Rebecca A Betensky
Rebecca Betensky
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Chair of the Department of Biostatistics
Professor of Biostatistics
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Professional overview
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Prior to NYU, Dr. Betensky was Professor of Biostatistics at the Harvard T.H. Chan School of Public Health. She was director of the Harvard Catalyst (Clinical and Translational Science Award) Biostatistics Program; director of the Data and Statistics Core for the Massachusetts Alzheimer’s Disease Research Center; and director of the Biostatistics Neurology Core at Massachusetts General Hospital. Previously, she was the Biostatistics Program Leader for the Dana-Farber/Harvard Cancer Center.
Dr. Betensky’s research focuses on methods for the analysis of censored and truncated outcomes and covariates, which frequently arise from the subsampling of cohort studies. She has a long-time interest in clinical trials, and has written on the evaluation of biomarkers and the use and interpretation of p-values. She has collaborated extensively in studies in neurologic diseases, and serves as statistical editor for Annals of Neurology.
Dr. Betensky was awarded, and directed for 15 years, an NIH T32 training program in neurostatistics and neuroepidemiology for pre- and post-doctoral students in biostatistics and epidemiology and for clinician-scientists. She previously directed Harvard’s Biostatistics programs to promote and support diversity at all levels in the field of quantitative public health. She was also a member of the BMRD Study Section for review of NIH statistical methodology grants; on committees for the Institute of Medicine; and a co-chair of the technical advisory committee for the scientific registry of transplant recipients.
Dr. Betensky an elected Fellow of the American Statistical Association and of the International Statistical Institute, and is a past recipient of the Spiegelman Award from the American Public Health Association. She currently serves as a member of the Board of Scientific Counselors for Clinical Science and Epidemiology at the National Cancer Institute.
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Education
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AB, Mathematics, Harvard University, Cambridge, MAPhD, Statistics, Stanford University, Stanford, CA
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Areas of research and study
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BiologyBiostatisticsNeuroepidemiologyNeurologyNeurostatisticsTranslational science
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Publications
Publications
A computationally simple test of homogeneity of odds ratios for twin data
AbstractBetensky, R., Hudson, J. I., Jones, C. A., Hu, F., Wang, B., Chen, C., & Xu, X. (n.d.).Publication year
2001Journal title
Genetic EpidemiologyVolume
20Issue
2Page(s)
228-238AbstractIt is of interest to compare measures of association of binary traits among samples of bivariate data. One example is the comparison of association within a sample of monozygotic (MZ) twins to that within a sample of dizygotic (DZ) twins. A larger association in the MZ twins suggests that the trait of interest may have a genetic component. The Bivariate data in this example are binary traits for the twins in each pair. Another example is the comparison of a measure of Hardy-Weinberg disequilibrium across several populations. The bivariate data in this example are the two alleles comprising the genotype of interest. We propose using derived logistic regression equations from the full exponential model for the bivariate outcomes to test for homogeneity. We adjust for correlation among outcomes via generalized estimating equations. This modeling approach allows for adjustment for individual-level and pair-level covariates and thereby allows for testing for gene x environment interactions. Further, we extend the model to allow for simultaneous analysis of two diseases, which allows for testing for a genetic component to the coaggregation of two diseases. In contrast to approaches proposed by previous authors, no special software is required; our approach can be easily implemented in standard software packages. We compare our results to those of other methods proposed in the literature for data from the Vietnam Era Twin Study. We apply our methods also to the Anqing Twin Study and data on major depression and generalized anxiety disorder from the Virginia Twin Register.Computationally simple accelerated failure time regression for interval censored data
AbstractBetensky, R., Rabinowitz, D., & Tsiatis, A. A. (n.d.).Publication year
2001Journal title
BiometrikaVolume
88Issue
3Page(s)
