"We struggled - boy, did we struggle - with this decision"

June 12, 2017 10:53 AM

In Tarceva, Genentech discovered that they had a perfectly-targeted drug: Only patients with specific mutations in their epidermal growth factor receptor gene responded to the cancer-controlling drug. But there was one big problem: They were already selling $150 million a year worth of the drug to cancer patients for whom it didn't work.
posted by clawsoon (51 comments total)

The companies also recruited patients whose cancers had responded to the drug, and then trained and paid them to talk to others in what it called the “Patient Ambassador Program,” his lawsuit said.

The companies discouraged doctors from testing patients for the mutation, the lawsuit said, because they knew it would reduce sales.

Flames. Flames, on the side of my face.

Warning: Flames on the side of one's face may have side effects including throwing shit across the room and involuntary cursing.
posted by Etrigan at 11:00 AM on June 12, 2017 [39 favorites]

I should've put this in the post: Article is by Melody Petersen, who wrote Our Daily Meds, which includes multiple examples of this sort of standard pharmaceutical ethics. Side effects of the book may include permanent flaming face.
posted by clawsoon at 11:03 AM on June 12, 2017 [8 favorites]

Warning: Flames on the side of one's face may have side effects including throwing shit across the room and involuntary cursing.

"Talk to your doctor about whether flames on the side of your face are right for you."
posted by mandolin conspiracy at 11:03 AM on June 12, 2017 [59 favorites]

$7800 a month for something that does nothing. And, unlike goggles, we don't even know if it has any long term health issues.

The companies also recruited patients whose cancers had responded to the drug, and then trained and paid them to talk to others in what it called the “Patient Ambassador Program,” his lawsuit said.

The companies discouraged doctors from testing patients for the mutation, the lawsuit said, because they knew it would reduce sales.
Flames. Flames, on the side of my face.

Warning: Flames on the side of one's face may have side effects including throwing shit across the room and involuntary cursing.
posted by Etrigan at 1:00 PM on June 12 [1 favorite +] [!]

Seriously, dude. REALLY disappointed with the lack of rhyming.
posted by Samizdata at 11:10 AM on June 12, 2017 [5 favorites]

The idea that protecting the revenue base is potentially more important than sharing the evidence about who the drug actually helps puts me in mind of the Ford Pinto business.
posted by nubs at 11:10 AM on June 12, 2017 [2 favorites]

Isn't the rash developed from taking Tarceva an indicator of the EGFR mutation?
posted by Apocryphon at 11:12 AM on June 12, 2017 [1 favorite]

The companies discouraged doctors from testing patients for the mutation, the lawsuit said, because they knew it would reduce sales.

Wow. Class action time? The article talks about a government suit under the False Claims Act, but does that preclude individuals who took the drug and endured the side effects, or who took the drug instead of an effective drug, when Genentech knew-or-should-have-known that it could not possibly help them, from suing? Does it prevent insurance companies that paid for treatment that Genentech knew-or-should-have-known was ineffective from suing?
posted by ROU_Xenophobe at 11:13 AM on June 12, 2017 [6 favorites]

In the post, it should be "Genentech," not to be confused with security company "Genetec" or any possible "Genetech" that exists out there.
posted by explosion at 11:13 AM on June 12, 2017

“We were presented with a single study … that has some design flaws showing some very modest or even minimal benefit,” added Ron Richardson, an oncologist at the Mayo Clinic who also voted against the approval. “I don’t think the sponsor answered the question on the value of this drug.”

The FDA did not take the experts’ advice.

The agency employee signing the 2010 approval letter was Robert Justice, a former Genentech senior scientist.

That's one way to get something approved.
posted by mandolin conspiracy at 11:15 AM on June 12, 2017 [23 favorites]

Thanks, explosion, I've asked the mods to fix.
posted by clawsoon at 11:16 AM on June 12, 2017

Sufficiently advanced "business" is indistinguishable from a common hustle.
posted by ryanshepard at 11:16 AM on June 12, 2017 [27 favorites]

[A committee of experts] voted 12-1 against expanding Tarceva’s approval.

