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A Framework for Safety Evaluation Throughout the Product Development Life-Cycle

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Abstract

Evaluation of the safety profile of medicines is moving from a more reactive approach, where safety experts and statisticians have been primarily focusing on the review of clinical trial data and spontaneous reports, to a more proactive endeavor with cross-functional teams strategically evolving their understanding of the safety profile. They do this by anticipating the ultimate benefit–risk profile and its related risk management implications from the start of development. The proposed approach is based on assessments of integrated program-level safety data. These data stem from multiple sources such as preclinical information; clinical and spontaneous adverse event reports; epidemiological, real-world, and registry data; as well as, potentially, data from social media. Blended qualitative and quantitative evaluations allow integration of data from diverse sources. Adding to this, a collaborative multidisciplinary view, which is focused on continuous learning and decision-making via diverse safety management teams, ensures that companies look at their growing safety database and associated risk management implications from every relevant perspective. This multifaceted and iterative approach starts early in the development of a new medicine, continues into the post-marketing setting, and wanes as the product matures and the safety profile becomes more well understood. Not only does this satisfy regulatory requirements but, crucially, it provides the healthcare system and treated patients with a better understanding of the drug’s safety profile.

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Acknowledgements

We would like to acknowledge Jacqueline Corrigan-Curay, Bruce Binkowitz, Jay Herson, and Janet Wittes for helping us to refine our framework.

Disclaimer

This article reflects the views of the individual authors and should not be construed to represent the views or policies of their companies.

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Authors and Affiliations

  1. Clinical Safety Statistics, Merck & Co, Inc, RY 34-A318, 126 E Lincoln Ave, Rahway, NJ, 07065-4607, USA

    Greg Ball

  2. Drug Safety and Risk Management, Vifor Pharma Management Ltd, Glattbrugg, Switzerland

    Tjark Reblin

  3. Covilance LLC, Belmont, CA, USA

    James Buchanan

  4. Pharmacovigilance and Patient Safety, AbbVie, North Chicago, IL, USA

    Barbara A. Hendrickson

  5. Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Research Triangle Park, NC, USA

    Eric Lewis

  6. Division of Biostatistics, The Ohio State University College of Public Health, Columbus, OH, USA

    Patrick M. Schnell

  7. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA

    Frank W. Rockhold

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  1. Greg Ball
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  2. Tjark Reblin
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  3. James Buchanan
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  4. Barbara A. Hendrickson
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  6. Patrick M. Schnell
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Correspondence to Greg Ball.

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Conflict of interest

Dr. Schnell reports personal fees from Merck & Co, Inc, outside the submitted work. Dr. Rockhold reports grants from AstraZeneca, grants and personal fees from Janssen, personal fees from Merck Research Labs, personal fees from Merck Healthcare KGaA, personal fees from Novo Nordisk, personal fees from Rhythm, personal fees from KLSMC, personal fees from Aldeyra, personal fees from Complexa, personal fees from Sarepta, grants and personal fees from Eidos, grants from American Regent, grants from Reneuron, personal fees from Phathom, other from Athira, other from Spencer Healthcare, other from Datavant, grants from BMS, outside the submitted work.

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Ball, G., Reblin, T., Buchanan, J. et al. A Framework for Safety Evaluation Throughout the Product Development Life-Cycle. Ther Innov Regul Sci 54, 821–830 (2020). https://doi.org/10.1007/s43441-019-00021-5

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