Drug Shortages: A Deadly Problem With No Cure in Sight
So is the Food and Drug Administration. Unfortunately, the FDA's hands are pretty much tied when it comes to taking steps that could ease this crisis. It's powerless to demand that a drug company produce a particular medication simply because it's becoming dangerously unavailable.
How bad is this situation? A recent survey of health care professionals found the U.S. is experiencing drug shortages of "epic proportion that are often associated with third-world countries." This unprecedented, and growing, shortage of critically important medications is affecting care and endangering patients' lives.
"For the past year-and-a-half we've seen quite an escalation in the report of drug shortages," says Bona Benjamin, director of Medication-Use Quality Improvement with the American Society of Health-System Pharmacists (ASHP). "And resolving the shortages is becoming more difficult."
A Warning in July
Injectable drugs used in hospitals are those most in short supply. Oral drugs or those filled at the local pharmacy are not as prone to shortages. The affected drugs include vital medications such as chemotherapy, antibiotics, analgesics (painkillers), anesthetics and more. Such shortages can compromise therapy or delay treatment, putting patients at risk -- sometimes even of death.
The Institute for Safe Medication Practices in July clearly warned of the severe problem. An ISMP survey of more than 1,800 health care practitioners (68% of them pharmacists) from July to September revealed at least two deaths as a result of a morphine shortage when a substitute was misused.
Respondents were most alarmed by the use of less desirable, unfamiliar and often more expensive alternative drugs. They were concerned of potential for errors, poor patient outcomes or preventable adverse drug events. For example, using a substitute of an unavailable drug resulted in an overdosing error that led to the death of a 16-year-old boy in an emergency room, ISMP President Michael Cohen wrote in July.
In another example, the diuretic furosemide, "is in very very short supply," the ASHP's Benjamin says. APP, American Regent, and Hospira all make the drug but couldn't explain the shortage, according to the ASHP. "This is a real problem because many patients who are acutely ill need a diuretic to help them remove unwanted fluids. As a result, the only other drug in the same class is now in a shortage situation, too," says Benjamin. "Some hospitals can't get either drug."
"It's Pretty Serious"
At least "with the diuretic situation, despite the shortage, there are some alternatives," Benjamin explains. But when it comes another category with a shortage, oncology drugs -- used to treat cancer --"there isn't really an alternative agent," she says. When asked how doctors treat cancer patients in such cases, Benjamin quite frankly says, "Well, they can't in some situations." She adds: "We've heard that patients have been halted in mid-therapy and that some of the research trials had to be halted. It's pretty serious."
"You have to picture yourself telling a cancer patient that you have effective therapy, except that one of the components of that therapy is unavailable," says Dr. Michael Link, a pediatric oncologist and president-elect of the American Society of Clinical Oncology (ASCO). "And at a time when the patients themselves are under such stress, they don't need you to add to it."
Link says "a multitude of drugs" have recently become unavailable, adding, "some of them, unfortunately, are key drugs used for multiple different cancers in adults and children, and are key players in management." Some of them have possible workarounds or substitutions, "but in other cases there is not a good substitution," he says.
Chemotherapy drugs such as doxorubicin, etoposide, vincristine and cisplatin that treat breast, gastric, ovarian, thyroid, small cell lung, lymphoma and other cancers, unfortunately have no recognized standard alternatives for the majority of clinical situations, Link said in a previous interview with ASCO.
"This is where things are getting more worrisome, and patient care is clearly being affected," Link told DailyFinance. The options are to use an alternative, to leave out a drug from a regimen or to delay treatment, none of which is good. Cancer patients' lives, including children's, are at risk, and the shortages can hurt their survival.
"One of the important things is that we don't want to add to the worry that patients undergoing cancer therapy already have," says Link. "It's important for them to talk with their physician to make certain whether the problem will affect them, what solutions can be offered to them and whether there's anything they have to be concerned about at all."
It's difficult to listen to the level of frustration revealed by doctors, pharmacists and health care professionals who deal with this problem daily. Commenting on when an alternative for a lifesaving drug also became unavailable, one respondent to the ISMP survey said: "I guess patients just have to die." Another asked: "What do I tell our breast and lymphoma patients? You had a curable disease, but not anymore because there is no drug available?"
This isn't what anyone would expect in today's advanced Western world. Early in November, the American Society of Anesthesiologists, ASCO, the ASHP, and the ISMP conducted a drug-shortage summit aimed at understanding the situation's scope, discussing necessary changes in public policy and developing an action plan. Also participating in the summit were pharmaceutical manufacturers, wholesalers and distributors, the FDA and others.
