Research Topics
| B FreidlinSummaryAffiliation: National Institutes of Health Country: USA Publications
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Detail Information
Publications
Proposal for the use of progression-free survival in unblinded randomized trialsBoris Freidlin
Biometric Research Branch and the Clinical Investigations Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA
J Clin Oncol 25:2122-6. 2007..This proposal, possibly combined with central review of progression scans for these two time points, essentially eliminates any bias, with little risk of major efficiency loss compared with using the reported progression times...
Stopping clinical trials early for benefit: impact on estimationBoris Freidlin
Biometric Research Branch, National Cancer Institute, Bethesda, MD, USA
Clin Trials 6:119-25. 2009..It has been suggested in the literature that the well-known bias of treatment-effect estimators due to the possibility of early stopping for positive results is a major concern with interim monitoring...- Borrowing information across subgroups in phase II trials: is it useful?Boris Freidlin
Biometric Research Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda 20892, Maryland, USA
Clin Cancer Res 19:1326-34. 2013..When there is strong rationale for expecting a uniform level of activity across the subgroups, approaches using simple pooling of information across subgroups may be useful... 
Randomized phase II trial designs with biomarkersBoris Freidlin
Biometric Research Branch, EPN 8129, National Cancer Institute, Bethesda, MD 20852, USA
J Clin Oncol 30:3304-9. 2012..Evaluations of the proposed trial design using simulations and published data demonstrate that it works well in providing recommendations for phase III trial design...- Assessing causal relationships between treatments and clinical outcomes: always read the fine printB Freidlin
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 6130 Executive Plaza, Bethesda, MD 20892, USA
Bone Marrow Transplant 47:626-32. 2012..At the same time, we illustrate how careful application of special statistical methods for assessment of treatment-outcome causation can be instrumental in complementing existing randomized evidence and guiding design of future research... - Release of data from an ongoing randomized clinical trial for sample size adjustment or planningBoris Freidlin
Biometric Research Branch, EPN 8122, National Cancer Institute, Bethesda, MD 20892 7434, USA
Stat Med 26:4074-82. 2007..A simple approach to minimizing the effect of the data release is suggested... - Testing treatment effects in the presence of competing risksBoris Freidlin
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 6130 Executive Blvd EPN 8122, MSC 7434, Bethesda, MD 20892 7434, USA
Stat Med 24:1703-12. 2005.... - A general inefficacy interim monitoring rule for randomized clinical trialsBoris Freidlin
Biometric Research Branch, National Cancer Institute, Bethesda, MD, USA
Clin Trials 7:197-208. 2010..To balance patient interests against the need for acquiring evidence it is desirable to stop a study for inefficacy as soon as convincing evidence that the new therapy is not beneficial becomes available... - Randomized clinical trials with biomarkers: design issuesBoris Freidlin
Biometric Research Branch, EPN 8122, National Cancer Institute, Bethesda, MD 20892, USA
J Natl Cancer Inst 102:152-60. 2010..We conclude that, in most settings, randomized biomarker-stratified designs (ie, designs that use the biomarker to guide analysis but not treatment assignment) should be used to obtain a rigorous assessment of biomarker clinical utility... - The cross-validated adaptive signature designBoris Freidlin
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland 20892, USA
Clin Cancer Res 16:691-8. 2010..However, due to the high-dimensional nature of the genomic data, developing a reliable classifier by the time the definitive phase III trail is designed may not be feasible... - A comment on futility monitoringBoris Freidlin
Biometric Research Branch, National Cancer Institute, Bethesda, MD 20892, USA
Control Clin Trials 23:355-66. 2002..Thus, aggressive monitoring rules may fail to provide sufficiently convincing evidence to influence clinical practice or to establish a standard of treatment... - Multi-arm clinical trials of new agents: some design considerationsBoris Freidlin
Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland, USA
