FDA Loses Another Free Speech Case

by on August 10, 2015 at 7:28 am in Law, Medicine, Political Science | Permalink

WSJ: A federal court in New York delivered a setback to the Food and Drug Administration, ruling the agency can’t bar a drug company from marketing a pill for off-label use as long as the claims are truthful.

The decision by the federal district court in the Southern District of New York, is the latest of a line of such cases. It concerns the Irish company Amarin Pharma Inc. and its fish-oil-derived drug Vascepa, and it has been closely watched by the pharmaceutical industry. The company asked the court to stop the FDA from enforcing its off-label marketing ban, and the court agreed.

The ruling is important because in the last few years the FDA has extracted billions of dollars in settlements from pharmaceutical firms for engaging in what appears to be constitutionally protected speech. In fact, the courts have repeatedly ruled that FDA and Congressional restrictions on truthful and non-misleading off-label marketing are unconstitutional.

In Washington Legal Foundation v. Friedman, for example, the DC court issued an injunction preventing the FDA from prohibiting, restricting, sanctioning or otherwise seeking to limit pharmaceutical and device manufactures from disseminating information about off-label uses from peer-reviewed professional journals or textbooks. In U.S. v. Caronia the court (2nd circuit) reversed a criminal conviction and said that the FDA cannot criminalize truthful promotion of off-label uses of approved drugs. Indeed, the court in that case defended the utility of such promotion:

…prohibiting off-label promotion by a pharmaceutical manufacturer while simultaneously allowing off-label use “paternalistically” interferes with the ability of physicians and patients to receive potentially relevant treatment information; such barriers to information about off-label use could inhibit, to the public’s detriment, informed and intelligent treatment decisions. See Va. Bd. of Pharmacy v. Va. Citizens Consumer Council, Inc., 425 U.S. 748, 770 (1976)

…See also Sorrell, 131 S. Ct. at 2670- 72 (“[The] fear that [physicians, sophisticated and experienced customers,] would make bad decisions if given truthful information” cannot justify content-based burdens on speech.”) (citing sources);

…Liquormart, 517 U.S. at 503 (“[B]ans against truthful, nonmisleading commercial speech . . . usually rest solely on the offensive assumption that the public will respond ‘irrationally’ to the truth. . . . The First Amendment directs us to be especially skeptical of regulations that seek to keep people in the dark for what the government perceives to be their own good.”).

In Washington Legal Foundation v. Henney the court summed up concisely:

The First Amendment is premised upon the idea that people do not need the government’s permission to engage in truthful, nonmisleading speech about lawful activity.

(By the way, it’s this line of cases that makes me think that 23andMe has a strong first amendment case for presenting to customers information about their own DNA.)

The courts were exactly correct. Off-label uses of approved drugs are a vital part of the discovery process of modern medicine. New uses for old drugs are often discovered through serendipity and close observation in the field. Indeed, modern medicine moves faster than the FDA and it often happens that the first-line therapy is an off-label treatment. Prohibiting firms from truthfully discussing such treatments with physicians is not just unconstitutional it’s also paternalistic and harmful to patient welfare.

This case, Amarin v FDA, is especially egregious because the company wants to discuss with physicians the results of its own FDA-approved trial. Amarin has a fish-oil derived drug designed to reduce triglyceride levels and it already has approval to sell and market this drug in patients with very high levels of triglycerides. It also wanted approval to sell the drugs in patients with high (but not very high levels) and it conducted an FDA-approved trial that showed that the drug is safe and effective at reducing triglyceride levels in this set of patients.

Although the trial was successful the FDA, for reasons discussed below, refused to grant approval. Amarin isn’t disputing the refusal but they wanted to tell physicians the results of the trial and then let the physicians and their patients decide whether reducing triglyceride levels is something that they want to do given currently existing evidence about triglyceride levels and heart attacks. The FDA threatened to pursue civil and possibly criminal charges but the court has now precluded the FDA from those pursuits.

Aside from the first amendment issues, the case is also interesting as another example of how a capricious FDA can kill innovation through regulation uncertainty. (The story is similar in many respects to that told by Joseph Gulfo in Innovation Breakdown, see my review).

