Recent Posts

Cytel Case Study Series III: Dose Finding & Dose Response Modeling in Pediatric Asthma

Posted by Cytel

Oct 22, 2015 2:28:53 PM

Read More

Topics: Case Study, Pediatric, MCP-Mod

MCPMod: An Introduction

Posted by Cytel

Oct 15, 2015 5:31:00 PM

The method for dose-response modeling that is widely called MCPMod allows a sponsor to measure the likelihood that particular dose-response curves are the right mathematical model for a given set of data. Since several different dose-response curves might be able to fit the data, how can you determine which is the best curve for your purposes?

Read More

Topics: MCP-Mod

Statistical Primer for Cardiovascular Research

Posted by Cytel

Oct 13, 2015 4:39:00 PM

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. 

Read More

Topics: Cardiovascular

Being a Statistician: An Art, a Science or Just Job?

Posted by Cytel

Oct 8, 2015 4:25:00 PM

A recent American Statistical Association conference featured a town hall meeting to discuss the role of the statistician within the pharmaceutical industry, and in particular within the subfield of precision medicine. The panel of distinguished academics, regulators and members of industry confronted the concern that the era of precision medicine heralds an emerging need for statisticians to play a different role than the ones normally associated with technique and craft. Statisticians are now charged with discovering insightful applications to new statistical methodologies, and ensuring that clinical development reflects as many innovative statistical methods as necessary to achieve a successful study. According to the panel, statisticians may even find themselves in a position where they are required to anticipate scientific and technological advances for a study’s benefit.

Read More

Topics: Statistical Programming, statistical communication

2 Methods for Evaluating Biomarker Subpopulations in (Adaptive Enrichment) Time to Event Trials

Posted by Cytel

Oct 5, 2015 4:14:58 PM

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 clearly it is rejected for F too. Similarly, if it is rejected for S and not for S' then the therapy is effective for the biomarker subpopulation, and ineffective for the rest of the population.

As it turns out, whether or not a given biomarker is indeed a predictive biomarker should affect the choice of statistical methodology in time-to-event trials.

Read More

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

5 Skills Needed by All Highly Effective Statisticians

Posted by Cytel

Sep 29, 2015 5:02:00 PM

The Head of the DIA’s Adaptive Design Working Group Asks Us to Consider 5 ‘Soft-Skills’ All Effective Statisticians Should Cultivate

The advent of adaptive designs has meant that statisticians have a new role to play in the drug development process. Not only are they responsible for tackling the precise statistical issues that can arise during the course of a study, but their knowledge and vision can result in innovations that substantially alter study design, strategic decision-making, probability of trial success and level of revenue.  

Given this new role played by statisticians, what skills do statisticians now need to cultivate to be as effective as possible in the boardroom and on their project teams?

Read More

Topics: Statistical Analysis, Entrepreneurship, Clinical Development Strategy

Cytel Case Study Series II: Adaptive Bayesian Design with Informative Prior

Posted by Cytel

Sep 15, 2015 3:56:42 PM


Read More

Topics: Bayesian Methods, Cytel Consulting, Case Study, Adaptive Clinical Trials

Cytel Case Studies Series #1: Using Simulation for Accelerated Early Phase Drug Development

Posted by Cytel

Sep 4, 2015 10:30:00 AM

Our Client's Challenge:

Can knowledge of the relationship between biomarkers and clinical endpoints help us to optimize an early development program and improve the probability of selecting the right dose in Phase 3?

Our client approached us hoping to expedite dose-finding with biomarkers in Phase 1b, and to design an optimal Phase 2b clinical endpoint trial to maximize probability of correct Phase 3 dose selection.

Read More

Topics: Cytel Consulting, Early Phase Trials, Clinical Development Strategy, Proof-of-Concept, Case Study, Biomarkers, Simulations

Modern Early Phase Clinical Trial Design Primer

Posted by Cytel

Sep 1, 2015 4:01:39 PM

If you’re in the practice of conducting early phase clinical trials, you’ve probably heard that modern trial designs include a number of new methodologies. There’s CRM and BLRM, model-based methods versus rule-based methods, and a number of other developments that might affect your clinical strategy. Each of these methods affects operational, financial and regulatory objectives in unique ways.

As a part of this year’s Joint Statistical Meeting, Cytel statisticians created a primer to go along with a workshop for early phase clinical trial design.

