Rebecca A Betensky
Chair of the Department of Biostatistics
Professor of Biostatistics
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.
AB, Mathematics, Harvard University, Cambridge, MAPhD, Statistics, Stanford University, Stanford, CA
Areas of research and study
Genomic and Transcriptomic Analyses of NF1-Mutant Melanoma Identify Potential Targeted Approach for Treatment
Neuropathology-Independent Association between APOE Genotype and Cognitive Decline Rate in the Normal Aging-Early Alzheimer Continuum
Nonparametric bounds for the survivor function under general dependent truncationQian, J., & Betensky, R. A. (n.d.).
Journal titleScandinavian Journal of Statistics
Page(s)327-357AbstractTruncation occurs in cohort studies with complex sampling schemes. When truncation is ignored or incorrectly assumed to be independent of the event time in the observable region, bias can result. We derive completely nonparametric bounds for the survivor function under truncation and censoring; these extend prior nonparametric bounds derived in the absence of truncation. We also define a hazard ratio function that links the unobservable region in which event time is less than truncation time, to the observable region in which event time is greater than truncation time, under dependent truncation. When this function can be bounded, and the probability of truncation is known approximately, it yields narrower bounds than the purely nonparametric bounds. Importantly, our approach targets the true marginal survivor function over its entire support, and is not restricted to the observable region, unlike alternative estimators. We evaluate the methods in simulations and in clinical applications.
APOE ε4 and late-life cognition: mediation by structural brain imaging markers
Association between lower body temperature and increased tau pathology in cognitively normal older adults
Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia
Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia
Nonparametric estimation of the survival distribution under covariate-induced dependent truncation
Platelet Function Is Associated With Dementia Risk in the Framingham Heart StudyRamos-Cejudo, J., Johnson, A. D., Beiser, A., Seshadri, S., Salinas, J., Berger, J. S., Fillmore, N. R., Do, N., Zheng, C., Kovbasyuk, Z., Ardekani, B. A., Nunzio, P., Bubu, O. M., Parekh, A., Convit, A., Betensky, R. A., Wisniewski, T. M., & Osorio, R. S. (n.d.).
Journal titleJournal of the American Heart Association
Issue9AbstractBACKGROUND: Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to investigate whether platelet function in middle age is independently associated with future risk of AD. METHODS AND RESULTS: We examined associations of baseline platelet function with incident dementia risk in the community-based FHS (Framingham Heart Study) longitudinal cohorts. The association between platelet function and risk of dementia was evaluated using the cumulative incidence function and inverse probability weighted Cox proportional cause-specific hazards regression models, with adjustment for demographic and clinical covariates. Platelet aggregation response was measured by light transmission aggregometry. The final study sample included 1847 FHS participants (average age, 53.0 years; 57.5% women). During follow-up (median, 20.5 years), we observed 154 cases of incident dementia, of which 121 were AD cases. Results from weighted models indicated that platelet aggregation response to adenosine diphosphate 1.0 µmol/L was independently and positively associated with dementia risk, and it was preceded in importance only by age and hypertension. Sensitivity analyses showed associations with the same directionality for participants defined as adenosine diphosphate hyper-responders, as well as the platelet response to 0.1 µmol/L epinephrine. CONCLUSIONS: Our study shows individuals free of antiplatelet therapy with a higher platelet response are at higher risk of dementia in late life during a 20-year follow-up, reinforcing the role of platelet function in AD risk. This suggests that platelet phenotypes may be associated with the rate of dementia and potentially have prognostic value.
Sex and Race Differences in the Evaluation and Treatment of Young Adults Presenting to the Emergency Department With Chest Pain
Transformation model based regression with dependently truncated and independently censored dataQian, J., Chiou, S. H., & Betensky, R. A. (n.d.).
Journal titleJournal of the Royal Statistical Society. Series C: Applied Statistics
Page(s)395-416AbstractTruncated survival data arise when the event time is observed only if it falls within a subject specific region. The conventional risk-set adjusted Kaplan–Meier estimator or Cox model can be used for estimation of the event time distribution or regression coefficient. However, the validity of these approaches relies on the assumption of quasi-independence between truncation and event times. One model that can be used for the estimation of the survival function under dependent truncation is a structural transformation model that relates a latent, quasi-independent truncation time to the observed dependent truncation time and the event time. The transformation model approach is appealing for its simple interpretation, computational simplicity and flexibility. In this paper, we extend the transformation model approach to the regression setting. We propose three methods based on this model, in addition to a piecewise transformation model that adds greater flexibility. We investigate the performance of the proposed models through simulation studies and apply them to a study on cognitive decline in Alzheimer's disease from the National Alzheimer's Coordinating Center. We have developed an R package, tranSurv, for implementation of our method.
