The problem of drug shortages in the treatment of cancer in children is described in this Medpage Today article. What caught my attention about the article was the name of the drug being discussed, vincristine. I recognized it as part of the chemotherapy regimen that my mother had been treated with, twenty years ago.
From the article: "Acute lymphoblastic leukemia (ALL) accounts for about one-fourth of all childhood cancers. As such, when drug shortages hit the pediatric cancer population, patients with ALL are particularly affected.
The latest shortage hitting ALL patients is that of vincristine, a chemotherapeutic that is the "bread and butter" for oncologists treating ALL and other childhood cancers, said Yoram Unguru, MD, of the Herman and Walter Samuelson Children's Hospital at Sinai in Baltimore and Johns Hopkins Berman Institute of Bioethics."
"The current vincristine shortage is the result of manufacturing delays (the drug is manufactured by Pfizer), which has been exacerbated by the fact that the other manufacturer of the drug, Teva, discontinued production earlier this year. The company has since reversed that decision, but shortages are expected to continue through the rest of this year."
"When it comes to chemotherapy, particularly for kids with cancer, we don't have alternatives," Unguru told Medpage Today. "And even if we think we have alternatives, they don't always pan out."
"...Another example is the mechlorethamine shortage that occurred about a decade ago....when you are talking about a disease like childhood leukemia, where there is no alternative, and these are lifesaving drugs, drugs that serve as a back bone of our treatment protocols, then you don't have to be a rocket scientist to appreciate the significance of the shortages."
"Acute Lymphoblastic Leukemia (ALL) is a good example of the problem oncologists and patients and their families face when a drug is unavailable," said Unguru. "If you look at the past decade, eight of the 10 drugs commonly used to treat and cure ALL have been in short supply at some point. It's just harrowing."
A little background on the drug vincristine; it is not newly developed. It was first isolated in 1961. It has a botanical source, it is a vinca alkaloid derived from the Madagascar periwinkle.
As I read the article, I wondered what was driving the shortage. I already knew that it wasn't one of the brand new drugs that was scarce and expensive. Since it is sourced from a plant, I considered that perhaps the Madagascar periwinkle was in short supply or maybe even endangered. But this was not indicated. Nearly at the end of the article the mystery was solved.
Said Dr. Unguru: "... this problem is self-inflicted. We have a market-driven healthcare system and pharmaceutical companies have obligations to shareholders. They view the production and distribution of drugs in a different manner than patients and clinicians do."
From the Wikipedia article: "The wholesale cost in the developing world is between US$1.80 and US$42.60 per dose." So the bottom line is that the manufacturers aren't making enough money from an older, inexpensive drug, which nevertheless is crucial to saving lives. So they devote their energies and resources to more lucrative production.
The Healthpages article suggests stockpiling crucial drugs "...that would basically serve as an insurance policy for the next market failure."
Or maybe we need to face the fact that in some cases the "market" isn't the solution, it is the problem.
Yes, this happens all the time in the world of chronic cancers that require lifelong oral chemo treatment.
ReplyDeleteThere is currently a shortage of anagrelide, another older drug. The shortage is worldwide, as reported by the FDA, which has the responsibility of tracking shortages, but has no power to do anything about it.
Anagrelide helps manage relatively rare blood cancers, and it is not the first-line drug of choice for most people. That makes its consumer group very small. But those who need it are in a bind.
Doctors have been advising patients in anagrelide to ration the drug, to switch to a less desirable or wildly expensive new drug contraindicated in many patients and not covered by most insurance companies, or to have frequent phlebotomies to "strain out" excess blood cells, which is costly, time-consuming, and fatiguing.
No, the market is not the answer.
This seems like an area where some government involvement could help. Maybe some R&D money in return for keeping these needed drugs stocked. Definitely an issue that needs to be addressed by healthcare reformers.
DeleteAn R&D bribe to try to entice manufacturers to keep making drugs that people need to stay alive simply encourages drug makers to create shortages of drugs in order to get R&D money.
DeleteThe government could contract with companies interested in making them or get them through vetted foreign sources willing to ramp up production.
The UK is a big manufacturer drugs that may no longer be kosher in the EU when Brexit goes through. They may find the idea of stocking an American market attractive.
India at one point wanted to get into providing generics in African markets. Maybe they would help us, too!
I'm pretty sure the atorvastatin I take is made in India. I was under the impression that they were already supplying generics.
DeleteYou are right.
DeleteI looked at 12 manufacturers that make generic hydroxyurea, my chemo, all but two are Indian. Shortages are less likely because it is also used to manage more common cancers in the end stage.
Last I read, some Indian companies may be focusing more on making specialty drugs for American companies. They have cheaper labor, and if Trump manages to force drug prices down, profit margins can still stay high by paying less to make the meds overseas.
"Or maybe we need to face the fact that in some cases the "market" isn't the solution, it is the problem."
ReplyDeleteNot surprisingly, I don't agree with this conclusion.
The shortage seems to have three causes:
1. The primary manufacturer, Pfizer, is having manufacturing issues that are hampering its ability to meet demand.
2. Roughly simultaneously, the manufacturer of a generic equivalent, Teva, elected to discontinue production, apparently because the drug wasn't profitable.
3. Roughly simultaneously, patient demand increased.
The market share of Teva ranged from small (15%) to insignificant (3%), so it's not clear what part of the current shortage is attributable to Teva's decision. Nor is it clear that, had Teva not discontinued its production, it would have been able to instantly meet the increased demand stemming from Pfizer's manufacturing constraints.
