Regulatory withdrawal of medicines marketed with uncertain benefits: the bevacizumab case study.

Agnes Vitry,Vikky Entwistle,Elizabeth Roughead,Tuan Nguyen

doi:10.1186/s40545-015-0046-2

Agnes Vitry, Vikky Entwistle + Show 2 more

Open Access

https://doi.org/10.1186/s40545-015-0046-2

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Abstract

BackgroundWithdrawal of conditional regulatory approval or subsidization of new medicines when subsequent evidence does not confirm early trial results may not be well understood or accepted by the public. ObjectivesWe present a case study of the US Food and Drug Administration (FDA)’s decision to withdraw the indication of bevacizumab for the treatment of advanced breast cancer and include an analysis of the reactions of stakeholders with a view to identifying opportunities for improving risk management for new medicines with conditional approval or funding.MethodsWe drew on a range of information sources, including FDA documents, medical journals and media reports, to describe the evidentiary basis of the FDA decisions. We analysed the reactions and perspectives of the stakeholders.ResultsIn 2008 bevacizumab was granted conditional approval for treatment of advanced breast cancer by the FDA pending submission of supplementary satisfactory evidence. In 2011 the FDA decision to withdraw the indication was met with a hostile reaction from many clinicians and cancer survivors. There were different interpretations of the therapeutic value of bevacizumab with strong beliefs among cancer survivors that the medicine was effective and potential harm was manageable. High expectations of the public may have been encouraged by overly positive media reports and limited understanding by the public of the complexity of the scientific evaluation of new medicines and of the regulatory processes.ConclusionsImproving understanding and acceptance of approval or coverage schemes conditional to evidence development may require the development of risk management plans by regulatory and funding institutions. They may include a range of strategies such as requirements for formal patient acknowledgment of the conditional availability of the medicine, ‘black-triangle’ equivalent labels that identify full approval is based on pending evidence, and ongoing communication with the media, public and health professionals.

Highlights

In the United States, the Food and Drug Administration (FDA) has implemented an accelerated approval program for medicines that appear to provide a benefit for serious or life-threatening illnesses lacking satisfactory treatments [1]
Improving understanding and acceptance of approval or coverage schemes conditional to evidence development may require the development of risk management plans by regulatory and funding institutions
From the FDA website documents were retrieved related to the Oncologic Drug Advisory Committee (ODAC) meetings, transcripts and public submissions to the FDA, and the final 69-page document by Margaret Hamburg, the FDA commissioner explaining the reasons for bevacizumab withdrawal

Summary

Introduction

In the United States, the Food and Drug Administration (FDA) has implemented an accelerated approval program for medicines that appear to provide a benefit for serious or life-threatening illnesses lacking satisfactory treatments [1]. Under this program, medicines are given a conditional approval based on clinical trial data that. The withdrawal was highly contested, and this is a case from which other countries with schemes for regulatory approval or coverage conditional on evidence development could usefully learn We analysed both the basis of the FDA’s decisions and stakeholders’ reactions to them with a view to informing the development of risk management plans conditional approval or funding schemes. Withdrawal of conditional regulatory approval or subsidization of new medicines when subsequent evidence does not confirm early trial results may not be well understood or accepted by the public

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