consequently if used as a non‐inferiority test, the type I error rate (which is equal to the one‐sided non‐coverage probability) can be inflated. The only exception is the Gart‐Nam ‘skewness‐corrected’ method, which we express using modified notation in order to include a bias correction for improved small‐sample performance, and an optional continuity correction for those seeking more conservative coverage. Using a weighted average of two complementary methods, we also define a new hybrid method that almost matches the performance of the Gart‐Nam interval. Copyright © 2014 John Wiley & Sons, Ltd.