April 9, 2013

An omission, a recommendation, and a prediction.

The President’s Council of Advisors on Science and Technology (PCAST) recently issued a report to the President of the United States on propelling innovation in drug discovery, development, and evaluation [1]. It is well worth your time to read the entire report. The Council stated that the pace of new therapeutic development has not kept up with the explosion in scientific knowledge of cancer, heart disease, diabetes, and other devastating diseases. Their recommended actions have the audacious goal of doubling, over the next decade, the rate of invention of new medicines for patients, while increasing drug safety.

As one might expect, a wide range of issues must be solved before this goal can be realized. In this essay, I focus on 2 aspects of the report I found most interesting; one is an omission, the other a radical departure from common practice. And I make my own prediction in the realm of audacity.

First, let’s consider something I consider a critical omission from the PCAST recommendations. The report posits (p. viii):

Accelerating the translation of biological insights into new medicines requires developing powerful new scientific knowledge, methodology, and tools. Academic scientists tend not to pursue such work, because it is seen as ‘too applied’ and because it often requires multidisciplinary teams rather than individual academic labs.

I find it difficult to imagine how we are going to accelerate innovation unless we come to grips with the need to work in teams. When we talk about tools, more often than not we are referring to the technical aspects of research and development (R&D), such as new equipment for measurement of a phenomenon of interest. We do not speak of new tools for enhancing team work and knowledge synthesis related to the management aspects of R&D. Yet, a comprehensive, interdisciplinary synthesis of available data and experience should play a central role in the innovation that leads to new medicines. This knowledge synthesis is essential for the proper design, analysis, and interpretation of studies, and for the assembly and presentation of evidence in successful regulatory submissions. Unfortunately, cross-functional, interdisciplinary knowledge synthesis is lacking in many R&D programs. What often passes for “synthesis” is merely a collection of separate facts and study results from various disciplines. Without true synthesis of knowledge, erroneous assessments of the value of drug assets can be made, causing allocation of resources to unproductive development programs [2]. We will revisit the comment about academic scientists in my prediction below.

The other aspect of the report that I found interesting is a key recommendation from PCAST, which concerns the relationship between representatives from the US Food and Drug Administration (FDA) and the drug development teams. The report says (p. 46):

Sponsors need a clear, consistent, and timely understanding of FDA concerns about their drug development plan, yet they often express frustration that this understanding can be difficult to obtain for two reasons. First, FDA staff is stretched thin addressing formal PDUFA [Prescription Drug User Fee Act] milestones due to insufficient total funding from Federal appropriations and PDUFA. Second, the review process for each drug lacks a single high level individual tasked with responsibility for providing clear, consistent ongoing advice to the sponsor. As a drug progresses from the pre-investigational stage (pre-IND) to final consideration for approval (NDA), many staff across divisions and offices are involved in the review.

The solution proposed by PCAST would be for the FDA to designate, for each drug development project, a senior staff member to serve as “pre-market review leader.” This individual would have the authority and accountability for integrating the input, resolving conflicting opinions within the FDA and with other stakeholders, and communicating informally in a timely ongoing manner.

This solution is quite radical. As described in the report (p. 46):

This individual would be a ‘quarterback’ for the drug development project, with responsibility for providing sponsors with substantive, informal, clear, and timely advice, and for coordinating and leading FDA responses across diverse areas, including toxicology, trial design, manufacturing and clinical use, and for ensuring that timely decisions are made to resolve outstanding FDA review issues. Pre-market review leaders would be valuable for all sponsors, and could be especially helpful for small companies bringing their first product through a regulatory approval. Such a system could greatly improve regulatory certainty, timeliness of FDA decisions, and encourage innovators and investment in innovation.

This type of system is commonly used in the defense and aerospace industries and is long overdue in the biomedical innovation ecosystem. The representative of the Department of Defense or relevant funding agency is an integral member of the project team and is involved in all aspects of design and decision-making, especially in ensuring that all relevant stakeholders are properly represented.

Which leads me to my audacious prediction — I predict that the company or academic institution that embraces the strategy of forming comprehensive interdisciplinary teams with representatives from all stakeholders, including the FDA, and that puts into place innovative management strategies to ensure the proper functioning of these teams, will, over time, come to dominate the drug discovery and development landscape in their chosen technical competence areas.

One final point. The comment in the report about academic scientists (p. viii); namely, “Academic scientists tend not to pursue such work, because it is seen as ‘too applied’ and because it often requires multi-disciplinary teams rather than individual academic labs” describes a malfunctioning innovation environment that we can ill-afford. This lack of interdisciplinary collaboration has important implications for the success of biomedical research that originates in academia and is, in fact, a key obstacle to accelerating innovation.


Are you hooked? Check out the previous Pharma of the Future? blog entry, The drama in drug development. Or visit the Pharma of the Future archive to catch up with the future of pharmacometrics.

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[1] Executive Office of the President, President’s Council of Advisors on Science and Technology. Report to the President on propelling innovation in drug discovery, development, and evaluation. http://www.whitehouse.gov/sites/default/files/microsites/ostp/pcast-fda-final.pdf. Published September 25, 2012. Accessed April 1, 2013.

[2] Grasela T, Slusser R. Innovation ecosystems in pharma: collaboration at the boundaries between disciplines. AAPS Newsmagazine. 2012;Dec:22-25.

 

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An omission, a recommendation, and a prediction.

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