UChicago Researchers Establish Benchmark for Off-Label Use of Expensive Cancer Drugs


Health economics researchers led by Rena Conti, PhD, assistant professor of pediatrics at the University of Chicago, established a benchmark for the rate at which common chemotherapy treatments are used “off label,” meaning outside the uses approved by the Food and Drug Administration (FDA).

Using objective national data, their study, published Feb. 20, 2013, in the Journal of Clinical Oncology, found that in 2010 the ten most commonly prescribed patent-protected intravenous anticancer drugs were used off label about 30 percent of the time.

The paper, for the first time, quantifies the rate of off-label use of these commonly used chemotherapy regimens. Equally important, it shows that only about half of all off-label use is supported by clinical guidelines.

The 10 drugs included in the study are costly, with national spending on the 10 drugs totaling close to $12 billion in 2010. According to study results, approximately $2.5 billion was spent on drugs used in an off-label setting.

The authors caution that their research doesn’t explore the implications of this pattern. The study only quantifies it.

“We set out to better understand the role of regulatory agencies and physician opinion in prescribing behavior,” Conti said.  “Our study was designed to learn how often branded cancer drugs are used in clinical contexts without approval by the Food and Drug Administration.”

According to an editorial in the journal by Monika Krzyzanowska of the University of Toronto, “Conti, et al, provide us with the most comprehensive, to-date, contemporaneous snapshot of off-label prescribing in the United States.”

Conti and colleagues at the University of Chicago, Harvard, and Memorial Sloan Kettering found that 70 percent of the drug use examined was within FDA guidelines. Another 14 percent, “a sizeable proportion of off-label use,” according to Conti, conformed to off-label indications supported by the National Comprehensive Cancer Network (NCCN), an expert advisory board. Ten percent of off-label use was unsupported by the NCCN but consistent with FDA-approved cancer site – differing in disease stage, but not type (e.g., use in a patient with Stage I colorectal cancer, when FDA approval is for use in Stage III colorectal cancer).

Rena Conti, PhD, testifies before a Senate panel on prescription drug shortages in 2011

“It is clear from our results that physician judgment and expert opinion drive a sizable percentage of these drugs’ use, both in terms of evaluating each individual patient’s needs and disease progression, and in terms of referring to expert guidelines and compendia established by leading oncology colleagues,” Conti said.

Do these finding suggest that cancer patient are receiving inappropriate and inferior care?

“For certain drugs, wrote Krzyzanowska, “the answer is yes.”  For example, for two of the drugs studied, more than two-thirds of use was off label.

But “off-label use does not necessarily mean “inappropriate use.”  For many rare cancers, the editorial explains, there are too few patients to complete the appropriate clinical trial, thus “there may never be enough evidence to support a labeling indication.”

“When it comes to drug spending, there is no question oncologists face direct financial incentives to use expensive infused and injected chemotherapies in the outpatient setting,” Conti said.  However, the study did not examine whether financial incentives prompted use in the on- or off-label setting.  “These incentives drive use of these drugs generally, but we have no reason to believe that it drives off-label use more so than on-label use at this time,” she said.

The data analyzed by researchers had some limitations. Authors were unable to distinguish on-label use with specific patient and tumor characteristics, beyond cancer stage and treatment line, and could not examine use that is indicated in combination therapy with another drug.  Thus, “our study likely over estimates on-label use and underestimates off-label use,” Conti said.

Conti, R., Bernstein, A., Villaflor, V., Schilsky, R., Rosenthal, M., & Bach, P. (2013). Prevalence of Off-Label Use and Spending in 2010 Among Patent-Protected Chemotherapies in a Population-Based Cohort of Medical Oncologists Journal of Clinical Oncology DOI: 10.1200/JCO.2012.42.7252

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