How can the CMO/Biostatistician connection improve clinical development?

Posted by Cytel

Jun 7, 2016 8:00:00 AM

 At the recent CMO Summit East  James ( Jim) Bolognese, Cytel’s Senior Director of Strategic Consulting, and Lou Vaickus,MD, FACP, Founder and President of aktaPD jointly explored how the critical connection between a CMO and a biostatistician can help enhance communication with internal and external stakeholders, ensure patient safety and ultimately improve clinical development efficiency.  Below you can catch up with some of the key topics they covered and watch the video of the presentation. 

 

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Topics: Clinical Development Strategy, go-no-go, clinical development, biostatistics, p value


2 Talks on Early Phase Go/No-GO Decision Making

Posted by Cytel

Nov 12, 2015 4:00:00 PM

Last week Cytel joined forces with Sanofi/Genzyme to devote a full day of workshops and talks related to modern methods in early phase oncology. Patrick Mitchell, an Associate Director of Statistical Sciences at Astra Zeneca, gave this talk on Bayesian go/no-go decision-making in an early phase oncology event study. 

Astra Zeneca recently invited Cytel to take part in a collaborative initiative to develop software for go/no-go decision-making. Pat demonstrates the uses of this proprietary software in early phase oncology. 

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Topics: Bayesian Methods, Early Phase Trials, Clinical Development Strategy, go-no-go


The 24 Hour Work Day

Posted by Esha Senchaudhuri

Nov 5, 2015 3:34:15 PM

People Together-4

Oftentimes people perceive a tradeoff between speed and quality. The faster you do something the more likely you are to make mistakes. Then again, checking everything carefully means things take a longer time.

Right?  

What if you could promise a team that could work 24-7?

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Topics: Data Management, Clinical Research Services, Clinical Development Strategy


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?

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Topics: Statistical Analysis, Entrepreneurship, Clinical Development Strategy


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.

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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

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


Aligning Clinical Development & Regulatory Objectives for Cardiovascular Outcome Trials

Posted by Esha Senchaudhuri

Jun 11, 2015 5:21:09 PM

DIA_DC_Cyrus

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?

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Topics: Cardiovascular, Clinical Development Strategy, Adaptive Clinical Trials


How to Use Outsourcing to Reduce Clinical Development Risk

Posted by Esha Senchaudhuri

May 28, 2015 4:47:00 PM

Risks in drug development range from taking the wrong drugs forward to Phase 3 to investing in a drug development program at a time when regulatory standards are evolving, or competition is catching up with comparable products.

There is a particular source of risk, however, which deserves special attention. Currently, the pharmaceutical and biologics industry outsources approximately $25 billion dollars worth of clinical development projects. That is over a quarter of the $98 billion dollars currently devoted to clinical drug development.

This naturally raises several questions:

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Topics: Data Management, Clinical Research Services, outsourcing, Clinical Development Strategy


Seamless Adaptive Clinical Trials: Now that we get the statistics, what’s really at stake?

Posted by Esha Senchaudhuri

May 20, 2015 5:56:47 PM

Seamless adaptive clinical trials have gained popularity for reducing the projected time it takes to complete the process of drug development.  However, a study by Cuffe et al., shows that despite a tremendous amount of statistical knowledge about seamless trials, sponsors remain unsure about how to calculate the financial and operational costs of a seamless clinical development program [1]. This in turn results in many unnecessary risks and missed opportunities. This post offers advice on what you need to keep in mind in order to implement a successful seamless adaptive clinical study.

 

 

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Topics: Phase 1, Early Phase Trials, Clinical Development Strategy, Phase 3, Adaptive Clinical Trials, phase 2


New Articles on Adaptive Clinical Trials & Adaptive Financing

Posted by Esha Senchaudhuri

Apr 30, 2015 5:00:00 PM

Adaptive financing (not to be confused with adaptive licensing) explores how biotechs, pharmaceuticals and potential investors, can use adaptive designs for more strategic financial decision-making, as well as for efficient drug development.  

