IT SOUNDS like a problem striking poor and developing countries: shortages of critical, lifesaving drugs, resulting in severely compromised patient care and delays in important studies in the treatment of cancer and other serious diseases.

But it's happening right here in the U.S.--the world's wealthiest nation.

According to recent reports, drug shortages in the U.S. have spiked in recent years--nearly tripling from 61 drugs in 2005 to 178 in 2010. That number is expected to be even higher by the end of 2011. According to the Food and Drug Administration (FDA), the main drugs affected are cancer drugs, anesthetics, electrolytes and various other drugs used in emergency rooms.

According to Bloomberg News, more than half of hospitals and medical centers surveyed by the American Society of Health-System Pharmacists said that drug shortages had compromised patient care in the past year.

Howard Koh, an assistant secretary of health for the Department of Health and Human Services, recently testified to Congress that these drug shortages are causing hundreds of clinical trials to be stopped or delayed. As Koh told Congress in writing in September, "The inability to obtain adequate supplies of these cancer drugs for research has resulted in promising clinical trials being suspended indefinitely and patient enrollment being abruptly halted." More than 300 clinical studies being paid for by the National Cancer Institute involve a drug that is in short supply, according to Koh.

In an interview with NPR the same month, Koh called the shortages nothing short of "a dire public health situation."

According to the Wall Street Journal, some of the cancer drugs in short supply include decades-old chemotherapy drugs that "are still the backbone of cancer treatment... doxorubicin, often used to treat breast cancer, and cytarabine, a leukemia drug that has no substitute."

Frighteningly, because drug companies are not legally required to notify anyone when they've stopped making a drug, hospitals and physicians can sometimes be left in the lurch, scrambling to provide alternative treatments or forced to delay treatment for critically ill patients while they search for an alternative source.

A majority of hospitals have actually been forced, according to the Journal, to ration drugs this year as a result of the shortage of key cancer and other critical-care drugs. Hospitals and clinics have also reported delaying cancer treatment or switching to alternative drugs that might not be as effective as a result of the shortages.

According to an Associated Press review of industry reports and interviews with experts, there were at least 15 patient deaths in the past 15 months that can be directly attributed to the drug shortages--either because the right drug wasn't available or because of dosing errors or other problems in administering or preparing alternative medicines. The actual number of deaths is likely much higher, say experts.

In the worst case, earlier this year there were nine patient deaths and 10 other patients harmed in Alabama due to bacterial contamination of a hand-mixed batch of liquid nutrition given via feeding tubes--because the sterile pre-mixed liquid wasn't available.

"How, in the United States of America, could critical lifesaving or life-prolonging drugs be in short supply?" asked Jay Cuetara, a cancer patient who said his chemotherapy was delayed when his hospital ran out of the drugs, at a press conference held by the Obama administration in late October.

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WHAT'S TO blame for this shortfall of critical drugs? Simply put, the profit-seeking behavior of pharmaceutical companies.

As the Wall Street Journal reported:

Most of the shortages involve older drugs administered by injection or intravenously...They are mainly generic, not highly profitable and are now made by only one or two companies...

The shortages are growing more severe, in part because of industry consolidation and manufacturing problems in the past year. When one company runs into a manufacturing problem with a product or decides to quit making a drug, competing companies can't quickly fill the void.

As Salon.com columnist Mary Elizabeth Williams, herself a cancer survivor, noted last month, "Because the profit margins on several of these drugs are small, companies have less incentive to keep making them."

The Associated Press reported, "Companies abandoning the injected generic drug market because the profit margins are slim. Producing these sterile medicines is far more complicated and expensive than stamping out pills, and it can take about three weeks to produce a batch."

But some people are making out like bandits in this crisis. Some 97 percent of hospitals and medical centers surveyed by the American Society of Health-System Pharmacists said the drug shortages drove up costs through purchases from so-called "gray market" resellers. Such resellers, according to a report by Premier Healthcare Alliance, inflate prices by an average of 650 percent. One leukemia drug whose typical contract price is about $12 per vial was being sold at $990 per vial--more than 80 times higher--while a drug used to treat high blood pressure that was normally priced at $25.90 was being sold at $1,200 due to a drug shortage.

According to the Associated Press:

The drugs with the highest markups were for critically ill patients needing anesthesia or other medicines for surgery or for emergency care, cancer, infectious diseases and pain management...

The pitches hospitals get from the secondary distributors generally say they have small batches of specific drugs that are hard or impossible to find. "Are you enjoying this crazy 'roller coaster ride' of pharmaceutical shortages?...I utilize over 60 vendors to locate and procure needed pharmaceuticals to assist when you have shortage needs," one reads.