To wit: Amarin wanted approval to sell its drug to patients with high levels of triglycerides and they obtained a special protocol agreement (SPA) from the FDA to run a study in this population. Quoting the court:

An SPA agreement is a written agreement that a manufacturer may enter into with the FDA, which sets out the design and size parameters for clinical trials of a new drug, and the conditions under which the FDA would approve the drug. For the manufacturer, such an agreement minimizes development risk by providing regulatory predictability: Provided that the manufacturer follows the procedure set in the SPA agreement and the drug proves meets the benchmarks for effectiveness set in the agreement, the FDA must approve the drug.

The results of the study were good:

The ANCHOR study achieved each numeric objective that the SPA Agreement had set: The results showed that Vascepa produced a statistically significant decrease in triglyceride levels in persons with persistently high triglycerides, as well as in other lipid, lipoprotein, and inflammatory biomarkers.

…Because Amarin had met all requirements for approval set out in the ANCHOR SPA Agreement, Amarin anticipated that the FDA would approve Vascepa for the additional use that Amarin sought, i.e., by patients with persistently high triglycerides.

Instead of approving the drug, however, the FDA rescinded their agreement. The FDA argued that although the drug did reduce triglyceride levels it was no longer certain that reducing triglyceride levels would reduce cardiovascular events.

Can you imagine the tailspin this sent researchers at Amarin into when they learned that the drug would not be approved despite passing all the agreed upon tests? (Read Gulfo for a vivid account of his case).

Who will invest in bio-medical advances with this kind of risk? Sergei Brin said that he didn’t want to invest in health care because “It’s just a painful business to be in . . . the regulatory burden in the U.S. is so high that I think it would dissuade a lot of entrepreneurs.” It’s precisely this kind of regulatory uncertainty that an SPA was meant to avoid. By rescinding their agreement, the FDA is sending the message to investors that no one is safe.

1 Jan August 10, 2015 at 7:46 am

This will ultimately remove any incentive for drug companies to seek FDA review of these secondary uses of medications. Doctors simply aren’t equipped to evaluate the evidence for every off label use of every drug a company brings in. They bring a nice lunch, stroke the physician’s ego for a few minutes, tell him it’s totally a good idea to use the drug off label and leave. When it turns out to not work, the patients and the tax payers lose.

2 XVO August 10, 2015 at 7:54 am

That’s the doctors responsibility. If we can’t trust doctors to do their due diligence, who can we trust?

We can’t trust ourselves, we can’t trust the doctors, we can’t trust the drug companies. We can only trust Jan and her unshakable faith in the FDA.

3 Jan August 10, 2015 at 8:18 am

I trust the FDA more than individual doctors. It is an agency whose job it is to evaluate and ensure the safety and efficacy of these products.

If you found that unicorn of a doctor who can independently evaluate the individual efficacy of every single drug he prescribes, I’d love to know his methods. I also assume he doesn’t carry malpractice insurance.

4 FC August 10, 2015 at 8:33 am

So there are these things called universities that hire people to study stuff and publish what they learn. It is rumored that they existed even before the FDA, hallowed be its name.

5 Jan August 10, 2015 at 8:56 am

It is well-demonstrated Industry-sponsored research suffers from systematic bias, including publication bias. Although the FDA cannot ferret out all the conflicts of interest and problems with clinical trials that companies generate–because it goes very deep–the problems would be so much worse if there were no independent party charged with reviewing these studies.

http://jama.jamanetwork.com/article.aspx?articleid=182478

6 enoriverbend August 10, 2015 at 10:33 am

@Jan

“It is well-demonstrated Industry-sponsored research suffers from systematic bias, including publication bias”

Just curious, Jan, is it your impression that the FDA has no systematic bias? It’s certainly not my impression.

7 prior_approval August 10, 2015 at 10:41 am

‘It’s certainly not my impression.’

Well, it comes to things like this, the FDA is truly systemically biased – ‘Since no one really knew what made them healthful, the springs’ radioactivity was as good a guess as any. Entrepreneurs started bottling the water and selling it as “Radon Water.” But rivals soon pointed out a problem: Radon’s half-life is just 3.82 days. By the time the bottle reached the customer, most of the radiation would be gone.

