Donald A Berry

..Here, I explain the rationale underlying Bayesian clinical trials, and discuss the potential of such trials to improve the effectiveness of drug development...

..Our study provides an example in which Bayesian predictive modeling provided earlier information than otherwise and therefore it shortened the time line of the development of a therapeutic strategy...

..We analyzed data from CALGB 9342, which tested three doses of paclitaxel in women with advanced disease, to determine whether response and outcomes differed according to HER2, hormone receptor, and p53 status...

..So we will never be able to use a software package with default settings to resolve all problems of multiplicities. Every problem has unique aspects. And all problems require understanding the substantive area of application...

..However, the lessons apply quite generally. I consider both frequentist and Bayesian statistical approaches...

..A wholly new paradigm for drug development exemplifying personalized medicine is evinced by an adaptive trial called I-SPY2, in which drugs from many companies are evaluated in the same trial--a phase II screening process...

..The Bayesian statistical approach is ideally suited for such investigations because it is inherently synthetic and because it is philosophically uninhibited regarding the ability to analyze all the available evidence...

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..We used modeling techniques to assess the relative and absolute contributions of screening mammography and adjuvant treatment to the reduction in breast-cancer mortality in the United States from 1975 to 2000...

..A related concern is subset analysis. I give a statistical argument that estrogen-receptor status is predictive of the benefits of chemotherapy in node-positive breast cancer...

..Many studies including meta-analyses have evaluated the efficacy and safety of vitamin E and have yielded varying results. Illuminating and resolving these disparities requires addressing study variability and model uncertainty...

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..We include simulations of additional levels of missing and mistyped data to show the algorithm's utility and flexibility...

..Such modeling also enables earlier decision making. Case studies 2 and 3 deal with trials that were shorter and smaller, respectively, because of such modeling...

..Individual trials have had limited power to show overall benefit or benefits within subsets...

..One of these studies included 2 doses of atorvastatin, and substantial additional information is available in the literature about the effect of atorvastatin on LDL-C level lowering...

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..We demonstrate the algorithm's utility and robustness through simulations of levels of missing and misscored molecular-size data...

..Method of detection appears to be an important prognostic factor, even after adjusting for known tumor characteristics. This finding suggests that clinical trialists should routinely collect information about method of detection...

..We present data from 54 maize hybrids and 586 maize inbreds that were profiled using 195 SSR loci including simulations of additional levels of missing and mistyped data to demonstrate the utility and flexibility of this algorithm...

..Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy...

..To assess the effect of tumor detection method (screening versus symptom-based diagnosis) in predicting breast cancer survival and investigate how biological features of breast cancer are related to the tumor detection method...

..72 in the validation set and outperformed other prediction tools (P = .02). CONCLUSION: Our nomograms predict pCR accurately and can serve as a basis to integrate future molecular markers into a clinical prediction model...

..The simulations show that the proposed design saves sample size, has better power, and efficiently assigns more patients to doses with higher efficacy levels...

..Such an approach will be even more important as additional information about the genetics of various cancers becomes available...

..The contributions of other causes to the change in incidence seem less likely to have played a major role but have not been excluded...

..The new design uses fewer patients, and can more effectively assign patients to the better treatment arms. We demonstrate these properties through simulation studies...

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..In some disease and treatment settings, an improvement in PFS does not result in an improved OS...

..To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) -positive breast cancer...

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..The Bayesian approach is being used increasingly in medical research. In particular, it has become a standard in designing clinical trials at the University of Texas M. D. Anderson Cancer Center...

..To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial...

..By increasing the number of prognostic markers that can give independent information about patient outcome, physicians will be better able to determine optimal treatment approaches for individual patients...

..In this prospective randomized trial, the role of paclitaxel was evaluated in an adjuvant setting to determine its impact on reducing the risk of recurrence in patients with operable breast cancer...

..We retrospectively studied whether Her2/neu-positive disease was associated with locoregional recurrence (LRR) after postmastectomy radiotherapy (RT) for breast cancer...

..Complete remission was achieved in 2 of 6 minimally pre-treated patients. We conclude that the combination of azacitidine and cytarabine is feasible but has limited activity in relapsed/refractory AML...

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..To revise the American Joint Committee on Cancer staging system for breast carcinoma...

..We analyzed the outcomes of single-agent phase II clinical trials in non-small cell lung cancer (NSCLC) to determine trial parameters that predicted clinical activity...

..25% in controls. Elacytarabine has monotherapy activity in patients with advanced AML. This study provides proof-of-concept that lipid esterification of nucleoside analogues is clinically relevant...

..These tools may be useful when counseling patients about treatment options, and a web-based interface is now available to help guide patients and physicians in these decisions...

..We had knowledge of the simulation models at the time we performed the analyses...

..This novel MDM2-regulated pathway is likely to play a biologically relevant role in cancer metastasis...

..To assess survival of patients with metastatic breast cancer treated with high-dose chemotherapy (HDC) versus standard-dose chemotherapy (SDC)...

..The prognostic index gets its power from combining prognostic biomarkers. It can be very powerful even when there are few markers that are predictive...

..The finding of fibroblastic osteosarcoma in all three patients raises the question of whether coexistent hyperparathyroidism may modify the cytologic and histologic features of the malignancy...

..Epigenetic therapy using decitabine, a DNA hypomethylating agent, is clinically effective for the treatment of MDS. Therefore, we investigated the association between DNA methylation and clinical outcome in MDS...

..We review the current status of biomarker development in lymphoma, and discuss novel biomarker-directed clinical trial designs for lymphoma...

..A prospective, randomized study was conducted in patients aged 50 years or older with untreated, adverse karyotype, acute myeloid leukemia (AML) to assess troxacitabine-based regimes as induction therapy...

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..We give examples to illustrate our method and we describe its application to other types of problems...

..Cancer and Leukemia Group B Protocol 9342 was initiated to determine the optimal dose of paclitaxel administered as a 3-hour infusion every 3 weeks to women with metastatic breast cancer...

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..This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival...

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..For the frequentist, they have well-characterized type I and II error rates and in some cases lead to a reduction in the mean sample size...

..We compared toxicity of older and younger patients in three randomized trials of adjuvant chemotherapy...

..At least 7 models for estimating the probabilities of having a mutation are used widely in clinical and scientific activities; however, the merits and limitations of these models are not fully understood...

..We hypothesized that HER2 positivity predicts a benefit from adjuvant doxorubicin doses above standard levels, from the addition of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide, or from both...

..A secondary aim was to assess if a higher dose (10 mcg/kg/day) of G-CSF is more efficacious than the conventional dose (5 mcg/kg/day) in this setting...

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..This study examines racial differences in clinical outcomes in the setting of two large cooperative group randomized clinical trials...

..Existing studies have focused on Ashkenazi Jews (AJ) or on families from outside the United States. In this article, we consider the US population using the largest US-based cohort to date of both AJ and non-AJ families...

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..We present the results from a large, prospective evaluation of the first rapid molecular SLN test, the Breast Lymph Node (BLN) Assay...

..Pravastatin has a predominantly delayed antiatherogenic effect, and aspirin has an immediate antiplatelet effect, raising the possibility of additive clinical benefits...