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Robert J. Gray, PhD


Researcher


Researcher

  • Professor of Biostatistics, Harvard T.H. Chan School of Public Health

Contact Information

  • Office Phone Number(617) 632-2446
  • Fax(617) 632-2444

Bio

Dr. Gray completed his PhD in statistics at Oregon State University in 1982. After joining DFCI as a postdoctoral fellow, he became a faculty member in 1984. He has worked extensively on methods for the analysis of censored failure-time data and competing-risks problems. He has also been a statistician with the Eastern Cooperative Oncology Group, and in 2001 became the head of the ECOG Statistical Center.

Location

Dana-Farber Cancer Institute
450 Brookline Avenue
CLS 11002
Boston MA, 02215
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Research

Clinical Trials and Statistical Methods for Cancer Research

Our major research activities involve the design and analysis of clinical trials and the study of related statistical issues. The Statistical Center for the Eastern Cooperative Oncology Group, headed by Dr. Gray, is involved in dozens of studies which often include biological correlative endpoints and quality-of-life evaluations, as well as evaluations of primary efficacy. Current research interests include methods of adjustment for treatment noncompliance, design and analysis of studies with competing-risks endpoints, methods for analyzing correlated failure-time data, dependent censoring (related to incomplete follow-up of disease status), issues of interim analysis of clinical data, and analysis of high-dimensional laboratory data.

Correlated failure-time data can arise in a variety of settings, such as multicenter clinical trials, in which patient outcomes may vary by center. Correlated data methods for estimating the effects of baseline characteristics on the prognosis of cancer patients have been developed. These methods generally involve solving estimating equations, which depend on families of weight functions that can be used to incorporate information on the degree and structure of the dependence in the data. In theory, incorporating such information should improve prognostic estimates of effects, but attempts to do so have not been very successful. We have investigated the magnitude of the gains possible in both linear failure-time models and proportional hazards models. From this work, we have developed new approaches for estimation using linear-models that closely approximate the weight functions that minimize the sampling variation of the estimated effects.

The presence of competing causes of failure for the primary end point in a clinical trial is another problem that makes interpretation and analysis difficult. For example, in studies of treatment for elderly patients with breast cancer, the primary end point might be prolonging time to disease recurrence or time to breast cancer mortality. But some patients may develop other diseases and die without experiencing failure of the primary end point for the study, thus creating complications for the statistical analysis. Related problems can occur in examining the effect of radiotherapy on controlling disease at the site where it is applied, when there are competing risks of disease at other sites. We have developed models that directly estimate the effect of factors on the probability of observable events in these competing-risks settings, and have successfully applied these models to local failure rates in breast cancer patients.

Progression-based failure-time endpoints in clinical trials require adherence to a regular schedule of disease evaluations. When protocol treatment is terminated without documented progression, the disease evaluation schedule may not be followed, or results of evaluations may not be reported. Patients withdrawn from study without documented progression often have different risk for progression than those continuing on study, and the lack of further information on disease status for these patients potentially biases statistical analyses. In current work, we are investigating the potential impact of these biases and developing methods for exploring the sensitivity of analyses to incomplete follow-up on disease status.