You might go so far as to say that Radon Water was a rip-off, which is exactly the pitch the Radium Ore Revigator company used to sell its “better,” “more scientific” product: a watercooler lined with a serious amount of carnotite, an ore of uranium and radium that undergoes radioactive decay, yielding radon gas. Storing any water in this cooler overnight would give you fresh, potent, invigorating radon water to drink by morning. Unfortunately for those who used them, Revigators actually worked.’ http://www.popsci.com/scitech/article/2004-08/healthy-glow-drink-radiation

8 msgkings August 10, 2015 at 11:42 am

p_a is so impressed with this scoop he’s posted it twice…best satire indeed

9 msgkings August 10, 2015 at 11:45 am

I’ll tell you who was systemically biased….Nazis were!

https://en.wikipedia.org/wiki/Nazi_Germany

And this was way after Americans could get a nice drink of Radon Water!

10 Jan August 10, 2015 at 1:05 pm

@enoriverbend

My impression if FDA’s systematic bias is in the direction of ensuring safety rather than getting drugs on the market faster at the risk of harming patients. This is real. However, there are various remedies written into the law, such as compassionate use and humanitarian use exemptions, that allow patients to access life-saving therapies not approved by FDA. A patient will not die for lack of access to an experimental treatment that a manufacturer willingly makes available to them under these exemptions.

11 Hazel Meade August 10, 2015 at 1:21 pm

Even with those exceptions, the systematic bias will lead to some doctors and patients not being aware of off-label uses, and thus never being directed to commpassionate use or humanitarian use exemptions. You have to know something is possible in order to try it.

12 Jan August 10, 2015 at 1:42 pm

That’s true for some undefined number of doctors and patients, yes. To address that problem and get drugs to patients as soon as possible, FDA has created a number of programs in recent years that accelerate access to medications faster than they otherwise would be approved.

http://blogs.fda.gov/fdavoice/index.php/2014/05/fdas-final-guidance-on-expedited-drug-approvals-fueling-innovation-and-helping-patients/

13 Hazel Meade August 10, 2015 at 3:24 pm

That doesn’t really address the problem. The FDA has biases. Those biases will lead to some drugs not being approved, being approved improperly, or not having off-label uses approved. A faster approval process changes none of that.

14 Jan August 10, 2015 at 3:51 pm

Actually, some of these processes let drugs onto the market faster and with less evidence than would otherwise be required. So they do directly address the problem.

But out of curiosity, how big is the problem? How many drugs that should have been approved do you think the FDA denied in the last say 10 years? And on what basis were they denied?

15 Hazel Meade August 10, 2015 at 5:37 pm

No, you’re not getting it. “Faster and with less evidence” does not equate to “less systematically biased decisions”.

I also would love to see a study comparing the opportunity cost of pre-market approval (lives lost due to drugs not approved) compared to the benefits (lives saved due to drugs kept off the market). I don’t know of one offhand, but maybe there is something out there.

16 Rich Berger August 10, 2015 at 8:56 am

The obvious answer is to make the FDA an advisory agency only, so that Jan can be protected from her own bad decisions. The rest of us can trust our own judgement, including upon whom we rely for advice.

17 Jan August 10, 2015 at 9:10 am

Yes, let’s do that. It’ll be really great for children with uninformed parents and doctors. Babies with flippers, anyone?

18 Turkey Vulture August 10, 2015 at 10:09 am

(Guy whose doctor just recommended him a particular course of treatment because the sales rep had magnificent breasts)

19 Cliff August 10, 2015 at 10:23 am

Jan’s model of the world: parents don’t care about their children enough to check if their medication is FDA approved, doctors don’t care about their patients or their livelihoods enough to prescribe FDA approved medications, but the FDA is full of public servants who care about nothing but doing a great job and saving lives.

20 Jan August 10, 2015 at 1:00 pm

Cliff’s model of the world: All parents are smart, caring and informed enough check if their kid’s medication is FDA approved, but lets not have an FDA. Doctors are all well-meaning do-gooders in the business to help people,and they would never make a mistake due to laziness or unintentional ignorance.

