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The Pharma = Evil Narrative

flying cadeucii“People hate pharma,” my Forbes colleague Matthew Herper observed recently–and at times I can understand why. There’s not much to admire about executives like Martin Shkreli, or businesses like Valeant.

But I’ve started to worry that the “pharma = evil” narrative has become so ingrained that it’s taking on a life of its own, as readers instinctively anticipate this storyline, and journalists reflexively provide it. Coverage of a recently announced innovative training collaboration between Johns Hopkins and MedImmune (a subsidiary of AstraZeneca ), for instance, focused primarily on potential conflicts of interest.

(Disclosure/reminder: I work at DNAnexus, a health data management company in Silicon Valley and Boston; our partners include universities, government agencies and private companies.)

This narrow view, however, not only fails to capture the urgent need for effective, new therapies, it overlooks entirely the vital role played by companies in translating fragile but promising scientific ideas into robust medicines for patients.

For university “discoveries to matter most,” says former UCSF Chancellor, Genentech executive and current CEO of the Gates Foundation Susan Desmond-Hellman, “they need to get to humans.”

She adds, “The easiest thing to do to avoid conflicts is to never talk to industry, never interact with industry and have nothing to do with it–and no patients would benefit from [academic] discoveries.”

Desmond-Hellmann is hardly alone; many innovative academic physicians and scientists recognize the importance and value of close private-sector relationships. As UCSF professor and serial entrepreneur Atul Butte has recently emphasized, this is “the right way to truly change the world, by going beyond writing papers.”

Companies are exquisitely focused on driving the science from research paper to marketed product–a journey that simply wouldn’t happen without the concentrated effort, broad expertise (from medicinal chemistry to data management) and significant capital resources companies bring to this process. Even so, the trek is perilous, the failure rate notoriously high.

While academic training traditionally assumes a future in academic science is the ideal outcome for students, trainees may discover a passion for some of the more translational aspects, which industry does best. It’s hard to see how broader exposure to a range of career paths and opportunities would not be in the best interest of graduate and medical students.

The concern that working with industry scientists will somehow contaminate the purity of academia is especially hard to stomach in the context of science’s ongoing reproducibility crisis, the observation that a surprising number of published scientific results don’t seem repeatable. As Robert Califf, the newly installed head of the FDA, has pointed out, on balance, “academic analyses have more major errors and are not as reproducible as industry analyses.” (Califf also pointed out issues that seem more common in industry-funded studies, including framing of the questions and comprehensiveness of the analysis.)

Because companies often use licensed academic research as a starting point, industry researchers are constantly pressure-testing the scientific literature, and are often the first to discover replication problems–though they might do a better job of publicly pointing these out.

There is also increasing awareness that many flaws originally attributed to industry research–such as failing to report results to a designated government website and publish results in a journal–seem at least as common in academic research, suggesting these issues are more systemic.

Academics and industry researchers each tend to believe they are responsible for the heavy lifting of new medicine development, yet the truth is the process is far more difficult and daunting than either group tends to appreciate, and there’s essential work that must be done every step along the way.

Turning science into medicines is an important and worthy challenge, pursued with passion, intelligence and integrity by many physicians and scientists. New medicines do not fall easily and inevitably out of academic research, but require deliberate, painstaking development–and unreasonably resilient drug hunters able to cope with a staggeringly high failure rate.

We should encourage innovative partnerships that bridge the translational divide, and inspire more journalists to capture the value of this difficult and ambitious mission.

David Shaywitz is based in Mountain View, California. He is Chief Medical Officer at DNAnexus, a Mountain View based company and holds an adjunct appointment, Visiting Scientist, in the Department of Biomedical Informatics at Harvard Medical School. 

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12 replies »

  1. Thank you for sharing. Alfa Chemistry provides an integrated platform with small molecule APIs/intermediates development and manufacturing capabilities from preclinical to commercial stages. http://www.alfa-chemistry.com/

  2. Pretty typical…anyone who suggests that the hyper regulated medical /health sector (state mandates/ACA/Hitech/etc) might benefit from a little thought and care before layering on another layer of regulation and central control (such as banning drug ads) is labeled an uber free market ideologue.

    Re Brian’s well presented thoughts, here is my attempt at a reply:

    1) By making huge campaign contributions, Pharma has convinced Congress that it would be harmful for Medicare to negotiate pricing. The result is that we pay ANY price they ask for an FDA approved drug, no questions asked. It’s hard to imagine a better sweetheart deal than this..

    a. economists who understand the effects of monopsony (where a single dominant butyer controls the market)…can tell you this is not a good idea….the unintended consequences obliterate the face value benefits.

    b. And lobbying!…shocking that an org. might pay folks to counter the threat of more regulation!

