This article originally appeared on HRMA (http://www.hfma.org/Leadership/Archives/2016/Summer/Taking_Action_Against_Drug_Shortages/) on July 28, 2016.
Although the severity of drug shortages has eased somewhat in recent years, providers still are frequently unable to offer patients the medications they need. Many organizations have developed innovative strategies and action plans to help them manage the clinical, financial, and ethical implications of drug shortages.
"We are now in a sustained era of drug shortages, although we are not at the critical level today that we were back in 2012 and 2013," says Deborah A. Pasko, PharmD, MHA, director of medication safety and quality, American Society of Health-System Pharmacists (ASHP), Bethesda, Md. "The country is still facing ongoing issues, sometimes with lifesaving medications."
Recently, shortages of antibiotics and antimicrobials have been in the spotlight, as have the limited supplies of drugs used in oncology, anesthesiology, and emergent settings. IV fluids also have floated on and off the drug shortage list in recent months, Pasko says.
In 2011, President Barack Obama issued an executive order requiring manufacturers to give a heads-up to the U.S. Food and Drug Administration (FDA) about impending drug shortages. The following year, the Food and Drug Administration Safety and Innovation Act (FDASIA) became law, requiring manufacturers to notify the FDA at least six months before an interruption or as soon as possible.
Erin R. Fox, PharmD, director, Drug Information Service, University of Utah Health Care, says a law requiring manufacturers to notify the FDA when they suspect a drug shortage has helped mitigate the problem, but it is not enough. (Photo: Kristan Jacobsen)
"FDASIA has helped decrease the number of drug shortages because the FDA can now do more on the prevention end," says Erin R. Fox, PharmD, director, Drug Information Service, University of Utah Health Care, Salt Lake City. Such preventive measures may include helping manufacturers remedy production problems and expediting inspections of alternative manufacturing sites, among other strategies.
But as Fox and her co-authors noted in a recentHealth Affairs article, FDASIA has not been enough.a
"Hospitals are still having trouble sourcing medications," Fox says. "Sometimes, the right drug is available but the right form isn't. For example, premixed heparin drips are used in almost every hospital across the country, but when there are shortages, hospitals have to compound their own. At the end of the day, patients are still getting treated, but hospitals and providers have to do a lot of work to manage through that shortage. It's frustrating for providers to have to spend so much time on a supply chain failure."
Business decisions by drug manufacturers are one reason for persistent drug shortages, Fox says. "If there is a problem at the factory, some companies may choose to not fix that problem and to manufacture products that return a larger profit," she says. Another issue is that many drugs in short supply are single-sourced, meaning they are made by only one or two manufacturers.
Drug shortages are not a problem in the United States alone, Fox says. "Because we have a global pharmaceutical market, there is not a country that is immune to drug shortages."
Acknowledging the Impact
Drug shortages often have significant clinical, safety, operational, and research implications. "From a clinical and ethical standpoint, if there is a drug in shortage that is used for multiple indications, health systems have to decide which populations they will use their small supply of drug for," ASHP's Pasko says.
One example is alprostadil, a medication used in neonates with congenital heart defects and in liver transplant patients. Institutions that treat both types of patients may have to decide which patients are going to receive the drug and for which indication. Substituting drugs also raises the risk of medication errors if providers are not familiar with the dosing and administration required for alternative products.
Safety issues are a key concern. In fact, the Institute for Safe Medication Practices has published medication safety information regarding shortages that have resulted in patient harm.
From an operational standpoint, drug shortages often require workarounds that reduce efficiency, Pasko says. For example, a shortage of the premixed maintenance IV fluid known as D5/0.45NS requires staff to create their own by adding sodium chloride to liter bags of Dextrose 5%.
Research initiatives also can suffer. "In drug shortages, the FDA has said that the priority should be patient care areas, so providers may need to delay or cancel research because of the unavailability of products," Pasko says.
Yoram Unguru, MD, MS, MA, a pediatric hematologist/oncologist at the Herman and Walter Samuelson Children’s Hospital at Sinai and the Berman Institute of Bioethics, Johns Hopkins University, Baltimore, has co-authored guidelines on managing drug shortages in pediatric oncology.
Drug shortages contribute to rising healthcare costs. A 2014 analysis by Premier found that purchasing costlier generic substitutes for drugs in short supply drove up costs an average of $229.7 million annually. In fact, the figure is likely much higher because it does not include the drugs purchased from off-contract distributors nor the cost of using therapeutic alternatives. It also omits indirect costs such as the labor required to research alternatives, change processes, and educate staff, says Michael J. Alkire, COO, Premier, Inc., Charlotte, N.C.
