[Ip-health] NYT: Drug Shortages Forcing Hard Decisions on Rationing Treatments

Zack Struver zack.struver at keionline.org
Fri Jan 29 11:13:35 PST 2016


Drug Shortages Forcing Hard Decisions on Rationing Treatments

By SHERI FINK    JAN. 29, 2016
CLEVELAND — In the operating room at the Cleveland Clinic, Dr. Brian
Fitzsimons has long relied on a decades-old drug to prevent hemorrhages in
patients undergoing open-heart surgery. The drug, aminocaproic acid, is
widely used, cheap and safe. “It never hurt,” he said. “It only helps.”

Then manufacturing issues caused a national shortage. “We essentially did
military-style triage,” said Dr. Fitzsimons, an anesthesiologist,
restricting the limited supply to patients at the highest risk of bleeding
complications. Those who do not get the once-standard treatment at the
clinic, the nation’s largest cardiac center, are not told. “The patient is
asleep,” he said. “The family never knows about it.”

In recent years, shortages of all sorts of drugs — anesthetics,
painkillers, antibiotics, cancer treatments — have become the new normal in
American medicine. The American Society of Health-System Pharmacists
currently lists inadequate supplies of more than 150 drugs and
therapeutics, for reasons ranging from manufacturing problems to federal
safety crackdowns to drugmakers abandoning low-profit products. But while
such shortages have periodically drawn attention, the rationing that
results from them has been largely hidden from patients and the public.

At medical institutions across the country, choices about who gets drugs
have often been made in ad hoc ways that have resulted in contradictory
conclusions, murky ethical reasoning and medically questionable practices,
according to interviews with dozens of doctors, hospital officials and
government regulators.

Some institutions have formal committees that include ethicists and patient
representatives; in other places, individual physicians, pharmacists and
even drug company executives decide which patients receive a needed drug —
and which do not.

An international group of pediatric cancer specialists was so troubled
about the profession’s unsystematic approach to distributing scarce
medicine that it developed rationing guidelines that are being released
Friday in The Journal of the National Cancer Institute.

“It was painful,” said Dr. Yoram Unguru, an oncologist at the Children’s
Hospital at Sinai in Baltimore and a faculty member at the Berman Institute
of Bioethics at Johns Hopkins University. “We kept coming back to wow,
we’ve got that tragic choice: two kids in front of you, you only have
enough for one. How do you choose?”

At the Cleveland Clinic, which has been unusually proactive in dealing with
shortages and allowed a reporter access to personnel making decisions about
them, one scarce leukemia drug, daunorubicin, was saved for patients in
clinical trials, to avoid making the results invalid by substituting
another drug. But when a different drug, methotrexate, was in short supply,
pediatricians stopped giving it to all patients who required high doses,
including those in research trials. “We didn’t want to say just because
you’re on a clinical trial you get an advantage,” Dr. Rabi Hanna said.

Patients’ weight can be taken into account. Obese patients, who researchers
found needed up to three times the amount of an antibiotic before surgery
than average-size patients, were given only the standard dose at the
Cleveland hospital until a shortage subsided.

Some institutions prioritize based on age; others do not. Marc Earl, a
Cleveland Clinic pharmacist, said children were not favored over adults
during chemotherapy shortages. But at other hospitals, they have been,
because of their potentially longer life span or because they sometimes
require smaller doses of a drug.

“We do play the pediatric card for sure,” said Alix Dabb, a pharmacy
specialist in pediatric oncology at Johns Hopkins Hospital. Dr. Kenneth
Cohen, director of pediatric neuro-oncology there, and his colleagues were
close to being forced into making “very, very hard decisions,” he said.
“The discussions became, ‘Why are two kids more important than one adult?’”

Ning-Tsu Kuo, a pharmacist at the Cleveland hospital’s home infusion
pharmacy, said children came first during shortages of nutritional products
such as intravenous vitamins and fats for patients who cannot absorb food.
The logic was that adults have more reserve. But after one man pleaded not
to have his dose cut, Dr. Kuo agreed. When reprimanded by colleagues, she
recalled saying: “Patients are not equally the same. You need to look case
by case.”

