Drug Shortages

Drug Shortages

Lack of certain medications raises issues related to care, access

By Ann Freestone, BA’89

Drug shortages are the new normal according to Mark Malesker, BSPha’86, PharmD’88, professor of pharmacy practice and medicine at the Creighton University School of Pharmacy and Health Professions.

Currently, there are more than 150 medications in short supply, including cancer treatments, antibiotics, heart medications, vaccines, oncology drugs, anesthetics and painkillers. “It’s all across the board,” says Malesker.   

The shortages can have serious consequences, especially when they include life-sustaining medications.

In a 2012-2013 survey, about 83 percent of randomly selected U.S. oncologists reported that they were unable to prescribe the preferred chemotherapy agent because of shortages at least once during the previous six months. In a letter published in The New England Journal of Medicine, the survey’s authors wrote that more than one-third of respondents said they had to delay treatment “and make difficult choices about which patients to exclude.”

A drug shortage occurs when demand exceeds supply. The American Society of Health-System Pharmacists (ASHP) and the Food and Drug Administration (FDA) both track the availability and shortage of drugs, using different methods.

According to Malesker, the shortages have been traced since the early 2000s.

“It’s better now. The FDA has recognized shortages affect quality of care and has tried to take action,” says Malesker. “The number is not as bad as 10 years ago, which was well over 200 [medications in short supply], but there still are shortages that affect how care is provided on a daily basis. The bottom line is it’s still a problem.” In fact, shortages affect 1 percent of prescriptions, according to Malesker.  

As a practicing pharmacist, Malesker has witnessed firsthand how medication shortages in the hospital setting have impacted patient care. He has had to help decide on alternative patient therapies when standard therapies are in a shortage or when the manufacturer has discontinued certain products.

“Patients have been frustrated when a medication ordered for them is not able to be delivered, especially patients waiting to receive chemotherapy treatments,” says Malesker.

Why the Shortages?

Katharine Van Tassel, professor of law and director of Health Law Programs at Creighton, is a nationally recognized scholar in health care law, including food and drug law. Although the reasons for the shortages are many, Van Tassel says quality problems at the manufacturers reign as the major one.

“According to statistics maintained by the FDA, the majority [66 percent] of the problem is caused by quality issues in manufacturing,” says Van Tassel. “The FDA will shut down a drug manufacturing plant that is potentially producing unsafe drugs. The FDA can’t allow manufacturers to put a product on the market that will cause people to get sick.” She says the issues range from aging facilities and equipment to even fungus and bacteria in drugs.  

Beyond manufacturing problems, other common issues that can lead to shortages include increased demand, unavailable raw materials, natural disasters and consolidation of companies, which results in fewer companies making the same drug.

“We see a lot of consolidation of drug companies,” says Drew Roberts, Pharm.D., assistant professor of pharmacy sciences, “and that, in turn, can result in fewer companies making a generic drug after they merge company portfolios. The fewer companies that make a drug, the more difficult it is to respond to a shortage of that drug.”

Peter Silberstein, M.D., chief of hematology and oncology at Creighton and chief of oncology at the Veterans Hospital, has experienced shortages on intravenous generic drugs for chemotherapy.

“I think that the major reason for the shortage of drugs is due to the economic incentives of drug manufacturers. There is very little profit margin on generic drugs, so that there are only a few manufacturers making these drugs and these manufacturers have stopped producing these if their expenses rise or profits fall,” he says. “There are very few manufacturers producing inexpensive, commonly used, generic intravenous chemotherapy, which is used in both children and adults.” He points out that there is less of a shortage in Europe, where the payment is larger for intravenous generic drugs.

Looking at the Options

When there is a shortage, clinicians and pharmacists look for alternatives.

“Most of the alternative treatments would be recognized treatments that shouldn’t impact the patient in a negative way,” says Malesker.

There can, however, be downsides. According to Philip Gregory, Pharm.D., an associate professor of pharmacy practice, “Clinics and hospitals have a core set of drugs they use. Then they have a change because a drug is on shortage, and the substitute may not be familiar to everyone, which can lead to the incorrect dose, administration, etc.”  

Gregory is also the director of the Center for Drug Information and Evidence-Based Practice in the School of Pharmacy and Health Professions. Dedicated to serving health professionals, the center provides evidence-based, timely and unbiased information and consultations in an effort to improve patient care.

Calls come into the center from across the country from pharmacists wanting to know how to deal with a shortage. From an anecdotal perspective, he says, calls have increased. The center also provides a training environment to prepare Creighton students and post-graduate residents and fellows to meet the challenges of their future careers.  

Gregory says another issue is patients may not always be getting the most effective drug with an alternative treatment. Consider one example. A 2012 article in The New England Journal of Medicine (“The Impact of Drug Shortages on Children with Cancer”) explained that children with Hodgkin’s lymphoma using a substitute drug had higher relapse rates.     

According to Silberstein, “When there is a shortage of a chemotherapy drug, then a workaround solution (often sub-optimal) is done for that drug for a specific type of cancer.” He says the workarounds can include the following: determine who needs it the most, change the dose, use a more expensive drug, choose a different regimen or buy from other suppliers and pay more (often on the “gray market,” that middle ground between products sold legally and illegal products sold on the black market). He points out the two-year cancer-free survival for pediatric patients with Hodgkin’s disease fell from 88 percent to 75 percent when treated with a substitute drug.  

Alternative treatments may also have side effects that the preferred drug did not. Charles Youngblood, M.D., interim chair of anesthesiology at Creighton University School of Medicine and associate professor, saw this firsthand while working at another institution. When there was a shortage of propofol, a drug that is used for sedation, the alternative drug had side effects.

“This sounds horrible, but those people felt like they were burning right before going to sleep,” he says. “Sometimes you have no other choice.”    

