Reefer Madness Revisited

Chronic pain is a major problem in this country. To combat it, doctors are prescribing—some would say overprescribing—opioids such as Vicodin and OxyContin. Americans consume about 90% of the world's supply of these dangerous drugs. According to the Centers for Disease Control, opioid overdose deaths have increased from 4,030 in 1999 to 16, 651 in 2010. That's an average of 46 deaths per day, more than heroin and cocaine combined. Sixty percent of these folks have a legitimate doctor's prescription. If only someone could come up with a safer way of treating pain. . . . .

Marijuana has been shown to be effective in treating chronic pain. A survey of medical marijuana users in Canada found that 68% of them used it as a substitute for prescription drugs. The three main reasons given were fewer withdrawal symptoms, fewer side effects, and better symptom management. Marijuana can also be effectively combined with opioids to allow patients to use lower doses of opioids. If you can locate someone who has died from a marijuana overdose, you have a scoop. In July, New York became the twenty-third state to legalize marijuana for medical use.

Marcus Bachhuber and his colleagues published a new study of the effects of marijuana legalization on opiate deaths in the Journal of the American Medical Association this week. It's not a controlled experiment; it's a before-after comparison group design. While there is some ambiguity about how to interpret it, the study has a number of important strengths.

The authors counted opioid deaths on death certificates from all 50 states between 1999 and 2010. By 1999, three states (California, Oregon and Washington) had already legalized medical marijuana. Another ten states legalized it while the study was in progress. (The remaining ten states changed their laws after 2010.) The death rates from opioids were compared between those states that had legalized medical marijuana (the marijuana states) and those that had not (the comparison states). They also compared death rates within the marijuana states from before to after legalization. The design statistically controlled two variables that are known to affect the opioid death rate, the unemployment rate and state policies regulating prescription drugs.

• Those states in which medical marijuana was legal at the time had a 24.8% lower mean annual opioid mortality rate than the comparison states. The marijuana states had 1729 fewer death than would otherwise be expected in 2010 alone. The results were unchanged when suspected suicides were eliminated.
• In the ten states that legalized marijuana between 1999 and 2010, the drop in the death rate from opioids coincided with the change in the law. It took a couple of years for the full effect of the legal change to be realized. On average, the death rate dropped 20% in the first year, 25% in the second, and peaked at 33% in the fifth and sixth years.
  
  

In searching for possible hidden confounds, our attention is naturally draw toward possible differences between the marijuana and comparison states that might have affected overdose deaths. There is a possible selection bias. The marijuana states are more progressive, and it's possible, but not obvious, that political liberalism might reduce painkiller deaths in other ways. However, when the death rates are compared from before to after the legalization, the marijuana states become their own controls.

It is important to note that in order to explain the results, a potential confound would not only have to be more prevalent in the marijuana states, it would also have to have occurred at about the time legalization took effect. One of the strengths of this study is that the drop in deaths coincides with the onset of legalization even though the law changed at different times in different states. This makes it less plausible that historical events affecting several states simultaneously could account for the results.

Almost all news reports about this study quote drug experts who urge caution when drawing conclusions from the study, although they usually don't specify what they think is wrong with it. One expert, Dr. Andrew Kolodny, is quoted in Newsweek as suggesting that states that legalized medical marijuana might also impose more restrictions on the prescribing of painkillers, apparently not realizing that the authors had anticipated this possibility and found that prescription monitoring laws were not associated with lower overdose death rates. (The reporter did not correct his error, allowing readers to assume that he had made a valid point.) Of course, most articles also contain the obligatory vague words of warning about the alleged dangers of the devil's weed.

The study makes a fairly strong case for the immediate legalization of medical marijuana at the federal level and in the remaining states. Why is medical marijuana still illegal? As the Bachhuber study suggests, medical marijuana is a serious threat to the profits of pharmaceutical companies. Given the opportunity, chronic pain sufferers are likely to substitute marijuana for more expensive and dangerous prescription drugs. Journalist Lee Fang points out that the groups leading the fight against relaxing marijuana laws, such as the Partnership for Drug-Free Kids, receive a large portion of their funding from the pharmaceutical companies that market analgesic opioides. Several leading anti-marijuana academic experts also serve as paid consultants to big pharma. Here is Fang being interviewed by Chris Hayes.

