Dec 19, 2011
Optimal cancer treatment, which can offer cures or extend apatient’s life by months, years, or even decades, could bederailed by a lack of supply of critical therapies. Drug shortages,which first became widespread in the mid-2000s, are becoming anincreasingly serious problem in health care and in oncologyspecifically. As of the time of this writing, the U.S. Food and DrugAdministration (FDA) reported 232 drugs in short supply in 2011,breaking the previous year’s record of 211 drugs in shortage.
The agents in scarce supply tend to be older, generic, injectable drugsthat are the backbone of standard chemotherapy (either alone or incombination) for common adult and pediatric cancers.
When a drug is unavailable, patients are faced with the dishearteningoptions of switching to an alternative therapy (which may be moreexpensive, more toxic, and/or less effective), receiving treatment at adifferent site where the drug is available (which may be much furtherfrom the patient’s home), or—if no alternativetherapy is available—delaying treatment altogether until asupply of the necessary drug can be found (which may adversely affectsurvival).
Cascadingproblems for practices, researchers
Oncology care providers also face a significant cost from drugshortages, and not simply because the next-best therapy may be moreexpensive. Practices may have to turn away patients because they do nothave adequate supplies of a treatment. They must also dedicatesignificant staff time to tracking down supplies of drugs in shortageand developing systems for managing or rationing the small stock thatthey have, often not knowing when—or if—newsupplies will come in.
In addition to the immediate impact of drug shortages on patientscurrently undergoing active treatment, clinical research is alsothreatened by the dearth of several agents. More than 300 NCI-fundedclinical trials depend on a drug in short supply, reported Howard K.Koh, MD, MPH, an Assistant Secretary of Health in the U.S. Departmentof Health and Human Services (HHS), in September 2011.
Below, common questions about drug shortages are addressed. ASCOmembers are encouraged to request more information or share experiencesand perspectives on the issue by sending an email topublicpolicy@asco.org or by leaving a comment in the “DrugShortages: How Is Your Practice Managing?” forum.
Whatis causing these drug shortages?
There is no single root cause that makes a drug vulnerable to supplyproblems, but rather several underlying causes:
- Drug discontinuation.Pharmaceutical companies are not required to continue producing a drug,even if it is needed by many patients. Some companies have chosen todiscontinue the production of less-profitable older generic drugs infavor of newer more-profitable agents. With production of genericagents concentrated among a small number of companies, an interruptionin manufacturing at a single location can lead to a serious shortage.(Read Dr. Peter Yu’s blog on the topic.)
- Manufacturing problems. Ascarcity of raw materials, FDA compliance issues, and production orshipping delays can lead a manufacturer to slow or temporarily stop itsproduction of a particular drug.
- Quality issues. The majorityof drugs in shortage are sterile injectables, which are manufacturedwith a complex multistep process to ensure their safety and quality.This yields more opportunity for manufacturing errors or contaminationthat render a batch unsafe or unusable. Because of their complexity,sterile injectables are more expensive to produce, which may lead acompany to focus on manufacturing more-profitable oral drugs.
- Regulatory requirements.Maintaining or obtaining active approved applications from the FDA tomanufacture older generic drugs may lead companies to shut downproduction of particular agents rather than try to fulfill what manyperceive as expensive and time-consuming regulatory requirements.
- Free-market limitations. The2003 Medicare Modernization Act (MMA) led to greater transparency indrug pricing and changed the way that most intravenous drugs arereimbursed by Medicare. Reimbursement is now based on thedrug’s average selling price (ASP) plus 6%, which may make itdifficult for companies to raise the price of a drug even if there isincreased demand—leaving companies little incentive toincrease their production of low-margin drugs.
Howhas ASCO been addressing drug shortages?
ASCO has been carefully monitoring drug shortages and has beenparticularly active on the issue over the past year.
In January 2011, ASCO, along with the American Society ofAnesthesiologists (ASA), the American Society of Health-SystemPharmacists (ASHP), and the Institute for Safe Medication Practices(ISMP), issued preliminary recommendations to help ease thedrug-shortage crisis. The recommendations stemmed from the November2010 Drug Shortages Summit jointly convened by the organizations.
In February 2011, ASCO supported the introduction of the PreservingAccess to Life-Saving Medications Act in the Senate (S. 296, introducedby Senators Amy Klobuchar [D-Minn.] and Robert Casey [D-Pa.], andsubsequently H.R. 2245, introduced by Representatives Tom Rooney[R-Fla.] and Diana DeGette [D-Colo.] in June 2011). Although there aresome small differences between the Senate and House versions of thebill, if passed, this act would require a manufacturer to formallynotify the FDA six months before discontinuing or interrupting theproduction of any drug.
