The Iterative Development of Medicines Through the European Medicine Agency's Adaptive Pathway Approach

Abstract

The development of novel regulatory tools such as adaptive clinical trial design and utilization of real-world evidence are topics of high interest. Recently, the European Medicines Agency (EMA) introduced the Adaptive Pathways (AP) that represents an innovative tool in healthcare systems allowing the early dialogue with multiple stakeholders on promising and innovative medicinal products in areas with an high unmet medical need. The innovative aspect in the AP is the early involvement of several stakeholders such as pharmaceutical industry, the Academia, Health Technology Assessment (HTA) bodies, and patient representatives bringing their real experience with the disease and their expectations about the treatment. AP is not a new licensing tool but an opportunity for a very early discussions, before starting the phase II studies, among all stakeholders, including regulators, companies, HTA bodies, and patient representatives on a new potential medicine in areas of high unmet medical need. The aim of this paper is to describe the evolution of the AP approach from the beginning of the pilot project to date, highlighting major advances, and achievement at European level.

European Medicines Agency’s Priority Medicines Scheme at 2 Years: An Evaluation of Clinical Studies Supporting Eligible Drugs

“…In addition, reliance on studies with small sample sizes after the PRIME designation may indicate growing regulatory confidence in learning from even the smallest numbers of patients. PRIME studies fit within this regulatory landscape, which is evolving toward adaptive pathways , and seem consistent with the EMA's rethinking of evidence generation over medicines' life‐cycle …”

“…PRIME studies fit within this regulatory landscape, which is evolving toward adaptive pathways, and seem consistent with the EMA's rethinking of evidence generation over medicines' life-cycle. 22 The picture of PRIME medicines' evidence base that arises from our analysis underlines the importance of postapproval confirmatory studies. Single-arm trials suffer from a range of biases, such as regression to the mean, patient selection effects, or variability in historical controls, as well as from confounding.…”

Improving Interactions Between Health Technology Assessment Bodies and Regulatory Agencies: A Systematic Review and Cross-Sectional Survey on Processes, Progress, Outcomes, and Challenges

“…However, this mechanism is criticized as outdated and that it ignores the complexities of health technologies, as well as the diversity in population features and disease progression ( 3 ). Hence, there has been a push for a shift from the traditional approach, which relies on extensive testing and the marketing authorization for large groups of patients (with a single decision point focus) to a procedure that employs periodic or staged assessment and reassessment using an evolving evidence base ( 81 , 82 ). There have been a number of proposals ( Supplementary Table 8 ) advocating for planned adaptive approaches to drug licensing using terms such as “staggered entry,” “adaptive approval,” and “progressive authorization.” However, much of the conceptual framework of adaptive licensing emanated from the New Drug Development Paradigms (NEWDIGS) collaboration that started in 2010 as an initiative of the Massachusetts Institute of Technology (MIT) and was hosted by the MIT Center for Biomedical Innovation ( 81 ).…”

“…In Europe, the EMA early access and registration tools include Priority Medicine (PRIME) (85), conditional marketing, and authorization and approval under exceptional circumstances (86), as well as compassionate use exist (87). Hence, the concept of AP is not necessarily a new licensing pathway but a way of getting clinical data in order to design a smart development program to meet the evidentiary needs (82,83).…”

Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antibacterial Agents: A Review

“…The EMA introduced with Adaptive Pathways a new tool to accelerate the proceeding accessibility of highly needed drugs by approving them in earlier stages to small and well-defined populations [ 26 ]. After the withdrawal of big companies from the US antibiotics market as a result of unfavorable financial prospects [ 27 ], the FDA started the project Generating Antibiotic Incentives Now (GAIN) in 2012, to make the development of new agents more profitable and attractive [ 28 ].…”