I say "roughly simultaneously" because Teva gave the FDA something like six months' warning that it would be discontinuing the product line, and at the time that decision was made, Teva claims that it had no knowledge of any looming manufacturing problems at Pfizer, its competitor. Teva also claims in a statement that, had it known about the looming supply shortfall from Pfizer, it would have continued to manufacture the equivalent. That commitment may stem from Teva's leaders' concern for patients, or the company's self-interest in gaining market share (and presumably profitability) or, possibly, both.
For its part, Pfizer expects to have manufacturing cranked back up to meet demand again by early in 2020 - perhaps as early as January (next month).
Here are some implications I draw from this set of facts and claims:
1. Teva can't make a decision in its self-interest (discontinue an unprofitable product line) without FDA approval. This implies that this process of withdrawing from the market already is heavily regulated by the government.
2. If the FDA is supposed to be acting as a watchdog overseeing the industry to prevent shortages of these critical meds, it didn't do a very good job in this instance. Apparently it permitted Teva to shut down production while being unaware of a looming shortage from Pfizer and also unaware of an increase in patient demand.
It's tragic when there is a shortage of meds for cancer patients. The market can't always prevent shortages; they occur in many industries for many products and services. To take a much less life-critical example: I see shortages, also caused by manufacturing bottlenecks, in my working world all the time for high-tech items like servers, switches and routers. These typically are short-term and sporadic. Let's home the same is true of Vincristine supply.
In my view, even though it's not always perfect or perfectly responsive, the market is the most efficient mechanism for addressing shortages. If what Pfizer is reporting about boosting its manufacturing capacity in the near future is true, then we see the market at work: a manufacturer is responding to market incentives. It would be better for patients if Pfizer could move faster, but whether that is possible, I don't know. I don't know what is required to fix a manufacturing problem, or to boost current manufacturing capacity. It often isn't instantaneous in manufacturing.
I don't know very much about how drug products like Vincristine are regulated by the government, nor the impact that government involvement in healthcare (Medicare, Medicaid, et al) has on manufacturer prices for these products. Nor do I know whether there are manufacturers and/or stockpiles outside the US that would permit the US to supplement its supply with imports. I suspect the supply and pricing for Vincristine is a complicated mix of private interests, government regulation and, perhaps, government incentives.
Sometimes the reasons for a shortage are complex (for instance the Shingrix shortage last year that was caused by the manufacturer urging doctors and pharmacies to push it at everyone, even those who had Zoster protection and could have waited), but often it just boils down to money: Generics don't make you money unless you have a high volume of patients.
DeleteIn the case of vincristin and methotrexate, the demand will likely spark someone to produce it eventually. In the case of anagrelide, you're SOL.
I don't know that gummint is the answer, either, but the market responds only when sick, bald children can be trotted out to create adverse publicity. Or if you get a creature like Shkreli who is so odious that his greed backfires.
POTUS moved to fix everything yesterday. As usual, he moved with conceptual announcements of how it is going to be. How it is going to be is that 1) states, including and maybe starting with Florida, will be able to import drugs from Canada for their residents. Drugs in Canada are a lot cheaper than drugs in the United States, as the folks in New Hampshire have long known. And 2) drug companies will be allowed to import their own drugs from Canada. HHS Secretary Alex Azar took a government jet to Tallahassee to stand by Gov. Ron deSantis and hail Trump's initiative as this concept was rolled out.
ReplyDeleteThe details, Azar said, are To Come.
One detail I predict, if this thing becomes law or executive order or Wish of the POTUS, however it gets there: The price of drugs will go through the roof in Canada. Just sayin'.
Puerto Rico used to be a pharmaceutical manufacturing center, employing up to 18000 people. Even prior to Hurricane Maria they were having problems, such as competing with cheap labor in the devloping countries. After the hurricane, they have yet to recover. I don't know if their problems would have affected the shortages we were discussing.
ReplyDeleteSo I went back and read some of the comments on the article. There was one that said "its all Obamacare's fault!" ( huh?) A bunch said they should use naturopathic remedies. One mentioned Laetrile, didn't know anyone was still touting that. Another said "the government should be doing something about this instead of pursuing baseless impeachment charges." People's skills in logic and reasoning were on full display .
ReplyDeleteI moderate discussions for a cancer group. The number of people who pose as patients who are actually selling snake oil and fad diets is a problem.
DeleteThere is also a lot of chemo-shaming that goes on among patients a la, "you are just poisoning yourself." Most of these patients believe that cancer is brought on by inflammation (the hot new medical term) caused by stress, poor diet, and lack of exercise. In other words YOU caused your own cancer and only YOU can fix it by getting off your lazy ass.
I have a theory that a lot of this seems from general American antipathy to weakness and illness. Americans in these groups are, strikingly, the ones who don't ever tell other people they're sick for fear of losing jobs or having people "treat me different."
How do we foster a Christian acceptance of human weakness in such a society?
I don't know, I guess maybe point to St. Paul's words, "...he said to me, “My grace is sufficient for you, for power is made perfect in weakness.” I will rather boast most gladly of my weaknesses, in order that the power of Christ may dwell with me." (2 Corinthians 12:10)
DeleteI know what you mean about victim blaming with cancer. People are always trying to figure out what they did to cause it. Likely nothing.
Our old priest used to scoff at people who were always talking about "pulling yourself up by your bootstraps." He had one of the CCD kids demonstrate that it can't be done. Then he showed how a bunch of people helping someone up worked better and made everyone feel good at the same time. Loved that guy.
DeleteWe're all weak in some way. Perhaps those who blame the sick for their own illnesses--as if we'd all live forever if we all ate organic carrots and spinach juice--are the weakest of all.
I've had people I liked and respected who probably died from the effects of smoking, booze, overeating, etc. Didn't make me feel better about it. Seeing what probably awaits me if I make it to my 90s, I may start smoking, eating doughnuts, snorting crystal meth, and base jumping in my 80s.
Delete