As usual, we can say (this time, with enthusiasm) that more research is needed. The good news is that the Drug Enforcement Administration has increased its annual allotment of cannabis for clinical research from 21 kilograms to 650 kilograms—still too little—in response to demand from investigators.

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Legalized Bribery

Evergreening

Taming the Gift Culture

Legalized Bribery

Ever wonder why health care costs so much in this country, and why we get such poor outcomes in return? Here's a small piece of the puzzle.

The New York Times reports that an obscure paragraph in the recent “fiscal cliff” bill extends a delay in implementation of Medicare price controls on Sensipar, a drug used by kidney dialysis patients, for two years. The drug is manufactured by Amgen. The delay will cost Medicare—and ultimately taxpayers—$500 million. The section of the bill (Section 762) is not tranparent and does not mention Amgen by name. It's one of many examples of pork that are buried in a bill that was supposed to reduce the deficit.

Here are the details. Currently, Medicare pays for dialysis drugs individually. They determined that this created an incentive to overprescribe medication that was useless and possibly harmful. The change, now postponed, was that Medicare would pay a single, bundled rate for dialysis treatment.  That was a threat to Amgen's profits.

According to the Times, this decision was made by Senator Max Baucus (D-MT), chair of the Senate Finance Committee, and Senator Orrin Hatch (R-UT), the ranking Republican on the committee. It was subsequently approved by Senate Minority Leader Mitch McConnell (R-KY) and Vice President Joe Biden, who negotiated the “fiscal cliff” agreement. Amgen has made over $5 million in political contributions since 2007, including $67,750 to Senator Baucus, $59,000 to Senator Hatch, $73,000 to Senator McConnell, and $141,000 to President Obama's two presidential campaigns.

Sen. Mitch McConnell
(or possibly a turtle)

The Times quotes aides to Senators Baucus and Hatch and an Amgen spokesperson as saying that the delay was justified because it would “give Medicare and health care providers the time they need to accommodate complicated changes in federal reimbursement for kidney care.” The price restraints were originally scheduled to begin in 2012. Congress granted Amgen a two year delay until 2014. The “fiscal cliff” bill extends that delay until 2016. How much time do they need?

An aide to Senator Baucus added that, “What is the best policy for Montanans and people across the country is at the heart of every decision Chairman Baucus makes.” But none of the people contacted attempted to justify the decision on medical grounds.

Amgen is the world's largest biotech corporation, with $15.6 billion in revenue in 2011. It has 74 lobbyists in Washington, including former chiefs of staff of both Senators Baucus and McConnell. Senator Hatch's leading staff member on health care policy is a former Amgen employee.

On December 19, Amgen pleaded guilty to illegally marketing Aranesp, an anti-anemia drug, for purposes the FDA had explicitly not approved. The $762 million settlement was a new record for a biotech company.

I think incidents like this pose a serious threat for single-payer advocates. One of the major arguments against single payer, which resonates strongly with the general public, is that the federal government can't be trusted to run a health care system that will provide quality medical care at a reasonable price. We usually try to counter that argument by pointing out that all other countries with single-payer systems achieve better health outcomes than we do at lower cost.

However, the United States is not like other industrialized countries. It's possible that our level of political corruption is so much higher than other countries as to make us not comparable to them. If so, it's impossible to predict how single payer would fare in this country. Of course, despite our corruption, Medicare is still cheaper than private insurance. However, if Congress ever passes a single payer bill, it is important that it contain safeguards that insulate the system from corporate and political interference.

Update (1/31/13)

The liberal organization Progressives United has latched onto this story and is asking people to sign a petition to the CEO of Amgen asking him to give back the $500 million. (Good luck on that!) The petition can be found here.