In July 2011, representatives from the oncology community, includingASCO President Michael P. Link, MD, a pharmacist, and a cancer patientaffected by the shortages, discussed the issue at a special CapitolHill briefing.
In September 2011, the ASCO Government Relations Committee sponsored areception for Congressional members and staffers to discuss drugshortages and other legislative issues relevant to cancer care. Inattendance were Representatives John Carney (D-Del.), Brett Guthrie(R-Ky.), Ron Kind (D-Wis.), and John Barrow (D-Ga.), as well as keystaff from 22 Congressional offices. Later that month, ASCOrepresentatives expressed the urgent need for policymakers to engage inserious efforts to solve and prevent cancer drug shortages at a publicworkshop held by the FDA.
Also in September, W. Charles Penley, MD, of Tennessee Oncology andChair-Elect of ASCO’s Government Relations Committee,testified at a hearing of the House Energy and Commerce Subcommittee onHealth. He spoke on ASCO’s behalf and also represented hispractice, which has experienced ongoing problems with drugsin short supply for the past year. Dr. Penley’s complete testimony is available at ascoaction.asco.org.
“The hearing was scheduled because many government agencieshave been getting reports of drug shortages,” said Dr.Penley. “We were glad to provide testimony on behalf of ourmembers and patients because it brought the issue to a much higherlevel ofpublic attention.”
In October 2011, ASCO supported an amendment to the fiscal year 2012Senate Agriculture Appropriations bill that would give the FDA $10million to address drug shortages. The amendment, filed by SenatorRobert Casey (D-Pa.) gives the Office of the Commissioner of the FDAincreased funding to “remedy the current drug-shortagecrisis and to prevent future shortages.”
On October 31, President Barack Obama issued an executive order,supported by ASCO, directing the FDA to curb drug shortages bybroadening its reporting of potential shortages, expediting regulatoryreviews, and working with the Department of Justice to investigateillegal price gouging or stockpiling. President Obama also offeredsupport for the bipartisan House and Senate legislation that wouldrequire drug manufacturers to give the FDA prior notice of a shortage.
Whatsolutions have been proposed?
Numerous solutions have been suggested to address the drug-shortagecrisis; a true resolution of the issue will likely require severalelements in combination. Some of the proposed solutions include:
- offering financialincentives for manufacturers to continue producing or increaseproduction of generic sterile injectables, such as tax breaks,stipends, or market exclusivity;
- amending the 2003 MMA toincrease reimbursement and eliminate de facto price controls on genericdrugs;
- forming a nonprofitorganization that will import and manufacture drugs to maintain asteady supply;
- creating a nationalstockpile of cancer medicines, similar to the existing stockpile ofantibiotics at the CDC;
- decreasing administrativeand regulatory barriers to encourage manufacturers to enter or remainin the generic market; and
- empowering the FDA withincreased authority to manage shortages.
Whatdrugs are currently in short supply?
The FDA and the ASHP maintain current lists of drugs in short supply ontheir respective websites:
In addition to chemotherapeutic agents, drugs in short supply includesurgical anesthetics, emergency medications, and intravenouselectrolytes.
Mypractice/institution is experiencing a drug shortage. What can I do?
To report a shortage situation or supply issue to the FDA, send anemail to drugshortages@fda.hhs.gov. You can send a report to ASHP usingan online form at ashp.org/drugshortages/report/. Using the ASHP formgenerates a simultaneous email to ASHP, the FDA, and the University ofUtah Drug Information Service, which tracks shortages for ASHP.
You’re also encouraged to keep ASCO apprised of anydrug-shortage situations in your community by contactingpublicpolicy@asco.org. Share yourexperience with drug shortages, recommend solutions, and confer withcolleagues in the “Drug Shortages: How is Your PracticeManaging?” forum. You can find guidanceon how to contact your Congressional representative about legislationrelated to oncology drug shortages by visiting ASCO’s ACTNetwork (capwiz.com/asco).
Dr. Penley recommends that ASCO members work to raise awareness aboutdrug shortages at the local level. “If a drug shortage arisesin your community and it’s having a direct, personal impacton patients, speak with your local media outlets to continue to keepthe level of interest high. We have to keep this issue in the forefrontfor policymakers,” he said.
Whatis the drug shortage “gray market”?