Some common causes for the shortages include manufacturing difficulties, natural disasters that affect production, reductions in the supply of raw materials (of which 80% come from outside the U.S.), unexpected increases in demand, voluntary recalls, manufacturer business decisions, FDA enforcement actions to ensure public safety and artificial shortages due to stockpiling.
The chemotherapy drugs listed earlier are in short supply mainly because generic-drug maker Teva's (TEVA) California plant was shut down following an FDA warning letter on manufacturing violations. Other producers can't keep up with the increased demand.
Both the ASHP and FDA maintain drug-shortage lists. The FDA's includes nearly 60 medically necessary products. The ASHP list is even more comprehensive, with over 140 drugs.
No Authority Over Business Decisions
"We're doing everything we can within our current regulatory authority," says Valerie Jensen, associate director of the FDA's drug-shortages program. "We're working to resolve every drug shortage on our list. It's a very long list right now, and it's been long throughout this year. We've resolved a lot of them, but we still have a lot of them that we're working on."
Jensen explains: "What we can do is work with a company on its manufacturing problems." The FDA tries to resolve these as quickly as possible while ensuring public safety. "Also, if a firm has expired inventory of a needed drug and it can give us data to support a longer expiration date, we're glad to review that," she adds.
But when it comes to a company's business decisions, the FDA has no authority. Some companies have decided it's not worth their trouble to produce a certain drug anymore. Such was the case when Teva decided to discontinue the widely used anesthetic propofol. Basically, Teva said it's too hard to make and barely profitable.
A recent trend concerns discontinuation of older products that aren't as profitable as newer ones or that have to regain FDA approvals -- a resource-intensive process. Others simply take lower precedent in production over more profitable drugs.
"Right now we just don't have any authority at all to require companies to increase production or to require other firms to come on the market," Jensen says. FDA also can't require firms to continue making a product, and drugmakers aren't required to report shortages or discontinuations, except for sole manufacturers in certain circumstances.
"We would like to have them report on all discontinuations and shortages, but that's not something we can require, just encourage them to do," Jensen says. She explains that early notifications from manufacturers on issues that could cause shortages have been most helpful because, she says, "many times we can resolve the issue before it becomes a shortage."
Formal Notifications Are Needed
Indeed, lack of advance notice has been a major concern. "We have a situation where companies can just stop making a drug without notifying the FDA, or anyone as a matter of fact. And the first time you find out about it is when you can't get the supply," ISMP President Cohen says.
He explains that early notifications would also give doctors, pharmacists and nurses time to find a potential substitute and learn about it so that dispensing errors can be minimized. "We think there should be formal notification to the FDA so the agency would be able to help facilitate the manufacturing of the drug," he adds.
"We realize that this has significant impact on patients, so we're doing everything that we can," Jensen says. But is the FDA or the Health and Human Services Department doing all it can? Jensen declines to discuss creating public policy to deal with this problem, and the HHS didn't respond to repeated attempts to get comment.
Benjamin would certainly like to see a more comprehensive public policy to deal with the shortages. "There are a number of actions the agency can take to prevent, forestall or mitigate the effects of the shortage," she says. "In rare, but critical cases, the FDA can authorize importation of a drug."
Can Incentives Help Solve the Problem?
At least one U.S. Senator, Amy Klobuchar (D-Minn.), is paying attention. Klobuchar sent a letter in December to FDA Commissioner Margaret Hamburg requesting "immediate action" to ensure adequate supplies of essential drugs. Klobuchar said she'll also introduce legislation in January that would require pharmaceutical companies to notify the FDA when they decide to limit or discontinue production of drugs, and give the FDA the authority to expedite approval for substitute treatments or the importation of drugs.
Similarly, the HHS is providing incentive programs for converting to electronic health records. And the FDA is promoting the development of orphan drugs -- those that treat rare diseases -- through incentives and grants. With some shortages stemming from business decisions, why shouldn't the FDA develop an incentive program to manage the drug shortage problem?
"Incentives have been discussed as a way to manage shortages," Benjamin says. "Expedited review of approved new drug applications, supplemental applications and new or altered production lines have been suggested. How effective these would be has yet to be determined."
Less Time to Treat Patients
What about some type of incentive payment for companies reporting early about possible shortage-causing problems? Cohen adds: "I don't know exactly how that would work, but to me, that is one of the most critical needs legislative-wise."
And what about those taking advantage of the situation and charging exorbitant prices for drugs in short supply, or the inequitable distribution of drugs, or hoarding? Who should make sure that such practices don't happen?
Doctors, hospitals and pharmacists spend more and more resources on managing the shortage problem instead of treating patients. "Whatever the cause, drug shortages have become a key patient-safety concern in health care today," the ISMP wrote back in July, adding that there isn't "a glimmer hope for any improvement in the near future." There should be no shortage of public awareness and concern over this situation.