The fate of investigational cancer therapies often depends upon which side of “the pond” is making the decision, a disconnect that is driven by the use of differing criteria and processes.
For example, the United States often approves cancer therapies using a fast-track process, while that accelerated approach is seldom used in England or Canada, according to two studies published in JAMA Internal Medicine.
In the first study, Avi Cherla, MSc, of the London School of Economics and Political Science, London, U.K., and colleagues, sought to assess the agreement between European and FDA decisions regarding drugs qualifying for accelerated approval by the FDA.
“Numerous cancer drugs have received accelerated approval from the U.S. Food and Drug Administration (FDA) based on clinical trial outcomes that are otherwise not acceptable for traditional FDA approval; the accelerated approval process allows outcomes based on surrogate measures that are only reasonably likely to estimate clinical benefits. In England, the National Institute for Health and Care Excellence (NICE) evaluates the clinical benefits and cost-effectiveness of drugs after they have received regulatory approval and issues recommendations regarding their coverage in the National Health Service (NHS),” they explained.
In this retrospective study, Cherla et al compared cancer drug indications receiving accelerated approval by the FDA with the same drug indications pairs in England.
From 1992 to 2017, 87 cancer drug indications received accelerated approval from the FDA. Despite the fact that 60% of the NICE approval decisions for oncology drugs were based on the same surrogate markers used for accelerated FDA approval, 30 of the 87 cancer drug indications granted accelerated approval by the FDA were not reviewed by either the NHS or NICE, and 12 were denied authorization or coverage due to insufficient data on their safety, clinical efficacy, or cost-effectiveness.
Further, Cherla and colleagues found that NHS coverage of accelerated approval drugs was often dependent on negotiations for added price concessions, additional data, or restriction to specific patient subpopulations.
“The discordance between the U.S. and England in the evaluation of cancer drugs granted FDA accelerated approval is likely owing to the routine use of comparative clinical and cost-effectiveness assessments by NICE for coverage decisions,” they concluded.
In a related study, also published in JAMA Internal Medicine, Daniel E. Meyers, MD, MSc, of the University of Calgary, Calgary, Alberta, Canada, and colleagues studied cancer drugs recommended in Canada by the pan-Canadian Oncology Drug Review (pCODR). They studied all cancer drugs with indications for solid tumors with a completed reimbursement recommendation from the pCODR.
Between 2011 and 2020, pCODR issued 104 reimbursement recommendations, of which 78 (75.0%) were given a positive recommendation, 72 (92.3%) of which were conditional. Only 50.0% of those that received a positive recommendation showed overall survival (OS) benefit, with modest median OS gains of 3.7 months.
Meyers and colleagues concluded: “These results suggest that, although the pCODR helps filter out some cancer drugs with low quality of evidence and low magnitude of benefit, cancer drugs without meaningful patient benefit continue to enter the Canadian market; these findings are important for making reimbursement policy decisions globally.”
In their invited commentary, Vinay Prasad, MD, MPH, of the University of California, San Francisco, and Myung S. Kim, MD, of Oregon Health and Science University, Portland, Oregon, noted that these two studies highlight several points:
- Very few FDA-approved cancer drugs receive broad coverage in England or Canada.
- Unlike England and Canada, U.S. coverage decisions are not based on survival, benefits to quality of life, or costs.
- FDA approvals of cancer drugs greatly influences other countries in decisions on drug approval, coverage, and pricing.
- Cancer drugs available in all three countries may not be as beneficial as clinicians hope they will be for cancer patients: “…the cancer drugs available in England, Canada, and the U.S. are not as good as physicians would hope for patients. Only 34 of 52 drugs that were considered by NICE had shown survival benefits at any point. In Canada, the median improvement in survival among covered drugs was just 3.7 months.”
In light of these points, the authors stressed the need for better policies for cancer drugs in the U.S.
“It is hard to not view the entire global cancer drug ecosystem as broken. Many cancer drugs come to market in the U.S. and, eventually, globally at unaffordable prices and with massive uncertainty about their benefits and harms. Their uptake is often delayed in high-income Western nations because of justified and persistent doubts about value,” Prasad and Kim wrote.
“The goal of drug policy in all nations is to maximally improve outcomes with every dollar spent. Achieving this may even involve setting higher standards for new drugs at the time of approval… the U.S. should understand and pay attention to the dynamics of drug approval in other countries. We should consider the possibility that our drug policy has negative repercussions for patients with cancer worldwide,” they concluded.
Limitations of the study from Cherla et al include its limited inclusion of cancer drugs first approved through the FDA’s accelerated approval process, use of only publicly available EMA and NICE drug evaluations, the exclusion of drug indications that preceded the formation of NICE, and failure to validate surrogate measures used for accelerated approval.
Limitations of the study from Meyers and colleagues include the failure to assess the role of cost or cost-efficacy in the pCODR’s decision-making process, failure to assess characteristics other than quality of evidence on trial phase and randomization, and the limited use of only data available at the time of pCODR’s decisions.
Only a fraction of cancer drugs approved in the US receive broad coverage in England and Canada.
Regulators in England and Canada more likely to approve cancer drugs only after price negotiations.
Liz Meszaros, Contributing Writer, BreakingMED™
Cherla, Meyers, and Kim reported no disclosures.
Prasad reported grants from Arnold Ventures Research; personal fees from Johns Hopkins Press, Medscape, UnitedHealthcare, New Century Health, and Evicore; and honoraria from medical centers, nonprofits, and professional societies outside the submitted work, as well as hosting a podcast called Plenary Session that has Patreon backers.
Cat ID: 118
Topic ID: 78,118,730,118,935,192,725,925