Cytel Blog

The Cytel Trial Design Innovations (CTDI) Webinar Series recently hosted a webinar on designing event-based studies. Such studies are essential to designing high-efficiency clinical trials in certain therapeutic areas, but they add a number of challenges to the already complex landscape of adaptive trials.

The webinar was held on January 23rd, featuring Biostatistician and pioneering Bayesian trial-designer Pantelis Vlachos. We had the opportunity to sit down with Dr. Vlachos and speak about innovative trial designs and their benefits, adaptations and interim looks in oncology and cardiovascular, the challenges of designing event-based studies more generally, and how Cytel’s array of software tools, particularly East^®, has enabled trial sponsors to fully consider their options in the design of high-efficiency clinical trials.

January’s Cytel Trial Design Innovations (CTDI) Webinar Series will feature Biostatistician and pioneering Bayesian trial-designer Pantelis Vlachos. Next week, Dr. Vlachos will speak on high-efficiency trial design for Event-Based Studies, particularly in oncology and cardiovascular trials. In this blog post, we offer a glimpse of Dr. Vlachos’ last CTDI Webinar (February 2019) on high-efficiency trial design using enrichment strategies.

Don't miss next week's webinar "Designing Event-based Studies: Reduce Sample Size and Increase Predictability"! Click on the button below to register.

In this blog we share a case study of work our strategic consulting team conducted supporting accurate event prediction for a cardiovascular outcomes research trial using the Major Adverse Cardiac Events ( MACE) composite endpoint. 

 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 led a packed workshop tackling the advantages and limitations of adaptive designs within this space.

In honor of World Obesity Day (celebrated on Oct. 11 2015) here is an American Heart Association Statistical Primer on Cardiovascular Research. Cardiovascular outcome trials (sometimes called CVOTs) are clinical trials that are critical for determining the safety of new anti-obesity and diabetes drugs. Early CVOTs like TECOS and SAVOR-TIMI enrolled over 14,000 and 16,000 patients respectively.

Cyrus Mehta, president and co-founder of Cytel, has been on the forefront of developing novel designs to shorten the length of these trials while maintaining high statistical rigor. In this primer he provides an overview of fixed sample, GS and adaptive designs for cardiovascular trials. Other topics include: adaptive sample size re-estimation, and SSR with enrichment for high and low risk subpopulations. 

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

In August 2006 AstraZeneca completed the ARISE trial, which aimed to determine whether AGI-1067 was effective in reducing atherosclerosis in patients with acute coronary artery disease [1][2]. A double-blind, placebo controlled, Phase 3 trial, the primary efficacy endpoint was a composite endpoint which included major adverse cardiovascular events (MACE) like cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction and non-fatal stroke. However, it also included two less serious but more frequently observed events, namely hospitalization due to coronary revascularization and hospitalization due to unstable angina with evidence of ischemia [2]. 

When the FDA first began to require pharmaceuticals to perform cardiovascular outcome trials to establish the safety of certain new drugs, many worried that this new regulatory requirement would diminish investments in therapeutic areas like diabetes and obesity [1]. CVOTs are typically designed as massive time-to-event trials that need to enroll several thousands of patients to establish safety [2][3]. The sheer number of patients and size of the trial increases the time that it takes for these drugs to get to market.

So what is it the makes US and EU regulatory strategy different for diabetes and weightloss drugs, and how should this effect clinical development strategy?

A well-timed interim analysis can generally supply added benefits to the operational and administrative aspects of a clinical trial. Particularly when clean data and safety adjudications provide information that is instrumental for stopping a trial early or informing sensitive interim decisions, the timing of an interim look may play a crucial role in leveraging all of the flexibility that a complex, adaptive design has to offer.