“For example,” writes Zoran Antonijevic, Senior Director at Cytel Consulting, “Reduction in costs and development time can be accomplished by combining stages of development, or by early stopping for efficacy or futility. Investment risks at late stage of development can be reduced by incorporating a sample size reassessment at an interim analysis, or simply by incorporating stopping rules for efficacy and/or futility."

Zoran has just edited a volume of Clinical Investigation featuring articles on the financial and developmental benefits of adaptive clinical trial design. The volume contains a broad spectrum of issues beginning with a couple of articles on adaptive financing by Tessella’s Tom Parke, and Christopher Weir of the Health Services Research Unit at the University of Edinburgh. 

The volume also stresses the pivotal nature of dose-finding for efficient development, with contributions on Phase 2 oncology trials from Anastasia Ivanova, Guochen Song, Olga Marchenko and Stergios Moschos; as well as Meinhard Kieser, Stefan Englert and Geraldine Rauch. Thomas Jaki also explains the use of multi-arm trials in treatment selection with a look at an Alzheimer’s case.

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Topics: Clinical Development Strategy, Adaptive Clinical Trials, Adaptive Finance


Dose-finding with Sequential Parallel Comparison Designs

Posted by Esha Senchaudhuri

Apr 23, 2015 3:53:00 PM

Last week the Cytel Blog discussed the benefits of using the Adaptive Maximizing Design [AM Design] for dose-finding trials involving clinical utility limiting therapies. However, there are other ways that a dose-finding trial can make use of frequent-adaptation maximizing designs. Here we look at what happens to early phase clinical development when an AM Design combines with another adaptive design that is slowly gaining popularity, namely the Sequential Parallel Comparison Design. 

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Topics: Cytel Consulting, Early Phase Trials, Clinical Development Strategy, Adaptive Clinical Trials, psychiatry and neuroscience


Adaptive SSR for Small Sample Sizes?

Posted by Esha Senchaudhuri

Apr 21, 2015 6:09:28 PM

“We shouldn’t use an adaptive design, our sample size is too small.”

Most clinical trial planners have heard this line of reasoning so often it has come to be taken as true. Never mind the fact that the first product to receive FDA approval using an adaptive sample size re-estimation design, was for a genetic condition affecting fewer than two thousand children worldwide [1].

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Topics: Clinical Research Services, Rare Disease, Clinical Development Strategy, Adaptive Clinical Trials


Relative Clinical Efficiency and Phase 2 Biomarker Studies

Posted by Esha Senchaudhuri

Apr 9, 2015 11:37:00 AM

Last year. Nature Reviews Drug Discovery asked the FDA’s Tatiana Prowell (Hematology & Oncology Products Division) about the most common pitfalls confronting clinical trials in oncology. She cited the late stage evaluations of biomarkers as one of three critical issues leading to regulatory failure [1]. The primary lesson: those who want to test biomarkers need to start earlier.  

OncoMed’s Eric Holmgren recently expanded on the nature of the problem, at a Cytel and ASA sponsored symposium on Statistical Innovations in Clinical Development. According to Holgren, the use of biomarker testing during Phase 2 can satisfy many forward-looking objectives. The objectives to prioritize, however, should depend quite significantly on a clinical trial sponsor’s resource constraints and asset value, and in particular on pre-Phase 2 costs. He considers three scenarios to illustrate how the investment undertaken in pre-Phase 2 studies should shape the objectives of Phase 2.

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Topics: Oncology, Predictive Enrichment, Precision Medicine, Clinical Development Strategy, Statistical Innovations in Clinical Development


Monte Carlo Simulations II: Reassessing Strategic Options During an Interim Look

Posted by Esha Senchaudhuri

Apr 2, 2015 1:32:00 PM

 

Midway through a trial is a terrible time to realize that you need a new strategy to complete the study. Sadly, it is typically midway through a trial when drug supply, patient recruitment and budget all tend to deviate from the planned development path. Sometimes this is because the initial plan utilized idealized assumptions, (i.e. non-random patient enrollment), which failed to give the desired ballpark estimate of timelines and resource constraints. Other times, responding to unexpected operational or statistical challenges might have proven difficult due to inflexible trial designs [1].