Evergreening

The Incidental Economist (a blog) alerted me to an article by medical student Nicholas Downing and three colleagues exposing the outrageous shenanigans of Abbott Laboratories, maker of fenofibrate, a lipid-modifying drug that claims to reduce the risk of heart disease.

In the U. S., patent protection on a new drug expires after 20 years. Since the clock starts ticking before clinical trials can begin, by the time a drug gets Food and Drug Administration (FDA) approval, it typically has seven to twelve years of patent protection. After that, other companies are free to sell generic equivalents, which usually cost less than half the price of the original. The goal of pharmaceutical houses is to extend that patent protection as long as possible by whatever means necessary.

Abbott did not do the research and development that led to fenofibrate. They bought it from another company. They marketed it as Tricor-1 in 1998. However, their patent was about to expire, and in 2000, another company, Novapharm, announced its intention to produce a generic version. Abbott then filed suit for patent infringement. This was a frivolous lawsuit, but such suits are routine because when they are filed, they automatically result in an injunction against the generic company which prevents them from marketing the generic for 30 months. Drug companies almost always lose these infringement cases, but they file them anyway because the amount of money they make during the 30 month waiting period is far greater than the cost of the lawsuit.

The 30 months also gave Abbott time to get a patent for Tricor-2 and introduce it to the market. Tricor-2 was identical to Tricor-1 except for the dosage. Because it was the same, no new clinical trials were required. By the time the 30 month period had expired, Tricor-1 was no longer available and Tricor-2 had cornered 97% of the fenofibrate market. It was useless to produce the generic version of Tricor-1 because Tricor-2 had different dosage levels, and pharmacists can only substitute generics when the dosage levels are the same.

So the generic company announced its intention to produce a generic Tricor-2. At this point, the story begins to resemble the plot of the film Groundhog Day. New lawsuit by Abbott. Another 30 month wait. Abbott announces Tricor-3. It captures 96% of the market. Generic company intends to produce generic Tricor-3. New lawsuit. Another 30 month wait. Abbott announces Filibrix. Filibrix is fenofibric acid rather than fenofibrate, which requires new clinical trials, but gets them an additional three years of patent protection extending it to 2012.

By this time, the generic companies had noticed the futility of their strategy, so they filed suit against Abbott for violation of the Sherman Antitrust Act. Abbott eventually settled that suit for $300 million, which was about 4% of what they made selling various versions of fenofibrate. The authors estimate that the cost to the public of using Abbott's versions of fenofibrate rather than their generic equivalents is $700 million a year.

This is not an isolated incident. Several other drug companies have done the same thing.  When the patent is about to expire on one of their lucrative drugs, they make a trivial change and market it under a new name in order to extend their period of exclusivity. This common practice is called “evergreening.” (Get it?) It succeeds in part because doctors don't pay attention to what's going on. However, even if they had known about Abbott's psychopathic behavior, there was nothing doctors or pharmacists could do because no generic equivalent of fenofibrate has yet made it to the market.

To add insult to injury, a large outcome study published in 2005 showed that fenofibrate was ineffective in reducing the risk of cardiovascular disease. But apparently the doctors weren't paying attention to that either, because as of 2010, fenofibrate sales were still increasing.

There is a serious problem with the FDA's system of granting patents. They only require clinical trials that compare the new drug with a placebo—an inactive pill that supposedly controls for patient expectations. This allows different drug companies to market nearly identical drugs, none of which are more effective than the others. It also allows companies like Abbott to “evergreen” by relabeling old drugs under new names. A more sensible standard would be to compare the proposed new drug to the best existing treatment and only grant a patent if the new drug produces a significant improvement in patient outcomes.