The FDA did not take the experts’ advice.

The agency employee signing the 2010 approval letter was Robert Justice, a former Genentech senior scientist.

Regulatory capture in action. How on earth does the FDA not have conflict of interest rules preventing that kind of bullshit?

This is by no means Genentech's first brush with corruption.
posted by jedicus at 11:17 AM on June 12, 2017 [21 favorites]

Mod note: Fixed the spelling in the post and tags.
posted by cortex (staff) at 11:20 AM on June 12, 2017 [2 favorites]

Beyond the direct harms to people who were unnecessarily taking a drug with harmful side effects this kind of shit is also galling because it undermines public faith in modern biomedicine.
posted by en forme de poire at 11:25 AM on June 12, 2017 [20 favorites]

Unfortunately, blockbuster drug development is a lot like blockbuster movie development: Spend tens of millions on promotion so that you can guarantee hundreds of millions in sales before anybody figures out whether the product sucks or not.
posted by clawsoon at 11:32 AM on June 12, 2017 [4 favorites]

en forme de poire: this kind of shit is also galling because it undermines public faith in modern biomedicine.

And what makes it worse is that this particular drug is a great drug, created using great scientific work. It's just not a drug that pleases profit-oriented Wall Street analysts.
posted by clawsoon at 11:43 AM on June 12, 2017 [9 favorites]

Time to cry havoc and let slip the hogs of war.
posted by indubitable at 11:48 AM on June 12, 2017 [2 favorites]

No need to worry, everyone, justice will be done: there will be some lawsuits for pocket change that will be worked into the next few quarters' budgets, and a few token executives will be shuffled around or let go with hefty severance bonuses.
posted by Sangermaine at 11:55 AM on June 12, 2017 [3 favorites]

Well this is pretty terrifying. Genentech makes my immunosuppressant.

Which I'm getting intravenously tomorrow.
posted by bile and syntax at 12:11 PM on June 12, 2017 [3 favorites]

Also, the answer to this is MORE & BETTER FDA, not LESS REGULATIONS.

If you think this is sketchy, imagine what removing regulations to fast track drugs would do.
posted by lalochezia at 12:19 PM on June 12, 2017 [30 favorites]

imagine what removing regulations to fast track drugs would do.

It would allow Trump to claim "I have approved 3x as many new cancer treating drugs in one year as Obama managed to in 8 years"
posted by Cosine at 12:26 PM on June 12, 2017 [15 favorites]

"Fucking Genentech. We were a vendor... wretched hive of scum and villainy doesn't come close."

Huh. My only exposure to them has been through non-profit work, where they were a major supporter of LGBT orgs, mostly through one of their former executives. I had no idea they were evil, unlike many of our other corporate donors.
posted by klangklangston at 12:26 PM on June 12, 2017 [2 favorites]

"It would allow Trump to claim "I have approved 3x as many new cancer treating drugs in one year as Obama managed to in 8 years""

Might be worth it if we could convince Trump that the appropriate way to test drugs is to have Trump ingest them himself.
posted by klangklangston at 12:27 PM on June 12, 2017 [6 favorites]

Apocryphon: Isn't the rash developed from taking Tarceva an indicator of the EGFR mutation?

Looks like you're right - and they knew that as early as 2007. Oddly, survival was also better for people on the placebo who developed a rash.
posted by clawsoon at 12:39 PM on June 12, 2017 [1 favorite]

Might be worth it if we could convince Trump that the appropriate way to test drugs is to have Trump ingest them himself.

That's a good way to get him to grow to 150 feet in height and develop heat vision, and nobody wants that.
posted by GenjiandProust at 12:43 PM on June 12, 2017 [8 favorites]

“Let’s prove efficacy [of new pharmaceutical drugs] after they’ve been legalized,” [Jim] O’Neill said in an August 2014 speech at a biotech conference.