‘Downright Scary’

Such decisions have real consequences. For some shortages, doctors can soon
see the effects of rationing, such as increased pain or nausea when drugs
typically used to control symptoms are withheld, or patients who have to
undergo invasive surgery to control cancer when anti-tumor medications are

Studies have associated alternative treatments during drug shortages with
higher rates of medication errors, side effects, disease progression and
deaths. For example, children with Hodgkin’s lymphoma who received a
substitute to the preferred drug had a higher rate of relapse, researchers
found, and adults with a genetic disorder called Fabry disease had
decreased kidney function when their medication was cut by two-thirds. One
alternative guideline adopted during a shortage of intravenous
nitroglycerin “was downright scary from a clinical perspective,” according
to Dr. Nicole Lurie, a senior federal health official.

Physicians say that many of the changes they are compelled to make appear
to do no harm. But, they acknowledge, typically no one is tracking outcomes
in patients who get a drug and others who get a substitute or delayed

Doctors and hospitals often do not tell patients about shortages and the
resulting rationing because they do not want them to worry, especially when
alternative drugs are available, or because they feel it would stir up too
much anger.

Dr. Ivan Hsia, an anesthesiologist in Ontario, Canada, said many physicians
in his field adopt what he called “the paternalistic model — like I’ll
inform them when I think it’s unsafe enough to inform them.”

When he and his colleagues surveyed hundreds of patients at the Mayo
Clinics in Arizona and Florida and others in Canada about their
preferences, the results surprised him. Most wanted to know about a drug
shortage that might affect their care during elective surgery, even if
there was only a minor difference in potential side effects, and many said
they would delay surgery.

When the study was published last year in the journal Anesthesia and
Analgesia, an accompanying editorial urged health professionals to disclose
shortages and their implications. “Patients want to know and they should
know,” the editorial said. “There is no ethical ambiguity.”

Dr. Eric Kodish, a children’s cancer doctor who heads the Cleveland
Clinic’s center for ethics, humanities and spiritual care, said patients
should be told. “It’s their bodies and their lives that are on the line.”

Indeed, Beverly Smith, a Cleveland patient who has Crohn’s disease, said
she had no idea that an important ingredient had been removed from the
daily intravenous nutritional treatments she depends on until she developed
side effects from the deficiency. “Why didn’t anybody tell me?” she asked.

Who Gets Preference?

In a basement storeroom filled with plastic crates and cardboard boxes,
Chris Snyder, a Cleveland Clinic pharmacist and the point man for drug
shortages, spends part of each workday poring over the hospital’s drug

He tracks a list of shortages that included more than 75 drugs the first
week of January. Dr. Snyder moves stocks among the hospital’s campuses,
identifies alternatives, and — in the most dire situations — helps devise
and enforce restrictions on which drugs can be ordered for which types of

Many drugs are made by only one manufacturer, so production or safety
problems at a single plant can have big effects. For another company to
begin making the products and getting them approved by regulators requires
the right combination of manufacturing capabilities and economic incentives.

The chances of getting a drug also depend in part on where a patient
happens to live, how adept the local hospital is at finding — and hoarding
— scarce drugs, or a patient’s access to a major medical center.

The Cleveland Clinic, for example, has an advanced compounding room where
workers swaddled in disposable gowns, bouffant caps and blue gloves mix up
remedies from raw ingredients. During a shortage of papaverine, a drug used
for surgery on blood vessels, the clinic produced its own version. When
other hospitals began asking about it, Dr. Snyder said he had to tell them,
“It’s a franchised recipe we can’t give out.”

At Cleveland, decisions about conserving, substituting and allocating
scarce drugs typically are made by small groups of doctors and pharmacists;
Dr. Kodish’s ethics committee is not involved. But such decisions are not
always made by doctors or hospitals. One company, Janssen, chose to ration
its ovarian cancer and multiple myeloma drug Doxil on a
first-come-first-served basis during a prolonged shortage.