In our capitalist wonderland, it's useless to urge “corporate persons” such as Abbott to behave more responsibly. They will pursue profit however they can. It's probably also unrealistic to expect doctors to read medical journals or prescribe available generics. They get their pharmaceutical information from drug salespersons bearing gifts—everything from ballpoint pens to free trips to Las Vegas (to attend a medical “seminar,” of course). It would be nice if Congress would make this legalized bribery illegal, but since they're doing the same thing, that's not likely to happen.

Downing and his colleagues only suggest one governmental remedy—elimination of the 30 month hold on the generic during a lawsuit. Otherwise, they just recommend consciousness raising among patients, doctors, and pharmacists. Good luck with that.

Taming the Gift Culture

As Paul Ricci noted last week, one point about which supporters of single payer health care agree with conservative critics of the Affordable Care Act (ACA) is that it doesn't do enough to contain costs. That's where the agreement stops. We disagree about the major reasons that health care costs so much more in the U.S. than other industrialized countries; hence, we disagree about how to reduce costs. Advocates of single payer note that costs are certain to be higher when both medical care and health insurance are provided by corporations that are motivated to maximize profits.

To be fair, however, the ACA does contain some provisions to reign in costs, but without altering the basic economic structure of the system. One of these reforms was announced the other day. Manufacturers of drugs, medical devices and medical supplies used by Medicare and Medicaid patients will soon be required to report all payments and gifts they make to doctors or teaching hospitals. The data will be posted on a government-run website that will be searchable by the name of the doctor.

The New York Times reports that 25% of doctors report receiving cash payments and two-thirds report receiving gifts from drug and medical device manufacturers. This includes research and consulting fees; food, travel and entertainment; free samples (“the first bag of heroin is free”); plus all those incidentals such as pens and tote bags with the manufacturer's name on the side. (One doctor's son said that it wasn't until he was eight years old that he realized not all frisbees had the word “Merck” printed on them.) These gifts can result in doctors prescribing expensive new drugs that are no more effective than generics, or requiring tests and procedures that have no real benefit to the patient.

Doctors are embedded in what anthropologists call a gift culture, a network of reciprocal favors in which there is no explicit agreement as to when and how the favor will be repaid. These favors create feelings of obligation to the benefactor, obligations that may be repaid many times over, but the lack of an explicit quid pro quo reduces awareness of the corruption that is actually taking place.

Many years ago, social psychologist Bob Cialdini reported how a little gift can go a long way. Hare Krishna disciples who handed out paper flowers at airports, for example, were paid back many times over by voluntary contributions from recipients. There are several studies showing that this works in a medical context. For example, Orlowsky and Wateska (1992) examined the effects on doctors of free trips to seminars in sunbelt locations sponsored by the manufacturers of two relatively new prescription drugs. Their data showed significant increases in prescriptions of the two drugs in comparison to other hospitals, and in comparison to other drugs having the same effects. Interestingly, 17 out 20 doctors in the study stated unequivocally that the free trip would not influence their behavior.

This disclosure requirement is certainly a step in the right direction. My question is whether it goes far enough. Lawrence Lessig, in his new book about political corruption, Republic Lost, calls transparency a “reform that doesn't reform.” Have you ever looked at one of those lists of contributors to a political campaign? Did it help you? Most of them are people and organizations you've never heard of. The list provides little information about what these contributors wanted or how they were repaid after the election.

Similar lists of medical company gifts and payments may not be very useful to consumers. How many of them will consult the website in advance of a visit to the doctor? Even if they do, the fact that General Electric is on a doctor's list of contributors only helps if you know that GE manufactures the device that will be used to scan your internal organs. The fact that a drug company is on the list is useless unless you have memorized which drugs that company markets. In some cases, the absence of a corporation from the list may be more meaningful than its presence.

This website may be useful to researchers and investigative reporters, and this could benefit consumers indirectly if their studies are reported by the media. The existence of the list could also embarrass some doctors into refusing gifts, although I wouldn't count on that, since almost all doctors erroneously believe that gifts have no effect on their decisions.

But the real problem is that this is only a half-baked reform. Since we know the unfortunate effects payments and gifts have, they should be banned, not reported on some obscure government website.