Medicine Adaptive Pathways to Patients (MAPPs): Using Regulatory Innovation to Defeat Eroom’s Law
Medicine Adaptive Pathways to Patients (MAPPs) build on the stratification breakthroughs of personalized medicine to facilitate new types of clinical trials that adapt to a given patient’s response. At their core, MAPPs will have a limited commercial marketing authorization for a patient group who has access to new therapeutic agents while validating additional clinical endpoints at the same time. This gives MAPPs a theoretical ability to run trials that fulfil both the efficacy requirements for authorization…
Drug Designs Fulfilling the Requirements of Clinical Trials Aiming at Personalizing Medicine
In this review, we focus on trial designs aiming at personalized medicine in the context of early phase trials for initial marker validation, as well as in the context of larger definitive trials. Designs for biomarker validation are broadly classified as retrospective (i.e., using data from previously well-conducted randomized controlled trials (RCT)) versus prospective (enrichment, all-comers, hybrid or adaptive)…
The Changing World of Drug Development: An Academic Research Organization’s Perspective
Cancer poses a considerable economic burden to healthcare systems worldwide, so healthcare payers will only pay for “performance” in the future. It is likely that new “wonders” have emerged and as a scientific community we need to learn how we can make future cancer research more efficient. Clinical trials must be based on optimized trial designs with sound methodologies and high qualities. These multidisciplinary therapeutic strategies need to be in the new generation of patient treatment planning…
Integrative Oncology Drug Discovery Accompanied by Preclinical Translational Research as Prerequisite for Clinical Development
It is now generally accepted that target-specific compounds require specific new development programs. But, even for new drugs with general mode of action (i.e. chemotherapy), tailored treatment approaches, such as specific schedules or combinations, have been shown to improve the therapeutic outcome. New translational research approaches, starting already at target identification and validation will allow to define the optimal patient population for clinical development…
The spectrum of clinical trials aiming at personalizing medicine
All anticancer molecularly targeted agents on the market today have been approved with one or no companion diagnostic based on a specific genomic molecular alteration. Now, some molecular alterations have been described across different tumor types, although with variable prevalence and functional impact. The latter raises the question of whether treatment decision should be mainly based on molecular biology, independently of tumor location and histology. This approach refers to what is commonly named personalized medicine and can today be addressed in clinical trials, since major advances in high throughput technologies allow depicting most druggable molecular alterations for an affordable cost in a timeframe that is compatible with clinical practice.
From Genomic Data Analysis to Drug Development: A New Generation of Trials Using Molecular Marker Assessment in Breast Cancer
This article highlights the evolution of the sequencing technologies, the current molecular screening efforts and their impact on drug development as well as novel successful trial designs, focusing on the hormone receptor positive breast cancer patients.
The current design of oncology phase I clinical trials: progressing from algorithms to statistical models
In this article we examine how phase I trial designs for anti-cancer agents have developed over the past few decades. We review the use of algorithmic, relatively non- statistical designs, and then describe nonparametric and parametric statistically-driven designs that have better operating characteristics than algorithmic designs. We then follow with a description of how the original parametric design, known as the continual reassessment method (CRM), has been generalized and expanded to create designs for many complex settings that occur in early-phase oncology trials. We conclude with a discussion of outstanding issues and controversies that continue to exist with phase I trial designs.