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IN LATE October, the Obama administration finally addressed the crisis, with Obama ordering the FDA to take new steps to send out early warnings about looming shortages and try to avert them. "Even though the FDA has successfully prevented an actual crisis, this is one of those slow-rolling problems that could end up resulting in disaster for patients and health care facilities all over the country," Obama said.

The families of the 15 patients documented to have died as a result of drug shortages might disagree with the Obama administration on whether we're in an "actual" crisis, of course.

Additionally, Obama ordered the FDA to work with the Justice Department to "examine whether potential shortages have led to illegal price gouging or stockpiling of life-saving medications." Likewise, the FDA is reportedly planning to more than double the size of its office dealing with shortages--to a whopping 11 people.

The Obama administration also announced that it "sent a letter to drug manufacturers reminding them of their responsibility to report the discontinuation of certain drugs to the FDA. The letter also encourages companies to voluntarily disclose to FDA potential prescription drug shortages in cases where disclosure is not currently required by law."

Well, that's telling them!

Realistically, such measures amount to little more than a drop in the bucket and will do little to solve the ongoing crisis. While an early warning system is necessary in order to not leave patients and hospitals scrambling for critical drugs, if a manufacturer decides to stop production on a key drug and no other company steps forward to start making it (because profit margins are deemed too low, for example), patients and hospitals will still be left without the drugs they desperately need.

And although it's illegal for pharmaceutical companies to create a monopoly or conspire to create a medicine shortage (and thus artificially raise prices), there's currently no federal law against price gouging on prescription drugs,

The Bloomberg News declared:

The administration's plan won't ease shortages because drug makers have little incentive to raise output when Medicare and Medicaid, the two big U.S. public health programs, limit how fast the price of a drug can rise, said Devon Herrick, senior fellow at the national Center for Policy Analysis, a policy research organization in Dallas.

"Firms have little incentive to ramp up production," Herrick said.

It's true that firms have little incentive to ramp up production--but the main problem isn't the price controls instituted by Medicare and Medicaid on drug manufacturers.

Instead, the real problem is that health care overall, and the pharmaceutical industry in particular, is a for-profit system. In fact, the decision of multimillion-dollar pharmaceutical companies to discontinue making a lifesaving generic drug makes a perverse sort of sense under a system in which profit margins dictate the logic of which drugs get produced. After all, why produce a low-profit generic antibiotic, when you could instead be developing new patents on more profitable drugs like the next Viagra?

According to the Associated Press, for example, "shortages of a common cancer drug named leucovorin didn't start until the FDA approved a similar competitor that worked as well but, because it was new, was 58 times more expensive."

Sometimes, "you have to look the patient in the eye and say, 'I can't treat you. I certainly can't treat you the way I meant to treat you,'" Dr. James Speyer, medical director of the clinical cancer center at New York University Langone Medical Center, told the Associated Press.

Speyer said, "Obama's action is important but doesn't address one key part of the problem--drug profits...Unfortunately, we're going to be living with the problems of these shortages for some time."

Republicans, of course, were quick to condemn even Obama's token stand against the pharmaceutical industry, saying that the "real problem" was price controls instituted by Medicare and Medicaid. In other words, lift the price controls and let the "free market" sort it out.

But there's no real solution to be found in manufacturing these drugs only to price them out of the reach of vast numbers of people (especially the 50 million Americans who lack health insurance).

As Mary Elizabeth Williams put it:

Survival isn't just for those who, as Herman Cain puts it, can only "blame yourselves" for not being rich. And death and disease are not just for those who, like Ron Paul, think that's "what freedom is all about--taking your own risks."

All the riches and "freedom" in the world won't save your ass if you don't have access to the right treatment. And when effective medicine isn't getting out there because the financial incentive isn't compelling enough, it's just plain sickening.

Pay Attention: How Big Pharma Contrived the Great American Adderall Drought
By Moe Tkacik, The Fix
Posted on November 22, 2011, Printed on November 23, 2011
http://www.alternet.org/story/153176/pay_attention%3A_how_big_pharma_contrived_the_great_american_adderall_drought

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When Jay V.'s pharmacist told him about the nationwide Adderall shortages last weekend, he reacted as any economically rational finance professional would, and attempted to bribe her. Whatever the cost, "it's cheaper than cocaine," his reasoning went. And even if it isn't, you can’t put a price on never having to go back to doing bumps in the work bathroom to get through late night deal committee meetings, can you?

