Drug Shortages

16-15 Drug Shortages

Reed Pence: Doctors have an incredible array of medications to treat disease. Some drugs attack the disease itself, like chemotherapy drugs. Others, like anesthesia, assist in surgery or other procedures. And some drugs such as pain medications treat the symptoms of disease or trauma. Doctors can use the very best medications for a given patient- unless they can’t get the drug at all. Drug shortages are surprisingly common.

Dr. Yoram Unguru: These drug shortages have been going on in their current form for well over 10 years, and they reached a peak just a couple of years ago with 320 drugs in short supply. And they span the classes of drugs. So it’s not just chemotherapy, which is what I’m interested in per se. It’s really drugs of all class. So it’s critical care drugs, antibiotics, ICU drugs, essential electrolytes and minerals. There’s actually a shortage, believe it or not, of normal saline, that’s saltwater.

Pence: That’s Dr. Yoram Unguru, a Pediatric Hematologist-Oncologist at Children’s Hospital at Sinai in Baltimore and a faculty member at the Berman Institute of Bioethics at Johns Hopkins University.

Unguru: Presently, if you look at the data, there’s somewhere around 150-155 drugs in short supply. The majority of these drugs belong to a class of, let’s call generic sterile injectables and what that is really in English is that these are drugs that are often given in the form of an IV solution. These are drugs that have been around for decades. The important thing to keep in mind is that they are the backbone of proven and life-saving regiments for kids with cancer and the added insult here is that we have very few, if any, alternatives. So it’s not that you have an ear infection and you have your choice of a variety of antibiotics to treat it and one of them is short, you’re talking about very specific drugs that are required for a given childhood cancer, and without them, there is no alternative.

Bona Benjamin: We do have quite a few drugs in short supply now and there are quite a few of them that are critically important to care. I could give you some examples of those but I think one of the most striking is BCG vaccine, which is used for bladder cancer and it has very few alternatives in the drug armamentarium. The usual alternative is surgery and so this is really serious for patients with bladder cancer.

Pence: Pharmacist Bona Benjamin is Director of Medication Use Quality Improvement for the American Society of Health System Pharmacists. She says there are a lot of complicated reasons some of these drugs are in short supply, and we’ll talk about those reasons in a few minutes. But whatever the reason, the effect is the same. Pharmacists and doctors now find it part of their unfortunate routine to work around shortages and try to be prepared for them.

Benjamin: At one time, shortages were kind of an incidental thing that was just kind of annoying. Now, drug shortages are an everyday issue in patient care. So most hospitals, in fact probably all, have proactively developed protocols that help their care providers with choosing alternative drugs or what we call “conservation protocol” when the drug becomes short. So you would review your drug inventory and your drug utilization statistics, you would pick the drug that you know are critical to care, and, for those, you would develop backup plans.

Pence: Benjamin says the goal is to make the shortage invisible to the patient. Simple steps may involve conserving drugs—using smaller IV bags of saline, for example, rather than a large one, and expecting to throw out what’s left. After those steps, things get a little tougher.

Benjamin: What we first look for are therapeutic equivalents or therapeutic alternatives that may not be equivalent but are similar in their abilities to produce a specific outcome for a patient, so for instance, for antibiotics, there are many drugs in the class of antibiotics. If you don’t have one, you have many options to pick from that might be just as well or might even do better but are maybe more expensive, or maybe are a little more difficult to prepare and administer. But, you have a lot of alternatives.

Dr. Brian Fitzsimons: We haven’t been pushed to a point where we have felt that it’s been unsafe to practice because of those shortages.

Pence: That’s Dr. Brian Fitzsimons, a Cardiac Anesthesiologist at the Cleveland Clinic Foundation.

Fitzsimons: We’ve always been able to find substitutes. It’s usually a question of them tailoring an anesthetic prescription around a different side-effect or just biting the bullet and absorbing the cost, the higher cost for those drugs.

Pence: However, where no substitutes exist, Benjamin says the scrambling begins.

Benjamin: For drugs like sodium chloride injection, there really isn’t a lot of alternatives for patients who are severely dehydrated. So, your planning may involve something like, “Can we compound this drug from, say FDA-approved injectable components” or “Can we find a way to perhaps share the supply among all the organizations in a particular area so that all patients have the advantage or access to all that we have here?”

Pence: However, if a drug in short supply has no substitute, no way to compound it, and nowhere else to get it, that leaves doctors having to stretch what little they’ve got until it runs out. They have to make life and death decisions… to ration.