21 Hazel Meade August 10, 2015 at 1:33 pm

What makes you think the FDA is less susceptible to laziness or unintentional ignorance ?
Large bureaucracies can obscure information just as well as individual fallibility. It’s nice to have a group of people whose job it is to sift through data and make efficacy judgements, but that is a process provided by other forums, like academic journals. Also there are plenty of consumers who don’t trust the FDA and won’t believe it (see vaccines). I’m not sure why a single government agency is supposed to be superior to a variety of private organizations who essentially do the same thing, whether it’s via peer-reviewed scientific articles or consumer-reports style advocacy.
I imagine that absent the FDA, there would be a number of different groups doing drug analysis and review in various flavors from ultra-paranoid-naturalist to experimental to traditional-scientific-method. Consumers (doctors and patients) could pick whose advice to take based on their inclinations.

22 Jan August 10, 2015 at 1:52 pm

FDA’s #1 responsibility is to verify these drugs are safe and effective. Individual doctor X who has literally dozens of responsibilities just isn’t going to be able to do as good a job. Also, FDA has the ability to require raw data from clinical trials companies use to market their drugs. A doctor can’t demand data and pour over research designs and outcomes, run alternative analyses. It’s just not feasible.

Any private organization you want to set up to do this voluntarily is welcome to. Their audience can be all these people who don’t trust the FDA. It’s not clear to me how they would be funded or why they would be any better than FDA.

23 Hazel Meade August 10, 2015 at 3:17 pm

It’s not clear to me why they would be worse. There would probably be several with competing philosophies. Some more risk-averse than others.
Patients and doctors who are more risk-averse could select only medications recommended by the most risk-averse organization.

24 Jan August 10, 2015 at 3:57 pm

Can you quantify how “bad” you think FDA is? As far as I know, the agency has improved on almost every measure of speed of approval and access in recent years.

What country has adopted an alternative, private system? If there is a market for a better type of system as an FDA alternative, wouldn’t the market have addressed it in one of the many countries out there? At least in one of those countries that has only a nominal pharmaceutical regulatory structure (with no real enforcement of anything)?

25 Erick August 10, 2015 at 9:06 am

Since this ruling only affects truthful statements by drug companies, how does anything you wrote make sense?

26 Jan August 10, 2015 at 9:15 am

There is no mechanism to evaluate what is truthful or not truthful for off-label marketing. See my other comment about quality of industry sponsored research. This completely sidesteps the review process has FDA has. If there is no process to evaluate the “truthful statements” the companies are pointing to, there is no oversight.

27 Cliff August 10, 2015 at 10:25 am

Jan, there is a very simple mechanism. Look at what they state, look at whether it is true. The end.

28 prior_approval August 10, 2015 at 10:46 am

You mean like this? – ‘Rofecoxib was shown to improve premenstrual acne vulgaris in a placebo controlled study.’

Or do you mean like this? – ‘In addition to its own studies, on September 23, 2004, Merck apparently received information about new research by the FDA that supported previous findings of increased risk of heart attack among rofecoxib users (Grassley, 2004). FDA analysts estimated that Vioxx caused between 88,000 and 139,000 heart attacks, 30 to 40 percent of which were probably fatal, in the five years the drug was on the market.’

https://en.wikipedia.org/wiki/Rofecoxib

29 Jeff R. August 10, 2015 at 11:55 am

Good thing the FDA was there to protect all the people who died. Oh, wait….

30 Jan August 10, 2015 at 1:07 pm

If it were cut and dry we wouldn’t need an FDA. You’re being flip, but this is an argument that some actually use. It is completely baseless.

31 Jan August 10, 2015 at 1:09 pm

@Jeff R,

Merck hid data from the FDA and lied about it for years. If the agency didn’t exist, how many more people would have died?

32 Moreno Klaus August 10, 2015 at 1:15 pm

Cliff…your mood affiliation is amusing 😉

33 mulp August 10, 2015 at 4:22 pm

“Jan, there is a very simple mechanism. Look at what they state, look at whether it is true. The end. ”

Hanson says climate change is caused by human activity and is already causing hazardous changes, citing thousands of research studies by universities and private not for profits, thus providing far strong evidence of “truth” that the drug companies claiming “free speech right” to convince doctors to bill taxpayers for high monopoly profit drugs.

