An interesting article in the Journal of Clinical Oncology (via yesterday’s Jerusalem Post) argues that the U.S. Food and Drug Administration practice of approving many oral cancer drugs for use only after patients have fasted is putting patients at increased risk of overdosing, and causes them to “flush costly medicines down the toilet.”
According to the article by Mark Ratain, a professor of medicine at the University of Chicago Medical Center, many oral drugs are absorbed more effectively when taken with food — particularly fat-soluble drugs. But at the FDA’s insistence, dosage levels for most oral cancer drugs are “based on data from patients who take their pills on an empty stomach” because of the variability in diets among cancer patients. When going through chemotherapy, patients’ appetites will vary substantially, as will the amount and types of food they’ll eat. Ratain argues that patients who eat too soon after taking their medicines will therefore be put at a substantial risk of overdose because too much of the drug will then be absorbed. And, because most cancer drugs are fairly toxic, he argues that “risk of overdose is clearly more compelling” than the risk arising from dietary variability, and suggests that the FDA change its policies accordingly.
You’d think that reducing the risk of overdose would be a compelling argument on its own, but Ratain takes his plea too far by trying to make an economic argument as well. He suggests that, by approving oral cancer medicines for use with food, doctors could lower the doses they prescribe. That in turn would help patients save tens of thousands of dollars , since many of these drugs cost thousands of dollars each month. Taking a drug such as Zytiga (abiraterone acetate) after fasting “means the amount of the drug available to fight cancer is decreased by 80 to 90 percent,” Ratain points out. “At least three-quarters of it, at a per-patient cost of about $5,000 a month, is literally wasted. It gets excreted and flushed away.” Instead, taking it with food “would save patients and their payers approximately $3,750 per month at current prices.”
The problem in this thinking is that drug pricing doesn’t work so simply. Zytiga and other new medicines aren’t expensive because it costs so much more to produce a 250 mg pill than to produce a 25 mg pill. They’re expensive because of the huge fixed costs of developing, testing, and seeking FDA approval just to get to market. After laying out close to $1 billion before the products can even be sold, it typically costs a drug manufacturer pennies — or at most, a few dollars — to make each pill, regardless of the dose. In effect, a drug like Zytiga would cost somewhere in the neighborhood of $5,000 per patient per month whether the recommended dose was 25 mg, 250 mg, or 2500 mg.
Drug manufacturers have some ability to charge variable prices — offering steep discounts for low-income patients, or bulk buyers like the VA health program, or overseas purchasers in countries with strict price controls, for example. In an industry like pharmaceuticals, characterized by declining marginal costs, any time the company can make a sale at a price that exceeds the marginal cost of producing an extra unit that would not have been sold at the higher price, that still brings in net revenue and helps to off-set the fixed costs. But they can’t charge every patient a price below average costs and expect to stay in business for very long. In a sense, we should see drug pricing as a manufacturer’s attempt to set a per-patient fee, not a per-pill fee.
So, Dr. Ratain has my full-fledged support for his effort to rationalize oncology drug dosing. But we shouldn’t be fooled into thinking that his proposal will save anyone money by reducing drug dosages.