Drug shortages cause higher rates of medication errors, delayed treatment of life-saving medications and inferior outcomes, and even death.
This article first appeared November 28, 2018 on Medpage Today.
By Shannon Firth
WASHINGTON -- With drug shortages endangering patients, frustrating providers, and costing hospitals millions each year, stakeholders debated strategies to fix the problem during a day-long meeting hosted by the FDA and the Duke Margolis Center for Health Policy.
In late 2017, the FDA listed 39 new drug and biologic shortages and 41 continuing shortages, and noted briefing documents from Duke. While that was an improvement from the peak shortage years of 2011-2013, many of the drugs that remain in short supply are essential to care. Most are older generic drugs, and many are injectables rather than oral medications, said panelists.
Impact on Patient Care
"We've been in continuous drug shortage mode for over 10 years now," said Ritu Sahni MD, MPH, an advocate for the National Association of EMS Physicians and an audience participant.
Sanhi described shortages of injectable opioids, injectable anti-emetics, and cardiac arrest medications, and called for tracking, monitoring, and categorizing emergency medications uniquely.
"When those are unavailable to my crew in the back of an ambulance driving 30 miles an hour or 60 miles an hour, there's no other choice," he said. "This is life-threatening and immediate stuff."
Another audience participant said that even simple products that have been under shortage like "normal saline" can save lives. Other medications like magnesium sulfate, and drugs used for hypertensive crises have also been in short supply.
"It's becoming increasingly difficult to provide appropriate care and safe care," said Jessica Hardesty, MD, an obstetrician.
Drug shortages cause higher rates of medication errors, delayed treatment of life-saving medications and inferior outcomes, and even death, said Yoram Unguru, MD, a pediatric hematologist/oncologist at the Herman and Walter Samuelson Children's Hospital at Sinai in Baltimore.
In addition, substituting an alternative drug for standard of care can have consequences, said Unguru, a meeting panelist.
In 2009, during a shortage of mechlorethamine, which is used to treat patients with Hodgkins lymphoma, cyclophosphamide was used as a substitute in 40 teenagers. He said that their event-free survival rate was 12.5% lower than expected with the usual agent.
While there weren't any deaths in the group given the alternative treatment, those adolescents did experience "more rounds of toxic therapy" such as stem cell transplants, for which long-term effects are still uncertain, Unguru said. (A 2012 article in The New England Journal of Medicine reviewed the mechlorethamine shortage.)
Drug shortages can also lead to medication errors, noted panelists.
In a recent survey from the Institute for Safe Medication Practices (ISMP), 21% of the 300 respondents (which include pharmacy directors, pharmacy managers, pharmacy purchasing agents, pharmacy technicians, and medication safety officers) said that they knew of "at least one medication error related to a drug shortage" that happened in the 6 months preceding the survey. In written descriptions, the most common related to the wrong dose or wrong concentration of medicine.
Root Causes
In order to craft solutions to these problems, stakeholders first explored their causes.
Blair Childs, senior vice president of public affairs for healthcare consulting firm, Premier Inc., cited four common ones.
A drug shortage may be triggered when one manufacturer dramatically drops its market price -- often for "high-demand products" -- to secure market share, thereby driving other producers out. The manufacturer will then often leverage "barriers to entry" to the market to rebuild its profit margin. (In some instances, the manufacturers undercutting the market may be overseas, he noted.)
A second cause of shortages involves Drug Efficacy Study Implementation (DESI) drugs, the approximately 3,000 older drugs that lack the same safety and efficacy research as products introduced after 1962 legislation began requiring such evidence.
To encourage manufacturers to complete these studies, FDA policy forces all other companies to leave the market once one company has submitted an NDA. Prices for these products are often very low and can increase dramatically once a single manufacturer gains the monopoly, Childs said.
Another well-known reason for shortages include production issues that dry up supplies. Disruptions to the active pharmaceutical ingredient (API) suppliers, such as an impurity that leads to a recall of a product, can also lead to a product shortage. Changes in API requirements can have the same effect. For instance, a change to the monograph for potassium chloride led to a shortage.
One other situation that can create a drug shortage is the "grey market", wherein industry players buy large quantities of a product for resale to hospitals at jacked-up prices.
Prices on the grey market for some products have increased 300%-1600%, Childs said.
Finding Solutions
A consortium of hospitals along with the Department of Veterans Affairs set up CivicaRx earlier this year, with the specific mission to produce low-price generic drugs that are in high demand.
Martin VanTrieste, PharmD, the venture's president and CEO, said he believes that all drug shortages have economic causes at their core, and suggested that competition and sustainable, fair prices are key to resolving the problem.
Manufacturers also need to build redundancy into their supply chain instead of using a single source. One of the reasons for the medication shortages caused by Hurricane Maria was this lack of redundancy, he said.
Finally, VanTrieste said that greater transparency is needed. He's called on the FDA countless times to force drug sellers to make their suppliers' identities and locations public, without success. CivicaRx, however, is entirely transparent about its manufacturing processes, he said.
Rena Conti, PhD, associate research director for the Biopharma and Public Policy at the Institute for Health System Innovation and Policy at Boston University, seconded the need for more transparency.
"There must be reasons why there's so much asymmetric information," Conti said, noting that many of the answers related to drug shortages could be found in contracts which are now "shielded" from public view.
Price is also a driver, she said: "Maybe the pricing signal doesn't work here."
Policies that dampen the pricing signal, such as bundled payments or consumer price index penalties -- wherein generic manufacturers are forced to pay rebates when the average manufacturer price outpaces inflation -- may discourage participation. She wondered aloud whether loosening such constraints might draw more suppliers to the market.
Because the supply of both the base ingredient and the fill-and-finish products is so constrained, and the number of willing industry players are few, she suggested thinking "really outside the box" for potential suppliers, considering both importation as well as unconventional possibilities, such as universities or the Department of Defense. The latter may want to produce drugs for national security reasons, she said.
Erin Fox, PharmD, a University of Utah College of Pharmacy faculty member who has studied the issue, told MedPage Today that importation is only useful as a "last resort.
Imported drugs, in her experience, are often priced higher, and can end up sitting on the shelf unused, because they lack the proper bar codes and labels to be easily scanned into systems.
Speaking on the panel, Fox stressed the need to think of APIs as part of national security. "If we let other countries control our [APIs], we may be at risk."
As for price, Fox noted that because of how diagnosis-related group (DRG) payments work, hospitals already under cost pressures often aren't paid for products such as saline or anti-emetics.
Fox suggested that it's worth rethinking DRG payments and perhaps considering a different reimbursement model.