So, basically, let's offload R&D costs and risks onto the public. Lovely.
posted by grumpybear69 at 1:05 PM on June 12, 2017 [6 favorites]

Offloading more R&D costs into the public might actually be a good idea, if you take that to mean publicly funded drug development and trials. The incentives are so fucked up in pharma that lately I kind of think maybe drug development shouldn't be done by private industry at all. Using the public as lab mice is another thing, though.
posted by en forme de poire at 1:16 PM on June 12, 2017 [15 favorites]

[A committee of experts] voted 12-1 against expanding Tarceva’s approval.

The FDA did not take the experts’ advice.

The agency employee signing the 2010 approval letter was Robert Justice, a former Genentech senior scientist.

jedicus: Regulatory capture in action. How on earth does the FDA not have conflict of interest rules preventing that kind of bullshit?

So this rough argument features prominently in many liberal-themed failures to understand regulatory action, but just because it is easy to understand and attracts lots of eyeballs with all the flames it produces doesn't make it any less wrong. The FDA has a direct interest in hiring regulators out of the industries it regulates not just because thats where the people who know what they're doing come from but also because they will know where bodies are buried and how to navigate the unique sorts of bullshit perpetrated by different companies. Having former industry employees and people who have done research relevant enough to industry to be worth them paying for it on our payroll is a good thing. While there is a problem in the congress, and particularly the defense sector, where clearly people shamelessly leave their congressional seats and Pentagon jobs to cushy 'consultant positions' on handshakes, the dynamics that create that bullshit aren't really a thing at the academic and regulatory agencies in anywhere near the same way. Indeed, a job at the FDA is something one almost always advances through and then retires in.

There is a reason why the LA Times left its clickbaitey libel unsaid and implied, which is only more unfortunate for how the current political environment makes it only that much more important that the general public pay attention for once rather than just allow it to be led from one flame to the next. Its important for the general public to guide congress through the complex philosophical and economic questions underlying just how solid data should be before we allow dying patients to try new drugs so that congress can provide appropriate direction to the FDA.
posted by Blasdelb at 1:17 PM on June 12, 2017 [14 favorites]

Its important for the general public to guide congress through the complex philosophical and economic questions underlying just how solid data should be before we allow dying patients to try new drugs so that congress can provide appropriate direction to the FDA.

This would be the same general public that lobbied congress relentlessly on behalf of the quack medicine "supplement" industry in the early 90s to ensure their snake oil could be marketed and sold with essentially no oversight, right?

Sorry. You're absolutely correct, of course, but the current times make it difficult to trust in the general public to do the responsible thing in governing themselves.
posted by biogeo at 1:33 PM on June 12, 2017 [3 favorites]

bullshit perpetrated by different companies

perpetrated by different companies

different companies

different

DIFFERENT

This guy had worked for the company that his decision benefited. Do we know whether he still had stock in the company? Whether his wife works for them? Whether he just liked the people who worked there and wanted them to succeed? Whether he worked on this actual thing?

Any reasonable system would have been so afraid of "clickbaitey libel" (i.e., a patently obvious conflict of interest) that Justice would have recused himself long before the panel made its recommendation.
posted by Etrigan at 1:34 PM on June 12, 2017 [11 favorites]

Yes, you need experts and some of those experts can come from industry, but Justice worked directly for Genentech. If the decision was ultimately his and his alone, that is a problem. Recusal is necessary not just to prevent impropriety, but also to prevent the appearance of impropriety.
posted by soelo at 1:34 PM on June 12, 2017 [28 favorites]

Blasdelb: The FDA has a direct interest in hiring regulators out of the industries it regulates not just because thats where the people who know what they're doing come from but also because they will know where bodies are buried and how to navigate the unique sorts of bullshit perpetrated by different companies. Having former industry employees and people who have done research relevant enough to industry to be worth them paying for it on our payroll is a good thing.

