Industry Incentives May Drive Pricier Anti-VEGF Drug Use

Diana Swift

June 23, 2016

Ophthalmologists who receive incentives from industry are more likely to administer costlier drugs, according to a new report that adds another piece to the puzzle of physician–industry interactions.

Published online June 23 in JAMA Ophthalmology, researchers found a significant association between reported pharmaceutical firm payments and increased use of antivascular endothelial growth factor (VEGF) injections with aflibercept and ranibizumab. At $1960 and $1985 per dose, respectively, both agents are substantially more expensive than bevacizumab, an antiangiogenic originally developed for colon cancer and repackaged for ophthalmological use at an average cost of $60 per dose.

Using 2013 data from the Centers for Medicare & Medicaid Services (CMS) Open Payments program of the Physician Payments Sunshine Act, Stanford C. Taylor, MD, from the Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, Missouri, and colleagues analyzed the association between industry payments received by US ophthalmologists and the number and type of anti-VEGF injections administered.

Aimed at transparency, the act requires industry to report any transfers of value to physicians, whether cash, meals, entertainment, gifts, stock, travel, accommodation, or other emoluments.

Of the 3011 ophthalmologists reimbursed by CMS for more than 2.2 million anti-VEGF injections in 2013, 38.0% of them received $1.3 million in industry payments for ranibizumab and aflibercept from their manufacturers, Genentech and Regeneron Pharmaceuticals. In all, 1835 physicians gave 476,885 aflibercept injections, 1629 physicians gave 641,963 ranibizumab injections, and 2854 physicians gave 1,082,279 bevacizumab injections.

Positive associations emerged between reported higher industry payments and the following: total injection use (r = 0.24; 95% confidence interval [CI], 0.22 - 0.26; P < .001), aflibercept and ranibizumab injections (r = 0.32; 95% CI, 0.29 - 0.34; P < .001), and the percentage of injections per physician for aflibercept or ranibizumab (r = −0.27; 95% CI, −0.25 to −0.29; P < .001).

For bevacizumab, the association between more industry payments and injection was weaker (r = 0.07; 95% CI, 0.04 - 0.09; P < .001).

Ophthalmologists receiving industry incentives performed a median of 53.6% (interquartile range, 23.0% - 82.67%) of their injections for neovascular eye disease with the more expensive anti-VEGF agents, compared with just 16.5% (interquartile range, 0% - 54.0%) of injections by ophthalmologists who did not receive incentives (P < .001).

Moreover, use of the expensive agents appeared to increase as the value or number of the incentives increased. For example, the 115 physicians reportedly receiving more than $1000 from industry gave 79% of their injections with aflibercept and ranibizumab; for those receiving more than five payments from industry, that proportion was 78.1%.

Last year, a study of CMS data revealed that, as a specialty group, ophthalmologists received relatively low payments from industry, with a mean per physician payment in 2013 of $195. Most single payments were less than $100, and 88% of ophthalmologists received less than $500 in total industry remuneration.

But as other researchers have noted, even small benefits may be influential. In a subgroup analysis in the current study, Dr Taylor and colleagues found that just $1 to $25 in reported industry benefits was linked to a greater likelihood of a physician's injecting with aflibercept and ranibizumab compared with no incentives.

Despite the positive associations observed, the authors conceded that similar to earlier research, theirs established no direct causal connection. "As in prior studies, our work fails to prove a causative relationship, but it implicates industry interactions as a possible contributory factor on a physician's decision making," Dr Taylor and colleagues write.

In an invited commentary, Paul R. Lichter, MD, from the W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, went further, saying common sense suggests a cause-and-effect relationship may exist. "[The investigators] found that pharmaceutical industry financial incentives to physicians, obviously given to influence prescribing behavior, are strongly correlated with that behavior, namely, prescribing the most expensive anti-VEGF drugs for intravitreous injection when a far less expensive alternative is equally effective."

He cited a ProPublica report from March 2016 in which 2014 Open Payments data demonstrated a correlation between higher industry payments to physicians and increasing amounts of brand-name drugs prescribed by those physicians compared with physicians who received no payments. "In addition, the ProPublica analysis revealed that physicians who receive industry payments of any amount, such as a meal, are at least twice as likely to prescribe brand name drugs than those physicians who received no industry payments," Dr Richter writes.

He noted less visible physician benefits such as industry rebates to high users of drugs and airline mileage accrual when drugs are purchased on credit cards.

Although cause and effect has not been proven, Dr Richter writes, "industry likely has the proof of cause and effect or would not continue to spend billions of marketing dollars annually toward an outcome that was not achieved."

He added that the public's perception that industry benefits do not influence the decisions of their trusted physicians may not be rational. "Because it is common knowledge that financial incentives drive behavior, it would take unconventional thinking to believe that using the industry-supported anti-VEGF drugs has nothing to do with financial payments, gifts, and incentives provided to physicians — by industry and the government — to use them." Dr Richter writes.

He also pointed out the futility of making physicians responsible for holding down healthcare costs at the expense of their incomes and criticized Congress's decision not to interfere with free-market drug pricing or the legality of industry rebates that promote specific drug use. "If the public wants to reduce the portion of health care costs that physicians control, there will have to be financial disincentives for physicians who prescribe more costly medicine," Dr Richter writes, adding that the Patient Protection and Affordable Care Act is a step toward that goal.

This study was supported by grants from the Washington University Institute of Clinical and Translational Sciences. The Department of Ophthalmology at Washington University is supported by an unrestricted grant from the Research to Prevent Blindness Inc, New York City. The authors and the editorial commentator have disclosed no relevant financial relationships.

JAMA Ophthalmol. Published online June 23, 2016. Article full text, Commentary extract

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