Another company, Jazz Pharmaceuticals, recently consulted a small group of
oncologists to recommend how to allocate its cancer drug, Erwinase, if it
ever became necessary. “Who deserves the drug more than anyone else?” said
Dr. Wendy Stock, a leukemia specialist at the University of Chicago
Medicine, who participated in the discussion. “We gave them some guidelines
on that. ”

In a survey of cancer doctors conducted in 2012 and 2013, 83 percent of
respondents who regularly prescribed cancer drugs reported having been
unable to provide the preferred chemotherapy agent at least once during the
previous six months. More than a third of them said they had to delay
treatment “and make difficult choices about which patients to exclude,”
according to a letter published in The New England Journal of Medicine.

The threat of future shortages in children’s treatments is serious enough
that Dr. Peter Adamson, who leads the Children’s Oncology Group, the
largest international group of children’s cancer researchers, assigned his
organization to set priorities. “We’ve been forced into what we think is a
highly unethical corner,” he said in an interview.

The effort, led by Dr. Unguru, the Baltimore oncologist, recommended that
the drugs be rationed based on the ability to save lives or years of life,
including curability of a child’s cancer and the importance of the drug in
improving the chances. It also recommended that children participating in
clinical research should not get priority over those who are not, because
of concerns about coercing families into trials. The group also advised
that allocation decisions be public.

A recent shortage of a therapy for bladder cancer, BCG, demonstrates how
the lack of national guidance can lead to very different decisions. One
Cleveland Clinic urologist, Dr. Andrew Stephenson, said he came up with BCG
rationing guidelines that were used with dozens of patients after being
shared with colleagues. “We tried to reserve the BCG for those patients who
needed it the most,” he said.

Merck, the manufacturer, said it filled requests from a waiting list in the
order received, and left rationing decisions to doctors. Some cancer
centers reduced the length of BCG treatment from three years to one,
because the benefit may be smaller after the first year. Others restricted
BCG to patients whose tumors were mostly likely to spread or recur. And
still others decided to reduce the typical dose so that each vial could be
used for three patients instead of one, which some experts say raises
questions about efficacy. Some outpatient clinics just ran out.

In interviews and comments on a support website, Inspire, patients seemed
confused about why they were or were not getting BCG. “I found out people
were getting it in different parts of the country,” said Don Keating, whose
bladder cancer was diagnosed in 2014. He was told by his doctor in Boston
that he needed BCG, but that it was not available.

Mr. Keating had to wait about six months before obtaining the drug, during
which time his cancer recurred. “I believe if I had gotten it when it was
first prescribed, I wouldn’t have had to go through those operations,” he

Many urologists said they saw similar recurrences possibly due to the
shortage, and that some patients underwent high-risk bladder removal
surgery that probably would have been avoided if BCG had been fully

Dr. Kamal Pohar, a urologist at Ohio State University’s cancer hospital,
said he remembered driving home, wondering if he was making the right calls
for his patients. “I can still feel the stress,” he said. “I’ve never been
faced with this.” Supplies of BCG are again adequate, Merck and doctors

The vagaries in distribution and inconsistencies in rationing have led to
calls for change. Doctors and others have suggested the creation of a
clearinghouse of scarce drugs and voluntary sharing to promote equitable
access for patients. Others argue that there should be a registry of
patients given nonstandard treatments so the results can be tracked.

Dr. Lurie, the federal health official in charge of emergency preparedness
and response, said that the government was working to encourage hospitals
to conserve and substitute drugs to avoid a crisis and trying to fill gaps
in manufacturing. Steps taken by the Food and Drug Administration have also
helped reduce the number of shortages, she said.

Still, she argued that tools developed for disaster response, including
ethical and procedural guidelines, should be applied. “Different places
around the country are each doing their best to patch together their own
guidelines,” she said, adding, “if they’re doing anything at all.”

Zack Struver, Communications and Research Associate
Knowledge Ecology International
zack.struver at keionline.org
Twitter: @zstruver <https://twitter.com/zstruver>
Office: +1 (202) 332-2670 Cell: +1 (914) 582-1428

More information about the Ip-health mailing list