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  • Perspective
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The value of anticancer drugs — a regulatory view

Nature Reviews Clinical Oncology volume 19, pages 207–215 (2022)Cite this article

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Abstract

The high prices of new anticancer drugs and the marginal added benefit perceived by some stakeholders have fuelled a debate on the value of anticancer drugs in the European Union, even though an agreed definition of what constitutes a drug’s value does not exist. In this Perspective, we discuss the value of drugs from different viewpoints and objectives of decision makers: for regulators, assessment of the benefit–risk balance of a drug is a cornerstone for approval; payers rely on cost-effectiveness analyses carried out by health technology assessment agencies for reimbursement decisions; for patients, treatment choices are based on personal preferences and attitudes to risk; and clinicians can use several scales (such as the ESMO Magnitude of Clinical Benefit Scale (ESMO–MCBS)) that have been developed as an attempt to measure value objectively. Although a unique definition that fully captures the concept of value is unlikely to emerge, herein we discuss the importance of understanding different perspectives, and how regulators can help to inform different decision makers.

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Fig. 1: Clinical trials versus real-world evidence.

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Authors and Affiliations

  1. Oncology & Haematology Office, European Medicines Agency, Amsterdam, Netherlands

    Francesco Pignatti, Douwe Postmus & Julio Delgado

  2. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

    Ulla Wilking, Nils Wilking & Jonas Bergh

  3. Department of Epidemiology, University of Groningen, University Medical Centre, Groningen, Netherlands

    Douwe Postmus

  4. Department of Haematology, Hospital Clinic, Barcelona, Spain

    Julio Delgado

  5. Breast Cancer Centre, Theme Cancer, Karolinska University Hospital, Karolinska Comprehensive Cancer Centre, Solna, Sweden

    Jonas Bergh

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F.P., U.W., D.P., N.W. and J.D. researched data for the article; all the authors discussed the manuscript contents; F.P., U.W. and J.D. wrote the article; and all the authors reviewed it before submission.

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Correspondence to Julio Delgado.

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Dedication

We dedicate this paper to Bertil Jonsson, clinical assessor, Medical Products Agency, Sweden, and past vice-chairman of the EMA Scientific Advice Working Party and of the Oncology Working Party.

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Nature Reviews Clinical Oncology thanks J. Del Paggio, C. A. Uyl-de Groot and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Benefit–risk evaluations

Together with evaluation of the ‘quality’, ‘safety’ and ‘efficacy’ of a new drug, the evaluation of the benefit−risk balance is the cornerstone of the scientific opinions of regulatory agencies (including the EMA) when assessing new drug applications. This evaluation is based on the balance between the favourable effects (benefits) of a medicine against its unfavourable effects (harms, commonly referred to as ‘risks’). Regulatory agencies can only recommend authorization of medicines with a positive benefit–risk balance. In conventional marketing authorizations, regulatory agencies do not evaluate the benefit–risk balance of medicines in the context of all approved drugs for the same indication, but instead base their assessments on the ‘absolute’ benefit–risk (exclusively the benefits versus the harms from the drug).

Cost-effectiveness

Cost-effectiveness analysis compares the relative costs and relative effects of two or more courses of action. Effects can be measured, for example, in years of life gained from the intervention or number of surgical procedures avoided85.

Effectiveness

This term refers to the extent to which an intervention is able to cause the intended pharmacological effects when provided under the usual circumstances of health-care practice, also referred to as ‘in real life’. Effectiveness is distinguished from efficacy to refer to the smaller magnitude of effects often assumed or observed at the population level when the medicine is provided under the usual circumstances compared with the ideal circumstances of a controlled clinical trial setting (owing, among other things, to patient selection or monitoring)84. This concept is mainly used in the context of health technology assessment and is not a regulatory requirement for a marketing authorization of new medicines.

Efficacy

This term generally refers to the ability of a medicine to cause the intended pharmacological effects (referred to as ‘benefits’ or ‘favourable effects’, as opposed to ‘harms’, ‘risks’ or ‘unfavourable effects’) under ideal circumstances. In oncology, efficacy is often measured directly using clinical outcomes such as overall survival in randomized controlled trials. Efficacy is often distinguished from ‘activity’, typically measured in single-arm trials and evaluating a pharmacodynamic effect that is not necessarily associated with a clinical effect, such as tumour shrinkage on imaging. Efficacy is also often distinguished from ‘effectiveness’84.

Health technology assessment

(HTA). Systematic evaluation of the properties and effects of a health technology, addressing its intended and unintended consequences, and aimed at informing decision-making. HTAs involve evaluation of clinical effectiveness, safety, cost-effectiveness and, when broadly applied, societal, ethical and legal aspects. A major application of HTAs is in informing reimbursement and coverage decisions by insurers and national health-care systems.

Relative effectiveness

Comparison of an intervention with available treatments — that is, this term refers to the extent to which an intervention does more good than harm compared with one or more alternative interventions under the usual circumstances of health-care practice. The concept differs from ‘effectiveness’ owing to its comparative nature84. A similar distinction exists for efficacy and relative efficacy. This concept is mainly used in the context of health technology assessment and is not a regulatory requirement for a marketing authorization of new medicines.

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Pignatti, F., Wilking, U., Postmus, D. et al. The value of anticancer drugs — a regulatory view. Nat Rev Clin Oncol 19, 207–215 (2022). https://doi.org/10.1038/s41571-021-00584-z

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