703-711AbstractAn approach is presented for fitting the accelerated failure time model to interval censored data that does not involve computing the nonparametric maximum likelihood estimate of the distribution function at the residuals. The approach involves estimating equations computed with the examination times from the same individual treated as if they had actually been obtained from different individuals. The dependence between different measurements obtained from the same individual is then accounted for in the calculation of the standard error of the regression coefficients. The approach is applicable to interval censored data in settings in which examinations continue to occur regardless of whether the failure time has occurred. Simulations are presented to assess the behaviour of the approach, and the methodology is illustrated through an application to data from an AIDS clinical trial.Local likelihood analysis of survival data with censored intermediate events
AbstractBebchuk, J. D., & Betensky, R. (n.d.).Publication year
2001Journal title
Journal of the American Statistical AssociationVolume
96Issue
454Page(s)
449-457AbstractAIDS Clinical Trials Group protocol 193A was a randomized trial designed to compare survival and progression-free survival among patients on different treatment regimens. A complicating feature of the analysis of progression-free survival is that different censoring mechanisms operated on progression and survival, which resulted in more complete information on survival. A simple analysis that uses the minimum of the times to progression and survival and the minimum of the corresponding censoring times may sacrifice the extra information available on survival. To address this problem, we have developed a method that exploits the bivariate nature of these data and thereby uses all of the available information. We obtain smooth, nonparametric estimates of the hazard functions for a terminal event, before and after the occurrence of an intermediate event. These hazards can be used to estimate the distribution of progression-free survival. Our method uses local likelihood estimation, which assumes that the underlying true hazard functions can be approximated locally by polynomials. We use an iterative imputation algorithm to perform the estimation when the intermediate events are right censored.Molecular subtypes of anaplastic oligodendroglioma : Implications for patient management at diagnosis
AbstractIno, Y., Betensky, R., Zlatescu, M. C., Sasaki, H., Macdonald, D. R., Stemmer-Rachamimov, A. O., Ramsay, D. A., Cairncross, J. G., & Louis, D. N. (n.d.).Publication year
2001Journal title
Clinical Cancer ResearchVolume
7Issue
4Page(s)
839-845AbstractPurpose: In a prior study of anaplastic oligodendrogliomas treated with chemotherapy at diagnosis or at recurrence after radiotherapy, allelic loss of chromosome 1p correlated with better chemotherapeutic response and overall survival. However, in this group of patients in whom therapeutic management was not uniform, loss of 1p did not identify all chemosensitive tumors, nor did all patients whose tumors harbor a 1p loss have long survival. Experimental Design: To clarify the clinical relevance of molecular genetic testing at the time of diagnosis for patients with anaplastic oligodendrogliomas, we studied a larger, more homogeneous group of 50 patients with histologically defined anaplastic oligodendrogliomas treated with a chemotherapeutic regimen as the principal initial therapy. Results: We demonstrate that these tumors can be divided genetically into four therapeutically and prognostically relevant subgroups. Patients whose tumors have combined but isolated losses of 1p and 19q have marked and durable responses to chemotherapy associated with long survival, with or without postoperative radiation therapy. Other tumors with chromosome 1p alterations also respond to chemotherapy, but with shorter duration of response and patient survival. Tumors lacking 1p loss can also be divided into two subgroups: those with TP53 mutations, which may also respond to chemotherapy but recur quickly, and those without TP53 mutations, which are poorly responsive, aggressive tumors that are clinically and genotypically similar to glioblastomas. Conclusions: These data raise the possibility, for the first time, that therapeutic decisions at the time of diagnosis might be tailored to particular genetic subtypes of anaplastic oligodendroglioma.Multivariate logistic regression for familial aggregation of two disorders. I. Development of models and methods
AbstractHudson, J. I., Laird, N. M., & Betensky, R. (n.d.).Publication year
2001Journal title
American Journal of EpidemiologyVolume
153Issue
5Page(s)
