Biomedical subjects

A C Tamhane

Publications and source records attributed to A C Tamhane.

10 recordsLinked to original sources

PubMed1998

Some new multiple-test procedures for dose finding.

In Tamhane, Hochberg, and Dunnett (1) we focused primarily on step-down test procedures based on contrasts among the sample means to find the minimum effective dose in a dose-response study. In the present article we use the global tests of Bartholomew (2,3) and Hayter (4) in these step-down procedures. We also propose a new step-down procedure that permits tests based on a class of contrasts [step and basin contrasts of Ruberg (5) are examples of such contrasts] that could not be used with the step-down procedures studied in our previous paper because of lack of control of the familywise error rate. A simulation study to compare the four procedures proposed in the present paper with the top four procedures from the previous article is carried out. It is found that the step-down procedure based on Bartholomew's test and the new step-down procedure based on step and modified basin contrasts generally perform better than the other procedures for a wide range of dose-response profiles.

Algorithms↗

PubMed1997

Multiple testing to establish superiority/equivalence of a new treatment compared with kappa standard treatments.

In this paper we develop multiple hypotheses testing procedures to compare a new treatment with a set of standard treatments in a clinical trial. The aim is to classify the new treatment with respect to each of the standards, by specifying those to which the new treatment is superior, those to which the new treatment is equivalent and those to which one can establish neither superiority nor equivalence. We propose several stepwise procedures and compare them with respect to their familywise error rates and power. The step-down methods SD1 and SD2 test for superiority first, followed by tests for equivalence for those comparisons where we cannot establish superiority. The step-up methods SU1 and SU2 test for equivalence first, followed by tests for superiority for those comparisons where we can establish at least equivalence. The methods SD3 and SU3 apply the tests for superiority and equivalence in pairs. All the methods require that we specify a threshold value delta > 0 in advance for defining equivalence. In applications where it is not possible to specify a value delta, we can use the method SD1 by testing for superiority first, followed by one-sided confidence limits on the efficacy differences for those comparisons where we cannot establish superiority.

Clinical Trials as Topic↗

PubMed1996

Multiple test procedures for dose finding.

The problem of identifying the lowest dose level for which the mean response differs from that at the zero dose level is considered. A general framework for stepwise testing procedures that use contrasts among the dose level means is proposed. Using this framework, several new procedures are derived. These and some existing procedures, including that of Williams (1971, Biometrics 27, 103-117; 1972, Biometrics 28, 519-531), are compared analytically and by an extensive simulation study for the normal theory balanced one-way layout case. It is pointed out that the procedures based on the so-called step and basin contrasts proposed by Ruberg (1989, Journal of American Statistical Association 84, 816-822) have excessively high type I familywise error rates (FWEs) and, hence, they should not be used. Some findings of the simulation study are as follows: For monotone dose mean configurations, Williams' procedure and two step-down test procedures based on Helmert and linear contrasts offer the best performance. For nonmonotone dose mean configurations, the performance of Williams' procedure does degrade somewhat, but the other two procedures are still the best. For more complex designs, a simple step-down test procedure that uses any alpha-level tests (not necessarily t-tests) to compare each dose level with the zero dose level controls the FWE and is the only alternative available, but its power is rather low, especially under nonmonotone configurations. Step-up procedures are generally dominated by step-down procedures when the same contrasts are used although the differences are not great.

Animals↗

PubMed1995

Step-up multiple testing of parameters with unequally correlated estimates.

We consider the problem of simultaneously testing k > or = to 2 hypotheses on parameters theta(1), ..., theta(k) using test statistics t(1), ..., t(k) such that a specified familywise error rate alpha is achieved. Dunnett and Tamhane (1992a) proposed a step-up multiple test procedure, in which testing starts with the hypothesis corresponding to the least significant test statistic and proceeds towards the most significant, stopping the first time a significant test result is obtained (and rejecting the hypotheses corresponding to that and any remaining test statistics). The parameter estimates used in the t statistics were assumed to be normally distributed with a common variance, which was a known multiple of an unknown sigma(2), and known correlations which were equal. In the present article, we show how the procedure can be extended to include unequally correlated parameter estimates. Unequal correlations occur, for example, in experiments involving comparisons among treatment groups with unequal sample sizes. We also compare the step-up and step-down multiple testing approaches and discuss applications to some biopharmaceutical testing problems.

Animals↗

PubMed1994

A model-based approach to estimate the AIDS-free time distribution in homosexual men using longitudinal data.