In the primer you will find: 

  • 1. An overview of 3+3, CRM, BLRM and mTPI methods
  • 2. A synopsis of basic concepts like Bayesian and frequentist statistics, models and rules, etc.
  • 3. Reflections on regulatory considerations
  • 4. Case studies and topical exercises with Cytel’s high-powered simulations
  • 5. A solution guide for those with access to Cytel's East software  

 Click to download the Primer

Read More

Topics: Bayesian Methods, CRM, Early Phase Trials, Clinical Development Strategy, BLRM

Special Update: US House of Representatives Passes 21st Century Cures Act

Posted by Cytel

Jul 10, 2015 12:54:00 PM

Here at Cytel, we are engaging in a small celebration this afternoon, as the US House of Representatives has just passed the FDA Reform Bill more generally known as the 21st Century Cures Act.

Although this bill is widely viewed as a reform bill, it will provide extensive funding to both the FDA and NIH to ensure that clinical and pharmaceutical research lives up to its potential to deliver life-saving technologies in a faster, smarter way.

Title II of the act contains approximately 150 pages on drug development. We're sure some of you have read it through and through. However, for those putting off their summer reading until August, here are 4 exciting developments that we want all of our friends and affiliates to be aware: 

Read More

Topics: Bayesian Methods, Regulation, Medical Devices, Adaptive Clinical Trials

3 Strategies to Combat Inferential Conservatism in Small Sample Sizes

Posted by Cytel

Jun 25, 2015 4:28:00 PM

When conducting a clinical trial with small or sparse data sets, statistical methods meant for large sample sizes may fail to obtain an accurate interpretation of data. This is where computationally challenging exact methods often come into play.

Exact methods, however, are inferentially conservative in the sense that due to small sample sizes, the actual Type 1 error rate is often smaller than the nominal (intended) rate [1]. There exists an array of strategies to combat this troublesome feature of exact tests, each of which varies along the parameter of computational complexity.

Read More

Topics: Sample Size, Exact Inference, exact statistics, Small Sample Sparse Data

New Cytel Whitepaper: Monte Carlo Simulations for Patient Recruitment

Posted by Cytel

Apr 13, 2015 11:23:00 AM

Cytel has published a new whitepaper on Monte Carlo Simulations for Patient Recruitment, which illustrates how a technique already popular within industrial and business environments is now changing the game of data-driven patient enrollment forecasting. 

Read More

Topics: White Paper, Software Simulations, patient enrollment, Monte Carlo

Data-Driven Trial Planning: An Interview with Pfizer's Chris Conklin

Posted by Cytel

Feb 12, 2015 2:59:00 PM

Data driven decision-making can ensure that every feasibility team achieves its enrollment milestones. By transforming how pharmaceutical companies and CROs conduct feasibility studies, new techniques in recruitment planning are affecting every aspect of trial planning and clinical development strategy.

We sat down with Chris Conklin, the Director of the Feasibility Center for Excellence at Pfizer (pictured below) to discuss innovative ways to think about enrollment factors, and how he uses high-precision forecasting tools like Cytel’s EnForeSys®.

Read More

Topics: Clinical Development Strategy, feasibility studies, patient enrollment

Clinical Development & Statistical Methodology for Cardiovascular Risk Assessment

Posted by Cytel

Feb 3, 2015 2:00:00 PM

A new publication co-authored by Cytel Co-Founder and President Cyrus Mehta considers a range of clinical development methods for cardiovascular outcome trials. Cardiovascular outcome trials, (often referred to as CVOTs), reflect safety standards implemented by the FDA and EMA to determine whether or not new drugs impose undue cardiovascular risk on patients. CVOTs typically occur after Phase 3 trials, and often make up for the slow rate of observed events by enrolling thousands of patients. This adds substantial delay in getting a drug to market.

In this paper, Cyrus and his co-authors explore how adaptive and group sequential methods might shorten this process without compromising the quality of the trial. In particular they consider increases in sample size and early stopping boundaries. They consider the possible benefits of unblinded sample size re-estimation (also known as the Promising Zone Design) in CVOT trials. 

Read More

Topics: Cardiovascular, Group Sequential, Adaptive Clinical Trials

Clinical Drug Development: Predictions & Trends for 2015

Posted by Cytel

Jan 6, 2015 4:00:00 PM

As we head into the new year, the life-sciences industry can look forward to some long awaited advances in pharmaceutical drug development. Here are our predictions for top trends to look out for in 2015.

