Category: FDA

Reverse Settlements, Part 3: Value of a Drug Patent

anupmalani Leave a comment

In this third post on reverse settlements, I examine whether traditional legal standards for judging whether a drug patent is valid captures the social value from a drug patent.  This is important because the FTC takes the position that reverse settlements extend the expected life of a drug company’s patent as compared to litigation over patent validity under traditional legal standards for judging patent validity.  I conclude that those standards may seriously undervalue the social benefit of drug patents, even invalid ones.  First, patent validity standards do not appreciate that all drug patents – valid or not – are necessary to compensate drug companies for conducting clinical trials, which are half the cost of all R&D and are socially valuable even if the drug patent is not valid.  Second, profits from a drug patent – even if the patent is invalid – sustains research on a large number of other drug patents – which may be valid.  That cross-subsidization suggests a branded drug company ought be judged on their portfolio of patents, not on individual patents. Traditional patent validity standards fail to do that.

To be clear, I understand that patent law standards for validity are not perfect, and I do not expect them to be.  What I suggest is that there is a worse fit between patent validity standards in the pharmaceutical industry than in other industries. This is relevant for antitrust analysis because, if patent validity standards undervalue drug patents, then eliminating reverse settlements undervalues them even further since these settlements putatively extend the expected patent life of drug patents.

Let me begin with my first substantive claim: all drug patents, whether valid or not, are socially useful.  All drug patents encourage production of useful public goods, specifically information about whether a drug works.  The main reason is that, unlike patents for other products, a patent for a drug is obtained before research on the drug is completed.  Specifically, drug companies obtain patents on molecules after lab and animal testing, but before clinical test, i.e., testing on humans.[1] Yet human testing is roughly half the cost of all drug R&D (DiMasi, Hansen, & Grabowski, 2003). Moreover, the results from clinical trials, which are made public as part of the drug approval process, are a public good.  Once a drug is shown to be effective, everyone knows whether the molecule is medically valuable.  If a company did not have a patent that could prevent other companies from producing that molecule, it would never conduct the trial in the first place!

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Life Cycle of the Fight to Label Innovative Ingredients Introduced Into Consumer Products – A Suggestion for Producers of Lab Grown Meat

kvantassel Leave a comment

Manufacturers assert that they have no obligation to provide consumers with notice through labeling when ingredients created through innovative technologies are introduced into consumer products designed for human consumption. On the other hand, consumers take the position that they have the right to know what ingredients are in these products, especially when ingredients are novel and the risks associated with exposure to them are unknown. Recent events suggest that this problem may be developing a life cycle that savvy manufacturers should be watching.  The first in what may be a series of examples of this life cycle is the conflict over the labeling of genetically modified plant ingredients in food.

From the outset, food manufacturers using GMO ingredients have declined to provide consumers notice of GMO content. The FDA has not mandated disclosure as it takes the position that the introduction of GMO ingredients into food is not material. This lack of transparency resulted in consumer rights groups testing products for GMO use and disclosing that use to consumers.  As consumers have become aware of the extensive use of GMOs in their food, a rising number have expressed the desire that these ingredients be labeled.  A recent ABC poll suggests that 93% of consumers now support mandatory disclosure of GMO content on labels.

When industry ignored this consumer preference, a market was created for products that are “GMO-free.” Thus, the practice of “GMO-free” labeling was born. The growing consumer labeling movement also triggered repeated attempts to pass labeling laws. While these efforts have been unsuccessful to date, they are gaining traction – for instance, it cost industry 40 million dollars to block California’s prop 37 calling for mandatory labeling last fall. With more legislative proposals cropping up (a ballot initiative in Washington State and legislative proposals in Connecticut, Vermont, New Mexico and Missouri), a growing consumer boycott of some organic or “natural” brands owned by major food companies and a recently introduced popular mobile app by Fooducate that allows consumers to check for GMO content in a growing number of products, industry may be seeing the writing on the wall. Just this year, Ben & Jerry’s Ice Cream has decided to remove GMO ingredients from its supply chain. And the Meridian Institute, which organizes discussion of major issues, convened a meeting in Washington last month that included executives from PepsiCo, ConAgra and about 20 other major food companies, as well as Wal-Mart and advocacy groups that favor labeling. See here.  Many are predicting that voluntary labeling may be right around the corner.

It appears that this life cycle of manufacturers’ refusal to disclose innovative ingredients with unknown risks and consumers’ reactive self-help measures may be repeating itself in the context of the use of nanotechnology in consumer products.

