No Quick Relief for Drug Shortages

In Toronto, some of the country's leading cancer centres are running out of chemotherapy drugs.

From Windsor to Ottawa, pharmacists have seen dwindling supplies of everything from heart and thyroid medications to antidepressants.

Doctors are grappling with shortages of common anesthetics and, most troubling, an irreplaceable muscle relaxant for intubating patients in an emergency.

And in Goderich, on Lake Huron, 66-year-old Diane Sallows wound up in hospital after the anti-seizure medication she had taken for years suddenly disappeared from pharmacy shelves.

With widespread and unpredictable drug shortages increasing in frequency and severity over the past two years, patients, doctors and pharmacists are all asking the same questions: Why is this happening, and when will it stop?

Similar scenarios are playing out across the country and around the world. In the U.S., as many as 15 deaths have been attributed to the shortages.

Some industry experts believe the situation is going to get worse unless Ottawa puts more pressure on the drug industry to avert future shortages.

"I think we all understand if maybe there's a fire at a plant or maybe there's an unexpected problem in one instance," said Dr. Malcolm Moore, head of medical oncology and hematology at Princess Margaret Hospital. "But when we're having so many problems with so many different drugs it makes you think there's something wrong with the whole system that needs to be fixed."

Last week, U.S. President Barack Obama ordered his country's Food and Drug Administration - which has been tracking shortages since 2005 - to take steps to get warnings out faster, investigate reports of price gouging and avert shortages altogether.

Health Canada, tasked with overseeing drug safety, but not its distribution, has left the industry to sort out the problem on its own.

In other words, no one is keeping an eye on our supply.

Drug makers have agreed to give advance warning about shortages through an online database they say will be up and running imminently. The move will help health professionals cope with the shortages, but it does not address the actual problem.

"It's not enough," said Moore. "It's a way of dealing with a crisis . . . but it's not a solution."

Annie Sallows has no idea why the medication that kept her daughter's seizures at bay for nearly six years disappeared from pharmacy shelves over the summer. But two weeks after Diane Sallows was switched, cold turkey, from primidone to a different anticonvulsant medication, she had a severe seizure and was rushed to hospital.

"It was very scary after her not having had a seizure in (so long)," her mom said.

Sallows was unable to move or speak for two weeks. She also developed pneumonia.

When the primidone supply vanished, it was patients and pharmacists who alerted epilepsy organizations and doctors, who in turn alerted government about the shortage.

It's difficult to measure the extent and impact of the drug shortages in numbers, because our government does not collect such data. In the U.S., where inventories are comparable to our own, there were 178 drugs in short supply last year, up from 61 in 2005, according to records kept by the FDA.

Doctors and physicians across both countries report shortages have caused delays in medical procedures, cancellations and prolonged hospital stays. They say alternative treatments do not work as well, can be more toxic, have unexpected side effects and may not work at all in some cases.

Shortages can also create a greater risk of medication error. In the U.S., two patients died during a morphine shortage after they were given another drug at a dosage intended for morphine. The country's Institute for Safe Medication Practices has collected evidence of more than 1,000 errors, near misses and "adverse outcomes" that can be connected to drug shortages.

According to Health Canada, "no risk to health" has been identified here.

Diane and Annie Sallows disagree. Others say the threat of running out of medications they rely on is enough to make them sick.

Trish Polhill went into panic mode in June when her Toronto pharmacy wasn't able to fill her primidone prescription.

"If abruptly withdrawn I can go into repeated seizures," the 62-year-old wrote in a letter to her MPP. "No one should ever be put in this position. It is sad that we are so co-dependent on the pharmaceutical industry."

There are no easy answers for why this is happening.The explanations are many and interconnected.

Pharmaceutical companies point to issues out of their control as the recent source of the surge: problems with raw materials - most of which are now produced in China and India, where quality standards are a concern - and regulatory measures that cause delays.

Many physicians and pharmacists don't buy that explanation, arguing that the shortages are caused by profit-driven decisions. They believe manufacturers will produce more of the drugs that make them more money and drop drugs that aren't as profitable.

A study by the U.S. Department of Health and Human Services found the central cause of the most recent shortages to be a combination of these factors, coupled with one major exacerbating issue: demand has increased while production has stayed the same. More drugs are needed but the plants that make them aren't getting any bigger.

Further, multiple mergers in the industry in recent years means fewer companies are producing drugs. With very little wiggle room in the system, makers are not easily able to boost production when supply is short.

In this kind of environment, even a small disruption anywhere along the supply chain - a quality problem or delivery delay, for example - can lead to far-reaching and persistent shortages, such as the ones we are seeing now.

Companies in the U.S. and Canada have plans in place to boost capacity, but it could take years before hospitals and pharmacies feel the effects of those changes.

At Princess Margaret, chemotherapy shortages have become such a problemthat the hospital has made it someone's job to keep tabs on the situation.

Since July, lead pharmacist Jin Huh has been pumping out weekly updates, keeping hospital staff informed about the rotating list of eight to 10 different drugs he says are always in short supply - chemotherapies used to treat everything from leukemia to ovarian cancer.

"They run the whole gamut," Huh said. "It's not just one group of patients affected."

The hospital wants to avoid having to cancel treatments, as doctors were forced to do one Friday in May when they unexpectedly ran out of carboplatin, a drug commonly used to treat ovarian cancer.

"When you're dealing with serious illnesses like cancer, you don't like to be in a position where you might be running out of a drug on a weekend," said Moore, the hospital's oncology head. "That smacks of maybe treating people in a war zone or in a Third World country."

The treatments were rescheduled when a new supply was found, but chemotherapy drugs remain in short supply across the country and doctors have been forced to ration them.

Since regulators in the U.S. began documenting and monitoring drug shortages more than five years ago, the situation has only worsened.

Part of the problem is that pharmaceutical companies are reluctant to provide details on the factors that lead to the shortages. An FDA analysis found that the information drug makers provide often lacks the detail needed to properly analyze and figure out how to avoid disruptions.

"There's only so much transparency that companies will offer as to why a certain drug is in supply or not," said Jeff Morrison of the Canadian Pharmacists Association.

When Canadian drug companies begin posting shortage alerts online, it will be up to them to decide exactly how much warning and information Canadians need.

And because the system is voluntary, they have no legal obligation to follow through.

"My view is that voluntary actions tend not to be that good," said Dr. Joel Lexchin, an emergency room doctor and professor of health policy at York University.

Lexchin and other industry experts argue transparency must be built into the system through regulation and that drug makers with a licence to produce a certain drug should face penalties if they fall short.

With a number of patents due to expire in the next few years, Lexchin and others worry the situation could get worse as those drugs become less profitable.

"If you want to make money by selling drugs then you should have to guarantee that you're going to be able to produce them," he said.

An article published in the New England Journal of Medicine last week argued drug companies should be required to present projections for demand and plans for meeting demand, and regulators should be given authority to revoke licences if goals are not met.

Predictably, drug makers disagree.

They say increased regulation would only complicate and slow the production process, and that it would be impossible to regulate when so many of the factors are out of their control.

What pharmacists say:

94% had trouble filling prescriptions in the last week

89% said drug shortages had greatly increased over the past year

70% said their patients' health outcomes were adversely affected

Canadian Pharmacists Association 2010 survey

What doctors say:

75% said drug shortages are a problem

46% said finding appropriate alternatives is a problem

33% said patients had run into financial difficulties filling new prescriptions

Canadian Medical Association January 2011 survey.

Originally published in Toronto Star.