Sparano JA, Gray R, Oktay MH, Entenberg D, Rohan T, Xue X, Donovan M, Peterson M, Shuber A, Hamilton DA, D'Alfonso T, Goldstein LJ, Gertler F, Davidson NE, Condeelis J, Jones J. A metastasis biomarker (MetaSite Breast™ Score) is associated with distant recurrence in hormone receptor-positive, HER2-negative early-stage breast cancer. NPJ Breast Cancer. 2017; 3:42.
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Orbay JL, Gray R, Vernon LL, Sandilands SM, Martin AR, Vignolo SM. The EFCR Approach and the Radial Septum-Understanding the Anatomy and Improving Volar Exposure for Distal Radius Fractures: Imagine What You Could Do With an Extra Inch. Tech Hand Up Extrem Surg. 2016 Dec; 20(4):155-160.
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Solin LJ, Gray R, Hughes LL, Wood WC, Lowen MA, Badve SS, Baehner FL, Ingle JN, Perez EA, Recht A, Sparano JA, Davidson NE. Reply to C. Shah et al. J Clin Oncol. 2016 May 20; 34(15):1824-5.
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Li S, Gray RJ. Estimating treatment effect in a proportional hazards model in randomized clinical trials with all-or-nothing compliance. Biometrics. 2016 Sep; 72(3):742-50.
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Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE, Dees EC, Perez EA, Olson JA, Zujewski J, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin P, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Atkins JN, Berenberg JL, Sledge GW. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2015 Nov 19; 373(21):2005-14.
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Solin LJ, Gray R, Hughes LL, Wood WC, Lowen MA, Badve SS, Baehner FL, Ingle JN, Perez EA, Recht A, Sparano JA, Davidson NE. Surgical Excision Without Radiation for Ductal Carcinoma in Situ of the Breast: 12-Year Results From the ECOG-ACRIN E5194 Study. J Clin Oncol. 2015 Nov 20; 33(33):3938-44.
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Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, Martino S, Wang M, Jones VE, Saphner TJ, Wolff AC, Wood WC, Davidson NE, Sledge GW, Sparano JA, Badve SS. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014 Sep 20; 32(27):2959-66.
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Gray RJ, Zujewski JA, Whelan TJ, Albain KS, Hayes D, Geyer CE, Dees EC, Perez EA, Keane MM, Vallejos Sologuren C, Goggins TF, Mayer IA, Brufsky A, Toppmeyer DL, Kaklamani VG, Atkins JN, Berenberg JL, Sledge GW. Recurrence score and clinicopathologic characteristics of TAILORx participants by race and ethnicity. J Clin Oncol. 2014 Sep 10; 32(26_suppl):36.
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Schneider BP, Li L, Shen F, Miller KD, Radovich M, O'Neill A, Gray RJ, Lane D, Flockhart DA, Jiang G, Wang Z, Lai D, Koller D, Pratt JH, Dang CT, Northfelt D, Perez EA, Shenkier T, Cobleigh M, Smith ML, Railey E, Partridge A, Gralow J, Sparano J, Davidson NE, Foroud T, Sledge GW. Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100. Br J Cancer. 2014 Sep 09; 111(6):1241-8.
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Solin LJ, Gray R, Baehner FL, Butler SM, Hughes LL, Yoshizawa C, Cherbavaz DB, Shak S, Page DL, Sledge GW, Davidson NE, Ingle JN, Perez EA, Wood WC, Sparano JA, Badve S. A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2013 May 15; 105(10):701-10.
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Freidlin B, Sun Z, Gray R, Korn EL. Phase III clinical trials that integrate treatment and biomarker evaluation. J Clin Oncol. 2013 Sep 01; 31(25):3158-61.
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Schneider BP, Gray RJ, Radovich M, Shen F, Vance G, Li L, Jiang G, Miller KD, Gralow JR, Dickler MN, Cobleigh MA, Perez EA, Shenkier TN, Vang Nielsen K, Müller S, Thor A, Sledge GW, Sparano JA, Davidson NE, Badve SS. Prognostic and predictive value of tumor vascular endothelial growth factor gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial. Clin Cancer Res. 2013 Mar 01; 19(5):1281-9.
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Hong F, Kahl BS, Gray R. Incremental value in outcome prediction with gene expression-based signatures in diffuse large B-cell lymphoma. Blood. 2013 Jan 03; 121(1):156-8.
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Tevaarwerk AJ, Gray RJ, Schneider BP, Smith ML, Wagner LI, Fetting JH, Davidson N, Goldstein LJ, Miller KD, Sparano JA. Survival in patients with metastatic recurrent breast cancer after adjuvant chemotherapy: little evidence of improvement over the past 30 years. Cancer. 2013 Mar 15; 119(6):1140-8.
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Sparano JA, Goldstein LJ, Davidson NE, Sledge GW, Gray R. TOP2A RNA expression and recurrence in estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2012 Jul; 134(2):751-7.
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Solin LJ, Gray R, Goldstein LJ, Recht A, Baehner FL, Shak S, Badve S, Perez EA, Shulman LN, Martino S, Davidson NE, Sledge GW, Sparano JA. Prognostic value of biologic subtype and the 21-gene recurrence score relative to local recurrence after breast conservation treatment with radiation for early stage breast carcinoma: results from the Eastern Cooperative Oncology Group E2197 study. Breast Cancer Res Treat. 2012 Jul; 134(2):683-92.
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Kim HT, Gray R. Three-component cure rate model for nonproportional hazards alternative in the design of randomized clinical trials. Clin Trials. 2012 Apr; 9(2):155-63.