Association of APOE Genotype With Heterogeneity of Cognitive Decline Rate in Alzheimer Disease
Comment on “Patient preference for cellulitis treatment: At-home care is preferred to hospital-based treatment”Shaw, K. S., Karagounis, T. K., Yin, L., Gibbon, G., Betensky, R. A., Lo Sicco, K. I., & Femia, A. N. (n.d.). In Journal of the American Academy of Dermatology.
Concordance measures and time-dependent ROC methods
COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia PatientsShaw, K. S., Yin, L., Shah, J. K., Sally, R. A., Svigos, K. S., Adotama, P. U., Tuan, H. H., Shapiro, J., Betensky, R. A., & Lo Siccoa, K. I. (n.d.).
Journal titleJournal of Drugs in Dermatology
Page(s)914-916AbstractEarly in the COVID-19 pandemic, anti-malarial agent hydroxychloroquine (HCQ) was touted as a potentially effective COVID-19 treatment due to its purported antiinflammatory and antiviral effects.
Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation
Displaying survival of patient groups defined by covariate paths: Extensions of the Kaplan-Meier estimatorJay, M., & Betensky, R. A. (n.d.).
Journal titleStatistics in Medicine
Page(s)2024-2036AbstractExtensions of the Kaplan-Meier estimator have been developed to illustrate the relationship between a time-varying covariate of interest and survival. In particular, Snapinn et al and Xu et al developed estimators to display survival for patients who always have a certain value of a time-varying covariate. These estimators properly handle time-varying covariates, but their clinical interpretation is limited. It is of greater clinical interest to display survival for patients whose covariates lie along certain defined paths. In this article, we propose extensions of Snapinn et al and Xu et al's estimators, providing crude and covariate-adjusted estimates of the survival function for patients defined by covariate paths. We also derive analytical variance estimators. We demonstrate the utility of these estimators with medical examples and a simulation study.
Estimation of the censoring distribution in clinical trials
Limitations of the Unified Multiple System Atrophy Rating Scale as outcome measure for clinical trials and a roadmap for improvementPalma, J. A., Vernetti, P. M., Perez, M. A., Krismer, F., Seppi, K., Fanciulli, A., Singer, W., Low, P., Biaggioni, I., Norcliffe-Kaufmann, L., Pellecchia, M. T., Martí, M. J., Kim, H. J., Merello, M., Stankovic, I., Poewe, W., Betensky, R., Wenning, G., & Kaufmann, H. (n.d.).
Journal titleClinical Autonomic Research
Page(s)157-164AbstractPurpose: The unified multiple system atrophy (MSA) rating scale (UMSARS) was developed almost 20 years ago as a clinical rating scale to capture multiple aspects of the disease. With its widespread use, the shortcomings of the UMSARS as a clinical outcome assessment (COA) have become increasingly apparent. We here summarize the shortcomings of the scale, confirm some of its limitations with data from the Natural History Study of the Synucleinopathies (NHSS), and suggest a framework to develop and validate an improved COA to be used in future clinical trials of disease-modifying drugs in patients with MSA. Methods: Expert consensus assessment of the limitations of the UMSARS and recommendations for the development and validation of a novel COA for MSA. We used UMSARS data from the ongoing NHSS (ClinicalTrials.gov: NCT01799915) to showcase some of these limitations. Results: The UMSARS in general, and specific items in particular, have limitations to detect change resulting in a ceiling effect. Some items have specific limitations including unclear anchoring descriptions, lack of correlation with disease severity, susceptibility to improve with symptomatic therapies (e.g., orthostatic hypotension, constipation, and bladder dysfunction), and redundancy, among others. Conclusions: Because of the limitations of the UMSARS, developing and validating an improved COA is a priority. The time is right for academic MSA clinicians together with industry, professional societies, and patient advocacy groups to develop and validate a new COA.
Mucocutaneous Manifestations of Multisystem Inflammatory Syndrome in Children during the COVID-19 PandemicYoung, T. K., Shaw, K. S., Shah, J. K., Noor, A., Alperin, R. A., Ratner, A. J., Orlow, S. J., Betensky, R. A., Shust, G. F., Kahn, P. J., & Oza, V. S. (n.d.).