Clearly Hanson is speaking truth as a free speech right that should be influencing spending billions of taxpayer dollars.

Is that your position on truth, free speech, and getting taxpayer money spent?

34 Doug August 10, 2015 at 5:58 pm

Huh??? Has someone here said that Hanson should be denied the right of petition? I don’t think many people would say Hanson does not have a the right to attempt to influence government spending by speaking about global warming. Certainly not many of the people who agree with this ruling…

35 Jeff R. August 10, 2015 at 6:21 pm

Jan, from p_a’s link:

On November 5, the medical journal The Lancet published a meta-analysis of the available studies on the safety of rofecoxib (Jüni et al., 2004). The authors concluded that, owing to the known cardiovascular risk, rofecoxib should have been withdrawn several years earlier. The Lancet published an editorial which condemned both Merck and the FDA for the continued availability of rofecoxib from 2000 until the recall.

In 2005, advisory panels in both the U.S. and Canada encouraged the return of rofecoxib to the market, stating that rofecoxib’s benefits outweighed the risks for some patients. The FDA advisory panel voted 17-15 to allow the drug to return to the market despite being found to increase heart risk. The vote in Canada was 12-1, and the Canadian panel noted that the cardiovascular risks from rofecoxib seemed to be no worse than those from ibuprofen—though the panel stated that further study was needed for all NSAIDs to fully understand their risk profiles. Notwithstanding these recommendations, Merck has not returned rofecoxib to the market.

36 Erick August 10, 2015 at 11:55 am

And yet somehow in thousands of lawsuits all over the country for all sorts of causes, and millions of instances of people resolving complicated matters outside of courtrooms as well, somehow people manage to determine the truth of things without the FDA weighing in.

37 Jan August 10, 2015 at 1:14 pm

Wait, massive litigation is the solution? That certainly sounds very efficient. Let me go tell my trial lawyer friends.

38 Hazel Meade August 10, 2015 at 1:38 pm

Massive litigation is the deterrent to making untruthful statements about off-label uses of drugs.
If the potential cost of litigation is high enough, drug companies will try to be as truthful and accurate as they can.

39 msgkings August 10, 2015 at 1:45 pm

@Hazel: so, hurray for trial lawyers? I thought John Edwards and his ilk were the scum of the earth?

40 Jan August 10, 2015 at 2:03 pm

Massive litigation of drug companies cannot prevent people dying stemming from a handful of people’s short-term desire to make lots of money and who would almost certainly not be held criminally liable for their actions. If you think drug companies won’t lie, take a look at settlements they’ve entered into the last 10 years. Then, tell me if you think those settlements have been a good deterrent against bad behavior.

41 The Original D August 10, 2015 at 3:09 pm

I’d like to see a chart of how many bonuses were rescinded after a class action lawsuit was resolved.

42 Hazel Meade August 10, 2015 at 3:20 pm

I don’t know why anyone thinks libertarians hate trial lawyers.
Liability is a cornerstone piece of libertarian legal theory.

Also, you’re again failing to see the opportunity cost. People die from lack of access to drugs that are unapproved, and will die from lack of awareness of off-label uses. Why is that acceptable and not the risk of a handful of people dying from some side-effect of a drug?
How do we know that number A is smaller than number B?

43 Jan August 10, 2015 at 4:04 pm

Hazel, what is the opportunity cost? If it is so terrible, one of the many libertarian organizations, or PhRMA itself, would have done a good study quantifying it. These numbers should be much easier to come up with than a “lives saved” figure given the data limitations (see 2nd paragraph).

I personally am a proponent of changing the law to require that detailed information about drug applications that FDA rejects are made publicly available. Right now, that is illegal, because PhRMA and conservatives oppose putting this info out there. It would help us much more easily understand how many dangerous products stops from entering the marketing and the basis on which those products were denied. “Lives saved” would follow.

Why is it acceptable to risk the lives of people so that we can make instant access to any experimental therapy a reality? (Just turning your question around.)

44 Jan August 10, 2015 at 4:06 pm

Sorry, typos. “It would help us much more easily understand how many dangerous products the FDA stops from entering the market, and the basis on which those products were denied.”