Drug Shortages Lead to Higher Costs
Finding Creative Solutions
When providers at University of Utah Health Care faced a shortage of piperacillin and tazobactam injection, they switched to a type that is premixed and frozen. "It's actually a huge hassle for our pharmacy operations because they have to make sure they have enough thawed so they have some ready to go, but they don't want to thaw too many doses because then the product might get wasted," Fox says. "We also had to change the settings in our smart pumps because the frozen concentration is different than if we use a vial and a bag."
Reserving medication. Like many other organizations, University of Utah Health Care also faced a shortage of nitroglycerin in its emergency department (ED) and critical care units. "We were able to reserve the nitroglycerin for patients' initial doses and then transfer patients to other therapies after 24 hours without affecting the quality of care," Fox says. "This allowed us to make sure we always had enough for patients in critical situations, such as those having a heart attack."
Preventing OR cancellations. When a company that produces irrigation solutions used during surgery had a manufacturing problem, University of Utah Health Care learned the following day that it would have only half of its usual amount of the solution. The pharmacy had to work with surgeons, operating room (OR) technicians, and nursing staff to determine how to move forward without canceling surgeries.
Fortunately, staff were able to use IV saline imported from Spain as an irrigation solution. "We had daily meetings with our supply chain folks to make sure we had the best plan in place and that everyone knew what to expect," Fox says. Although it took more work to implement the solution, no surgeries were canceled.
Making tough decisions. During chemotherapy shortages, the pharmacy staff would tally up the doses that each patient needed to complete his or her regimen and set that amount aside so they knew how much was left to start new patients on the drugs. By using this process, and by communicating frequently with the oncology team, they avoided a situation in which an allocation decision had to be made. Such a situation would entail consulting with the organization's pharmacy and therapeutics (P&T) committee and ethics committee to help make allocation decisions. "The decision on who gets the last vial of a lifesaving treatment should not be made by pharmacy alone," Fox says.
Developing an Allocation Framework
Although recommendations for allocating scarce, lifesaving medications exist, these models lack the sort of concrete guidance clinicians require when confronted with having to actually choose between equally deserving patients, says Yoram Unguru, MD, MS, MA, Division of Pediatric Hematology/Oncology at the Herman and Walter Samuelson Children's Hospital at Sinai and the Berman Institute of Bioethics, Johns Hopkins University, Baltimore. In fact, the majority of medical (adult) oncologists reported that they lacked allocation guidance altogether. Pediatric oncologists, on the other hand, were more likely to have center-level guidance but still lacked uniform and consistent ethical guidance.
"Too many hospitals have had to scramble when they have been in a bad situation without adequate drugs," Unguru says.
Mike Alkire, COO, Premier, Inc., says drug shortages continue to drive up pharmaceutical costs each year.
In response to this need, Unguru led a Children's Oncology Group task force and co-authored guidelines, published in the Journal of the National Cancer Institute, for organizations managing shortages of chemotherapy drugs for pediatric patients.b Although the guidance is specific to pediatric oncology, the principles and recommendations apply broadly across medical specialties. Faced with a drug shortage, the task force recommends a two-step process: first, implementing strategies to mitigate an existing shortage based on maximizing efficiency and minimizing waste, and second, elucidating actual prioritization that maximizes benefit according to total lives saved/life-years saved.
Allocating drugs to appropriate patients is a necessary strategy when conservation efforts are not enough. "These shortages are so prevalent that they require a thoughtful and nuanced approach," Unguru says. To help providers select which patients receive scarce drugs, he recommends that organizations establish multidisciplinary drug shortage committees that include physicians, nurses, pharmacists, psychologists, social workers, ethicists, and patients or patient advocates. Some hospitals also might find it appropriate to add a representative from risk management, to help minimize liability, as well as an executive from the C-suite.
When mitigation efforts fail, one of the factors that Unguru says should be considered during allocation is the threshold of curability. For example, a patient with an 80 percent chance of survival should receive priority over a patient with a 40 percent chance. Although physicians may opt to prioritize use of a scarce drug to treat more curable forms of cancers, they should remain mindful of the critical role that certain drugs have in the management of cancers with poorer outcomes. "Such a patient's only chance for a cure may be that one scarce drug, whereas the patient with the higher cure rate may have other options," Unguru says.
Unguru stresses that some factors should not enter the drug allocation decision-making process. Among these are a patient's age, race, developmental level, immigration status, and ability to pay.
Sidebar: Frequent Drug Shortages in 2016
Forecasting Future Problems
Leaders at Dana-Farber Cancer Institute, Boston, established a medication supply task force in July 2011, when shortages of chemotherapy agents had the potential to impact patient care. One example was the shortage of liposomal doxorubicin injection.