Journal titleJAMA Dermatology
Page(s)207-212AbstractImportance: To date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms. Objective: To describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020. Design, Setting, and Participants: A retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C. Main Outcomes and Measures: Laboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C. The characterization of mucocutaneous features was verified by 2 board-certified pediatric dermatologists. Results: Twenty-five children (11 girls [44%]; median age, 3 years [range, 0.7-17 years]) were identified who met definitional criteria for MIS-C; an additional 10 children (5 girls [50%]; median age, 1.7 years [range, 0.2-15 years]) were included as probable MIS-C cases (patients met all criteria with the exception of laboratory test evidence of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection or known exposure). The results of polymerase chain reaction tests for SARS-CoV-2 were positive for 10 patients (29%), and the results of SARS-CoV-2 immunoglobulin G tests were positive for 19 patients (54%). Of the 35 patients, 29 (83%) exhibited mucocutaneous changes, with conjunctival injection (n = 21), palmoplantar erythema (n = 18), lip hyperemia (n = 17), periorbital erythema and edema (n = 7), strawberry tongue (n = 8), and malar erythema (n = 6) being the most common findings. Recognition of mucocutaneous findings occurred a mean of 2.7 days (range, 1-7 days) after the onset of fever. The duration of mucocutaneous findings varied from hours to days (median duration, 5 days [range, 0-11 days]). Neither the presence nor absence of mucocutaneous findings was significantly associated with overall disease severity. Conclusions and Relevance: In this case series of hospitalized children with suspected MIS-C during the COVID-19 pandemic, a wide spectrum of mucocutaneous findings was identified. Despite their protean and transient nature, these mucocutaneous features serve as important clues in the recognition of MIS-C.
Reply to Tendler et al
Seizure risk with repetitive TMS: Survey results from over a half-million treatment sessions
The Neutrophil to Lymphocyte Ratio Is Associated With the Risk of Subsequent Dementia in the Framingham Heart Study
A pilot protocol to assess the feasibility of a virtual multiple crossover, randomized controlled trial design using methylphenidate in mild cognitive impairmentDesRuisseaux, L. A., Williams, V. J., McManus, A. J., Gupta, A. S., Carlyle, B. C., Azami, H., Gerber, J. A., Bolling, A. M., Cook, C. L., Betensky, R. A., & Arnold, S. E. (n.d.).
Issue1AbstractBackground: The conventional clinical trial design in Alzheimer’s disease (AD) and AD-related disorders (ADRDs) is the parallel-group randomized controlled trial. However, in heterogeneous disorders like AD/ADRDs, this design requires large sample sizes to detect meaningful effects in an “average” patient. They are very costly and, despite many attempts, have not yielded new treatments for many years. An alternative, the multi-crossover, randomized control trial (MCRCT) is a design in which each patient serves as their own control across successive, randomized blocks of active treatment and placebo. This design overcomes many limitations of parallel-group trials, yielding an unbiased assessment of treatment effect at the individual level (“N-of-1”) regardless of unique patient characteristics. The goal of the present study is to pilot a MCRCT of a potential symptomatic treatment, methylphenidate, for mild-stage AD/ADRDs, testing feasibility and compliance of participants in this design and efficacy of the drug using both standard and novel outcome measures suited for this design. Methods: Ten participants with mild cognitive impairment or mild-stage dementia due to AD/ADRDs will undergo a 4-week lead-in period followed by three, month-long treatment blocks (2 weeks of treatment with methylphenidate, 2 weeks placebo in random order). This trial will be conducted entirely virtually with an optional in-person screening visit. The primary outcome of interest is feasibility as measured by compliance and retention, with secondary and exploratory outcomes including cognition as measured by neuropsychological assessment at the end of each treatment period and daily brain games played throughout the study, actigraphy, and neuropsychiatric and functional assessments. Discussion: This pilot study will gauge the feasibility of conducting a virtual MCRCT for symptomatic treatment in early AD/ADRD. It will also compare home-based daily brain games with standard neuropsychological measures within a clinical trial for AD/ADRD. Particular attention will be paid to compliance, tolerability of drug and participation, learning effects, trends and stability of daily measures across blocks, medication carryover effects, and correlations between standard and brief daily assessments. These data will provide guidance for more efficient trial design and the use of potentially more robust, ecological outcome measures in AD/ADRD research. Trial registration: ClinicalTrials.gov, NCT03811847. Registered on 21 January 2019.
Accounting for incomplete testing in the estimation of epidemic parameters