Studies show substantial spending on cancer drugs that lack documented clinical benefit
Cancer drugs without documented clinical benefit are being used increasingly and account for a substantial amount of health care spending, according to results of two studies published in JAMA Internal Medicine.
Investigators of the studies, led by Harvard Pilgrim Health Care Institute, called for timely withdrawal of FDA approvals of drug indications for which confirmatory studies show no clinical benefit, as well as for health care systems to monitor spending more closely on drugs that lack documented OS benefit.
Anita Katharina Wagner, PharmD, MPH, DrPH, associate professor of population medicine in the department of population medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute, told Healio that use of and spending on drugs without documented benefits may have “downstream effects” on individual patient care quality, as well as “upstream effects” on resources for population health.
“Both studies were motivated by our view that regulatory decisions need to be understood in a system context,” said Wagner, senior author of the studies. “Our intent was to document cancer drug use and spending by type of evidence.”
Use and financial impact
The first study assessed use of and spending on oral targeted cancer drugs among U.S. residents with employer-sponsored insurance. It included 37,348 patients (mean age, 64.1 years; standard deviation, 13.1 years; 57.1% men) who had at least one of 44 new oral targeted drugs dispensed between 2011 and 2018.
Wagner and colleagues sought to determine the annual and cumulative numbers of patients who had dispensing events, as well as the annual and cumulative payment for eligible drugs.
Although a large percentage of patients (97%) received drugs that had evidence from existing randomized clinical trials, the percentage who received drugs without documented OS benefit rose from 12.7% in 2011 to 58.8% in 2018. Additionally, although 96.8% of the $3.5 billion estimated spending on new cancer drugs was for agents approved based on results of randomized clinical trials, cumulative spending on drugs without documented OS benefit ($1.8 billion) was greater than the amount spent on drugs with documented OS benefit ($1.7 billion) by the end of 2018.
“The goal of any medical intervention should be to help patients live better longer. Our findings suggest that cancer drugs without documented overall survival or quality-of-life benefits are adopted in the health system and account for substantial spending,” Huseyin Naci, MHS, PhD, associate professor of health policy at the London School of Economics and Political Science, said in a Harvard Pilgrim Health Care Institute press release.
Spending on withdrawn drugs
In the second study, researchers estimated Medicare spending on the 10 accelerated approval cancer drug indications reevaluated by the FDA in 2021 after confirmatory studies showed lack of OS benefit.
Researchers extracted aggregated annual spending for the four drugs used to treat cancer in the studies — atezolizumab (Tecentriq, Genentech), durvalumab (Imfinzi, AstraZeneca), nivolumab (Opdivo, Bristol Myers Squibb) and pembrolizumab (Keytruda, Merck) — from the Medicare Part B and Part D Drug Spending Dashboards from 2017 to 2019.
Results showed estimated monthly Medicare drug reimbursement ranged from approximately $9,850 to $13,400 in 2019 based on the average sales price for that year. Additionally, between 2017 and 2019, Medicare spending on the 10 accelerated approval indications increased to an estimated inflation-adjusted $569 million. Of that total, $171 million corresponded to indications voluntarily withdrawn by manufacturers and $498 million corresponded to indications reevaluated by the FDA, researchers reported.
“Unless the accelerated approval pathway is reformed, significant spending on drugs with no proven clinical benefit will likely continue,” Mahnum Shahzad, a PhD candidate in health policy and research fellow at Harvard Pilgrim Health Care Institute, said in the press release.
Taken together, both studies suggest solutions are needed to curtail wasteful health care spending on cancer drugs in the U.S. Wagner said some of this could come from the FDA.
“Within its existing regulations and powers, FDA could enforce timely completion of confirmatory trials and consistently withdraw approvals of indications for which clinical benefits are not documented,” Wagner told Healio.
With their studies, Wagner and colleagues also wrote that the increasing use of and spending on cancer drugs without documented OS benefit is also a reflection on the current U.S. cancer drug ecosystem, from drug development and regulation to pricing, reimbursement and advertising.
“Policy changes in this complex ecosystem likely need to be multipronged and are likely challenging and controversial as most require cooperation of stakeholders with different priorities. Yet, some changes may be more readily feasible than others,” Wagner said. “Among those may be FDA efforts to make explicit and easily accessible for patients, their clinicians, and others what is known and what is not known about the clinical benefits of newly approved, highly priced cancer drugs. Such efforts could start with consistent documentation of overall survival information in FDA-approved labeling.”
Wagner referenced a study published in JAMA Network in July that investigated how information on OS benefits is communicated through labeling. Additionally, she mentioned a study from Institute for Clinical and Economic Review, published in Future Medicine in August, in which researchers suggested a clear visual alert in labels of limited evidence underlying accelerated approvals, “akin to black box warnings.”
“The expectation for newly approved cancer drugs is that they help patients live better longer,” Wagner told Healio. “Future research should assess to what extent patients, clinicians, and the public understand what is known and what is not known about the clinical benefits and risks of newly approved cancer drugs and the tradeoffs of individual and societal spending on drugs without documented overall survival benefit.”
Fu M, et al. JAMA Intern Med. 2021;doi:10.1001/jamainternmed.2021.5983.
Shahzad M, et al. JAMA Intern Med. 2021;doi:10.1001/jamainternmed.2021.5989.
Two new studies examine rising cancer drug spending in the US. https://www.eurekalert.org/news-releases/931653. Published Oct. 18, 2021. Accessed Oct. 19, 2021.
For more information:
Anita Katharina Wagner, PharmD, MPH, DrPH, can be reached at Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, 401 Park Drive, Suite 401 E., Boston, MA 02215; email: firstname.lastname@example.org.