500-505AbstractThe question of whether two disorders cluster together, or coaggregate, within families often arises. This paper considers how to analyze familial aggregation of two disorders and presents two multivariate logistic regression methods that model both disorder outcomes simultaneously. The first, a proband predictive model, predicts a relative's outcomes (the presence or absence of each of the two disorders) by using the proband's disorder status. The second, a family predictive model derived from the quadratic exponential model, predicts a family member's outcomes by using all of the remaining family members' disorder statuses. The models are more realistic, flexible, and powerful than univariate models. Methods for estimation and testing account for the correlation of outcomes among family members and can be implemented by using commercial software.Multivariate logistic regression for familial aggregation of two disorders. II. Analysis of studies of eating and mood disorders
AbstractHudson, J. I., Laird, N. M., Betensky, R., Keck, P. E., & Pope, H. G. (n.d.).Publication year
2001Journal title
American Journal of EpidemiologyVolume
153Issue
5Page(s)
506-514AbstractFamily studies have suggested that eating disorders and mood disorders may coaggregate within families. Previous studies, however, have been limited by use of univariate modeling techniques and failure to account for the correlation of observations within families. To provide a more efficient analysis and to illustrate multivariate logistic regression models for familial aggregation of two disorders, the authors analyzed pooled data from two previously published family studies (conducted in Massachusetts in 1984-1986 and 1986-1987) by using multivariate proband predictive and family predictive models. Both models demonstrated a significant familial aggregation of mood disorders and familial coaggregation of eating and mood disorders. The magnitude of the coaggregation between eating and mood disorders was similar to that of the aggregation of mood disorders. Similar results were obtained with alternative models, including a traditional univariate proband predictive model. In comparison with the univariate model, the multivariate models provided greater flexibility, improved precision, and wider generality for interpreting aggregation effects.Nonparametric estimation in a cure model with random cure times
AbstractBetensky, R., & Schoenfeld, D. A. (n.d.).Publication year
2001Journal title
BiometricsVolume
57Issue
1Page(s)
282-286AbstractAcute respiratory distress syndrome (ARDS) is a life-threatening acute condition that sometimes follows pneumonia or surgery. Patients who recover and leave the hospital are considered to have been cured at the time they leave the hospital. These data differ from typical data in which cure is a possibility: death times are not observed for patients who are cured and cure times are observed and vary among patients. Here we apply a competing risks model to these data and show it to be equivalent to a mixture model, the more common approach for cure data. Further, we derive an estimator for the variance of the cumulative incidence function from the competing risks model, and thus for the cure rate, based on elementary calculations. We compare our variance estimator to Gray's (1988, Annals of Statistics 16, 1140-1154) estimator, which is based on counting process theory. We find our estimator to be slightly more accurate in small samples. We apply these results to data from an ARDS clinical trial.Optimally selected chi square statistics for equivalence testing
AbstractBetensky, R. (n.d.).Publication year
2001Journal title
Journal of Statistical Planning and InferenceVolume
93Issue
1-2Page(s)
247-257AbstractIn some experiments, the aim is to establish equivalence between treatment groups, rather than to establish greater efficacy of one group over another. Examples are drug bioavailability studies, in which it is desired to exhibit bioequivalence between a new formulation of a drug and the standard formulation, and studies of experimental conditions for biological assays, in which it is desired to exhibit equivalent assay response between fresh and non-fresh specimens. In many cases, the outcome measure is continuous, but the investigator prefers to dichotomize it on the basis of a threshold. If the threshold is selected to make the test statistic most favorable for equivalence, standard chi square percentile points are incorrect. Here, we derive asymptotically correct percentile points and significance levels for two approaches to equivalence testing.PTEN is a target of chromosome 10q loss in anaplastic oligodendrogliomas and PTEN alterations are associated with poor prognosis
AbstractSasaki, H., Zlatescu, M. C., Betensky, R., Ino, Y., Cairncross, J. G., & Louis, D. N. (n.d.).Publication year
2001Journal title
American Journal of PathologyVolume
159Issue
1Page(s)