I can see how it can be a good thing, but I suspect that whether it actually is a good thing depends on whether the person in question considers the everyday ethical slipperiness that pharmaceutical companies are liable to a bad thing or a normal way of doing business. Are they someone coming to the FDA because they were disturbed whenever marketing and profit considerations were put ahead of patient safety, or are they coming to the FDA because they think that the FDA needs to better understand the "needs of business"? Knowing where the bodies are buried doesn't help much if you're convinced that the bodies were given a proper Christian burial and there's no need to disturb them.
posted by clawsoon at 1:49 PM on June 12, 2017 [10 favorites]

I think Blasdelb meant "different" as in "assorted/diverse" not as in "distinct from this one" but the point about recusal is a good one, I think.
posted by en forme de poire at 1:49 PM on June 12, 2017 [2 favorites]

From the article:

One of Trump’s possible selections to head the FDA — Jim O’Neill, a Silicon Valley venture capitalist with no education in medicine or science — has raised the idea of approving drugs with no tests of their effectiveness.

“Let’s prove efficacy after they’ve been legalized,” O’Neill said in an August 2014 speech at a biotech conference.

That would mean more patients would become part of a continuing experiment and be prescribed medicines their doctors know little about.

As Mrs Bubba & I set poised on the edge of (her) rare type of cancer and the uncertainty of the doctors on how to proceed with treatment, I just can't begin to say how furious I am with people like this Jim O'Neill who seems to have an attitude of "let's throw everything at the wall and maybe something will stick!"
posted by beelzbubba at 2:03 PM on June 12, 2017 [17 favorites]

So this rough argument features prominently in many liberal-themed failures to understand regulatory action, but just because it is easy to understand and attracts lots of eyeballs with all the flames it produces doesn't make it any less wrong. The FDA has a direct interest in hiring regulators out of the industries it regulates not just because thats where the people who know what they're doing come from but also because they will know where bodies are buried and how to navigate the unique sorts of bullshit perpetrated by different companies. Having former industry employees and people who have done research relevant enough to industry to be worth them paying for it on our payroll is a good thing. While there is a problem in the congress, and particularly the defense sector, where clearly people shamelessly leave their congressional seats and Pentagon jobs to cushy 'consultant positions' on handshakes, the dynamics that create that bullshit aren't really a thing at the academic and regulatory agencies in anywhere near the same way. Indeed, a job at the FDA is something one almost always advances through and then retires in."

Bullshit right back at you.

A Look at how the Revolving Door Spins from FDA to Industry:

Prasad and his colleague Dr. Jeffrey Bien, an internal medicine resident also at OHSU, tracked 55 FDA reviewers in the hematology-oncology field from 2001 through 2010, using LinkedIn, PubMed and other publicly available job data. The researchers found that of the 26 reviewers who left the FDA during this period, 15 of them, or 57 percent, later worked or consulted for the biopharmaceutical industry. Put another way, about 27 percent of the total number of reviewers left their federal oversight posts to work for the industry they previously regulated.

posted by klangklangston at 2:12 PM on June 12, 2017 [11 favorites]

Tbh klang klang, I would rather the flow of regulators to private than vice versa.

It's not uncommon, after all, in many industries to hire people deeply familiar with regs/requirements to work in compliance or audit spaces.

Bladelb in abstract, your point has some validity, in that industry experience is valuable (and also one of the only places for people to work). However it boggles the mind that someone is allowed to run roughshod over conflict of interest like this, and given that the approval was issued despite the fact the medicine didn't work and it was called out by basically all the reviewers, it's pretty troubling.
posted by smoke at 2:22 PM on June 12, 2017 [7 favorites]

On the bright side to Genentech's board of directors and shareholders, the vast majority of people who were swindled by taking this drug are now dead and therefore won't be aware of this article in the LA Times.

*sigh*
posted by Big Al 8000 at 2:26 PM on June 12, 2017 [2 favorites]

beelzbubba: As Mrs Bubba & I set poised on the edge of (her) rare type of cancer and the uncertainty of the doctors on how to proceed with treatment, I just can't begin to say how furious I am with people like this Jim O'Neill who seems to have an attitude of "let's throw everything at the wall and maybe something will stick!"

I'm sorry to hear about your wife's cancer, and I hope she finds a treatment that works.

Sometimes access to unproven drugs is pushed by patient groups, like some of the early AIDS activists, in order to make the science to move faster. But pharma companies realized what a potent marketing tool patient groups could be, and patient group pushes for faster approvals became another arena in the conflict between profit and science.