Clin Cancer Res 14:4368-71. 2008..Relative to conducting separate RCTs for each experimental agent, this multi-arm design is shown to require a lower total sample size than multiple two-arm trials... - Evaluation of randomized discontinuation designBoris Freidlin
Biometric Research Branch, National Cancer Institute, Bethesda, MD 20892 7434, USA
J Clin Oncol 23:5094-8. 2005..Single-arm phase II trials may not be appropriate for testing cytostatic agents. We evaluate two kinds of randomized designs for the early development of target-based cytostatic agents... - Monitoring for lack of benefit: a critical component of a randomized clinical trialBoris Freidlin
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA
J Clin Oncol 27:629-33. 2009..On the other hand, we caution that some commonly used monitoring guidelines may result in stopping for lack of benefit even when a nontrivial beneficial effect is observed... - Efficiency robust tests for survival or ordered categorical dataB Freidlin
Biometric Research Branch, National Cancer Institute, Bethesda, Maryland 20892, USA
Biometrics 55:883-6. 1999..The second procedure, called the MX, uses the maximum of the optimal statistics. Both approaches yield efficiency robust procedures for survival analysis and ordinal categorical data. Guidelines for choosing between them are provided... - Randomized clinical trial design for assessing noninferiority when superiority is expectedBoris Freidlin
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA
J Clin Oncol 25:5019-23. 2007..This hybrid design can naturally incorporate a formal test of superiority as well as noninferiority... - Adaptive signature design: an adaptive clinical trial design for generating and prospectively testing a gene expression signature for sensitive patientsBoris Freidlin
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA
Clin Cancer Res 11:7872-8. 2005..Thus, there is a need for development of novel statistical methodology for rapid evaluation of these agents... - Biomarker-adaptive threshold design: a procedure for evaluating treatment with possible biomarker-defined subset effectWenyu Jiang
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, EPN 8122, National Cancer Institute, Bethesda, MD 20892, USA
J Natl Cancer Inst 99:1036-43. 2007..We propose a statistically rigorous biomarker-adaptive threshold phase III design for settings in which a putative biomarker to identify patients who are sensitive to the new agent is measured on a continuous or graded scale... - Targeting epidermal growth factor receptor--are we missing the mark?Janet E Dancey
Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892, USA
Lancet 362:62-4. 2003..Appropriately designed clinical trials are required to define the optimum dose, schedule, and sequence for these agents in combination with conventional therapies and other targeted agents... - A model to select regimens for phase III trials for patients with advanced-stage non-small cell lung cancerBoris Freidlin
Biometric Research Branch, National Cancer Institute, Bethesda, MD 20892, USA
Clin Cancer Res 9:917-22. 2003..CONCLUSION: The use of the expected power model provides an important enhancement to the screening of new therapies. Regimens with an expected power of >0.55 may be good candidates for testing in Phase III trials... - Unconditional versions of several tests commonly used in the analysis of contingency tablesB Freidlin
Biometric Research Branch, National Cancer Institute, Bethesda, Maryland 20892 7434, USA
Biometrics 55:264-7. 1999..The unconditional procedures are compared to the conditional ones by reanalyzing some published biomedical data... - Robust TDT-type candidate-gene association testsG Zheng
National Heart Lung and Blood Institute, Bethesda, MD 20892, USA
Ann Hum Genet 66:145-55. 2002..g. dominant through additive) a simple linear combination also performs well. In general, the MAX has better power properties than the TDT for the study of candidate genes when the mode of inheritance is unknown... - On power and efficiency robust linkage tests for affected sibsJ L Gastwirth
Division of Cancer Genetics and Epidemiology, National Cancer Institute, Bethesda, MD 20892, USA
Ann Hum Genet 64:443-53. 2000..When the minimal correlation is less than 0.5, an alternate robust procedure is proposed. The methods apply to combining data from sibships of different sizes... - Secondary leukemia or myelodysplastic syndrome after treatment with epipodophyllotoxinsM A Smith