45 mulp August 10, 2015 at 4:34 pm

If the FDA approves $100,000 drug x as safe and effective for medical condition y that is suffered by 500 people, then the drug company has the free speech right to get doctors to prescribe it for medical condition z that is suffered by 500,000,000 people who can be treated by a $20 drug when the patient is covered by Medicare or Medicaid??

After all, the FDA should not restrict the free speech right of drug companies to pick taxpayer pockets without taxpayers getting a say. Isn’t that the conservative position – the taxpayers can vote to have the government save their life, but have no right to make sure their life is being saved at cost instead of paying crony capitalist profits.

The FDA is We the People. The drug companies are just trying to get as much out of the pockets of We the People.

And if you argue the government should not be involved, fine, let’s start with all the weapons the government pays for that are massively expensive and do not protect us. al qaeda and ISIS and many others have proved no government is needed to wage war as individuals can raise private money and do it themselves.

46 Doug August 10, 2015 at 6:01 pm

The decision is about free speech. What Medicare and Medicaid pay for is an entirely separate issue.

47 Doug August 10, 2015 at 5:28 pm

Uh, of course there is, its called a court, which is where these disputes are playing out to begin with. The question is what legal standard should the court apply in deciding whether or not the FDA has a case. Whether the advertisement is truthful seems as good a standard as any. Or should the court just trust whatever the FDA says regardless of the evidence? If so, why involve the courts at all, why not just make the FDA the prosecutor and the judge?

48 KLO August 10, 2015 at 10:35 am

Marketing is almost always intentionally misleading.

Statins have been pitched to people who have not already had a heart attack or cardiac event, and indeed most sales are to individuals with moderately high cholesterol and no prior cardiac event. Despite this, there is essentially no evidence that these individuals benefit from statins. Billions have been paid, significant side effects endured, and, in all likelihood, there was no benefit whatsoever outside of what can be shown in a blood panel.

This will be the same thing. There is little evidence that lowering triglycerides in individuals with moderately high triglyceride levels is beneficial. But that does not mean that the marketing will not create the association in people’s mind so as to sell a drug that may very well not benefit people in their situation.

49 RoyL August 10, 2015 at 2:19 pm

Statins are widely prescribed to people for persistant high levels of triglycerides despite being known to increase chance of developing diabetes, potentially causing liver damage and muscle destruction, oh and diarrhea.

Drugs like lovaza and vascepa seem to work better than statins at getting what I suspect is an almost meaningless number down, but have side effects such as fishy smelling diarrhea and hives in some patients who are already allergic to fish.

Which seems safer?

Now I am glad to hear that the FDA thinks there is no value to reducing triglycerides, but they still approve plenty of drugs with known side effects that are far more dangerous than these prescription fish oil products.

And now they are angry that this significantly less dangerous drug is being marketed for use in people with a slightly lower threshold while still approving the more dangerous drug for the same condition. And this is protecting the public how?

50 mulp August 10, 2015 at 4:41 pm

Why not put together the report documenting the “seems to” and have the FDA approve the wider use?

Or is the cost of the drug like 10 cents a day because its a generic and no monopoly profits are possible to pay for the FDA labor cost for the expanded use?

51 RoyL August 11, 2015 at 3:56 am

Apparently the makers of Vascepa did do the trial, it was able to show that Vascepa did work to lower triglycerides in patients in the new cohort, a cohort for which the FDA has approved other drugs, and the FDA rejected the new label on the grounds that triglycerides weren’t worth controlling.

And yet the FDA has kept approval for more dangerous drugs to treat the exact same condition that is apparently not worth controlling.

Try as I might I can find no public safety benefit to this decision.

52 A Definite Beta Guy August 10, 2015 at 10:08 am

Agreed with Jan. The secondary effect is an increase in drug utilization rates (meaning lots more spending on drugs!) with little clinical evidence. As for trusting doctors….why would ANYONE trust a doctor? Doctors are not trained to dispense drugs. Why do you think we have pharmacists?

53 Keith August 10, 2015 at 10:18 am

Doctors are trained. We have pharmacists because of rent seeking. A robot could do a pharmacists job.

54 A Definite Beta Guy August 10, 2015 at 10:52 am

What’s your confidence in this belief?