“What’s happening is people are looking for an alternative,” says Gregory. “If there aren’t alternatives, then the provider says, ‘Who needs the drug the most?’ and has to make tough decisions.”

Tough Decisions

Amy Haddad, Ph.D., director of the Center for Health Policy and Ethics and the Dr. C.C. and Mabel L. Criss Endowed Chair in Health Sciences, is the president of the American Society for Bioethics and Humanities. She has written several books, including ones focusing on pharmacy ethics and another on health professional and patient interaction.

“When there’s not enough of any good, whether it’s health-related, food or other basic element to fulfill a human need, you have to turn to the principles of justice to fairly allocate what goods you have. Running out of a drug that would be considered a drug of first choice is hard but the decision is less difficult if there are equally efficacious alternatives. If you run out of life-sustaining drugs and there aren’t comparable alternatives, that makes the decision harder,” says Haddad. “There doesn’t seem to be a standard process even in large academic medical centers.” Despite the prevalence of scarcities, 69.6 percent of U.S. oncologists responding to a 2012-2013 survey reported that their cancer centers or practices lacked formal guidance for making decisions regarding allocation of drugs.  

Haddad points to the organ transplantation system, which uses select principles of justice such as prognosis and need, as a good example of a system to fairly allocate scarce, life-saving resources, i.e., vital organs. “With drugs, the process is not clear,” says Haddad. “We’re making decisions to allocate scarce resources that aren’t based on any standard ethical method of allocation nor is it transparent to patients.”   

When rationing must occur, she says there should be guidelines containing criteria on what makes patients better candidates to receive treatment, such as potential years of life that might be possible using a certain drug, among other considerations.  

Youngblood points to rationing succinylcholine, a drug that temporarily paralyzes the patient. “The biggest priority is to use it in trauma situations only,” says Youngblood. “We ration it and use it only if we absolutely have to.”

Sharing Information with Patients

So should the patient know that the treatment is an alternative one?

“Clinicians have to be transparent with patients. Patients have to be told and be involved in the decision,” says Haddad. “I can understand why clinicians don’t want to reveal this to patients, because the subtext seems to be saying, ‘This is normally what we’d do, the drug we would normally use in your case, but we can’t.’ But the patient needs to be engaged in the reality. We need to have health professionals share the fact that there is a drug shortage and spell out options to patients in light of the situation.”  

According to Gregory, “In an ideal world, they should know, but I can’t say they always do. Cancer patients are at the greatest risk because it’s life and death. If the drug goes on shortage, they have to change course. It’s unfathomable that would happen without a detailed discussion between the provider and patient.”   

Being forthcoming with patients doesn’t always happen. A study published in the journal Anesthesia and Analgesia found that most patients wanted to know about drug shortages that might affect their care during elective surgery, but most didn’t.

Advocating for Themselves

Patients can advocate for themselves by having the information on drug shortages at their fingertips. The ASHP website lists drugs that are not available, and the FDA has an app that prescribers and patients can use to receive notifications on drug shortages, says Malesker.  

Patients also need to have a close relationship with their pharmacist and prescriber.

“In the event the medication is on the shortage list, the pharmacist could work with the prescriber to find an alternative. It’s important in today’s world — especially for outpatients — to have a relationship with a single pharmacy,” says Malesker. “If something like that would occur, the pharmacist could communicate with the prescriber to find an alternative product. They know you, you know them, so they will work with you to make things work.”

No Silver Bullet

The federal government is tasked with leading the development of policies and regulations to help prevent shortages, says pharmacy professor Roberts. The President’s Executive Order 13588 in 2011 put drug companies on notice that they need to provide advance notice when they know a potential shortage is looming or possible.

“The FDA has opened up lines of communication between the drug industry and federal government to prevent drug shortages, to make sure they have advanced notice of potential shortages that allows the FDA to strategize so it doesn’t affect the public,” says Roberts. Since the president’s executive order, there has been a six-fold increase in notifications to the FDA.  

“For generic products, it’s easier to address the shortage if we have enough of a heads-up to inform other manufacturers of that drug that we need them to pick up the slack,” says Roberts.

But with a brand-name drug that is only being manufactured by one company, the FDA doesn’t have this option so quality and safety issues can have major effects on patients needing a brand-name medication. “If the shortage occurred with a brand-name medication, then it would be difficult to address the shortage, especially when alternative treatment options are limited,” he says.    

“From a macro perspective, it falls on the FDA and pharmaceutical industry working together to solve this problem,” says Roberts. “At a micro level, we have to train our doctors and pharmacists how to effectively strategize treatment of patients affected by drug shortages.”  

Van Tassel offers another solution. Since quality at the manufacturing level is the main problem causing drug shortages, Van Tassel says there needs to be legal incentives for manufacturers to improve.  

“The root cause lies in the hands of manufacturers,” she says. “Manufacturers should be investing in upgrading their processes, equipment and facilities to avoid or prevent future shutdowns, but there’s no legal incentive to do so. To break that chain we need legislation that requires best practices to prevent future shutdowns.”

To get manufacturers to use best practices, Van Tassel recommends people get involved in legislative solutions. “Advocate for change by writing to your legislators in your state,” she says.    

Van Tassel says the FDA can incentivize manufacturers to use best practices and is considering quality awards, which is more of a carrot versus a stick approach. “It would be like the Good Housekeeping award,” says Van Tassel.   

According to Gregory, “Few people have a handle on a solution to the problem. It’s a multifactorial problem that will not be solved soon.”

In fact, he says, the problem will only be compounded and points to cancer drugs as being especially complex, which often means more problems in manufacturing leading to the drugs getting on back order.

“As drug complexity grows, the problem will continue for quite some time.”