Esha Senchaudhuri

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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...

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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


Phase 2 Designs for Clinical Utility Limiting Therapies

Posted by Esha Senchaudhuri

Apr 16, 2015 5:28:00 PM

When testing certain types of new drugs it is known in advance that the adverse side-effects of the medication will limit dose selection. For example, it is well-established that for many new pain medications, the side effects of nausea and vomiting will place constraints on the selection of higher dose levels.

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Topics: Dose-Finding, 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...

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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...

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Topics: Clinical Development Strategy, patient enrollment, enforesys


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...

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Topics: Clinical Development Strategy, Multi-Arm Studies


Statistical and Operational Challenges of the VALOR Trial: Mehta on the Promising Zone

Posted by Esha Senchaudhuri

Mar 26, 2015 4:00:00 PM

Last year Sunesis completed the VALOR trial, the first clinical study to make use of the groundbreaking promising zone design. The promising zone design implements an unblinded sample re-estimation after an interim look, but only if conditional power during the interim look falls within a designated promising zone. Although the VALOR trial did not confirm the efficacy of the new therapeutic, it...

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Topics: Promising Zone, Statistical Innovations in Clinical Development, Adaptive Clinical Trials


How Bayesian Strategies Can Expedite a Pediatric Clincial Trial Time by 20 - 40%

Posted by Esha Senchaudhuri

Mar 20, 2015 4:29:00 PM

Sometimes a new candidate drug for a pediatric study has already been tested on adults for safety and efficacy. We know that the drug is likely to work quite differently in children, but we do not know the degree to which the effects will be different. As a result, a conventional approach is to discard much of the information that has already gathered during studies of adults, and then to start...

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Topics: Bayesian Methods, Adaptive Clinical Trials, Pediatric


How to Plan Interim Looks in Adaptive Clinical Trials: 3 Strategies

Posted by Esha Senchaudhuri

Mar 19, 2015 5:26:00 PM

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...

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Topics: Interim Analyses, Cardiovascular, Cytel Events, Statistical Innovations in Clinical Development


Monte Carlo Simulations for Patient Enrollment: A Presentation by the Director of Pfizer's Feasibility Center for Excellence

Posted by Esha Senchaudhuri

Mar 12, 2015 5:08:00 PM

Enforesys: Learn More Recently, we published an interview with Chris Conklin, the Director of the Center for Feasibility Excellence at Pfizer. During the interview, Chris spoke about how his team navigates the complex terrain of trial planning and patient recruitment, and achieves those high flying enrollment milestones for each and every trial. His key...

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Topics: Software Simulations, patient enrollment, Monte Carlo, What are...


Embracing the Adaptive Mindset

Posted by Esha Senchaudhuri

Mar 10, 2015 11:35:00 AM

Most of us are primed to think about the design of adaptive clinical trials as a narrow set of techniques applied to a specific set of problems. If you’re worried about the power of your study, for example, you can turn to your toolkit of adaptive methods and find a suitable use for sample size re-estimation. If the concern is getting the best possible dose, a multi-arm study which drops doses...

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Topics: Multi-Arm Studies


Adaptive vs. Group Sequential Designs in Survival Analysis

Posted by Esha Senchaudhuri

Mar 5, 2015 11:00:00 AM

View Slides

The Mehta-Pocock promising zone is often used to carry out unblinded sample size re-estimation during interim analysis. However, according to Jin Wang of Abbott Vascular, it can also be used to re-estimate follow-up times in the interim look of a survival analysis study.

According to simulations run by Jin, the Mehta-Pocock promising zone design...

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Successful Adaptive Confirmatory Dose-Response Pediatric Study

Posted by Esha Senchaudhuri

Feb 26, 2015 4:48:00 PM

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.

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Topics: Cyrus Mehta


How Proposed Regulatory Reforms Will Affect Your Clinical Trial

Posted by Esha Senchaudhuri

Feb 17, 2015 6:40:00 PM

21st Century Cures (also called Cures2015) is a bipartisan initiative undertaken by the Committee on Energy and Commerce of the US House of Representatives. Amongst the many factors motivating this landmark legislation is the concern  that regulatory procedures must keep up to date with innovations in clinical development. Cures2015 aims to reform the regulation of drugs, biologics and medical...

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


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,...

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


3 Key Trends in Clinical Trial Enrollment Forecasting

Posted by Esha Senchaudhuri

Feb 5, 2015 4:50:00 PM

Every clinical trial requires some manner of trial forecasting, normally for feasibility and patient enrollment. However, studies reveal that more than 50% of clinical trials fail to meet enrollment targets, and that enrollment is the most commonly cited reason for Phase 3 trial discontinuation [1].

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Topics: feasibility studies, patient enrollment


Adaptive Design and Bayesian Statistics: 5 Years Later (Podcast)

Posted by Esha Senchaudhuri

Jan 29, 2015 4:00:00 PM

February 2015 marks the five year anniversary of the FDA’s Guidance on Adaptive Design Clinical Trials for Drug and Biologics, as well as the FDA’s Guidance on the Use of Bayesian Statistics in Medical Device Clinical Trials. In honor of the five year anniversary of both sets of guidance, the DIA will hold a special joint conference between its Adaptive Design working group and its working group...

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Topics: Bayesian Methods, Adaptive Clinical Trials


How to Take Control of Your Enrollment Woes

Posted by Esha Senchaudhuri

Jan 27, 2015 4:01:00 PM

Last week we released an infographic on why Phase 3 trials fail. The numbers, while eye-opening, did not capture a related and equally important issue: Why are so many late stage clinical trials discontinued?

Nearly 50% of all Phase 3 trials that are submitted to the FDA fail upon first submission [1]. However, 25% of all trials that begin are never even submitted for review [2].  According to a...

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Topics: feasibility studies, patient enrollment, trial planning


Adaptive Clinical Trial Strategies for the Limited Early Phase Budget

Posted by Esha Senchaudhuri

Jan 22, 2015 9:00:00 AM

The Journal of the American Medical Association recently published an article entitled ‘The Anatomy of Medical Research: US and International Comparisons.’ The stated objective of the study was to “quantify total public and private investment and personnel (economic inputs) and to evaluate resulting patents, publications, drug and device approvals, and value created (economic outputs)“ [1]

...

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Topics: Dose-Finding, Early Phase Trials, Proof-of-Concept, Case Study


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


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