Development of new drugs is inherently complex and costly, with sources documenting up to $2.6 billion and over 9 years in investment to bring a new treatment to market. The high cost is driven, at least in part, by the failure rate for new compounds entering late-stage development, but also encompasses opportunity costs due to time and resources not spent on a developing an alternate treatment candidate, as well as investment in clinical trial infrastructure. Most importantly, these failures have an impact on patients— those who participate in the clinical trials associated with the testing of a failed drug candidate and those who will not benefit from having access to treatments that could have been developed instead. Given these considerations, late-stage development warrants further attention to understand why and how late-stage failures occur and to explore ways to improve the rate of success.

The goal of this collaborative, an ad hoc activity associated with the National Academies’ Forum on Drug Discovery, Development, and Translation, was to examine the contributing factors to late-stage failures and develop a set of key considerations for stakeholders to improve the probability of success in late-stage product development. In September 2020, collaborative participants published a journal article, The Failure to Fail Smartly, which examined the contributing factors towards the failure of late-stage clinical product development.

As of September 2020, the collaborative has sunset as a formal convening activity. The Forum may continue to support the dissemination of the publication resulting from this activity.

Objectives
With the participation of stakeholders involved in the development of drugs and/or biologics, this collaborative aimed to:

• Conduct structured, qualitative interviews with subject matter experts from across different sectors and disciplines; analyze the results; and pull out key themes.
• Perform a literature survey to supplement qualitative interviews
• Develop a set of key considerations for evaluation of late-stage product development.

Workplan
The project proceeded in four general phases:

• Discuss objectives and goals of this collaborative with members of the Forum. [complete]
• Develop an interview discussion guide; conduct structured, qualitative interviews with subject matter experts; and analyze interview responses. Simultaneously, conduct literature survey. [complete]
• Synthesize findings from interviews and literature survey and host a meeting to discuss and inform the results. [occurred October 2018]
• Publish a journal article on the contributing factors towards the failure of late-stage clinical product development [occurred September 2020 - https://www.nature.com/articles/d41573-020-00167-0]

The collaborative, which sunset in September 2020, was an ad hoc activity associated with the Forum on Drug Discovery, Development, and Translation (the Forum) at the National Academies of Sciences, Engineering, and Medicine (the National Academies). The work of the collaborative does not necessarily represent the views of any one organization, the Forum, or the National Academies and was not subjected to the review procedures of, nor was it a report or product of, the National Academies.