A model-based approach is developed to estimate the distribution of time from seroconversion to diagnosis with acquired immunodeficiency syndrome (AIDS) as a function of selected time-dependent covariates. The approach is applied to longitudinal data collected over 4 years of follow-up from 450 men seropositive for the human immunodeficiency virus (90 AIDS cases) and 62 seroconverters (nine AIDS cases) participating in the Chicago part of the Multicenter AIDS Cohort Study. Because of the periodic nature of monitoring, the seroconversion time is interval-censored for seroconverters and left-censored for seroprevalent cohort members; the end-point is right-censored for 413 individuals. Since serological monitoring is not continuous but only at regularly scheduled visit times, a model for the discrete hazard rate (DHR) is proposed that is a generalized linear model that relates the DHR to the covariate history through the complementary log-log link. Classification trees are used for preliminary screening of covariates to identify predictors of AIDS that should be incorporated into the DHR model. The missing seroconversion times for all men are imputed 100 times to obtain 100 completed datasets from which the parameters of the DHR are then estimated using the maximum-likelihood method. The final DHR model includes the following infection progression (marker) variables: CD4%, hemoglobin, p24 antigen, and CD4% x p24 antigen interaction. Using this DHR model, the discrete survival distribution of AIDS-free time is estimated for the given population. The jackknife procedure is used to assess the precision of the estimated survival distribution.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Exact repeated confidence intervals for Bernoulli parameters in a group sequential clinical trial.

This paper presents methods for constructing exact repeated confidence intervals (RCIs) for the success probability, p, of a single Bernoulli treatment and for the difference of success probabilities, delta = p1-p2, of two independent Bernoulli treatments in the context of a group sequential clinical trial. These RCIs calculated at each interim analysis are useful for evaluating the data in light of all the information available rather than relying on rigid stopping criteria used by repeated significance tests. Extensions to construction of RCIs for the relative risk p = p1/p2 and odds ratio psi = p1(1-p2)/p2(1-p1) are indicated.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Comparisons between a new drug and active and placebo controls in an efficacy clinical trial.

D'Agostino and Heeren (DH) discussed the multiple comparison issues that arise in evaluating both sensitivity and efficacy in over-the-counter drug trials. We propose a general definition of sensitivity that includes DH's definition as a special case. We also propose a test for sensitivity that coincides with the MIN test of Laska and Meisner at one extreme but has the advantage of identifying specific drugs satisfying the sensitivity criterion when some fail to do so. We suggest that the test of Dunnett as well as an extension of it may be useful for the efficacy comparisons.

Analysis of Variance↗

PubMed1991

Step-down multiple tests for comparing treatments with a control in unbalanced one-way layouts.

We show how a well-known multiple step-down significance testing procedure for comparing treatments with a control in balanced one-way layouts can be applied in unbalanced layouts (unequal sample sizes for the treatments). The method we describe has the advantage that it provides p-values, for each treatment versus control comparison, that take account of the multiple step-down testing nature of the procedure. These joint p-values can be used with any value of alpha, the fixed type I family wise error rate bound, that may be specified by the investigator. To determine the p-values, it is necessary to compute a multivariate Student t integral, for which a computer program is available. This procedure is more powerful than the step-down Bonferroni procedure of Holm and the single-step procedure of Dunnett. An example from the pharmaceutical literature is used to illustrate the procedure.

Animals↗

PubMed1991

Comparison of the hamster sperm motility assay to the mouse one-cell and two-cell embryo bioassays as quality control tests for in vitro fertilization.

The hamster sperm motility assay, mouse one-cell embryo, and mouse two-cell embryo bioassays were used to test modified Tyrode's solution and modified Ham's F-10 (Gibco, Grand Island, NY) medium prepared in tap water versus ultrapure water. Factors influencing the ability of each assay to discriminate water quality were evaluated to characterize these assays for quality control use in the in vitro fertilization laboratory. The hamster sperm motility assay reproducibly detected differences in treatment without significant interanimal, interanalyst, or interassay variation. Interanalyst and interanimal variation significantly affected the ability to detect treatment differences using the mouse bioassays. Sample sizes needed to predict clinically significant treatment effects were calculated using varying assay conditions. Ham's F-10 medium can be tested with the hamster sperm motility assay.

Analysis of Variance↗

PubMed1991

Clinical assessment of venous thromboembolic risk in surgical patients.

Prophylaxis against postoperative venous thromboembolism should be tailored according to the patient's level of risk. However, risk assessment is not yet in widespread use in surgical practice. In this study, 538 general surgical patients were prospectively assessed based on a scoring system containing 20 risk factors. Depending on the total risk factor score, the patients were grouped into low (0 to 1, 34.5%), moderate (2 to 4, 48.5%), or high risk (more than 4, 17.2%) categories. Statistically significant (p less than 0.0001) correlation was found between our results and those of three existing risk assessment systems. Overall, of the 538 patients, 37.2% received prophylaxis; 10%, 42.1%, and 76% received prophylaxis in the low-, moderate-, and high-risk categories, respectively. Mechanical prophylactic modalities (graduated elastic compression and sequential intermittent compression) were preferred over pharmacologic modalities. These results suggest that implementation of prophylaxis remains underutilized despite published reports, including NIH guidelines. Our results indicate that the majority of surgical patients seen in this suburban hospital have two or more risk factors for developing venous thromboembolism.

Adult↗