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McGhan LJ, Dueck AC, Gray RJ, Wasif N, McCullough AE, Pockaj BA. The changing landscape of axillary surgery: which breast cancer patients may still benefit from complete axillary lymph node dissection? J Surg Oncol. 2012 Sep 01; 106(3):254-9.
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McGhan LJ, Pockaj BA, Gray RJ, Bagaria SP, McLaughlin SA, Casey WJ, Rebecca AM, Wasif N. The impact of breast reconstruction on the decision to undergo contralateral prophylactic mastectomy. J Clin Oncol. 2011 Sep 20; 29(27_suppl):96.
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Sparano JA, Goldstein LJ, Childs BH, Shak S, Brassard D, Badve S, Baehner FL, Bugarini R, Rowley S, Perez EA, Shulman LN, Martino S, Davidson NE, Kenny PA, Sledge GW, Gray R. Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer. Clin Cancer Res. 2011 Nov 15; 17(22):7194-203.
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Manola JB, Gray RJ. When bad things happen to good studies. J Clin Oncol. 2011 Sep 10; 29(26):3497-9.
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McKenna P, Robinson AP, Neely D, Desjarlais MP, Carroll DC, Quinn MN, Yuan XH, Brenner CM, Burza M, Coury M, Gallegos P, Gray RJ, Lancaster KL, Li YT, Lin XX, Tresca O, Wahlström CG. Effect of lattice structure on energetic electron transport in solids irradiated by ultraintense laser pulses. Phys Rev Lett. 2011 May 06; 106(18):185004.
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Dodd LE, Korn EL, Freidlin B, Gray R, Bhattacharya S. An audit strategy for progression-free survival. Biometrics. 2011 Sep; 67(3):1092-9.
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Rao RD, Cobleigh MA, Gray R, Graham ML, Norton L, Martino S, Budd GT, Ingle JN, Wood WC. Phase III double-blind, placebo-controlled, prospective randomized trial of adjuvant tamoxifen vs. tamoxifen and fenretinide in postmenopausal women with positive receptors (EB193): an intergroup trial coordinated by the Eastern Cooperative Oncology Group. Med Oncol. 2011 Dec; 28 Suppl 1:S39-47.
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Gor PP, Su HI, Gray RJ, Gimotty PA, Horn M, Aplenc R, Vaughan WP, Tallman MS, Rebbeck TR, DeMichele A. Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study. Breast Cancer Res. 2010; 12(3):R26.
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Wang R, Lagakos SW, Gray RJ. Testing and interval estimation for two-sample survival comparisons with small sample sizes and unequal censoring. Biostatistics. 2010 Oct; 11(4):676-92.
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Freidlin B, Korn EL, Gray R. A general inefficacy interim monitoring rule for randomized clinical trials. Clin Trials. 2010 Jun; 7(3):197-208.
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Sparano JA, Goldstein LJ, Childs BH, Shak S, Brassard D, Badve S, Baehner FL, Bugarini R, Rowley S, Perez E, Shulman LN, Martino S, Davidson NE, Sledge GW, Gray R. Relationship between Topoisomerase 2A RNA Expression and Recurrence after Adjuvant Chemotherapy for Breast Cancer. Clin Cancer Res. 2009 Dec 15; 15(24):7693-7700.
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Bhattacharya S, Fyfe G, Gray RJ, Sargent DJ. Role of sensitivity analyses in assessing progression-free survival in late-stage oncology trials. J Clin Oncol. 2009 Dec 10; 27(35):5958-64.
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Hughes LL, Wang M, Page DL, Gray R, Solin LJ, Davidson NE, Lowen MA, Ingle JN, Recht A, Wood WC. Local excision alone without irradiation for ductal carcinoma in situ of the breast: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009 Nov 10; 27(32):5319-24.
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Gray R, Bhattacharya S, Bowden C, Miller K, Comis RL. Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2009 Oct 20; 27(30):4966-72.
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Agarwala SS, Gray RJ, Wong MK. Duration of high-dose interferon alpha-2b regimen for resected high-risk melanoma. J Clin Oncol. 2009 Sep 01; 27(25):e82-3; author reply e84.
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DeMichele A, Gray R, Horn M, Chen J, Aplenc R, Vaughan WP, Tallman MS. Host genetic variants in the interleukin-6 promoter predict poor outcome in patients with estrogen receptor-positive, node-positive breast cancer. Cancer Res. 2009 May 15; 69(10):4184-91.
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Ruan PK, Gray RJ. Analyses of cumulative incidence functions via non-parametric multiple imputation. Stat Med. 2008 Nov 29; 27(27):5709-24.
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Dahlberg SE, Gray RJ, Johnson BE. Gefitinib for recurrent non-small-cell lung cancer: all things are not created equal. J Clin Oncol. 2008 Sep 10; 26(26):4233-5.
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Gray RJ. Weighted analyses for cohort sampling designs. Lifetime Data Anal. 2009 Mar; 15(1):24-40.
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Goldstein LJ, Gray R, Badve S, Childs BH, Yoshizawa C, Rowley S, Shak S, Baehner FL, Ravdin PM, Davidson NE, Sledge GW, Perez EA, Shulman LN, Martino S, Sparano JA. Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features. J Clin Oncol. 2008 Sep 01; 26(25):4063-71.