    2) Pharma has convinced the FDA to water down the requirements for drug approval. A recent JAMA Int. Med. article showed that, between 2008-2012, two-thirds of the cancer drugs approved by the FDA received that approval based mostly on surrogate efficacy metrics, without evidence that they improve health outcomes or lengthen life. In other words, may drugs don’t work, and we’ve been convinced to pay >$100,000 for many of them.If

    If one is facing certain death, shouldn’t you have the right…with your docs concurrence…to try out a drug that shows positive preliminary results of “surrogate” measures (one is tumor shrinkage)? Some of these approvals have saved lives….some haven’t. Let patients and docs decide!

    3) By buying off Congress, Pharma has blocked purchasers from buying drugs outside US borders. So Harvoni is $1,350/pill here and $4/pill in India. Same drug.

    Yes, we have not yet imported third world country price controls….the impact of which have not been carefully considered. A radical proposal.

    4) With the complicity of the US patent process, pharma uses “evergreening” – making subtle changes to chemical composition that do not affect a drug’s clinical impact – to improperly extend their patents. Then they publicly scold other countries for failing to recognize and abide by our corrupt patent processes.

    Patents are good and encourage innovation….that is why the US is the source of so many great things. It is gross exaggeration to call this successful system “corrupt”. If you have suggestions for changes, they ought to be considered.

  3. “Free Market” uber alles. If private markets are “free,” then those who control them are “free” to collude and game them opaquely for their own transient benefit (notwithstanding that under neoliberal economic theory, such “control” simply cannot happen — that “free markets” are beneficent and wholly self-correcting). He Who Dies With The Most Toys WINS!

  4. David,

    This article is seriously naive and misguided. You begin by challenging the pharma = evil narrative, which is fine, if a stretch to anyone familiar with the facts of pharma’s business practices and power politics, and then you center on the dynamics between academic and industrial developers.

    Nobody I know thinks that developing new drugs isn’t important or that the process isn’t fraught with difficulties. That said, the mainstream of pharma’s reputation for profiteering and predation isn’t due to what happens in academic settings, but derives from the ways that industry has relentlessly spun and compromised policy and the market to unreasonably optimize revenues and margins.

    Some examples?

    1) By making huge campaign contributions, Pharma has convinced Congress that it would be harmful for Medicare to negotiate pricing. The result is that we pay ANY price they ask for an FDA approved drug, no questions asked. It’s hard to imagine a better sweetheart deal than this.

    2) Pharma has convinced the FDA to water down the requirements for drug approval. A recent JAMA Int. Med. article showed that, between 2008-2012, two-thirds of the cancer drugs approved by the FDA received that approval based mostly on surrogate efficacy metrics, without evidence that they improve health outcomes or lengthen life. In other words, may drugs don’t work, and we’ve been convinced to pay >$100,000 for many of them.

    3) By buying off Congress, Pharma has blocked purchasers from buying drugs outside US borders. So Harvoni is $1,350/pill here and $4/pill in India. Same drug.

    4) With the complicity of the US patent process, pharma uses “evergreening” – making subtle changes to chemical composition that do not affect a drug’s clinical impact – to improperly extend their patents. Then they publicly scold other countries for failing to recognize and abide by our corrupt patent processes.

    There’s much more, of course, but you get the idea. It might be helpful to hang out a little more around the people – organizational purchasers (businesses and unions) and patients – who actually pay the bills for drugs. Virtually every specialty drug is now priced above stop-loss attachment points, and the less than 1% of all drugs classified as special will consume more than half our total drug spend by 2018, more than we spend on physicians. A not so special example, one recent study showed that US costs for pertuzumab, a cancer drug from Genentech that delivers a 15 month increase in overall survival, costs $713,219 for each Quality Adjusted Life Year gained. The study’s authors said its US pricing is “unlikely to provide reasonable value for money spent in the United States compared with other interventions generally deemed cost effective.”

    Pharma is in a dangerous game of chicken, particularly with US corporations, with extreme pricing based on the idea that it is impossible for purchasers to deny paying for drugs at any price, even though that pricing threatens to cannibalize margins across every part of the US business enterprise. These practices are all intentional and by design. There is no sense of decency or proportion, and no indication that these practices will cease. In fact, recently Pharma announced that, because it was experiencing pushback on its practices, it had identified and was reaching out to 7,000 meta-decision makers in the US who could fortify its members positions.

    I can certainly understand that, in the polite arena of scientific development, these issues don’t seem pressing and so you might not think an extreme characterization is fitting. But that’s because you’ve chosen to not witness to the real carnage that’s occurring.

    Hope this is helpful.

  5. Paul – appreciate the thoughtful response – I remain unconvinced though. Certainly I think your arguments reflect the spin that PhRMA tends to put on things, but I remain unconvinced.

    1. Insurer profits are effectively limited by the ACA and mandatory Medical Loss Ratios. Hospital profits (including for profit hospitals and networks) often hover around 2%, rarely ever rising beyond 6-7%. I would argue that innovations in hospital care, surgical techniques, etc are more innovative and life-saving than producing the 16th ARB or Proton Pump Inhibitor.