Unguru: What do you do? Do you skip a dose? Do you give a lower dose? Let’s say you do decide that you want to allocate drugs among equally deserving kids, how do you go about doing that? Imagine that you’re the kid or that kid’s parents and suddenly your doctor says “You know what, we have enough drug for just a couple of you or one of you and the rest of you don’t get it?” You’re really put between a rock and a hard place and you are now suddenly having to sit with a kid and their parents and telling them, “We may not be able to cure your otherwise curable cancer” just because you don’t have a drug. That doesn’t seem right.

Pence: But how far do you go to grasp at straws? Unguru says sometimes doctors can find a drug that might be an alternative but with little data that it’s more effective. It can be a roll of the dice.

Unguru: In 2009, there was a shortage of an old tried and true chemotherapeutic called mechlorethamine, this is a particular chemotherapy drug that’s been around for decades and it’s used to treat adolescents and young adults with a form of Hodgkin’s lymphoma, a very common type of cancer and at the time of this shortage of this particular drug, evidence suggested that there was another drug that was as effective. So a number of the kids got that alternative drug in their cocktail and they had a much higher rate of their disease coming back and relapsing than the kids who got the standard of care, the mechlorethamine. And while there were no deaths associated with that, these kids got exposed to significantly more rounds of chemotherapy, even bone marrow transplantation and these are very toxic therapies so it’s not even clear what’s going to happen to these kids down the road.

Pence: A panel of children’s oncologists has drawn up guidelines on the allocation of scarce drugs because doctors say they need more help making those decisions fairly and ethically. Unguru was on the panel and he says one study found that 70% of adult cancer doctors don’t get guidance from their hospitals.

Unguru: Oftentimes these decisions are left until the rubber hits the road—there’s a shortage and it’s the bedside physician who is forced with having to make this decision. And in the heat of the moment, there’s no question, of course, that bedside physician is going to advocate for her patient. But that’s not the way you want to do it. Bedside decision-making is inefficient. It’s not very comfortable. It’s not very ethical. So we came up with a task force and we developed a whole set of recommendations for how one goes about doing this based on a couple of premises. One is, as much as possible we should mitigate these shortages based on maximizing efficiency and minimizing waste. So if you think about the water shortage in California, that’s a perfect example: you don’t water your lawn as much or you convert from grass to stone or some other means, that’s your first step. When you’re forced, however, to allocate, when you have no choice, then there’s a number of factors that we recommend.

Pence: Among the factors to consider? Curability and the importance of a particular drug to a patient’s condition. The guidelines don’t say to distinguish between children of different ages, but what about children versus adults? Some hospitals give preference to those with more life yet to live. Benjamin says it’s a lot like the ethics of organ transplant allocation but Unguru says it’s a national disgrace.

Unguru: We’re talking about curable diseases. We’re talking about the most vulnerable of vulnerable, kids with cancer. The status quo is actually forcing us essentially to serve as a death panel. This notion of having to pick which kid is more worthy of a drug is really untenable. Although an ethical framework for allocating is necessary and appropriate, that’s not the solution.

Pence: The solution, Unguru says, is solving the reasons shortages occur in the first place. Some of them are economic and result from government restrictions.

Unguru: More than 10 years ago, in an effort to try to curb these high costs, the government stepped in and passed something called the Medicare Prescription Drug Improvement and Modernization Act. And what that does it, it reimburses Medicare for these sterile injectables based on a very small margin, so some of the companies will say, “You know what? It takes a lot of effort and a lot of money to produce these drugs and if we’re not getting a lot of return on investment, we’re not going to continue to make them” and there’s very good data that shows that since that act was passed, there’s been an increase in these shortages.

Pence: Production problems are another common reason for shortages.

Benjamin: Injectables, even the very simple ones such as sodium chloride injection, which is just salt water, have a complex manufacturing process, which has many complicated steps. So there’s a lot of opportunities for something to go wrong.

Pence: And when something does go wrong, it’s not as if another company can ramp up production to make up the difference.

Unguru: Very few companies actually make these sterile generic injectables. As recently as just a few years ago, three companies, in particular, made 70% of all the sterile generic injectables. Now imagine that they have a problem with one of their production lines, suddenly you’ve got a shortage of a drug and it takes a long, long time. You can’t just call a friend and say, “Hey, can you make this for me?” it doesn’t work like that. These are very complicated lines, and oftentimes, because the production lines are very complicated, usually more than one drug is made on the same line. So if that line goes down for whatever reason, you can imagine that now you’re faced with not just one shortage, but with some others as well.

Pence: Unguru says government action to revise Medicare payment rules would be a good start to solve some of the drug shortages. Changing rules prohibiting the transfer of drugs between states could also help ease regional shortages. But he says a more basic change in how drugs are produced and paid for will likely be needed. In the meantime, hospitals will have to continue to stockpile critical care drugs and hope the supply stretches far enough.

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I’m Reed Pence.