Patients want cheaper medicine; the pharmaceutical industry wants to maximize revenue. Patients want information about the efficacy of certain drugs; the industry often seeks faster approvals for drugs — at which point the incentive to collect information about a drug has diminished, according to Vinay Prasad, assistant professor of medicine at the Oregon Health and Science University.

“Who is setting the narrative of what patients want?” he said.

posted by clawsoon at 2:30 PM on June 12, 2017 [4 favorites]

This is a disappointing and unsurprising story, but one of Genentech's targeted therapies will probably save my life. It cost my insurance company $10,000 a week, for a year.

The longer I live the more simultaneously impressed and disgusted I am with humanity and modern society. We have the capacity for such amazing things, and routinely behave like utter garbage. So, you know. I guess I'm jaded, but at this point I'm starting to think all we can do is wring out the bits of good from the bad.
posted by something something at 7:34 PM on June 12, 2017 [11 favorites]

You all might like this then. Visited the local doc because the drugs I'm on need the doc's blessing. I think pricing should not be the old car repair model of "you pay what we tell you to pay - we can't give you a quote" and more of "give me a quote". In the conversation I have a video recording of the staff I'm told this:

We offer a 23% discount if you don't use insurance. We offer another 24% discount if you pay in 30 days.

So think about this reframe: 50% of the medical cost is due to insurance JUST to satisfy federal regs on drugs because YOU the iphone wanting consumer can't grab a cuff and stethoscope, determine that due to flames on your face you have high blood pressure and then you can't use the same standard go-to list of meds and check to see if they are working based on you taking your own damned blood pressure.

And no doctor gives out scripts to let you take a 5 gallon can of gas, spread it at the base of the buildings of the bastards who get you to flame-face status, use the flame-face to ignite the gas as a way to get non-drug relief of your high blood pressure by getting rid of the stressing events causing flame-face high blood pressure.
posted by rough ashlar at 7:34 AM on June 13, 2017

That's a good way to get him to grow to 150 feet in height and develop heat vision, and nobody wants that.

The heat vision requires focus for a length of time and that just is not a concern.

The 150 foot tall? Meh, can't wreck a place worse than the Military he's in charge of can.

I'd be more worried about body horror Cronenberg every time he's on camera. Upside - I'm guessing it be a great way to loose weight due to the side effect of not being about to keep food down.
posted by rough ashlar at 7:39 AM on June 13, 2017 [1 favorite]

50% of the medical cost is due to insurance JUST to satisfy federal regs on drugs

You are reading this incorrectly. Insurance is actually saving 50% of the cost. This pricing discrepancy isn't anything about federal regulations.

If you don't have insurance, then they are quoting you the full list, retail price. But the insurance company doesn't pay the retail price. They pay the 50% discounted price because they have volume leverage over the pharmaceutical company. The insurance company is saving you money.

So when they say they will give you a 50% discount if you don't use insurance, they are just giving you a similar pricing break as they give the insurance company. Perhaps they realize they might lose a customer if they charge you the retail price so they are giving you the same price as through insurance.
posted by JackFlash at 7:55 AM on June 13, 2017 [2 favorites]

So when they say they will give you a 50% discount if you don't use insurance, they are just giving you a similar pricing break as they give the insurance company.

It's extra fun when they won't give you the price the insurance company pays. I've received quotes for services that were much, much higher than what the insurer eventually paid the provider. (I did not have to record anyone on video.)
posted by asperity at 8:07 AM on June 13, 2017

It's extra fun when they won't give you the price the insurance company pays.

The 'fun' is the utter inability to have these people give you a pricing sheet so you can do these comparisons as the consumer.

Used to be that way in car repair. Not now 'cuz the feds stepped in.
posted by rough ashlar at 8:37 AM on June 13, 2017

I've usually been able to get the pricing sheet -- but the experience I'm thinking of is when the insurer pays much, much less than I would have paid on my own according to their pricing sheet.
posted by asperity at 9:22 AM on June 13, 2017

I'm in industry, though not only have I never worked for Genentech, I've resented the favorable press (and at times stock) responses to even their mediocre crap. So I'm not sure which way my biases even out.

