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Boris Freidlin

Publications and source records attributed to Boris Freidlin.

23 records · Page 2Linked to original sources
PubMed2002

Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America.

BACKGROUND: 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. METHODS: Phase III trials from 1972 to 1992 for patients with limited-stage SCLC were identified. Patients with limited-stage SCLC treated during a similar time interval were also evaluated in the Surveillance, Epidemiology, and End Results (SEER) database. Trends were tested in the number of trials, in the number and gender of patients entered on trial, and in survival duration over time. RESULTS: Thirty trials involving 6564 patients were eligible for analyses. Nineteen trials (61%) involving 3626 patients were initiated within the first half of this time period (1972-1981). The median of median survival times of all patients treated on the control arms of the Phase III trials initiated between 1972 and 1981 and between 1982 and 1992 were 12.0 months (range, 10-16 months) and 17.0 months (range, 11-20 months), respectively (P < 0.001). Of 26 studies available for survival analysis, 5 (19%) showed a statistically significant survival prolongation in the experimental arm compared with the control arm with a median prolongation of 3.4 months (range, 1-5.2 months). All five evaluated some aspect of thoracic radiation therapy. Over a similar time period, there was a 6.4-month increase in the median survival of limited-stage SCLC patients listed in the SEER database (P < 0.0001) and a more than doubling of the 5-year survival from 5.2% to 12.1% (P = 0.0001). CONCLUSIONS: Analyses of the patients with limited-stage SCLC treated on Phase III trials in North America initiated between 1972 and 1992 and those listed in the SEER database show significant improvements in median survivals. Furthermore, the 5-year survival of patients with limited-stage SCLC listed in the SEER database has more than doubled over the last 25 years. Further research will be needed to determine the relative contribution of improved therapy, supportive care, and stage migration to this prolongation in survival.

Adult↗
PubMed2002

A testing procedure for survival data with few responders.

In the course of designing a clinical trial, investigators are often faced with the possibility that only a fraction of the patients will benefit from the experimental treatment. A proper clinical trial design requires prospective specification of the testing procedures to be used in the analysis. In the absence of reliable prognostic factors capable of identifying the appropriate subset of patients, there is a need for a test procedure that will be sensitive to a range of possible fractions of responders. Focusing on survival data, we propose guidelines for selecting a proper test procedure based on the anticipated proportion of responding patients. These guidelines suggest that the logrank test should be used when the fraction of responders is expected to be greater than 0.5, otherwise procedures based on weighted linear rank tests are preferable. Overall this approach provides good power properties when the treatment affects only a small proportion of patients while protecting against substantial loss of power when all patients are affected. Use of the procedure is illustrated with data from two published randomized studies.

Animals↗
PubMed2002

A comment on futility monitoring.

Futility monitoring of randomized clinical trials is becoming widely used. In this paper we discuss several concerns associated with aggressive monitoring for lack of activity in studies comparing experimental and control treatment arms: (1) stopping for futility when the experimental arm is doing better than the control arm, (2) conditional power not being low at the time of stopping, (3) potential loss of power to detect clinically interesting differences that are smaller than the design alternative, and (4) sensitivity of the power to the departure from the proportional hazards assumption. Our investigation suggests that aggressive futility rules do not generally reduce power (relative to less aggressive rules) under incorrect design assumptions such as overstatement of the target treatment effect or mild violations of the proportional hazards assumption. On the other hand, aggressive monitoring rules may result in an early termination for futility when the experimental arm is doing better than the control arm (in some cases nontrivially better, especially when trials are designed for unrealistically large effects). Thus, aggressive monitoring rules may fail to provide sufficiently convincing evidence to influence clinical practice or to establish a standard of treatment.

Guidelines as Topic↗
PubMed2002

Methods for assessing reproducibility of clustering patterns observed in analyses of microarray data.

MOTIVATION: Recent technological advances such as cDNA microarray technology have made it possible to simultaneously interrogate thousands of genes in a biological specimen. A cDNA microarray experiment produces a gene expression 'profile'. Often interest lies in discovering novel subgroupings, or 'clusters', of specimens based on their profiles, for example identification of new tumor taxonomies. Cluster analysis techniques such as hierarchical clustering and self-organizing maps have frequently been used for investigating structure in microarray data. However, clustering algorithms always detect clusters, even on random data, and it is easy to misinterpret the results without some objective measure of the reproducibility of the clusters. RESULTS: We present statistical methods for testing for overall clustering of gene expression profiles, and we define easily interpretable measures of cluster-specific reproducibility that facilitate understanding of the clustering structure. We apply these methods to elucidate structure in cDNA microarray gene expression profiles obtained on melanoma tumors and on prostate specimens.

Cluster Analysis↗