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Irresponsible Health Reporting? The N.Y. Times and the Perpetuation of Chemophobia

joleary 4 Comments

By Patrick O’Leary

When I read Susannah Meadows’s article in last week’s New York Times Magazine, The Boy with a Thorn in His Joints, I was at a bit of a loss how to respond. The article is Meadows’s account of dealing with her son’s juvenile idiopathic arthritis, and describes how, wary of the side effects of the treatment recommended by two well-regarded pediatric rheumatologists, she put her son on an alternative-medicine regime instead. Meadows relates how, on a regimen of probiotics, sour Montmorency cherry juice, fish oil, and something called four-marvels powder, her son underwent a near total recovery.

It should be noted, to her credit, that Meadows goes out of her way to acknowledge the anecdotal character of her experience. And, likewise to her credit, Meadows continued to work with her son’s doctors and take their concerns seriously throughout her son’s experiment with alternative medicine. But in spite of Meadows best journalistic instincts and her thorough reporting, her article perpetuates a dangerous misunderstanding. Throughout her article, Meadows makes an implicit distinction between pharmaceuticals and the substances (cherry juice, fish oil, four marvels powder) she was putting in her son’s body. But here’s the thing: the single most important distinction between the methotrexate her doctors recommended and the four marvels powder she chose to administer to her son is that the former has been proven safe and effective in “adequate and well-controlled investigations,” while the latter is essentially unregulated. The active ingredients in both substances are chemicals with hard-to-pronounce Latin names, the difference is just how much we know about these chemicals.

And that’s the point that Michelle M. Francl, a professor of chemistry at Bryn Mawr College, articulates far more eloquently and forcefully than I possibly could in her recent Slate article: Don’t Take Medical Advice From the New York Times Magazine: The dangerous chemophobia behind its popular story about childhood arthritis. Francl’s article is a must-read, and makes several extremely valuable points, but I particularly want to highlight just one of these. Susannah Meadows is an intelligent and experienced journalist, a wonderful commentator on politics and publishing, and clearly a mother whose love for her children is boundless. But she is not a doctor or a scientist, nor is she even a health or science reporter. Yet her anecdotal account of her own child’s illness is now probably the most widely disseminated article about treating juvenile arthritis ever, and it is one that perpetuates a basic and dangerous misunderstanding about the nature of medicine.

India Releases New Rules on Clinical Trial Injury

Holly Fernandez Lynch Leave a comment

Last week, the Indian government issued revised rules governing “compensation in case of injury or death during clinical trial.”  You’ve really got to read the whole thing, but some of the provisions are pretty remarkable:

  • “In the case of an injury occurring to the clinical trial subject, he or she shall be given free medical management as long as required.”  Note that this doesn’t say anything about the injury being study-related.
  • If an injury is related, then the subject is also entitled to financial compensation above any medical expenses.
  • If the subject dies as a result of clinical trial participation, his or her “nominees” would be entitled to financial compensation.
  • Injury or death will be considered related to trial participation in a variety of usual circumstances, including adverse effects of the investigational product and protocol violation or negligence.  But here’s the kicker: injury or death will be deemed trial-related, and therefore eligible for care/compensation, if it results from “failure of investigational product to provide intended therapeutic effect” or “use of placebo in a placebo-controlled trial”.  Read that again – if an investigational product doesn’t work, the sponsor will be liable for free medical care and further financial compensation.
Like all of the presidential bioethics commissions and many others that have considered this issue, I’m all for the adoption of reasonable and appropriate compensation systems to make subjects whole in the event of study-related injury.  And I think US policy is woefully inadequate on this score.  But the pendulum can also swing too far in the other direction.  Will sponsors take their trials elsewhere or will research in India still be worth it?
[H/T to Rebecca Li for the head’s up re: publication of the new rules.]

Goldacre on Pharma Research Credibility

fpasquale 11 Comments

By Frank Pasquale

Ben Goldacre is once again arguing that pharmaceutical “industry-funded trials are too common, can’t be trusted — and bring pills to market that likely don’t work.” The NY Times features his argument today. He has exhaustively compiled problematic practices that add up to a shocking claim: “the entire evidence base for medicine has been undermined by a casual lack of transparency.” For example, here’s one vignette from his most recent book:

In October 2010, a group of researchers were finally able to bring together all the trials that had ever been conducted on reboxetine. Through a long process of investigation — searching in academic journals but also arduously requesting data from the manufacturers and gathering documents from regulators — they were able to assemble all the data, both from trials that were published and from those that had never appeared in academic papers.