In the midst of the drug-shortage crisis, there have been reports thatsome secondary distributors are significantly marking up the prices ofagents in short supply—up to 20, 50, or even 80 times thetypical contract price of the drug. This price-gouging parallel marketis being referred to as the “gray market.”
Representative Elijah E. Cummings (D-Md.), ranking member of the HouseCommittee on Oversight and Government Reform, is leading aninvestigation into five pharmaceutical distributors reported to beengaged in gray-market drug sales.
“Price gouging for drugs that treat cancer in children issimply unconscionable,” Mr. Cummings said in an October 2011press release. “We want to know where these companies aregetting these drugs, and how much they are making inprofits.”
If your practice or institution is approached by a drug distributorselling scarce drugs at an exorbitant mark-up, you can send a report tothe Congressional “Gray Market” Tipline atforms.house.gov/oversight_majority/webforms/grey_market.html. Find more information on the Congressionalgray market investigation atdemocrats.oversight.house.gov.
Whatare ASCO leaders and members saying about drug shortages?
ASCO President Michael P. Link, MD, has been the Society’svoice in speaking with numerous media outlets about the serious issueof drug shortages:
“Something has to be done soon in order to try to alleviatethis problem. Right now we’re already seeing patient caresuffering.”
—“Authorities Perplexed by Drug Shortage Spike,” Reuters,October 2011
“These are drugs that have actually resulted in cures and arelife-saving. I’m a pediatric oncologist...and some of thesedrugs are really the whole therapy. We can now cure almost 80% ofchildren with cancer and without these drugs, our hands are tied. Thisis really a crisis for us.”
—“On Point with Tom Ashbrook,” NationalPublic Radio (NPR), October 2011
“[Leukemia is] the type of cancer that doesn’t havetime to wait [for a renewed supply of cytarabine].”
—“Coming Up Short,” The Economist,September 2011
“These shortages are just killing us. These drugs save lives,and it’s unconscionable that medicines that cost a couple ofbucks a vial are unavailable.”
—“U.S. Scrambling to Ease Shortage of Vital Medicine,” New York Times,August 2011
“You can imagine the conversation and I’m surethey’re going on all over—doctors have to telltheir patients or their patients’ parents that wecan’t give them the proven drug because we don’thave it.”
—“U.S. Cancer Drugs Shortage Has Doctors Scrambling,” Reuters,June 2011
Robert J. Mayer, MD, of the Dana-Farber Cancer Institute and an ASCOPast President, was quoted along with Dr. Link in the June 2011 Reutersarticle. On the issue of drug substitutions and alternative therapies,he offered the analogy, “One could say that substitutingPepsi for Coca-Cola doesn’t make a difference. Maybe it doesand maybe it doesn’t. But more often it might be substituting7-UP for Coca-Cola, and that might make a difference.”
Ezekiel J. Emanuel, MD, PhD, of the University of Pennsylvania,contributed an op-ed to the New York Timesin August 2011, in which he wrote: “You don’t haveto be a cynical capitalist to see that the long-term solution is tomake the production of generic cancer drugs more profitable. Most ofEurope, where brand-name drugs are cheaper than in the United States,while generics are slightly more expensive, has no shortage of thesecancer drugs....Scare-mongering about death panels and health carereform has diverted attention from real issues in our health caresystem. Shortages in curative cancer treatments are completelyunacceptable.”
Wherecan I find more information on oncology drug shortages?
Visit the following websites to find more information on drugshortages:
LIVESTRONG Blog Considers, “What If?”
Craig R. Nichols, MD, of Virginia Mason Medical Center, Seattle, an ASCO member and a LIVESTRONG Board of Directors member, contributed a guest blog post on livestrong.org, considering how his most famous patient—seven-time Tour de France winner, philanthropist, and testicular cancer survivor Lance Armstrong—would have fared if he had been diagnosed during the ongoing drug shortages.
Dr. Nichols wrote: “I’m often asked whether we gave Lance some sort of mythical special treatment or molecular wizardry reserved for celebrities and politicians. The answer is no. His recovery was due to tried-and-true treatments and medications like cisplatin, a drug developed in the mid-1960s. Today, cisplatin remains the cornerstone of cure for testicular cancer and is highly effective against many other malignancies. And this life-saving drug is on the Food and Drug Administration’s drug shortage list. . . . Were Lance diagnosed today, the odds would be stacked against him.”
Read Dr. Nichols’ complete post, “If Diagnosed Today, How Would America’s Most Famous Cancer Survivor Fare?".