359-367AbstractAllelic loss of 10q is a common genetic event in malignant gliomas, with three 10q tumor suppressor genes, ERCC6, PTEN, and DMBT1, putatively implicated in the most common type of malignant glioma, glioblastoma. Anaplastic oligodendroglioma, another type of malignant glioma, provides a unique opportunity to study the relevance of particular genetic alterations to chemosensitivity and survival. We therefore analyzed these three genes in 72 anaplastic oligodendrogliomas. Deletion mapping demonstrated 10q loss in 14 of 67 informative cases, with the PTEN and DMBT1 regions involved in all deletions but with the ERCC6 locus spared in two cases. Seven tumors had PTEN gene alterations; two had homozygous DMBT1 deletions, but at least one reflected unmasking of a germline DMBT1 deletion. No mutations were found in ERCC6 exon 2. Chemotherapeutic response occurred in two of the seven tumors with PTEN alterations, but with unexpected short survival times. PTEN gene alterations were not associated with poor therapeutic response in multivariate analysis, but were independently predictive of poor prognosis even after multivariate adjustment for both 10q and 1p loss. In anaplastic oligodendroglioma, therefore, PTEN is a target of 10q loss, and PTEN alterations are associated with poor prognosis, even in chemosensitive cases.Tumor location and growth pattern correlate with genetic signature in oligodendroglial neoplasms
AbstractZlatescu, M. C., TehraniYazdi, A. R., Sasaki, H., Megyesi, J. F., Betensky, R., Louis, D. N., & Cairncross, J. G. (n.d.).Publication year
2001Journal title
Cancer ResearchVolume
61Issue
18Page(s)
6713-6715AbstractMolecular genetic subsets of anaplastic oligodendroglioma behave in biologically distinct ways, in both their rates of growth and their responses to standard therapies. In a series of 64 cases, we evaluated whether allelic loss of chromosomal arms 1p and 19q, an early molecular event in the genesis of chemosensitive oligodendrogliomas, is related to tumor location and extent of tumor spread in the brain. We observed that tumor genotype was closely associated with tumor location (P < 0.001). Anaplastic oligodendrogliomas located in the frontal, parietal, and occipital lobes were significantly more likely to harbor allelic loss of chromosomal arms 1p and 19q than histologically indistinguishable tumors arising in the temporal lobe, insula, and diencephalon (P < 0.001). In addition, loss of heterozygosity for 1p and 19q was significantly associated with a bilateral pattern of growth (P = 0.037); all seven bilaterally distributed anaplastic oligodendrogliomas had 1p and 19q allelic loss. We conclude, therefore, that molecular subtypes of oligodendrogliomas may arise preferentially in certain lobes of the brain and have differential patterns of growth, with tumors having allelic loss of chromosomes 1p and 19q occurring most frequently in the frontal lobes and having a tendency for widespread growth across the midline. These findings encourage inquiries into the biological basis of such marked differences and already have implications for the current management of these neoplasms.α-synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins
AbstractSharon, R., Goldberg, M. S., Bar-Josef, I., Betensky, R., Shen, J., & Selkoe, D. J. (n.d.).Publication year
2001Journal title
Proceedings of the National Academy of Sciences of the United States of AmericaVolume
98Issue
16Page(s)
9110-9115Abstractα-Synuclein (αS) is a 140-residue neuronal protein that forms insoluble cytoplasmic aggregates in Parkinson's disease (PD) and several other neurodegenerative disorders. Two missense mutations (A53T and A30P) are linked to rare forms of familial PD. The normal function of αS is unknown, and cultured cell systems that model its modification from soluble monomers to aggregated forms have not been reported. Through a systematic centrifugal fractionation of mesencephalic neuronal cell lines and transgenic mouse brains expressing wild-type or A53T human αS, we observed unusual, previously unrecognized species of αS that migrate well above the 17-kDa monomeric form in denaturing gels. Incubation at 65°C of high-speed cytosols from cells or brains revealed a modified αS species migrating at ≈36 kDa and an extensive higher molecular mass αS-reactive smear. Extraction of the cytosols with chloroform/methanol or with a resin (Lipidex 1000) that binds fatty acids resulted in a similar pattern of higher molecular mass αS forms. On the basis of this effect of delipidation, we reexamined the primary structure of αS and detected a motif at the N and C termini that is homologous to a fatty acid-binding protein signature. In accord, we found that purified human αS binds oleic acid, with an apparent Kd of 12.5 μM. We also observed an enhanced association of A53T αS with microsomal membranes in both mesencephalic cells and transgenic mouse brains. We conclude that αS has biochemical properties and a structural motif that suggest it is a novel member of the fatty acid-binding protein family and may thus transport fatty acids between the aqueous and membrane phospholipid compartments of the neuronal cytoplasm.Alternative derivations of a rule for early stopping in favor of H0
AbstractBetensky, R. (n.d.).Publication year
2000Journal title
American StatisticianVolume
54Issue
1Page(s)
