Practical Challenges of the LUNG-MAP study

Posted by Cytel

Sep 27, 2016 9:24:00 AM

The Lung-MAP  trial is an innovative biomarker driven 'precision medicine' study which evaluates five novel agents for the treatment of patients with advanced squamous cell carcinoma of the lung.  As well as exploring therapeutic options for this indication, it also aims to improve the drug development process. 

At a Cytel seminar earlier in the year, Antje Hoering of CRAB presented to delegates on some of the practical challenges of the Lung-MAP study.

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Topics: Oncology, Precision Medicine, Clinical Development Strategy, Phase 3, phase 2, EDC


Evidence Based Medicine: 25 Years Later

Posted by Esha Senchaudhuri

Jul 27, 2015 5:47:00 PM

We were saddened to learn earlier this year, of the passing of Professor David Sackett. Widely recognized as the father of evidence based medicine, Professor Sackett confronted tough criticism in advancing the cause of evidence based medicine during the early nineties. During his four years at the Centre for Evidence Based Medicine at Oxford, Sackett’s team produced an array of books, articles, curricular and pedagogical practices, and software techniques which remain foundational to EBM's teaching and learning.

Evidence based medicine refers to the practice of incorporating “current best evidence” when determining care for individual patients [1]. Clinicians use their clinical expertise to specify the problem and the evidence necessary to solve it; the evidence itself, however, makes reference to biostatistics and epidemiology [2].More generally, evidence based medicine defends the view that clinicians should use both their clinical expertise and the findings of general clinical research in their practices, and that neither alone is sufficient to provide an appropriate level of care [1].

In a widely-cited paper, Sackett explains the irony of having to combat criticisms of championing a practice that was simultaneously ‘too old hat’ and yet also ‘too revolutionary’ [1]. In celebration of David Sackett, we consider Evidence Based Medicine in the early 1990s, and consider new developments twenty-five years later.  

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Topics: Precision Medicine, Evidence Based Medicine


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


Translational Statistics: How to Move Beyond the Comfort Zone

Posted by Esha Senchaudhuri

Nov 6, 2014 11:09:00 AM

Professor LJ Wei holds that rules are for lawyers, not (necessarily) clinicians. When designing modern clinical trials, the impetus is often to use “efficient and reliable procedures, to obtain clinically interpretable results with respect to risk-benefit analysis…” Yet these efficient and reliable procedures are often just conventions and rules that provide information that is incomplete or difficult to make clinically interpretable.

In a presentation to the East User Group Meeting, Professor Wei identifies 11 problematic areas that currently challenge trial designers. After giving an overview of the challenges that arise in each, Professor Wei provides a few simple solutions about how to overcome them. All the solutions, however, require moving beyond the comfort zone of conventional procedures.

In the slides attached Wei discusses:

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Topics: East, East 6.3, Access to Slides PDF, Trial Design, Trial Monitoring, Training and Education, Predictive Enrichment, Precision Medicine, Translational Statistics, Translational Medicine


New Exploratory Trial Method Translates into Better Financial Strategy

Posted by Esha Senchaudhuri

Nov 4, 2014 8:30:00 AM

A key stage of exploratory drug development is implementing a proof-of-concept study to demonstrate the safety of a drug. Given the importance of accurate dose-finding for Phase 3 success, methodological improvements to proof-of-concept studies in Phase 2 can translate into greater likelihood of getting a drug to market. 

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Topics: Oncology, Access to Slides PDF, Enrichment, Safety, Precision Medicine, Entrepreneurship, R&D, Adaptive Clinical Trials


5 Reasons to Invest in Adaptive Designs for Population Enrichment

Posted by Esha Senchaudhuri

Jul 8, 2014 6:00:00 AM

Predictive_Enrichment

The above graphic is from Cyrus Mehta's slides on 'Adaptive Population Enrichment for Oncology Trials with Time to Event Endpoints.'


 

Recent advances in precision medicine have meant that therapeutic treatments can now target subsets of a population that are most likely to respond well to treatment. Identification of such subsets largely relies on the presence or absence of particular biomarkers. In order to determine whether or not such biomarkers have predictive diagnostic capabilities, the biomarkers must first be validated as reliable predictive indicators, and thereafter as responding efficaciously to treatment.

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Topics: Oncology, Predictive Enrichment, Precision Medicine, Adaptive Clinical Trials


Adaptive Designs for Precision Medicine: A Look at Pfizer's Xalkori Trial (Slides Attached)

Posted by Esha Senchaudhuri

Jun 26, 2014 8:44:00 AM

The rise of biomarker based treatments in oncology has meant a reconceptualization of what constitutes a particular disease. According to the American Society for Clinical Oncology, “We can no longer think of cancer as one disease. Even something like lung cancer could be hundreds of different cancers, each defined by specific molecular characteristics requiring different treatment approaches.” [1] This means that many oncology trials are slowly moving from large-scale studies of generic populations, towards a system where targeted therapies are offered to smaller sets of patients who all possess certain genetic characteristics.

Nina Selaru of Pfizer Oncology, recently gave a talk at a Cytel Seminar in San Diego in which she described a trial for Xalkori, a therapy for non-small cell lung cancer (NSCLC). Pfizer conducted two Phase 3 trials for Xalkori, one for patients who possessed anaplastic lymphoma kinase (ALK-positive patients) and another for other ‘unselected’ patients. The ALK-positive patients were found to respond very well to treatment. Unfortunately, the ALK-positive patients also displayed certain characteristics not present in the other patients: they were younger, non-smokers who displayed signs of adenocarcinoma. There was concern that these characteristics were driving the efficacy of Xalkori.

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Topics: Oncology, Access to Slides PDF, Precision Medicine, Adaptive Clinical Trials


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