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Improving combination drug trials using ‘definitive screening designs’

Nature Biotechnology volume 40, pages 1720–1721 (2022)Cite this article

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As developers of high-complexity biologic cocktails, we read with interest the Feature by Strohbehn et al.1 in the December 2021 issue of Nature Biotechnology voicing concerns about the risk of unjustified patents for arguably obvious drug combinations. The current approach to clinical trial design is built for the development of single-agent therapies; it lacks the scalability needed to systematically explore the entire design space of combination therapies. Full factorial trial designs exploring all possible combinations and dosage levels would be infeasible even for the largest biopharmaceutical companies. Against this backdrop, it is not surprising that drug developers focus their efforts on the much smaller set of obvious combinations.

This is unfortunate. Gilead’s drug Harvoni (ledipasvir/sofosbuvi) demonstrates the power of drug combinations. Before its launch, the standard-of-care drugs for hepatitis C came with intense side effects and high price tags for both patients and healthcare payers. Harvoni—a combination of two antiviral compounds—changed everything. With a >94% 12-week cure rate and modest side effects2, it offers immediate relief to patients. Similar combination breakthroughs have happened in the management of HIV/AIDS and chemotherapy. Indeed, the term ‘drug cocktail’, which was coined in the context of HIV/AIDS, has penetrated the public lexicon to a degree that few other drug-development concepts have.

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Authors and Affiliations

  1. Lumen Bioscience, Seattle, WA, USA

    Michael Dodds, James Roberts & Brian Finrow

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  1. Michael Dodds
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Correspondence to Michael Dodds.

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The authors are employees of Lumen Bioscience.

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Dodds, M., Roberts, J. & Finrow, B. Improving combination drug trials using ‘definitive screening designs’. Nat Biotechnol 40, 1720–1721 (2022). https://doi.org/10.1038/s41587-022-01521-w

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