35-39AbstractIt is often desirable to stop a large clinical trial before its planned end if a null result seems inevitable. This early stopping can save considerable resources. It is especially appealing when an experimental treatment is being compared to a standard treatment. Three procedures for early stopping, all with different interpretations and derivations, are described and shown to produce identical rules for normal data and certain parameters. In some cases, this is unexpected and informative. The procedures differ in which of their parameters are adjusted from the fixed sample values to maintain the desired Type I error in this setting of multiple looks at the data.Alternative derivations of a rule for early stopping in favor of HO
AbstractBetensky, R. (n.d.).Publication year
2000Journal title
American StatisticianVolume
54Issue
1Page(s)
35-39AbstractIt is often desirable to stop a large clinical trial before its planned end if a null result seems inevitable. This early stopping can save considerable resources. It is especially appealing when an experimental treatment is being compared to a standard treatment. Three procedures for early stopping, all with different interpretations and derivations, are described and shown to produce identical rules for normal data and certain parameters. In some cases, this is unexpected and informative. The procedures differ in which of their parameters are adjusted from the fixed sample values to maintain the desired Type I error in this setting of multiple looks at the data.Approximating the distribution of maximally selected McNemar's statistics
AbstractRabinowitz, D., & Betensky, R. (n.d.).Publication year
2000Journal title
BiometricsVolume
56Issue
3Page(s)
897-902AbstractIt is common in epidemiologic analyses to summarize continuous outcomes as falling above or below a threshold. With paired data and with a threshold chosen without reference to the outcomes, McNemar's test of marginal homogeneity may be applied to the resulting dichotomous pairs when testing for equality of the marginal distributions of the underlying continuous outcomes. If the threshold is chosen to maximize the test statistic, however, referring the resulting test statistic to the nominal χ2 distribution is incorrect; Instead, the p-value must be adjusted for the multiple comparisons. Here the distribution of a maximally selected McNemar's statistic is derived, and it is shown that an approximation due to Durbin (1985, Journal of Applied Probability 22, 99-122) may be used to estimate approximate p-values. The methodology is illustrated by an application to measurements of insulin-like growth factor-I (IGF-I)in matched prostate cancer cases and controls from the Physicians' Health Study. The results of Simulation experiments that assess the accuracy of the approximation in moderate sample sizes are reported.Multiple imputation for simple estimation of the hazard function based on interval censored data
AbstractBebchuk, J. D., & Betensky, R. (n.d.).Publication year
2000Journal title
Statistics in MedicineVolume
19Issue
3Page(s)
405-419AbstractA data augmentation algorithm is presented for estimating the hazard function and pointwise variability intervals based on interval censored data. The algorithm extends that proposed by Tanner and Wong for grouped right censored data to interval censored data. It applies multiple imputation and local likelihood methods to obtain smooth non-parametric estimates for the hazard function. This approach considerably simplifies the problem of estimation for interval censored data as it transforms it into the more tractable problem of estimation for right censored data. The method is illustrated for two real data sets: times to breast cosmesis deterioration and times to HIV-1 infection for individuals with haemophilia. Simulations are presented to assess the effects of various parameters on the estimates and their variances. Copyright (C) 2000 John Wiley and Sons, Ltd.On nonidentifiability and noninformative censoring for current status data
AbstractBetensky, R. (n.d.).Publication year
2000Journal title
BiometrikaVolume
87Issue
1Page(s)
218-221AbstractThe event times and examination times that produce current status data are typically assumed to be independent. Here, an increasing sequence of nested models is considered for current status data, namely independence models, 'constant sum' models and models for which the conditional probability of the occurrence of the event prior to the examination time, given the examination time, is nondecreasing in the examination time. In the class of constant sum models, the distribution of the event time is identifiable and the examination times are noninformative. In the class of models with nondecreasing conditional probability, the distribution of the event time is nonidentifiable. Outside this class, the examination times cannot be ignored.Redistribution algorithms for censored data
AbstractBetensky, R. (n.d.).Publication year
2000Journal title
Statistics and Probability LettersVolume