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Goldstein LJ, Gray RJ, Bugarini R, Shak S, Badve SS, Baehner FL, Davidson NE, Sledge GW, Sparano JA. Predictive utility of progesterone receptor (PR) and multigene expression in identifying benefit from adjuvant doxorubicin plus cyclophosphamide (AC) or docetaxel (AT) in intergroup trial E2197. J Clin Oncol. 2008 May 20; 26(15_suppl):557.
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Ruan PK, Gray RJ. Sensitivity analysis of progression-free survival with dependent withdrawal. Stat Med. 2008 Apr 15; 27(8):1180-98.
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Freidlin B, Korn EL, George SL, Gray R. Randomized clinical trial design for assessing noninferiority when superiority is expected. J Clin Oncol. 2007 Nov 01; 25(31):5019-23.
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Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, Sparano JA, Hunsberger S, Enos RA, Gelber RD, Zujewski JA. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007 May 20; 25(15):2127-32.
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Freidlin B, Korn EL, Hunsberger S, Gray R, Saxman S, Zujewski JA. Proposal for the use of progression-free survival in unblinded randomized trials. J Clin Oncol. 2007 May 20; 25(15):2122-6.
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Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14; 355(24):2542-50.
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Gray R. Bayesian modeling approach to examining heterogeneity in censored survival analysis. Biometrics. 2006 Jun; 62(2):623; author reply 623-4.
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Gray R, Manola J, Saxman S, Wright J, Dutcher J, Atkins M, Carducci M, See W, Sweeney C, Liu G, Stein M, Dreicer R, Wilding G, DiPaola RS. Phase II clinical trial design: methods in translational research from the Genitourinary Committee at the Eastern Cooperative Oncology Group. Clin Cancer Res. 2006 Apr 01; 12(7 Pt 1):1966-9.
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Ruan PK, Gray RJ. A method for analyzing disease-specific mortality with missing cause of death information. Lifetime Data Anal. 2006 Mar; 12(1):35-51.
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Lee ML, Gray RJ, Björkbacka H, Freeman MW. Generalized rank tests for replicated microarray data. Stat Appl Genet Mol Biol. 2005; 4:Article3.
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Hughes LL, Gray RJ, Solin LJ, Robert NJ, Martino S, Tripathy D, Ingle JN, Wood WC. Efficacy of radiotherapy for ovarian ablation: results of a breast intergroup study. Cancer. 2004 Sep 01; 101(5):969-72.
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Sparano JA, Gray R, Giantonio B, O'Dwyer P, Comis RL. Evaluating antiangiogenesis agents in the clinic: the Eastern Cooperative Oncology Group Portfolio of Clinical Trials. Clin Cancer Res. 2004 Feb 15; 10(4):1206-11.
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Keller SM, Vangel MG, Wagner H, Schiller J, Herskovic A, Komaki R, Gray R, Marks RS, Perry MC, Livingston RB, Johnson DH. Second primary tumors following adjuvant therapy of resected stages II and IIIa non-small cell lung cancer. Lung Cancer. 2003 Oct; 42(1):79-86.
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Tallman MS, Gray R, Robert NJ, LeMaistre CF, Osborne CK, Vaughan WP, Gradishar WJ, Pisansky TM, Fetting J, Paietta E, Lazarus HM. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Engl J Med. 2003 Jul 03; 349(1):17-26.
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Gray RJ. Weighted estimating equations for linear regression analysis of clustered failure time data. Lifetime Data Anal. 2003 Jun; 9(2):123-38.
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Gray RJ, Li Y. Optimal weight functions for marginal proportional hazards analysis of clustered failure time data. Lifetime Data Anal. 2002 Mar; 8(1):5-19.
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Goldhirsch A, Gelber RD, Yothers G, Gray RJ, Green S, Bryant J, Gelber S, Castiglione-Gertsch M, Coates AS. Adjuvant therapy for very young women with breast cancer: need for tailored treatments. J Natl Cancer Inst Monogr. 2001; (30):44-51.
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Gray RJ. Estimation of regression parameters and the hazard function in transformed linear survival models. Biometrics. 2000 Jun; 56(2):571-6.
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Gray RJ. On tests for group variation with a small to moderate number of groups. Lifetime Data Anal. 1998; 4(2):139-48.
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D'Ambra MN, Gray RJ, Hillman R, Jones JW, Kim HC, Rawitscher R, Schnaper H, Szymanski I, Vlahakes GJ, Kaplan D, Lynch KE, Guilfoyle M, Abels RI. Effect of recombinant human erythropoietin on transfusion risk in coronary bypass patients. Ann Thorac Surg. 1997 Dec; 64(6):1686-93.
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Gray RJ. Spline-based tests in survival analysis. Biometrics. 1994 Sep; 50(3):640-52.
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Gray RJ. A Bayesian analysis of institutional effects in a multicenter cancer clinical trial. Biometrics. 1994 Mar; 50(1):244-53.
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Gray RJ. Some diagnostic methods for Cox regression models through hazard smoothing. Biometrics. 1990 Mar; 46(1):93-102.
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Gray RJ, Tsiatis AA. A linear rank test for use when the main interest is in differences in cure rates. Biometrics. 1989 Sep; 45(3):899-904.
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