But the quote that headlines this post is misleading, at least to the extent it sounds like this was an ethical quandary. It was almost certainly referring to a scientific problem rather than a bit of mustache twirling villainy--before you know how effective the drug is you have to decide who to enroll in your trial. You may suspect it works better for some people for others but that's it. There's a profit motive in doing the broad trial but there's also one doing the narrow one that's more likely to get approval. Erring in either direction costs money and hurts patients.

For example BMS made a mistake in perfectly good faith--going too broad with Opdivo trials--that'll probably cost them literal billions. You can't assume companies know the outcomes of trials when the point of the trial is to determine outcomes.

None of this excuses marketing or trying to discourage tests post-launch.
posted by mark k at 10:56 PM on June 13, 2017

mark k: But the quote that headlines this post is misleading, at least to the extent it sounds like this was an ethical quandary. It was almost certainly referring to a scientific problem rather than a bit of mustache twirling villainy

Here's the full quote, from a Genentech scientist speaking to other scientists:

“We struggled — boy, did we struggle — with this decision,” Waring told the crowd. “The company was obviously keen to protect its revenue base.”

He's saying that the dilemma was a ethical one, not a scientific one.
posted by clawsoon at 5:47 AM on June 14, 2017 [2 favorites]

Here is the same scientist, in 2006, giving the company's scientific reasoning for not limiting the number of patients in the trials:

He also pointed out that although initial studies indicated that more than 70 percent of the responders to Tarceva had mutations in EGFR, testing positive did not correlate with a survival advantage in small cell lung cancer patients because of the complex biology of the disease. Studies have shown that although patients who have EGFR mutations initially respond to these drugs, surviving tumor cells may acquire secondary resistance mutations and then progress, resulting in no survival benefit. But the drug also slows the growth of tumors in patients who do not have EGFR mutations, which can result in improved survival time.

Sounds reasonable. But then you add his 2014 statement about revenue, and the fact that company brought in up to $1.5 billion per year from the drug during the 10 years that it took for the company to get around to finding out that other scientists studying the drug before 2006 had got it right and the company had got it wrong, and you start to hope that Waring had at least a few sleepless nights over this.

From the article, it sounds like he didn't:

Waring, the former Genentech scientist, said in an interview that he believed the company had moved as quickly as it could in determining the drug only worked for those with the mutation.

If that's truly how long it takes, then the system's incentives are broken. The company has 20 years or so to make money from its patents; 10 or 15 of those years will be spent figuring out whether (and for whom) the drug works. During that time, the company has a strong incentive get a preliminary approval, then to test the drug on as many people as possible for whom it doesn't work in order to maximize revenue.

That's a system set up to maximize needless suffering.
posted by clawsoon at 7:35 AM on June 14, 2017 [1 favorite]

And here is the 2016 drug information correction sheet for Tarceva. It took them a trial involving 643 people to determine that the drug should be limited to only those with specific mutations. In the decade that it took for them to get around to completing that study, they earned billions of dollars off of hundreds of thousands of patients for whom the drug did nothing. Surely that study should've been done first?
posted by clawsoon at 7:52 AM on June 14, 2017

This literally happens all the time. Drug and medical device marketing has grown especially terrifying in the last 15-20 years -- think Risperdal, Invokana, Tasigna, TVM, hernia mesh, hell, even taking PPIs daily for more than 2 months increases your odds of renal failure by 96%.

Real talk, even if you are diagnosed with a fatal disease, you should (or have someone you know, love and trust who is capable of reading medical studies with a critical eye) always research the hell out of any surgical implant, prescription or OTC medications.

The only person who'll be your best health advocate for life is you, not your doctor, surgeon or physical therapist. Big Pharma does NOT want to help people get well. They want people to pay them a lot of money and then die before they can file successful product liability or failure to warn lawsuits.
posted by Unicorn on the cob at 11:58 AM on June 17, 2017

increases your odds of renal failure by 96%

From what to what?
posted by Etrigan at 1:34 PM on June 17, 2017 [1 favorite]