Gigi Hirsch

adaptive Licensing: Taking the Next Step in the Evolution of Drug approval

Traditional drug licensing approaches are based on binary decisions. At the moment of licensing, an experimental therapy is presumptively transformed into a fully vetted, safe, efficacious therapy. By contrast, adaptive licensing (AL) approaches are based on stepwise learning under conditions of acknowledged uncertainty, with iterative phases of data gathering and regulatory evaluation. This approach allows approval to align more closely with patient needs for timely access to new technologies and for data to inform medical decisions. The concept of AL embraces a range of perspectives. Some see AL as an evolutionary step, extending elements that are now in place. Others envision a transformative framework that may require legislative action before implementation. This article summarizes recent AL proposals; discusses how proposals might be translated into practice, with illustrations in different therapeutic areas; and identifies unresolved issues to inform decisions on the design and implementation of AL.

The future of drug development: advancing clinical trial design

Declining pharmaceutical industry productivity is well recognized by drug developers, regulatory authorities and patient groups. A key part of the problem is that clinical studies are increasingly expensive, driven by the rising costs of conducting Phase II and III trials. It is therefore crucial to ensure that these phases of drug development are conducted more efficiently and cost-effectively, and that attrition rates are reduced. In this article, we argue that moving from the traditional clinical development approach based on sequential, distinct phases towards a more integrated view that uses adaptive design tools to increase flexibility and maximize the use of accumulated knowledge could have an important role in achieving these goals. Applications and examples of the use of these tools — such as Bayesian methodologies — in early- and late-stage drug development are discussed, as well as the advantages, challenges and barriers to their more widespread implementation.

From Adaptive Licensing to Adaptive Pathways: Delivering a Flexible Life-Span Approach to Bring New Drugs to Patients

The concept of adaptive licensing (AL) has met with considerable interest. Yet some remain skeptical about its feasibility. Others argue that the focus and name of AL should be broadened. Against this background of ongoing debate, we examine the environmental changes that will likely make adaptive pathways the preferred approach in the future. The key drivers include: growing patient demand for timely access to promising therapies, emerging science leading to fragmentation of treatment populations, rising payer influence on product accessibility, and pressure on pharma/investors to ensure sustainability of drug development. We also discuss a number of environmental changes that will enable an adaptive paradigm. A life‐span approach to bringing innovation to patients is expected to help address the perceived access vs. evidence trade‐off, help de‐risk drug development, and lead to better outcomes for patients.

Accelerated Access to Innovative Medicines for Patients in need

There is broad agreement among health‐care stakeholders that more must be done to ensure that patients have timely access to new and innovative medicines. Assuming that industry will continue to develop such medicines at a sustainable rate, regulators and payers become the gatekeepers. Regulators, starting in the late 1980s/early 1990s, and, more recently, payers have implemented a variety of early‐access pathways or initiatives, and this practice is continuing even today. This article describes the specific approaches that have been taken in four economically developed regions, reviews their success rates, and suggests possible new directions.

Curing Consortium Fatigue

The complex pathology of consortium fatigue provides diagnostic data on how to improve collaboration in biomedical innovation. The complex pathology of consortium fatigue provides diagnostic data on how to improve collaboration in biomedical innovation.

Comparison of Stakeholder Metrics for Traditional and Adaptive Development and Licensing Approaches to Drug Development

This study evaluates whether an adaptive development and licensing approach to drug development, compared with approaches widely used today, might have tangible advantages across stakeholder groups, thereby facilitating the future adoption. Details involving actual and modeled clinical development and licensing programs for 3 case studies were used as inputs into a discounted cash flow spreadsheet model. Outputs included net present value and expected net present value, which are metrics considered as key incentives for pharmaceutical developers, and change in patient access over the product life and numbers of appropriately and inappropriately treated patients, which are metrics considered as key incentives for regulators, patients, and prescribers. Actual and modeled development programs were compared using an “adaptiveness” scoring algorithm. Generally, the more adaptive programs correlated with more favorable stakeholder outcomes. However, favorable outcomes may be overwhelmed in some cases, and the causative conditions and stakeholder reactions need to be defined.

Medicines Adaptive Pathways to Patients (MAPPs): A Story of International Collaboration Leading to Implementation

After nearly a decade of discussion, analysis, and development, the Medicines Adaptive Pathways to Patients (MAPPs) initiative is beginning to see acceptance from regulators, industry, patients, and payers, with the first live pilot project initiated under the guidance of the European Medicines Agency in 2014. Although it is a significant achievement to see the first asset being placed into human trials under an adaptive pathway, there is much to be learned regarding the multinational and multi-stakeholder effort that has driven the growing acceptance of MAPPs as a methodology and concept, as well as the need for continued and increasing international collaboration to foster the wider adoption of MAPPs. Changes in available science and technology, as well as a number of challenges in the current system, outlined in this paper, are transforming approaches to medicines development and approval. It is these challenges that have led directly to the groundbreaking MAPPs collaboration between the Massachusetts Institute of Technology Center for Biomedical Innovation’s New Drug Development Paradigms Initiative, the EMA, patient, payer and health technology assessment groups, the European Federation of Pharmaceutical Industries and Associations, and the Innovative Medicines Initiative—a European public-private partnership. This article examines the development of MAPPs, from inception of the concept, to the establishment of this trans-Atlantic initiative, and examines challenges for the future.

Adaptive Biomedical Innovation: Evolving Our Global System to Sustainably and Safely Bring New Medicines to Patients in Need.

The current system of biomedical innovation is unable to keep pace with scientific advancements. We propose to address this gap by reengineering innovation processes to accelerate reliable delivery of products that address unmet medical needs. Adaptive biomedical innovation (ABI) provides an integrative, strategic approach for process innovation. Although the term “ABI” is new, it encompasses fragmented “tools” that have been developed across the global pharmaceutical industry, and could accelerate the evolution of the system through more coordinated application. ABI involves bringing stakeholders together to set shared objectives, foster trust, structure decision‐making, and manage expectations through rapid‐cycle feedback loops that maximize product knowledge and reduce uncertainty in a continuous, adaptive, and sustainable learning healthcare system. Adaptive decision‐making, a core element of ABI, provides a framework for structuring decision‐making designed to manage two types of uncertainty – the maturity of scientific and clinical knowledge, and the behaviors of other critical stakeholders.

Adaptive Biomedical Innovation

Adaptive Biomedical Innovation (ABI) is a multistakeholder approach to product and process innovation aimed at accelerating the delivery of clinical value to patients and society. ABI offers the opportunity to transcend the fragmentation and linearity of decision‐making in our current model and create a common collaborative framework that optimizes the benefit and access of new medicines for patients as well as creating a more sustainable innovation ecosystem.

Access and availability of orphan drugs in the United States: advances or cruel hoaxes?

The Orphan Drug Act of 1983 in the United States collapsed the barrier between patients with rare diseases and promising drug treatments. Over the subsequent 30 years, > 400 ‘orphan drugs’ became available to them. However, with thousands of rare diseases still left with no treatments at all, many efforts are being put toward generating more investment for discovery, new clinical trial methods and more efficient approval processes. But, a new threat to access has emerged from the costs patients increasingly must bear. We call for a coordinated systems engineering approach that makes more treatments available to more people without unintended negative consequences on individual elements of the process.