Many cancer drugs that received accelerated approval based on “reasonably likely” evidence in the United States from 1995 to 2017 were either not reviewed or were denied use by European regulators and England’s drug assessment agency because of insufficient safety, clinical benefit, or cost-effectiveness, according to a new study published in JAMA Internal Medicine.
The study, by researchers from the London School of Economics and Political Science (LSE), Harvard (United States) and Queen’s University (Canada), evaluated the discordance between regulators in the US and England over the harms and benefits of cancer drugs receiving accelerated approval.
Ninety-three cancer drug indications received accelerated approval from the US Food and Drug Administration (FDA) between 1992 and 2017. Of these, 12 drug indications were not recommended by the European Medicines Agency or England’s drug assessment agency (The National Institute for Health and Care Excellence) because they were deemed to have insufficient safety, clinical benefit, or cost-effectiveness, and 30 drug indications were not reviewed, the research revealed.
Of those that were recommended for use in the NHS, 86% required the negotiation of additional confidential price discounts, the imposition of restricted indications that limited prescribing to specific patient subgroups, or the submission of additional evidence for clinical benefit. Most cancer drug indications that received accelerated approval were also approved in England based on surrogate measures rather than survival.
Avi Cherla, Senior Health Policy Associate at LSE Health and lead author of the study, said: “At the time of approval, many cancer drugs do not provide strong evidence for clinical benefit or comparative effectiveness. Increasing use of unvalidated surrogate measures will likely lead to greater uncertainty for patients and payers when evaluating the harms and benefits of drugs and deciding on funding decisions.”
Discordance between the US and England was likely owing to the use of uncertain evidence derived from unvalidated surrogate measures which is the basis for accelerated approval from the FDA, the report suggests. The authors caution that further accelerating drug review times in England will likely reduce the evidence available to NICE when making decisions.
The researchers also suggest that public insurers in the US can learn from the NHS. First, re-evaluating coverage decisions in the US when data on safety and overall survival becomes available would greatly reduce public expenditure and provide access to drugs with the strongest value. Second, for drugs which are still gathering data in the post-marketing period, access can be conditioned based on discounts or collection of further data for quality of life or overall survival.
"Assessment of Coverage in England of Cancer Drugs Qualifying for US Food and Drug Administration Accelerated Approval" by Avi Cherla, Huseyin Naci, Aaron S Kesselheim, Bishal Gyawali and Elias Mossialos is published by JAMA Internal Medicine.