55 Val DeLa August 10, 2015 at 1:07 pm

Highly confident. Some UC hospitals already have robot pharmacists, and their error rates are less than flesh and blood. Doctors are not trained to dispense drugs? You mean I just randomly prescribe based upon the weather?

56 Jan August 10, 2015 at 1:11 pm

@Keith and Val

Robots do a lot of pharmacists’ jobs already, especially a big mail order plants. But there are some things real pharmacists actually do that lean on their training and which a physician cannot do.

57 PD Shaw August 10, 2015 at 10:11 am

If the patient is harmed, the doctors will face a malpractice claim, either for straight negligence or lack of informed consent.

Doctors can learn about off-label uses independent of the sales people. I think FDA’s concern here was probably different. The drug company is in a position to claim that it’s drug was essentially approved by the FDA, when in fact it was not.

58 Jan August 10, 2015 at 1:13 pm

Doctors have insurance against that.

Doctors theoretically can learn about all this stuff, but again many studies are heavily biased, even those published in peer review journals. Physicians also don’t realistically have time to review all the studies of off-label uses of drugs that they could potentially prescribe.

59 Hazel Meade August 10, 2015 at 1:41 pm

Wonder what the insurance premiums are like for a doctor with a history of malpractice claims.

Doctors could rely on the recommendations of some private trusted organization like the AMA. Whose biases would be no worse than the FDA’s.

60 Jan August 10, 2015 at 2:08 pm

I wonder, too. Do you think the number of doctors making malpractice-worthy mistakes would increase or decrease if they were left to their own devices regarding which drugs are acceptable to use?

Do you think the AMA wants to eliminate the FDA? They have a lot of policy statements out there.

Let’s get to the bottom of which trusted organization would take this role over and whether the public wants that.

61 PD Shaw August 10, 2015 at 3:10 pm

Doctors don’t necessarily carry malpractice insurance. I assume Jan searches them out because they are more cautious.

62 Hazel Meade August 10, 2015 at 3:22 pm

The AMA loves the FDA, I’m sure. It pushes the cost of doing all this research off onto the general public.

63 Jan August 10, 2015 at 4:08 pm

Wait, I thought the doctors were all learned altruists who just want to help their patients. Why would they like the FDA it is stemming the flow of lifesaving medications to their patients. The doctors don’t pay for medical research last I checked, so what’s in it for them?

64 Hazel Meade August 10, 2015 at 5:33 pm

A) Not getting sued.
B) Reputation. Attracting wealthier patients. Higher income.

The kind of doctors who end up having concierge fees tends to be the ones who still publish papers and read medical journals after going into private practice.

65 Luis Pedro Coelho August 10, 2015 at 7:47 am

“By rescinding their agreement, the FDA is sending the message to investors that no one is safe.”

Indirectly, this also increases the cost of approved compounds, of course, as investors now require even more return on the ones that do get approved.

(Pharmaceutical cost is a bit of a red herring wrt overall health care costs, as they are a small percentage of overall spending, but high pharma costs are a problem in their own right).

66 Turkey Vulture August 10, 2015 at 9:55 am

The FDA could then ban off-label uses.

67 charlie August 10, 2015 at 10:59 am

I’m not sure how a company that sells purified fish oil is moving drug development forward.

I find their studies helpful — it strongly suggest fish oil is more potent that regular medicine wants to admit — but this isn’t cutting edge technology.

68 tjo August 10, 2015 at 11:18 am

This case seems particularly absurd, but it seems like a big assumption that peer-reviewed equals true.

In Washington Legal Foundation v. Friedman, for example, the DC court issued an injunction preventing the FDA from prohibiting, restricting, sanctioning or otherwise seeking to limit pharmaceutical and device manufactures from disseminating information about off-label uses from peer-reviewed professional journals or textbooks.

69 ThomasH August 10, 2015 at 11:28 am

The general point about pharmaceutical company communication is valid but so to the the FDA in not approving a drug not shown to effect health outcomes. If that discourages innovation in substances that affect some intermediate variable but not health, isn’t that valuable?