46Issue
4Page(s)
385-389AbstractEfron (Proceedings of the Fifth Berkeley Symposium, Vol. 4, University of California Press, Berkeley, CA, pp. 831-853) and Dinse (Amer. Statist. 39, 1985, 299-300) proposed redistribution of mass algorithms for survivor function estimation from right censored data. Dinse's algorithm is easily extended to survivor function estimation from interval censored data and is further extended to incorporate information on disease markers.Shipment impairs lymphocyte proliferative responses to microbial antigens
AbstractBetensky, R., Betensky, R. A., Connick, E., Devers, J., Landay, A. L., Nokta, M., Plaeger, S., Rosenblatt, H., Schmitz, J. L., Valentine, F., Wara, D., Weinberg, A., & Lederman, H. M. (n.d.).Publication year
2000Journal title
Clinical and Diagnostic Laboratory ImmunologyVolume
7Issue
5Page(s)
759-763AbstractLymphocyte proliferation assays (LPAs) are widely used to assess T-lymphocyte function of patients with human immunodeficiency virus infection and other primary and secondary immunodeficiency disorders. Since these assays require expertise not readily available at all clinical sites, specimens may be shipped to central labs for testing. We conducted a large multicenter study to evaluate the effects of shipping on assay performance and found significant loss of LPA activity. This may lead to erroneous results for individual subjects and introduce bias into multicenter trials.Simple approximations for the maximal transmission/disequilibrium test with a multi-allelic marker
AbstractBetensky, R., Betensky, R. A., & Rabinowitz, D. (n.d.).Publication year
2000Journal title
Annals of Human GeneticsVolume
64Issue
6Page(s)
567-574AbstractSpielman et al. (1993) popularized the transmission/disequilibrium test (TDT) to test for linkage between disease and marker loci that show a population association. Several authors have proposed extensions to the TDT for multi-allelic markers. Many of these approaches exhibit a 'swamping' effect in which a marker with a strong effect is not detected by a global test that includes many markers with no effect. To avoid this effect, Schaid (1996) proposed using the maximum of the bi-allelic TDT statistics computed for each allele versus all others combined. The maximal TDT statistic, however, no longer follows a chi-square distribution. Here, a refinement to Bonferroni's correction for multiple testing provided by Worsley (1982) based on maximal spanning trees is applied to calculate accurate upper bounds for the type I error and p-values for the maximal TDT. In addition, an accurate lower Bonferroni bound is applied to calculate power. This approach does not require any simulation-based analysis and is less conservative than the standard Bonferroni correction. The bounds are given for both the exact probability calculations and for those based on the normal approximation. The results are assessed through simulations.Two double-blinded, randomized, comparative trials of 4 Human Immunodeficiency Virus type 1 (HIV-1) envelope vaccines in HIV-1-infected individuals across a spectrum of disease severity : AIDS clinical trials groups 209 and 214
AbstractBetensky, R. (n.d.).Publication year
2000Journal title
Journal of Infectious DiseasesVolume
182Issue
5Page(s)
1357-1364AbstractThe potential role of human immunodeficiency virus type 1 (HIV-1)-specific immune responses in controlling viral replication in vivo has stimulated interest in enhancing virus-specific immunity by vaccinating infected individuals with HIV-1 or its components. These studies were undertaken to define patient populations most likely to respond to vaccination, with the induction of novel HIV-1-specific cellular immune responses, and to compare the safety and immunogenicity of several candidate recombinant HIV-1 envelope vaccines and adjuvants. New lymphoproliferative responses (LPRs) developed in 350 cells/mm3 and were usually strain restricted. Responders tended to be more likely than nonresponders to have an undetectable level of HIV-1 RNA at baseline (P =.067). Induction of new cellular immune responses by HIV-1 envelope vaccines is a function of the immunologic stage of disease and baseline plasma HIV-1 RNA level and exhibits considerable vaccine strain specificity.Using conditional logistic regression to fit proportional odds models to interval censored data
AbstractRabinowitz, D., Betensky, R., & Tsiatis, A. A. (n.d.).Publication year
2000Journal title
BiometricsVolume
56Issue
2Page(s)
511-518AbstractAn easily implemented approach to fitting the proportional odds regression model to interval-censored data is presented. The approach is based on using conditional logistic regression routines in standard statistical packages. Using conditional logistic regression allows the practitioner to sidestep complications that attend estimation of the baseline odds ratio function. The approach is applicable both for interval-censored data in settings in which examinations continue regardless of whether the event of interest has occurred and for current status data. The methodology is illustrated through an application to data from an AIDS study of the effect of treatment with ZDV+ddC versus ZDV alone on 50% drop in CD4 cell count from baseline level. Simulations are presented to assess the accuracy of the procedure.A non-parametric maximum likelihood estimator for bivariate interval censored data