Jay's pharmacist said she was reserving her supply for regular customers, but that the price had doubled and the clock was ticking. "They're down to one bottle,” Jay said, “and if I don't get them a prescription by the end of next week I forfeit my right to it." So long as he can tear himself away from one of the 16-hour days he cites as the reason he needs Adderall to begin with, he'll be fine. At least, for the next month or so….

If addiction is the kind of thing you think about a lot, it's easy to overlook its significance in the cold, objective Realpolitik scheme of things, which is this: it's a great fucking business model. From the British East India Company to the Bronfman clan to Duke University, history is redolent of abject mediocrities who owe their billions to Big Addiction.

The best of the addiction-based business models are "addiction-proof" addictive drug, and the Adderall story is at its core the saga of a nearly century-long quest for this unattainable ideal. Amphetamine salt—Adderall’s active ingredient—has been the subject of heady dispute within the medical profession since the drug company Smith, Kline and French began peddling the stuff in 1935, but for decades just about the only thing medical community generally agreed about was that it was not addictive. The SKF sales department did, however, have a term for the loyalty it engendered among consumers: “stick.”

The dawn of the Drug War eventually in the early 1970s eventually brought an end to the widespread use of those first-generation amphetamines, but naturally they "stuck" around in some circles. And then in the nineties, when upper-middle class America was stricken with a modern epidemic of ADD (and its “hyperactive” variant ADHD) necessitating widespread amphetamine use while simultaneously the nation’s truck stops and trailer parks began falling prey to the scourge of illegal amphetamines—and yet no one ever seemed to link the two—it appeared as though an element of cognitive dissonance about the stuff had also “stuck.” For the same reason crystal meth never found much "stick" as an ADD drug—although it's out there, under the brand name Desoxyn—Adderall users for the most part never identified as "addicts" before the nightmare shortages of this year.

You can map the spread of this rude (albeit unbearably drowsy) awakening on the message boards at ADDForums.com, whose administrators have painstakingly aggregated all Amphetamine Famine-relevant posts into a single "sticky" thread, starting with its early rumblings across flyover country in March, when the first unlucky ADD sufferers in pockets of Texas, Georgia and a few other states began to chronicle tales of the panicked multi-state manhunts and exorbitant ransoms to which they'd been subjected following the inevitable 15-minute pharmacy trip that wasn't. The real panic set in around mid-August, when a supply shock attributed to "back-to-school" season ravaged the suburbs.

A guy in New Jersey who'd been paying $9 for his monthly prescription for years suddenly had to scour every pharmacy in a 50-mile radius and cough up $99. A woman in Massachusetts reported calling 25 pharmacies and only finding one that would fill her prescription—for $408; a man from Massachusetts advised her to take his advice offered to share the spreadsheet of eastern Massachusetts and New Hampshire drug stores he'd compiled a few days while making the rounds trying to figure out where to fill his own prescription. (He'd listed 142 by the time he found—at #48—his meds.) Finally this month came the first plaintive posts from New York, where a young woman who'd spent all day running to different drug stores wondered whether it was more dehumanizing to be gazed upon as some sort of "crack addict" by so many pharmacists, or just "feel like a junky" to begin with, and Los Angeles, where an electrician on his third day without meds wrote plaintively:

"Been taking adderall for over 13 years and now I can't refill my script…What am I supposed to do? Just get over it? Just suck it up, go cold turkey and maybe I'll get my script filled in a few months? How can I keep working on dangerous equipment with high voltage everywhere and I can't focus? How can I commute 2 hours a day without falling asleep at the wheel? I feel so alone. Don't know where to go at this point."

(Brief PSA, if this is presently your problem, you have options: Try every Walgreen’s outlet first, followed by independents; expect higher prices; the 48th number you call just might be the charm; talk to your shrink about switching meds; and until you can get an appointment one ADD Forums user recommends something called Muscletech Neurocore. And don’t hold your breath. By most estimates, for reasons elucidated below, it will probably be several months before the Adderall supply is back to normal again.)

Adderall is one of hundreds of drugs from which the American health system is suffering a wrenching withdrawal. Across the spectrum of drugs, the crisis is so dire that earlier this month President Obama issued an executive order directing the Food and Drug Administration to take urgent (albeit not entirely specified) action to address it. But the vast majority of the drugs on the shortage lists are generic injectable drugs used in hospitals—delicate, low-profit, highly sensitive substances whose manufacturing plants can be decommissioned for months (or ever) over a few stray microbes. But Adderall is a high-margin pill or capsule (Adderall XR, or exended release—marketed as “abuse proof”) made from simple amphetamine salts; with close to a dozen manufacturers that rake in billions of dollars a year, its factories have suffered no major interruptions all year.