70 Curt F. August 10, 2015 at 11:53 am

The case raises another important policy issue that is being obscured by the focus on free-speech rights. Is it a good idea for the FDA to issue SPAs and then reverse itself? After all, that, and not Amarin’s special love of first amendment rights, is probably what led to the dispute in the first place. If the best available evidence changed over the course of the SPA study such that triglyceride levels were no longer seen as an indicator of health, why did the FDA feel confident enough to enter into the SPA in the first place?

71 JCW August 10, 2015 at 2:18 pm

+1

72 Jan August 10, 2015 at 4:32 pm

Yeah, FDA messed up on this one, I think. It’s not ideal, since the study had already started, but is it better if they identify a serious scientific issue in the study design and just let it be used anyway?

http://www.zacks.com/stock/news/147297/amarin-plunges-after-the-fda-denies-vascepa-spa-appeal

73 Curt F. August 10, 2015 at 5:37 pm

There is absolutely no reason to have SPAs if they can be unilaterally rescinded by the FDA. SPAs were intended to provide a mechanism by which the industry and the FDA could agree ahead of time which criteria would be used to judge the worthiness of NDAs.

If the FDA can unilaterally revoke the SPA, even if in response to valid scientific concerns, then there is no reason to have them in the first place. The FDA’s attitude is apparently “We’ll evaluate your application however we want; it depends on how on whether any new evidence comes out in the 3 years since you start your trial.” There’s no reason to deceive industry through supposed SPA agreements.

74 JCW August 10, 2015 at 2:17 pm

In general, I’m pretty sympathetic to the argument that FDA regulation is overburdensome and problematic in all kinds of ways. But this post elides the difference between the drug’s result–that it lowers triglyceride levels–and the manufacturer’s claim that it would reduce cardiac events. Fundamentally, the FDA didn’t trust the manufacturer when claimed that it just “wanted to tell physicians the results of the trial and then let the physicians and their patients decide whether reducing triglyceride levels is something that they want to do given currently existing evidence about triglyceride levels and heart attacks.” FDA assumed, probably correctly, that the manufacturer planned to advertise in ways that would mislead the consumer about the effectiveness of the medication in reducing cardiac events–because why else would you want to talk about heart attacks at all?

I think that FDA was probably wrong on the merits, particularly given the reversal of its prior agreement, but acting like this is a case of a poor, put-upon, charitable actor–just trying to discover new ways to make people healthy–being beaten up by the big government ogre strains credulity, to say the least. The FDA, rightly or wrongly, saw itself as clashing with a bad-faith actor and acted accordingly.

75 PD Shaw August 10, 2015 at 3:45 pm

It may not be clear from the discussion above, but the FDA approved one use, but not the other. It approved the use of Vascepa for treating adult patients with triglyceride levels above 500 mg/dL
of blood (“very high” levels), but disproved for levels between 200 and 499 mg/dL of blood (“high” levels) and who are already on statin therapy. I think there is certainly a line drawing concern here, where it might be reasonable for a doctor to consider “high,” but not “very high” levels to be worth a more proactive approached based upon total patient health history.

And the FDA’s rejection was due to “recent scientific studies have left it unclear whether reducing the triglyceride levels of persons with persistently high triglycerides reduces cardiovascular risk.” The FDA’s position was based upon new uncertainty; I’d probably feel differently if the entire science was determined to be junk.

76 PD Shaw August 10, 2015 at 4:43 pm

The FDA’s position was also inconsistent with it’s approvals of the same chemical being marketed as a dietary supplement. It makes me wonder if the real issues are not health and safety or speech, but managing the market with these assumptions:

1. Where possible it will be cheaper for the consumer to purchase drugs over the counter as a dietary supplement than through prescription;

2. In some cases, there is no benefit to physician interaction, and in some cases the physician poses the risk of increasing demand for a marginal product unnecessarily.

77 mikeInThe716 August 10, 2015 at 2:26 pm

Will this ease the chances for Adderall to get the nod for cognitive enhancement? There’s a market for generally law abiding, high achievers who, lacking Wall St money / contacts / amorality, would like this potential step up.

78 Jan August 10, 2015 at 4:27 pm

Hey, I saw Limitless. It’s a slippery slope.

79 DDI August 10, 2015 at 7:32 pm

Will anyone at the FDA be liable for trying to impose illegal bans? That’s probably too much to hope for.

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