"The goal of our task force is to monitor the commercial supply and work with physician leaders by disease specialty to come up with other treatment options in case we have a supply interruption, especially for those medications used for curative intent that do not have many alternatives," says Sylvia Bartel, RPh, MPH, vice president of pharmacy.
Asking tough questions. During the liposomal doxorubicin shortage, the task force convened a group of oncologists who treat different types of cancer and asked them to consider three key questions to determine which patient population should continue to be treated with this medication:
- Is there ongoing evidence of clinical benefit?
- Is an alternative treatment available that is equally effective?
- What would be the impact on the patient's outcome if the patient did not receive that drug or the alternative?
Ultimately, hematology/oncology disease leader representatives worked together and determined how to prioritize which patients required continued treatment with liposomal doxorubicin and which patients could receive other chemotherapy agents. For example, breast cancer patients could receive other chemotherapy agents, while most ovarian cancer patients would continue to receive liposomal doxorubicin. The task force also weighed the option of moving some patients into clinical trials if appropriate.
Bringing in experts. Membership of the multidisciplinary task force has evolved, and today the group includes Bartel, the physician who co-chairs the P&T committee, the adult inpatient medical director, the chief medical officer, the chief quality officer, the chief nursing officer, the risk manager, the physician director for satellite locations, a pediatric oncologist, an ethicist, the pharmacy business manager, a representative from finance, a representative from communications, and a member of the patient and family advisory council.
When a drug is in short supply, the task force also invites experts from the affected specialties to help them understand the impact and develop detailed strategies.
Anticipating payment issues. The representative from finance can help keep the task force aware of any payment-related issues. For example, when leucovorin, which helps prevent liver toxicity following methotrexate administration, is in short supply, providers often must use a much more expensive alternative. In normal circumstances, health plans would reject the use of the more costly drug. "Finance can help us know when we need to talk to payers regarding certain substitutions," Bartel says.
Involving the patient community. Dana-Farber established a hotline for patients to call if they have questions about drug shortages. "When patients hear about drug shortages, they want to know how it is affecting their care," Bartel says.
Managing the latest shortages. A recent example is all-trans retinoic acid (ATRA), which is used to treat acute promyelocytic leukemia. "It is very critical to start the drug early on, but it has been difficult to obtain in recent months," Bartel says. The task force researched the literature and found a formula for compounding the drug, then asked physicians for their views on compounding ATRA and what sort of patient monitoring would be required. Before compounding had to happen, the situation was resolved when the hospital's distributor was able to ship supplies from Hawaii. However, had the shortage become a reality, an additional consideration would have been how to ensure patient safety when compounding a product that is commercially available. Such considerations include patient education on measuring a liquid instead of taking capsules, Bartel says.
Another drug that has been challenging to obtain is bleomycin, which is used for curative purposes in Hodgkin's and testicular cancer. Bartel's team recently called the FDA to discuss possible importation of the drug. Bartel also talked internally with physicians about the possibility of dose conservation and of scheduling patients in cohorts so they could receive treatment at the same time to avoid any waste.
Compounding Needed Drugs
In the cases of some drug shortages, pharmacists at University of Michigan Health System (UMHS), Ann Arbor, Mich., can compound their own injectable drugs in their IV clean room if they can source the raw materials and verify stability and compounding formulations, says Deborah Wagner, PharmD, FASHP, pediatric safety coordinator and associate clinical professor of pharmacy and anesthesiology. For example, pharmacists followed strict protocols to compound their own IV solutions of calcium chloride, sodium bicarbonate, and sodium phosphate during a period from fall of 2012 into 2013 and longer due to national shortages and wholesaler lack of inventory.
"When we consider making our own drugs, we have our drug information service conduct a literature review to determine the formulations and protocols," Wagner says. "Some products, such as dexamethasone, we just can't make in the same formulation that is commercially available, or they might only be stable for such a short period of time, perhaps several days, so it is not really worth it. But if we can get a product that has stability data for 20 or 30 days, then it is probably worth compounding it here if we can do so safely and consistent with USP [U.S. Pharmacopeial Convention] guidelines."
More recently, Wagner and her team have been weighing the possibility of compounding tromethamine IV injection, which is no longer commercially available from the manufacturer at least for the foreseeable future. Thus far, the organization has restricted its use to the neonatal intensive care unit and created an electronic prescribing alert to inform providers of the ordering restrictions on the drug as well as a recommendation to consult with a pharmacist for alternatives or guidance.
Switching pumps. In early 2016, UMHS, along with other healthcare organizations, faced a critical shortage of the empty glass cartridges that are used to compound different concentrations of the opiate drugs that run on a patient-controlled analgesia (PCA) pump.