So what happened to all that Adderall? Actually, it goes back to that great fucking business model: the manufacturing shortage appears to many skeptics to be itself manufactured—orchestrated by the same company that got everyone hooked on the drug in the first place, Shire Plc, formerly Richwood Pharmaceuticals, which two generic competitors now accuse of hoarding.

Adderall itself was introduced by a then-unknown Richwood during another American attention deficit drug crisis, the Great Ritalin Scare of 1993. Back then, drastic shortages of that groundbreaking ADD drug prompted thousands of panicked parents to switch to Adderall, despite Richwood's dubious pedigree as the startup of a former Kentucky schoolteacher, Roger Griggs. Following in the tradition, Shire is now attempting to use contrived Adderall shortages as a chance to convert ADD sufferers (and their long-suffering parents) to the cause of their new(ish) ADD drug, Vyvanase.

Then as now, amphetamine-based ADD drugs have suffered periodic supply hiccups stemming from their strict regulation by the Drug Enforcement Administration, which levies annual quotas on the aggregate amount of stimulants it will allow to be legally produced each year.

By 1993 Griggs had spent a few years trying to sell pediatricians on what seemed like a no-brainer Ritalin alternative: dexedrine, marketed under his proprietary brand "Dextrostat." But dexedrine had a lot of negative abuse baggage from its heyday in the ‘60s and ‘70s, so Dextrostat never really took off. No matter: a less infamous diet drug of the era, Obetrol, concocted from a mixture of amphetamine salts containing 75% dexedrine with (supposedly) none of the baggage, and its factory was up for sale. Richwood pounced. By June 1994 it'd renamed Obetrol "Adderall,” and was selling it to pediatricians as a cheaper, more plentiful and longer-lasting alternative to Ritalin. They hadn't bothered notifying the FDA, which ordered the company to suspend Adderall marketing in November and conduct clinical trials. When the agency officially approved Adderall for ADD just over a year later, it still gave Richwood a two year headstart over the competition, and the indication in kids as young as three was an added bonus that allowed them to make up for lost time.


Today the $4 billion ADD drug industry is about ten times its 1996 size, and Adderall is the reigning market leader. Shire ultimately seeks to unseat with its latest drug, Vyvanse, a reformulated, “cleaner” version of dexadrine. This has been Shire's goal for four years now, since the company—which is now domiciled in Ireland to avoid taxes—spent a staggering $2.6 billion in cash acquiring New River Pharmaceuticals, the biotech that developed Vyvanse, in 2007. With the patent on Adderall XR set to end in 2009, Shire otherwise faced the prospect of a market flooded with cheap generics, a collapse in sales of its cash cow, and nothing in its pipeline because it didn’t actually develop drugs but merely sold them.

But where Adderall had a cheaper price and more potent effect in its favor the last time around, the selling point of Vyvanse is the opposite: it's considerably more expensive than Adderall—this is, after all, the whole point of getting people to switch—and its primary competitive advantage over other drugs is a certain kind of diminished potency: its molecular structure is specifically designed to render the drug impervious to serious junkie behavior. In clinical trials conducted on intravenous substance abusers, for example, injected Vyvanse proved barely more appealing than a placebo. Functionally, this makes Vyvanse a lot like Adderall XR, which is equally impossible to snort, crush, inject and whatever else junkies supposedly do. But from a business perspective it was the holiest of Holy Grails, because its active ingredient was an entirely new molecule, with its own dedicated line item within the DEA's roster of controlled substances and patent protection until 2023.

Initially, the company had been vying for the DEA to classify its new substance, "lisdexamphetamine", on a less restrictive schedule than other amphetamines, enabling doctors to write prescriptions for refills and other such conveniences. Its lobbying failed, though the agency can always reclassify it if Shire can marshal enough evidence of its magical "addiction proof" characteristics.

In the meantime Shire must convert devotees of all the old patent-expired amphetamines. This would be a tall order, since the effect of Vyvanse on the user is almost indistinguishable from that of Adderall (not to mention dexedrine) but the price tag is five or ten times as high. But nearly 50 years since "Obetrol" lost its patent, Shire maintains a partial corner on the Adderall market by the terms of two legal settlements it reached in 2006 with the generic manufacturers Teva Pharmaceuticals and Impax Laboratories. Those settlements awarded Teva and Impax the rights to sell generic Adderall XR starting in 2009—and subcontracted Shire with the job of actually manufacturing the drugs for both companies until Teva and Impax could handle production themselves. (Their applications to produce the drugs had been held up by Shire.)

