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How should we assess the clinical and cost effectiveness of histology independent cancer drugs?

BMJ 2020; 368 doi: (Published 02 January 2020) Cite this as: BMJ 2020;368:l6435
  1. Sophie Cooper, scientific adviser1,
  2. Jacoline C Bouvy, senior scientific adviser1,
  3. Lawrence Baker, research assistant2,
  4. Francois Maignen, principal scientific adviser1,
  5. Pall Jonsson, associate director1,
  6. Peter Clark, Cancer Drugs Fund clinical lead3,
  7. Stephen Palmer, professor4,
  8. Meindert Boysen, centre director1,
  9. Nick Crabb, programme director1
  1. 1National Institute for Health and Care Excellence (NICE), 10 Spring Gardens, London SW1A 2BU, UK
  2. 2Massachusetts Institute of Technology, USA
  3. 3NHS England, UK
  4. 4Centre for Health Economics, University of York, UK
  1. Correspondence to: J Bouvy jacoline.bouvy{at}

Sophie Cooper, Jacoline Bouvy and colleagues discuss the challenges that histology independent cancer drugs will pose for NICE and the NHS

A histology independent cancer drug targets all solid tumours with a certain genomic mutation, regardless of the primary tumour’s histology.1 The US Food and Drug Administration (FDA) has approved three histology independent drugs (pembrolizumab, larotrectinib, and entrectinib) since 2017, and the European Medicines Agency (EMA) approved the first histology independent drug for the European market in 2019 (larotrectinib) (fig 1). Health technology assessment (HTA) bodies, including the National Institute for Health and Care Excellence (NICE), will therefore soon have to assess the value of these drugs to healthcare systems. Histology independent drugs are indicated for a multitude of tumour types, as long as they express the mutation. The prevalence of these mutations is often low, so the clinical evidence to inform reimbursement decisions for histology independent drugs will be immature and based on studies with extremely small sample sizes. This will make it challenging to assess whether the drug will provide value for money to health systems such as the NHS.

Fig 1

Timeline of regulatory approvals of histology independent cancer drugs in the United States and Europe. Pembrolizumab was never submitted for a histology independent indication to the European Medicines Agency (EMA). FDA=Food and Drug Administration

Clinical evidence for histology independent cancer drugs

NICE in England requires evidence of a drug’s clinical and cost effectiveness to decide whether the drug should be recommended for use in the NHS. Methods to inform these recommendations are commonly referred to as HTA, and the organisations responsible for making these recommendations as HTA bodies. Methods and processes vary between countries, but HTA usually starts around the time a new drug receives a marketing authorisation from the EMA. National HTA bodies will assess the added value of the drug to their …

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