"We were at the point of not having enough compounded cartridges to get through the weekend with the number of patients we had currently using the product," Wagner says. "During emergency meetings with care providers, pharmacy, and nursing, we had to consider if we could switch patients from the PCA pumps to IV bolus injections, alternative concentrations, or other medications. The downside with IV bolus injections is that they require nurses to provide the injections every three to four hours and may create analgesic gaps in pain management as well as increases in nursing workload."
Ultimately, leaders at UMHS decided to accelerate their scheduled implementation of a new PCA pump, which did not require the cartridge that was in short supply, by one month. "It involved intensive education because we had to move up a major implementation that meant switching hundreds of pumps and educating hundreds of nurses in a shorter time than we had anticipated, and doing so safely," Wagner says.
Maintain detailed records. UMHS has a dedicated drug shortage committee that meets every Wednesday and Friday to discuss upcoming shortages and potential mitigation strategies.
The committee maintains a spreadsheet of each drug in short supply so next steps can be prioritized. "If there is critical shortage, we have someone from our computerized physician order entry support system run a report to determine patient utilization per day," Wagner says. "The supervisor of our automated dispensing machines is also able to tell us how much supply we have on the patient units versus in the central pharmacy inventory. Then we can decide what inventory we might be able to pull back into the central inventory to conserve our supply."
Sidebar: A Closer Look at Direct Contracting
Hospitals and health systems likely will face continued drug shortages in the near future. Healthcare leaders with experience managing drug shortages suggest the following strategies be used as part of an organization's action plan.
Tap a leader in your organization to forecast potential drug shortages. "You never want to learn at 3 p.m. on a Friday that a drug is in shortage, but it happens way too often," ASHP's Pasko says. She recommends the pharmacy director take the lead with a champion from the C-suite.
Create policies and procedures. ASHP has developed guidelines on managing drug shortages. Organizations can use this guidance to create their own playbook to implement during a shortage. University of Utah Health Care and Dana-Farber are among the organizations that have put an action plan on paper.
Use credible, real-time data to forecast problems. An organization's IT system should be able to build patient lists that include data on each drug, patient, date of first treatment, date of next anticipated treatment, and treatment intent (curative or palliative), Dana-Farber's Bartel says. This approach can help organizations anticipate usage and predict potential supply problems.
"Some organizations may need to add an expert from IT to their medication supply task force if they are not able to get real-time data from their system," Bartel says.
Have an appeals process for allocation decisions. "Part of doing this the right way is to ensure that allocation decisions are reasoned, explicit, public, and transparent," says Unguru, the framework advocate with Johns Hopkins. "Such a process will gain the public's trust that prioritization decisions are not made haphazardly or arbitrarily." Allowing patients and clinicians to challenge a decision not in their favor is part of a transparent and public process. The appeals committee could include members of the drug shortage committee along with a few additional members who can offer different perspectives.
Do not stockpile drugs. "Because most hospitals don't keep more than a three-day supply on hand, shortages can be critical because they don't have any supply to fall back on," UMHS's Wagner says. "However, stockpiling of drugs when there is a shortage just creates more problems downstream, creating artificial shortages or restricting product available to those in need."
Share expertise. "Before a recent saline shortage, our supply chain team had not experienced many shortages, although the pharmacy team had," says Fox of University of Utah Health Care. "We wanted to make sure all the ideas we had about managing a shortage could help our supply chain department."
Take on an emergency management mind-set. "Everyone has a disaster preparedness plan for an earthquake or flood, and a drug shortage can be like a mini disaster," Fox says. "You can leverage some of the communication tools that you might use in a disaster to keep everyone informed," Fox says.
Work with your group purchasing organization (GPO). Through a GPO, providers can take advantage of failure-to-supply clauses in contracts, which allow hospitals to receive monetary compensation when a drug is in short supply and more costly alternatives are purchased, says Premier's Alkire.
Keep standardizing. Alkire believes that providers should maintain their momentum toward formulary standardization. "As more healthcare systems standardize, we can create private-label programs and bring new products into the market that create a healthier supply and more competitive friction, which in the long run is healthier and better for pricing."
Finding a Better Way
Unguru stresses that drug conservation strategies and allocation frameworks are merely short-term solutions that will not correct the ongoing drug shortage problem. "There has to be a larger policy change that is grounded in coordination and cooperation, and that includes all the stakeholders, including patients, providers, government, and industry," he says. "A durable solution must also account for the underlying reasons for the shortage, which most experts agree are economic, manufacturing, and quality-related issues, as well as regulatory."
The bottom line, Unguru says, drawing on his experience with drug shortages: "As a society, we can no longer tolerate children with otherwise curable diseases lacking access to lifesaving medications."