AbstractBetensky, R., & Finkelstein, D. M. (n.d.).Publication year
1999Journal title
Statistics in MedicineVolume
18Issue
22Page(s)
3089-3100AbstractWe derive a non-parametric maximum likelihood estimator for bivariate interval censored data using standard techniques for constrained convex optimization. Our approach extends those taken for univariate interval censored data. We illustrate the estimator with bivariate data from an AIDS study.An extension of Kendall's coefficient of concordance to bivariate interval censored data
AbstractBetensky, R., & Finkelstein, D. M. (n.d.).Publication year
1999Journal title
Statistics in MedicineVolume
18Issue
22Page(s)
3101-3109AbstractNon-parametric tests of independence, as well as accompanying measures of association, are essential tools for the analysis of bivariate data. Such tests and measures have been developed for uncensored and right censored failure time data, but have not been developed for interval censored failure time data. Bivariate interval censored data arise in AIDS studies in which screening tests for early signs of viral and bacterial infection are done at clinic visits. Because of missed clinic visits, the actual times of first positive screening tests are interval censored. To handle such data, we propose an extension of Kendall's coefficient of concordance. We apply it to data from an AIDS study that recorded times of shedding of cytomegalovirus (CMV) and times of colonization of mycobacterium avium complex (MAC). We examine the performance of our proposed measure through a simulation study.Clinical trials using HIV-1 RNA-based primary endpoints : Statistical analysis and potential biases
AbstractMarschner, I. C., Betensky, R., DeGruttola, V., Hammer, S. M., & Kuritzkes, D. R. (n.d.).Publication year
1999Journal title
Journal of Acquired Immune Deficiency Syndromes and Human RetrovirologyVolume
20Issue
3Page(s)
220-227AbstractClinical trial endpoints based on magnitude of reduction in HIV-1 RNA levels provide an important complement to endpoints based on percentage of patients achieving complete virologic suppression. However, interpretation of magnitude of reduction can he biased by measurement limitations of virologic assays, particularly lower and upper limits of quantification. Using data from two AIDS Clinical Trials Group (ACTG) studies, widely used crude methods of analyzing HIV-1 RNA reductions were compared with methods that take into account censoring of HIV-1 RNA measurements. Such methods include Kaplan- Meier and censored regression analyses. It was found that standard crude methods of analysis consistently underestimated treatment effects. In some cases, the bias induced by crude methods masked statistically significant differences between treatment arms. Although statistically significant, adjustment for baseline HIV-1 RNA levels had little effect on estimated treatment differences. Furthermore, convenient parametric analyses performed as well as more complex nonparametric analyses. It is concluded that conveniently implemented censored data analyses should be conducted in preference to widely used crude analyses of magnitude of HIV-1 RNA reduction. To obtain complete information about virologic response to antiretroviral therapy, such analyses of magnitude of virologic response should be used to complement analyses of the percentage of patients having complete virologic suppression.Local EM estimation of the hazard function for interval-censored data
AbstractBetensky, R., Lindsey, J. C., Ryan, L. M., & Wand, M. P. (n.d.).Publication year
1999Journal title
BiometricsVolume
55Issue
1Page(s)
238-245AbstractWe propose a smooth hazard estimator for interval-censored survival data using the method of local likelihood. The model is fit using a local EM algorithm. The estimator is more descriptive than traditional empirical estimates in regions of concentrated information and takes on a parametric flavor in regions of sparse information. We derive two different standard error estimates for the smooth curve, one based on asymptotic theory and the other on the bootstrap. We illustrate the local EM method for times to breast cosmesis deterioration (Finkelstein, 1986, Biometrics 42, 845-854) and for times to HIV-1 infection for individuals with hemophilia (Kroner et al., 1994, Journal of AIDS 7, 279-286). Our hazard estimates for each of these data sets show interesting structures that would not be found using a standard parametric hazard model or empirical survivorship estimates.