National Cancer Institute, Bethesda, MD 20892, USA
J Clin Oncol 17:569-77. 1999..The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan to obtain reliable estimates of the risk of secondary leukemia after epipodophyllotoxin treatment... - Measurement error in the timing of events: effect on survival analyses in randomized clinical trialsEdward L Korn
Biometric Research Branch, National Cancer Institute, Bethesda, MD 20892, USA
Clin Trials 7:626-33. 2010.... - A posterior taleEdward L Korn
Biometric Research Branch, EPN 8129, National Cancer Institute, Bethesda, MD 20892 7434, USA
Biom J 49:346-50. 2007..The resolution of this apparent paradox is discussed as well as its relation to real-life problems involving data monitoring of clinical trials... - A note on controlling the number of false positivesEdward L Korn
Biometric Research Branch, National Cancer Institute, Bethesda, MD 20852 7434, USA
Biometrics 64:227-31. 2008..An example is given involving gene expression microarray data of breast cancer tumors... - Outcome--adaptive randomization: is it useful?Edward L Korn
Biometric Research Branch, EPN 8129, National Cancer Institute, Bethesda, MD 20892, USA
J Clin Oncol 29:771-6. 2011.... - Accrual experience of National Cancer Institute Cooperative Group phase III trials activated from 2000 to 2007Edward L Korn
Biometric Research Branch, EPN 8129, National Cancer Institute, Bethesda, MD 20892, USA
J Clin Oncol 28:5197-201. 2010..We examine in detail the accrual experience of the Cooperative Group phase III trials... - Blinded independent central review of progression-free survival in phase III clinical trials: important design element or unnecessary expense?Lori E Dodd
Division of Cancer Treatment and Diagnosis, Branches of Biometric Research, Investigational Drug, Cancer Investigations, and Diagnostic Imaging, National Cancer Institute, Rockville, MD 20892, USA
J Clin Oncol 26:3791-6. 2008..When such designs are not practical, BICR is not recommended as a general strategy for reducing bias. However, BICR may be useful as an auditing tool to assess the reliability of marginally positive results... - Stopping or reporting early for positive results in randomized clinical trials: the National Cancer Institute Cooperative Group experience from 1990 to 2005Edward L Korn
Biometric Research Branch and the Clinical Investigations Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD 20892, USA
J Clin Oncol 27:1712-21. 2009.... - The likelihood as statistical evidence in multiple comparisons in clinical trials: no free lunchEdward L Korn
Biometric Research Branch, EPN 8129, National Cancer Institute, Bethesda, MD 20892 7434, USA
Biom J 48:346-55. 2006.... - Methods for assessing reproducibility of clustering patterns observed in analyses of microarray dataLisa M McShane
National Cancer Institute, Biometric Research Branch, DCTD, NIH, Bethesda, MD 20892 7434, USA
Bioinformatics 18:1462-9. 2002..We apply these methods to elucidate structure in cDNA microarray gene expression profiles obtained on melanoma tumors and on prostate specimens... - Genomic control for association studies under various genetic modelsGang Zheng
Office of Biostatistics Research, DECA, National Heart, Lung and Blood Institute, 6701 Rockledge Drive, MSC 7938, Bethesda, Maryland 20892 7938, USA
Biometrics 61:186-92. 2005.... - Preliminary data release for randomized clinical trials of noninferiority: a new proposalEdward L Korn
Biometric Research Branch and Clinical Investigations Branch, Division of Cancer Treatment and Diagnosis, EPN 8128, National Cancer Institute, Bethesda, MD 20892, USA
J Clin Oncol 23:5831-6. 2005..Examples are given demonstrating how the proposal would work, along with a discussion of possible objections to the proposal... - Design issues of randomized phase II trials and a proposal for phase II screening trialsLawrence V Rubinstein
Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA
J Clin Oncol 23:7199-206. 2005.... - Robust genomic control for association studiesGang Zheng
Office of Biostatistics Research, Division of Epidemiology and Clinical Applications, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA
Am J Hum Genet 78:350-6. 2006..The properties of this robust genomic control test with 2 df are examined by simulation. This genomic control-adjusted 2-df test has control of type I error and achieves reasonable power, relative to the optimal tests for each model... - Conditional power calculations for clinical trials with historical controlsEdward L Korn
Biometric Research Branch, National Cancer Institute, Bethesda, MD 20892, USA
Stat Med 25:2922-31. 2006..We explain why a popular method for doing these calculations is wrong, and discuss alternative methods in the context of normal outcomes, binary outcomes, and time-to-event outcomes... - A testing procedure for survival data with few respondersBoris Freidlin
Biometric Research Branch, National Cancer Institute, 6130 Executive Blvd EPN 8122, MSC 7434, Bethesda, MD 20892 7434, USA
Stat Med 21:65-78. 2002..Use of the procedure is illustrated with data from two published randomized studies... - Efficiency robust tests for mapping quantitative trait loci using extremely discordant sib pairsBoris Freidlin
Biometric Research Branch, National Cancer Institute, Bethesda, MD 20892, USA
Hum Hered 55:117-24. 2003..The additional linkage information contained in the trait values can be incorporated by combining the Haseman-Elston regression method and a robust allele sharing test... - Inefficacy interim monitoring procedures in randomized clinical trials: the need to reportEdward L Korn
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA
Am J Bioeth 11:2-10. 2011..A survey of two leading medical journals suggests that this is not current practice... - Trend tests for case-control studies of genetic markers: power, sample size and robustnessB Freidlin
Biometric Research Branch, National Cancer Institute, Rockville, MD 20892, USA
Hum Hered 53:146-52. 2002..Simulation results of the robustness of these two tests indicate that the more computationally involved MAX test is preferable... - Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseasesK G Becker
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 95:9979-84. 1998..This nonrandom clustering supports a hypothesis that, in some cases, clinically distinct autoimmune diseases may be controlled by a common set of susceptibility genes... - Trends in reported incidence of primary malignant brain tumors in children in the United StatesM A Smith
Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA
J Natl Cancer Inst 90:1269-77. 1998.... - Second malignancies as a consequence of nucleoside analog therapy for chronic lymphoid leukemiasB D Cheson
The Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA
J Clin Oncol 17:2454-60. 1999..The purpose of the present study was to assess the frequency of second tumors in patients with CLL who are treated with fludarabine and in patients with HCL who are treated with DCF and CdA... - Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North AmericaPasi A Janne
Lowe Center for Thoracic Oncology, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Cancer 95:1528-38. 2002..To determine the changes in clinical trials and outcomes of patients with limited-stage small cell lung carcinoma (SCLC) treated on Phase III randomized trials initiated in North America between 1972 and 1992... - Data monitoring and large apparent treatment effectsEdward L Korn
Control Clin Trials 25:67-9; author reply 71-2. 2004 - A testing procedure for survival data with few respondersBoris Freidlin
Stat Med 23:1818-23. 2004 - Multinomial phase II trial designsBoris Freidlin
J Clin Oncol 20:599. 2002 - Strength of accumulating evidence and data monitoring committee decision makingStephen L George
Department of Biostatistics and Bioinformatics, Box 3958, Duke University Medical Center, Durham, NC 27710, USA
Stat Med 23:2659-72. 2004..In this paper we present results of a survey of 21 DMC members conducted to investigate how they evaluate accumulating evidence. The results indicate that some DMC members may be over-interpreting developing trends in the data... - A note on appropriate use of statistical tests of mutation rates from ordered groupsJoseph L Gastwirth
Department of Statistics, George Washington University, Washington, DC 20052, USA
Genet Test 8:437-40. 2004..In particular, the p value of the trend test on their data is noticeably lower (0.003) than 0.012 found by the standard test, providing stronger evidence for a relationship between allele frequency and Polish descent... - Erythropoietin to treat anaemia in patients with head and neck cancerBoris Freidlin
Lancet 363:81; author reply 81-2. 2004