As a pediatric hematologist-oncologist, Yoram Unguru, MD, has had his share of heart-wrenching conversations. “But one of the hardest is sitting down with a patient and family and telling them there’s a drug that’s part of the curative regimen, but it’s not available because there’s a shortage,” says Unguru, who works at the Herman and Walter Samuelson Children’s Hospital at Sinai in Baltimore, Maryland. “Patients and parents give you a look of complete incredulity. ‘What do you mean it’s not available?’ Even after I explain why these shortages exist, many patients and families still have a hard time believing that a life-saving medication isn’t available in the U.S.”
Dozens of medical associations have warned about the dire consequences drug shortages pose for this country. In 2017, 146 drugs ran short, according to the American Society of Health-System Pharmacists. Between January 2008 and March 2014, shortages for lifesaving therapies quadrupled and shortages of drugs for which there is no alternative more than doubled, according to an analysis published in Academic Emergency Medicine. In fact, the Food and Drug Administration (FDA) recently acknowledged that “many of these shortages have been for critical drug products and that they are having a tangible impact on patients.”
Yet shortages continue. Some occur when pharmaceutical companies halt production because of lapses in quality or concerns about meeting FDA standards. Others arise when the raw materials needed to make medications or medical supplies run low. And natural disasters can cause shortages. The hurricane that ravaged Puerto Rico in 2017 knocked out several major pharmaceutical and medical supply makers, leading to shortages of medications and IV saline bags.
“Patients and parents give you a look of complete incredulity. ‘What do you mean it’s not available?’”
Yoram Unguru, MD
Herman and Walter Samuelson Children’s Hospital at Sinai
As federal agencies work to address the ongoing crisis, frontline providers struggle to find workarounds when critical products become scarce or unavailable. “We’re basically scrambling to make sure that the quality of patient care is not affected,” says Erin Fox, PharmD, senior director of drug information and support services at the University of Utah Health System and a leading expert on drug shortages.
Here’s a look at what some teaching hospitals around the country are doing to protect patients in times of shortages:
Turning to substitutes
The simplest workaround when a shortage occurs is to find a substitute. If one broad spectrum antibiotic becomes unavailable, for example, it may be possible to switch to another. But even a simple substitution isn’t so simple.
Securing replacements costs money — for example, it cost an estimated $209 million for the purchase of pricier substitutes in 2013. It also adds to the workload of already overburdened staff. “If a substitute drug isn’t on the formulary or currently stocked, it needs to be added to all systems,” explains Fox, “including not just electronic health records but smart pump libraries, automated dispensing cabinets, and other parts of the system.” And whenever a medical team switches from a standard medication to a less-familiar one, there’s an increased risk of medical errors, which hospitals have to work hard to prevent.
In some cases, shortages forced changes in patient care. When the IV saline supplies needed to treat dehydrated patients fell short, emergency physicians at Brigham and Women’s Hospital experimented with using oral rehydration therapy instead. Although the strategy worked for patients with mild or moderate dehydration, using oral hydration takes longer than IV drips and requires extra effort from patients. What’s more, it isn’t a practical option for severely dehydrated patients.
Another alternative that some hospital teams have resorted to when IV saline bags aren’t available is having nurses give saline via IV injection — a workable solution, but one that consumes valuable nursing time.
Conserving limited supplies
When substitutes aren’t available, providers try to make the best use of the supplies they have.
For example, when severe shortages of sterile generic injectables for chemotherapies occurred, oncologists around the country turned to an approach called “cohorting” patients.
“Let’s say you have a 50-milligram dose in a vial, but you only need 15 milligrams for a young patient,” explains Unguru. “Usually you throw away the rest. In the face of shortages, we’ll bring a cohort of kids in at the same time who need the same drug and distribute what we have so nothing is wasted.”
This approach is not without potential drawbacks, though. “Some of those kids may not be due for that drug at that time, so the treatment course may be affected. We just don’t know. But if it’s a question of bringing them in two weeks earlier or having no drug at all, after discussing with the patient and parents, that’s the choice you make.”
Making their own
The FDA and some state pharmacy boards allow compounding pharmacies to make medications that become unavailable because of shortages. Some large hospitals have their own compounding pharmacies, but most turn to outside companies. “We’ve seen severe shortages of small doses of injectable opioids, for example, which are used in hospitals every day,” says Fox. “Compounding pharmacies can take a large vial of morphine and split it up into small syringes.” They can also compound generic drugs using the active ingredients.
But there are disadvantages. Hospital pharmacies usually don’t have much advance warning when there’s about to be a shortage of a medication, and it typically takes five to six weeks for outsourcing facilities to increase production of a particular drug. By law, they are allowed to begin production only when a product appears on the FDA shortage list, and that sometimes happens slowly. So compounding often isn’t a reliable solution; providers could run out of a needed drug long before a facility could begin production.
As one measure of the severity of shortages – as well as generic drug prices have become — a consortium of seven health care systems, including Intermountain Healthcare, Mayo Clinic, Ascension, SSM Health, and Trinity Health, recentlly announced plans to establish a nonprofit company to manufacture generic medications.
Reserving medications or delaying treatment
Sometimes, when supplies of critical drugs run short, hospitals have been forced to reserve them for the sickest patients.
When nitroglycerin was in shortage, for example, some emergency departments began to reserve it for initial doses and then switch to other medications after 24 hours. When supplies of the chemotherapy drug bleomycin became scarce, teams at pediatric oncology departments had to scramble to estimate how much they would need to treat children with cancer. “When the supply and the estimated demand don’t match up, there is no other choice than to prioritize patients and delay initiating treatment for some,” says Jill Beck, MD, a pediatric oncologist at the University of Nebraska Medical Center.
Choosing which patients get a drug — and which don’t — raises a host of thorny ethical questions. In 2015, a team of oncology and ethics experts led by Unguru drafted an ethical framework for allocating scarce lifesaving chemotherapy and supportive care drugs for children with cancer, published in the Journal of the National Cancer Institute.
Ideally, says Unguru, who is also on the faculty of the Johns Hopkins Berman Institute of Bioethics, allocation decisions should be evidence-based and take into account such factors as threshold of curability, prognosis, and the importance of a particular drug to a given patient’s outcome. “Allocation decision-making needs to be a transparent and nuanced process,” he says. “There should also be an appeal procedure in place for patients and families and for clinicians.” Such processes are complex and time-consuming, he admits. “But we can’t ask physicians at the bedside to make these decisions.”
Preparing for the next shortage
In July, FDA Commissioner Scott Gottlieb, MD, announced the formation of a new Drug Shortages Task Force to explore ways to address the underlying causes of shortages.
Meanwhile, with no end in sight, a growing number of hospitals and health care systems are putting teams and procedures in place to deal with the practical and ethical challenges shortages pose in order to anticipate and manage them more efficiently.
To provide guidance, the American Society of Health-System Pharmacists released new guidelines in 2018 for managing drug product shortages. That effort, led by the University of Utah Health’s Fox, covers both planning for drug-product shortages and responding when a shortage occurs.
Recommendations include:
- Creating an interdisciplinary drug shortage team to make decisions about drug and product supplies
- Developing a formal process for approving alternative therapies
- Conducting an operational assessment to evaluate the impact of a new drug shortage
- Establishing protocols for communication with patients or family members who are likely to be affected by a shortage
“Putting a plan and procedures in place can help a hospital respond quickly when a shortage occurs and mitigate at least some of the impact,” says Fox. “It’s an effort that takes time and valuable resources.”
But until the threat of shortages becomes a thing of the past, hospital leaders recognize that they have no other choice.