This seemed to work the way it usually does at first. In the spring of 2009 the price of Adderall XR plummeted along with Shire's profits. Sales nosedived to $67 million in the second quarter of the year from about $300 million in most of the quarters since it had been introduced. But the next year its Adderall XR numbers started creeping up again, reaching $100 million for the third quarter of 2010. Then in November, Impax sued Shire, alleging that the company was botching its orders, supplying fewer pills than desired or bailing altogether. Teva quickly filed an intervenor lawsuit, making similar allegations while maintaining its own right to "first dibs" on Shire's drugs, having been first to file its application with the FDA back in 2003. At the same time, insurance companies inexplicably began refusing to cover generic Adderall XR, variously claiming the generic wasn't yet FDA approved or that its "therapeutic equivalence" to the branded drug was still unproven.

That case is in discovery and slated to go to trial in spring. But all year, as users scoured the ends of the earth to fill their prescriptions, Shire's Adderall sales numbers kept edging up, finally hitting $150 million for the quarter that ended last month, while Impax—which booked $47 million in Adderall XR sales for the same quarter—continued to grouse about getting shortchanged. Without breaking out Adderall numbers, Teva announced that its generic drug sales in the U.S. for the same quarter had cratered by half. It was also a record $200 million quarter for Vyvanse.

But it was a most torturous quarter for ADD sufferers lacking the kind of health care plans that cover $400-a-month brand-name drugs, because if you couldn't afford to switch to Vyvanse or brand-name Adderall XR, you were stuck trying to switch to generic instant-release Adderall at the same time as a million other panicked tweakers…or failing that, Ritalin, which ran out of stock shortly thereafter…or failing that, ponying up the better part of an extra rent check to fill your prescription.

Shire has publicly blamed DEA quota restrictions for its anemic generic shipments; the DEA has issued an apparent denial, albeit one short on specifics. A chemist at one of the five authorized “active ingredient” manufacturers in the business of supplying pharmaceutical companies with amphetamine says he and his colleagues “have all been scratching our heads trying to figure out what's actually going on.”

The prevailing “water cooler” theory, according to the chemist, is that Shire is trying to “embarrass by making them look unreliable”—which could theoretically threaten some of their accounts, which could also in turn hurt their case in future applications to the DEA for a share of the annual amphetamine production quota. The DEA’s decisions to award quota of controlled substances is a somewhat mysterious process, but the aggregate number of about 26 million kilograms for 2011, up from 1.3 million in 1996, the year Adderall was introduced. And even that 26 million wasn’t high enough to accommodate the applications; the chemist says the agency recently granted the generic drugmaker CorePharma, which makes generic Adderall and dexedrine, just half the amphetamine allotment for which it had applied. So it stands to reason that if the agency lowers the quota in response to lower unit sales this year, the great amphetamine famine could be here to stay. And since Shire’s own quota for Vyvanse’s lisdexamphetamine is 9 million kilograms—hugely generous for such a new drug—it is more than prepared to accommodate a surge in new customers.

And what’s more, Shire has also been hard at work conceiving “sticky” new non-addictive addictions. The New River molecular innovation that makes lisdexamphetamine so underwhelming to shoot up could also soon take the Cindy McCain stigma out of opiates, and another Shire subsidiary discovered a mechanism by which cocaine can be safely administered in lab rats at up to 10 times the typically lethal dose. So while the stock is trading around an all-time high, it might be something to think about, if you have any disposable income left after filling this month’s prescription.

Moe Tkacik, formerly of the Wall Street Journal and Jezebel, is a writer and ADD sufferer in Washington, DC.

NounsareVerbs posted:
can anyone do a trip report on hyperfocus i don't really "get" the concept. I can focus very intently on something but that doesn't change the fact that I don't really give a shit sometimes about completing some required tasks so I will be prone to reading rhizzone instead. how does a drug make you "care more" about paying attention to a specific socially-expected task?

I have add without h so I get hyperfocus when I don't take it. Basically it just locks you into whatever you're doing and you won't stop until you're dehydrated and super tired. And whatever the thing is is really enjoyable while you're pushing through it.

The sort of super focus that people who don't have add get when they take amphetamines isn't quite the same, it's more frantic and rational. At least that's how it seems from the outside

Myfanwy posted:
As much as I really hate the american healthcare system, the market approach does seem to meet people's needs in a few specific areas.

the medical needs of a statesian are met in direct proportion with his/her stack of cash

aerdil posted:
we live in america.... obliterating our minds through the use of the pinnacle of western medical science is all we have