    Honestly, my biggest issue about this is that Pharma charges ridiculous prices and then argues they are forced to charge those prices because “R&D is expensive” – all the while turning in quarterly profits that are way above and beyond what anybody else records. If you need cash for R&D, make 5-7% profits (still a very nice return in just about any industry) and invest the rest of that into R&D. But right now the public is funding silly prices through insurance premiums and taxes – with little to no evidence that much of that is even going to R&D at all.

    2. It’s not just an isolated few getting headlines like Turim and Valeant. It’s old (and mainstay) drugs like Lantus and Humira recording year over year price increases. The pricing (before insurer discounts) of most drugs increases significantly year over year. Not 5000% spikes like Daraprim, but small increases in the 3-10% range. Any other industry where prices jumped that much every year would be tarred and feathered.

    3. Fair enough. Though I would say that just because an agency allows someone to get away with something doesn’t make it morally acceptable. It seems a little like saying “crime is cool, so long as you don’t get caught. If you don’t get caught, you bear no moral weight for the crime.”

    4. This one’s a matter of interpretation for sure – I agree. But I personally think it requires a leap of faith (particularly given Pharma’s history) to assume that bypassing the medical professionals and insurers to target patients directly with 30-60 second snippets comes from a place of pure motives. Particularly when the patients aren’t the payers.

    5. In theory, sure. But it gets dicey when it’s the insurer (not the aforementioned doctor or patient) paying for the brand combo – and by extension, the taxpayer when we are talking about Medicare and Medicaid. Particularly when you add in DTC advertising, copay cards so the patient isn’t actually paying any more (for the commercial plans), and crap like this: http://www.fiercepharma.com/regulatory/reckitt-petitions-fda-to-force-child-resistant-packaging-on-suboxone-rivals

    This isn’t (yet) an argument for particular controls or a particular system. It’s simply saying in response to the article that there’s a preponderance of data points from Vioxx to Valeant, Sovaldi to Sanofi (Lantus), Glaxo (fees for improper marketing) to Endo (“pay for delay”) – that suggest that Pharma will do or say just about anything to make as much money as possible – hence the Pharma = Evil narrative.

    Certainly there’s a story that can be told to portray pharma as courageous, misunderstand innovators working hard on the next penicillin because they love children so much (and who have to extort them because it’s necessary to save more children?). But, in my opinion, it takes a LOT of spin to get there.

  6. Ted,

    I will give it a try.

    1. How pharma records profit margins that dwarf insurers, hospitals, and everybody else except Medtronic

    Usually it is because insurers, hospitals etc are non profits. Beyond that, pharma companies are trying to come up with innovations that save lives or provide dramatic improvements in symptoms…while insurers and even hospitals provide necessary but more routine things like facilities or transaction processing services.

    2. Why extravagant year on year price increases are necessary

    Pricing is up to the owner of the product….most drugs do not have extravagant year over year increases. The few that grab the headlines can be the result of poor decision making by the pharma owner…or more often boneheaded regulator decisions that create temporary monopolies.

    3. Why negative trial data gets buried

    Ask the FDA. Any pharma company that hides negative data faces huge risks…civil or even criminal….so ask the FDA.

    4. Why DTC advertising still exists

    The owners of the pharma product have free speech…including the right to publicize their product features and benefits. You may think patients ought to be kept out of the loop, but I know many situations in which such advertising led to improved outcomes from questioning their doc on a medication they heard about from advertising. Do you really want to ban such speech?

    5. Why anytime something is about to go off patent, a fixed dose combination or reformulation of the brand just happens to show up…

    The owners of the drug want to extend their run of profits for their shareholders….so they offer a combo….big deal. The doc and the patient can decide if the convenience of the combo is worth paying for….or not. Do you want to take away the choice?

    Paul

  7. I agree with Ted.

    There is a pharma reality distortion field narrative that needs to be examined.

    We live in a complex world = both A and B can be true.

  8. I have respect for the scientists, and completely agree – making good drugs is really hard.

    But to get rid of the narrative, I need someone to explain to me (among other things):
    1. How pharma records profit margins that dwarf insurers, hospitals, and everybody else except Medtronic
    2. Why extravagant year on year price increases are necessary
    3. Why negative trial data gets buried
    4. Why DTC advertisting still exists
    5. Why anytime something is about to go off patent, a fixed dose combination or reformulation of the brand just happens to show up…

    Mostly, I’m just not sure how to reconcile “I need to charge ridiculous prices so I can afford R&D” with “Look shareholders, we just made 16% profits!”

  9. What % of new drugs are “translating fragile but promising scientific ideas into robust medicines for patients?”

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  10. Narratives = evil

    Here are some others running lose these days —

    1. Regulation will kill my product

    2. Doctors refuse to use technology

    3. Transparency makes all things better

    4. People will shop for healthcare if ______

    5. EMRs suck

    6. Measuring things is scientific, therefore better