Enforesys: Learn More We have spoken in some depth about how thorough planning and room for flexible decision-making can avoid some of these potential difficulties [1] [2] [3].  However, sometimes the specter of trial discontinuity arises anyway. Here is a scenario which recently confronted the Cytel Consulting Team.

 

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Topics: Clinical Development Strategy, patient enrollment, enforesys, Adaptive Clinical Trials


Leveraging the Flexibility of an Adaptive Clinical Trials: A Case Study

Posted by Esha Senchaudhuri

Mar 27, 2015 5:43:52 PM

We have often said that one of the greatest benefits of an adaptive clinical trial is the flexibility it affords for decision-making [1]. Often this flexibility is taken to mean that sponsors have some leeway to accommodate events - foreseen or unforeseen, challenging or advantageous - midway through a trial. However, when designing a trial, it is often possible to leverage this flexibility towards the sponsor's advantage. 

Recently, a client approached us, determined to select the best of eight candidate doses to move forward into a pivotal Phase 3 trial. Like many in their situation, our client worried that testing all eight doses would require unnecessary time and expense. However, given a variety of other constraints, a subpar Phase 3 dose was simply not an option.  

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Topics: Clinical Development Strategy, Adaptive Clinical Trials, Multi-Arm Studies


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®.

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Topics: Clinical Development Strategy, feasibility studies, patient enrollment


How to Shorten a Cardiovascular Outcome Trial By Two Years

Posted by Esha Senchaudhuri

Feb 10, 2015 5:28:00 PM

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. 

However, since the explosive controversy over the FDA’s conditional approval of anti-obesity drug Contrave four years ago, there is much we have learned about how to make these trials shorter while also diminishing the financial risks of investing in them. For example, one of our clients managed to shorten the expected study length of an a CVOT by two years using a four point MACE Assessment (see below). 

In this post, we explore some of the lessons we have learned when designing these large-scale clinical trials.  

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


Why Drugs Fail in Phase 3: A Cytel Infographic

Posted by Esha Senchaudhuri

Jan 20, 2015 10:30:03 AM

According to a recent Cytel Whitepaper on Adaptive Clinical Trials, 50% of Phase 3 trials eventually fail. This new Cytel Infographicoffers a breakdown of why so many drugs fail in Phase 3.

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Topics: Early Phase Trials, Clinical Development Strategy, Phase 3, Adaptive Clinical Trials


Simulation and Prediction for Adaptive Licensing Decision-Making

Posted by Esha Senchaudhuri

Jan 13, 2015 3:03:54 PM

Janus was the Roman God of transitions, a deity with two faces, one looking towards the past and the other the future. It was only a matter of time therefore, that clinical trial simulators, and other purveyors of predictive analytics would adopt him as an embodiment of their core initiatives. The aptly named Janus Initiative aims to model decision pathways in clinical development, using powerful simulations to help inform multiple stakeholders on adaptive licensing decisions. The objective is to give every stakeholder in the process a sense of what consequences his or her decision-making will have on other stakeholders involved.

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Topics: Prediction, Clinical Development Strategy, Software Simulations, Adaptive Licensing


Early Phase Development Strategy: Bayesian Methods for Go/No-Go Rules

Posted by Esha Senchaudhuri

Dec 18, 2014 3:40:00 PM

Earlier this week, we at Cytel enjoyed a riveting in-house discussion on the uses of Bayesian decision rules for Go/No-Go (GNG) decision-making. GNG rules establish the trajectory of a particular clinical program’s development by assessing whether or not a trial has met particular objects (e.g. target regions for PK, PD and safety endpoints.)

Traditionally, statisticians have used p-values and confidence intervals to construct GNG rules. However, moving to the Bayesian paradigm opens up exciting new possibilities for clinical development strategy. Our discussion earlier this week centered around three key benefits of using Bayesian statistics for GNG decision-making:

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Topics: Early Phase Trials, Clinical Development Strategy, Adaptive Clinical Trials


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