1: The Arrival of Adaptive Financing:

Adaptive financing was an idea that was cultivated and nurtured by members and affiliates of Cytel. It is the idea that a financial strategy can be built around outcomes that are observed at certain decision points during clinical development (for example, at interim analyses.) Constructing designs with adaptive financing in mind helps provide potential investors and study sponsors with a monetary ballpark of how much innovation will cost, and how much they have the potential to save. This helps overcome one of the biggest bottlenecks in implementing safer and more efficient adaptive trials, namely the perception by many in the industry that these trials are risky.

Read More

Topics: Entrepreneurship, Adaptive Clinical Trials

How to Incorporate New Technology into Your Clinical Development Strategy

Posted by Cytel

Dec 2, 2014 11:00:00 AM

During a recent DIA webinar on reinventing the clinical trial, Laurie Halloran (President of the Halloran Consulting Group) and Irving Dark (Senior Vice President at Cytel) weighed in on a wide array of recent technological breakthroughs that life sciences companies can leverage to simplify clinical development. Their discussion ranged from simple techniques to cut down the 80,000 sheets of paper used for the average clinical trial (“Take it to the Cloud!”) to remote centralized monitoring techniques that make use of cutting edge statistical innovations.

Read More

Topics: Data Management, Clinical Research Services, Entrepreneurship

Michael Proschan on 'Blinded Adaptations, Permutations and t-tests' (Link to Slides)

Posted by Cytel

Oct 30, 2014 10:28:00 AM

 During last week’s East Users Group Meeting, Michael Proschan of the NIH and NIAID, gave a presentation on ‘Blinded Adaptations, Permutations and t-tests.’ Given the close connection between adaptive t-tests and adaptive permutation tests, Proschan argued that it is possible to determine the validity of an adaptive t-test from the validity of an adaptive permutation test. Proschan concludes that in adaptive settings, “permutation tests are often valid in adaptive settings, even if blind is maintained.”

Michael's slides are available below. You can also find two of his recent papers on blinded adaptations in the 'Related Items of Interest' section.  

View Slides

Read More

Topics: permutations, Blind and Unblind Trials, t-tests, Adaptive Clinical Trials

FDA Industry Session Features Panel on "Seamless Adaptive Designs"

Posted by Cytel

Sep 16, 2014 3:30:00 PM

An FDA Industry Statistics Workshop on September 23 will feature a panel on seamless adaptive designs. Seamless adaptive designs are studies which are able to combine two stages of a clinical trial into one adaptive study, thereby cuting trial costs and reducing study length. The panel will feature Cytel Statistician Lingyun Liu,Lisa Kammerman of AstraZeneca, and Joshua Chen of Merck. The FDA's Sue-Jane Wang will be the featured discussant.

Read More

Topics: Cytel Consulting, Adaptive Clinical Trials

Congratulations Germany!

Posted by Cytel

Jul 14, 2014 11:49:00 AM

Congratulations to Germany for a fantastic World Cup victory! Records broken and beautiful moments marked this World Cup as extraordinary. We are excited to celebrate this achievement with all of our German colleagues and friends. As the attached article shows, Germany was up against some (statistically) impossible phenomena in the figure of Lionel Messi.  

Read More

Topics: Prediction, Statistical Analysis, Cytel Congratulates

De-Risking Drug Development using Adaptive Design

Posted by Cytel

May 13, 2014 8:31:00 AM

The VALOR trial recently applied a promising zone design to a Phase 3 evaluation of Vosaroxin, a candidate for the treatment of relapsed/refractory acute myeloid leukemia. CMO Dr. Adam Craig reports that there were intial anxieties about financing a trial that required 800 patients. However, a promising interim look raised investors' confidence in the treatment's success, leading to a high-powered trial of 712 patients.


To view a YouTube video of Dr. Adam Craig talking about the Phase 3 VALOR trial, click below.  

Read More

Topics: Oncology, Promising Zone, sample size re-estimation, Movers & Shapers, Adaptive Clinical Trials

The Cytel blog keeps you up to speed with the latest developments in biostatistics and clinical biometrics.  Sign up for updates direct to your inbox. You can unsubscribe at any time.


Posts by Topic

see all

Recent Posts