‘Truly a public health crisis’

Marie McCullough / The Philadelphia Inquirer

Since 2006, this country has had worsening shortages of sterile generic injectables — drugs given by shots or intravenously. Currently, more than 300 medicines crucial to treating cancer, infections, cardiac arrest, premature infants, pain and more are in short supply.

PHILADELPHIA — Rationing medical care is denounced as immoral in the United States, yet it goes on daily in hospitals, clinics, nursing homes, ambulances and pharmacies.

The reasons for this predicament are complex, and the fixes, elusive. The scope, however, is clear from surveys of medical and trade groups. The latest, a University of Pennsylvania poll of oncologists released last month, found 83 percent had dealt with shortages by delaying cancer treatments, omitting doses, using second-choice drugs or sending patients elsewhere.

“Oncologists are facing wrenching decisions about how to allocate lifesaving drugs,” said cancer specialist Keerthi Gogineni, who led the Penn survey.

Why aren’t patients and families up in arms?

They may not realize their care was compromised or complicated by a shortage unless their caregivers are unusually candid.

“Patients in an intensive care unit often don’t know they’ve been impacted,” said pharmacist Erin Fox, who tracks shortages as manager of the University of Utah’s drug-information service. “And the hospitals don’t want folks to talk about it. They don’t want to admit, ‘We had a patient who died because we didn’t have this drug.’”

The secret human toll is rising. In the last three years, dozens of deaths due to contaminated drugs have been linked to producers and vendors who have capitalized on shortages. The Institute for Safe Medication Practices in Horsham, Pa., received hundreds of reports of medication errors, near-disasters, and 15 deaths related to shortages when it surveyed 1,800 health-care practitioners in 2010.

“This is the worst I’ve ever seen in over 40 years as a pharmacist,” said Michael Cohen, ISMP president, who contributes to The Inquirer’s Checkup blog. “It’s truly a public health crisis.”

One group of patients has been acutely aware and outspoken about the crisis because it threatens their health every day.

These 30,000 Americans cannot eat by mouth, usually from digestive diseases. They must get all nourishment — from vitamins to fat — in a customized, sterile solution pumped into a heart vein.

Total parenteral nutrition, or TPN, is also vital temporarily for premature newborns and hospitalized patients who can’t eat.

“We were very vocal in outlining for (government officials) what we think needs to be done,” said Joan Bishop, director of the nonprofit Oley Foundation in Albany, N.Y., a TPN support network. “You can’t just let people starve.”

Among the group’s stalwart activists is Bettemarie Bond, 42, of Levittown, N.Y.. She suffers from rare digestive and metabolic disorders and has been on TPN since 1990. A single bite of, say, pizza, would set off excruciating inflammation in her pancreas and gut.

In her teens, doctors told Bond to prepare to be an invalid. Instead, helped by her parents and TPN specialists, she graduated from college, bought a house and became a pediatric occupational therapist. She works with autistic preschoolers and hides her infusion pumps in a snazzy backpack.

To do all this, Bond has to conserve energy; even taking a shower can exhaust her. The shortages add needless stress. Consider that severe selenium deficiency can cause heart damage, yet she has not had the trace element for almost a year. She has gone without IV multivitamins for months at a time. She also worries that her infusion pharmacist will run out of the only pain medication she can tolerate. “Without it, the pain would be unbearable,” she said.

Still, she considers herself lucky. “Some friends have had it much worse,” she said. “They’ve gotten lipids (fats) just once a week instead of daily. It’s affected their health.”

Though shortages occur in other developed countries, the U.S. is especially vulnerable, experts agree.

In a recent analysis, Food and Drug Administration officials cited a root problem: U.S. factories that make sterile injectables are few, aging and inadequate, and manufacturers have no economic incentives to upgrade. When equipment breaks or inspectors find problems, it’s often easier to quit making the injectables — which have high production costs and low profit margins — and divert the capacity to more lucrative products.

Only seven companies now make virtually all sterile injectables in the U.S., their plants running round the clock. Six have received repeated FDA warnings about safety lapses.

Experts cite other factors behind shortages, including hospital group purchasing contracts that drive down prices, hoarding and low insurance reimbursements.

“In Britain, prices are more regulated,” said Michael Link, a Stanford University pediatric oncologist. “The reimbursement rate for generics is higher, and on-patent drug reimbursement is lower.”

The FDA cannot order firms to make drugs, but recent legislation and a presidential order gave the agency more muscle. Last year, it began requiring companies to give early warnings of permanent and temporary drug discontinuations.

The agency also allowed temporary importation of a key ovarian cancer chemotherapy, as it did the year before for a leukemia drug.

But importation is not ideal. Many foreign factories do not meet FDA standards. And global transport of heavy glass vials adds to costs.

Last month, an industry group, the International Society for Pharmaceutical Engineering, released the first global survey of companies and others. The intent was to see if steps already taken by industry and regulators were working.

The answer was not so well.

Of 142 respondents with a shortage-prevention program, more than half said “the company was still unable to prevent a drug shortage.”

At the Institute for Safe Medication Practices, Michael Cohen has been dedicated to reducing drug errors and costs while improving quality. His work was honored with a 2005 MacArthur Foundation “genius” grant.

Shortages have set him back.

Medication errors have risen because practitioners are substituting unfamiliar drugs, formulations and concentrations. Lethal overdoses of a narcotic painkiller, adrenalin and a blood thinner have occurred, ISMP’s most recent survey in 2010 found.

Costs have soared and product quality has suffered with the emergence of a “gray market,” Cohen said. Shady vendors buy injectable drugs, often from “compounding” pharmacies, then resell the drugs at big markups. Compounding pharmacies, which are largely unregulated, can legally make only custom-order prescriptions, but some have become de facto factories to fill the shortage gap.

Their record has been spotty. In 2012, 48 people died and over 700 were sickened by fungal meningitis linked to spinal injections of steroids made by the New England Compounding Center in Framingham, Mass.

A few months ago, Cohen and leaders from the FDA, industry and medicine met to come up with new ideas to ease shortages.

Their list included extending product expiration dates, tax incentives for backup makers of key drugs, and curbing monopolistic buying practices.

But such proposals could take years to realize, Cohen said. Meanwhile, shortages continue.

“Imagine you go to the grocery store and milk, cheese, and all other sources of calcium are gone,” said Bishop of the Oley Foundation. “And the clerk says: ‘We don’t know when we’ll get any in.’”

What patients and their advocates can do

Patients have the most to lose from drug shortages — and the least control over the problem. Still, experts say you can be proactive:

• Be aware of drugs you may need that are in short supply, especially if you are planning surgery, are in cancer treatment, or have a chronic condition such as heart disease. The FDA, the University of Utah, and the American Society of Health-System Pharmacists keep online lists of drugs in short supply.

• Ask questions of health care providers. You (or your advocate) should ask whether your doctor is substituting, reducing, postponing or modifying a treatment because of a shortage. You should also know whether if your drug has come from a “compounding” pharmacy and if so, why.

• Push for change. Write to your elected officials. Join lobbying efforts by patient groups such as the Oley Foundation and the National Patient Advocate Foundation.