A recent publication in Biometrics ‘A Gatekeeping Procedure to Test a Primary and a Secondary Endpoint in a Group Sequential Design with Multiple Interim Looks’ greatly extends the results of Glimm et al. ( 2010) and Tamhane et al ( 2010) which studied the problem of testing a primary and secondary endpoint, subject to a gatekeeping constraint, using a group sequential design (GSD) with K = 2...

Topics: Cyrus Mehta, Statistical Analysis, Group Sequential, biostatistics, adaptive trials

 The Global Cardiovascular Clinical Trialists Forum is a key event bringing together leading experts from across the spectrum of opinion leaders, clinical trialists, investigators, regulators, statisticians and practitioners to address the most pressing questions in cardiovascular clinical development today.  At the December conference, eminent biostatisticians Cyrus Mehta and Stuart Pocock...

Topics: Cyrus Mehta, Cardiovascular, Cytel Events, biostatistics, adaptive designs, adaptive trials

Following the recent publication of their review article Adaptive Designs for Clinical Trials in the New England Journal of Medicine,  co-authors Cyrus Mehta ( President and Co-Founder of Cytel, and Adjunct Professor of Biostatistics at Harvard University) and Deepak L. Bhatt M.D C M.P.H. (Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart and...

Topics: Cyrus Mehta, Promising Zone, biostatistics, adaptive designs, adaptive trials

 'The aim of a discussion should not be victory but progress.'

This principle, expressed by the French essayist Joseph Joubert, applies effectively to the spirit of scientific debate. More specifically, within the clinical development space, the field of adaptive designs has seen its fair share of both discussion and progress. In this blog we’ll take a look at one debated area- the efficiency...

Topics: Cyrus Mehta, Adaptive Clinical Trials, adaptive sample size re-estimation, Lingyun Liu

One consideration every sponsor of a biomarker-stratified confirmatory trial must take into account, is whether to evaluate the biomarker subpopulation (S) against the rest of the population (S') or against the full population (F).

Mathematically, one would think this makes very little difference as F is partitioned into S and S'. If the null hypothesis is rejected for both S and S' then...

Topics: Cyrus Mehta, Enrichment, Simulation & Biomarkers, time-to-even trials, Biomarkers

Most people familiar with adaptive clinical trial designs are familiar with those statistical designs that reject the null hypothesis. These include now familiar designs like the promising zone design and the adaptive switch design. 

A newer breed of adaptive designs, however, aims to apply adaptation techniques to confidence intervals.

Topics: Cyrus Mehta, Exact Tests, Adaptive Clinical Trials

Powering a trial for superiority can be financially risky. In some instances it may also prove unnecessary.

Topics: Cyrus Mehta, Promising Zone, Cardiovascular, Adaptive Clinical Trials, Adaptive Finance

Cytel President and co-founder Cyrus Mehta has co-authored a paper on Infantile Hemangioma, recently published in the New England Journal of Medicine. The successful study was designed as an adaptive confirmatory dose-response which confirmed that 3mg per kilogram per day of propranolol for 6 months is an effective resolution for hemangioma.

Topics: Cyrus Mehta, Adaptive Clinical Trials

Cardiovascular outcome trials (CVOTs) have earned the reputation of being the untamable behemoths of the clinical world. Needless to say these trials are long and require extremely large sample-sizes. The Contrave LIGHT study required 8900 patients. The SAVOR TIMI trial enrolled 16,492 patients. Even the EXAMINE trial, which benefited from a promising zone design, required 650 patients. 

...

Topics: Cyrus Mehta, Promising Zone, Cytel Strategic Consulting, Interim Analyses, Program and Portfolio Optimization, Cardiovascular, Clinical Development Strategy, Adaptive Clinical Trials

 

The FDA requires sponsors of new antidiabetic drugs to conduct cardiovascular outcome trials (CVOTs). CVOTs demonstrate that new therapies do not place unacceptable cardiovascular risk on patients suffering from Type 2 diabetes. The average CVOT requires about 5000 patients and takes an average of 5 years to complete. However, a recent white paper by the Cardiac Safety Research Consortium...

Topics: Cyrus Mehta, Promising Zone, Trial Design, FDA, Interim Analyses, Cardiovascular, Adaptive Clinical Trials

As more clinical trials make use of adaptive designs, investors have come to realize that high quality trial designs can result in significant improvements to a trial’s financial risk profile. Regardless of a trial’s eventual success or failure, a well-constructed design provides a drug with the highest possible probability of success while mitigating financial risk.

Topics: Nitin Patel, Cyrus Mehta, Promising Zone, Trial Quality, Cytel Strategic Consulting, Trial Design, Entrepreneurship, Program and Portfolio Optimization, R&D, Adaptive Clinical Trials

Topics: Cyrus Mehta, Access to Paper PDF, Adaptive Clinical Trials

For the second installment of our StatXact 25th Anniversary Retrospective Series, Professor Joan Hilton (UC San Francisco) reflects on her pioneering work on exact conditional inferences.

Topics: StatXact, Cyrus Mehta, Exact Tests, Exact tests for categorical data, Webinar Slides

The core methodological problem that would eventually spur the development of Cytel’s StatXact software was first posed by Harvard’s Marvin Zelen at a computational seminar in the late 1970s. Zelen, a distinguished professor of statistical sciences and head of the Department of Biostatistics at Harvard University, was also serving as the Director of the Dana Farber Cancer Institute.

The...

Topics: StatXact, Nitin Patel, Cyrus Mehta, White Paper, Statistics Article full PDF, Oncology, Access to Paper PDF, Exact Tests, Marvin Zelen, Statistical Puzzles