When all this trial data was put together it produced a shocking picture. Seven trials had been conducted comparing reboxetine against placebo. Only one, conducted in 254 patients, had a neat, positive result, and that one was published in an academic journal for doctors and researchers to read. But six more trials were conducted in almost 10 times as many patients. All of them showed that reboxetine was no better than a dummy sugar pill. None of these trials were published. I had no idea they existed.

I have not come across a convincing industry or FDA response to Goldacre’s work. (I don’t find this brief letter particularly compelling.). He offers several case studies like the reboxetine one. Isn’t it time to fund systematic reviews of the evidence of effectiveness on all drugs?

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Finasteride as an FDA-Approved Baldness Remedy: Is It Effective?

Jonathan Darrow 2 Comments

By Jonathan J. Darrow

Questionable baldness remedies have been peddled since the beginning of medicine. According to Pliny (23-79 A.D.), ashes of seahorse could cure baldness.  Almost 2000 years later, the British Medical Association warned the public of the increasing “number of preparations put forward for the cure of baldness,” particularly those which “are not applied locally but taken internally.”  The purported active ingredient? “[H]aemoglobin.”  (see Secret Remedies (1909), page 114).

While the medicinal use of a seahorse or dried blood matter may sound fanciful to modern ears, one has to wonder whether today’s public is any less credulous: Worldwide, consumers have spent over $400 million per year on a modern baldness remedy known by the trade name Propecia (finasteride).  Has science finally triumphed over a medical condition that has persisted through millennia? Today’s consumers might rationally believe that its has, given that Propecia is FDA-approved for the treatment of alopecia (baldness).  FDA-approved remedies must, according to federal law (21 U.S.C. § 355(d)), prove their efficacy in well-controlled, clinical investigations.

Yet one need only walk through a crowded street to see that, if a baldness cure has truly arrived, a surprising number of people have not availed themselves of it. Is Propecia, then, not effective? Let us take a look at the official data. Read More

Save the Date – May 17th “Issues and Case Studies in Clinical Trial Data Sharing – What Have We Learned?”

The Petrie-Flom Center Staff Leave a comment

Please save the date for this upcoming conference at Harvard Law School on May 17, 2013:

Issues and Case Studies in Clinical Trial Data Sharing:

What Have We Learned?

Co-sponsored by the Multi-Regional Clinical Trial Center at Harvard University, and the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School

LOCATION:  Wasserstein Hall, Milstein West A, Harvard Law School

1585 Massachusetts Avenue, Cambridge, MA

Speakers and registration information to be announced shortly

May 17, 2013 (8AM – 6PM)

Objectives:

  • To discuss opportunities for and implications of emerging clinical trial data disclosure standards
  • To review evidence from recent case studies in clinical trial data disclosure, especially related to disclosure of participant-level data
  • To review the rationale behind disclosure requirements of patient-level data and discuss whether the case studies demonstrate the goals have been met
  • To identify potential areas of collaboration among stakeholder groups, such as the formation of working groups to provide recommendations or standards in this area
  • To review variance in regulatory approaches and areas for possible harmonization
  • To identify other key areas of learning that may inform policy in this important area moving forward
  • To use conference findings as basis of a publication in a peer-reviewed journal that captures the case studies, provides insights into these issues and offers recommendations for moving forward

Outsourcing the Up Goering of My Job Talk Paper to Forbes: Personalized Medicine, Personalized Regulation

mmeyer 1 Comment

By Michelle Meyer

So, one thing they say about being on the law teaching market is that you likely will never before have enjoyed — and, less happily, will likely never again enjoy — so much attention to your work and so many opportunities to discuss it. That’s totally true, and it’s totally fabulous. But there’s a flip side of that that they don’t tell you: after a while, you get burned out on talking about the same paper over and over again. You’ve likely moved on to other projects and are more excited about them, even if (or because) those projects build on your job talk paper. At this point in the process, your recitation of your job talk paper may have become rote and uninspired. You may, like me, have come to dread the act of rattling off your job talk paper’s thesis and why it matters.

And so it is that, having promised some months ago to blog my job talk paper on what I call the “heterogeneity problem” in research regulation, I have yet really to do so. I’ve blogged around the edges, to be sure (see, e.g., here, here, here, and here), but I can’t bring myself to explain the central thesis one more time. I also owe book editors (holla, Glenn and Holly!) a chapter on the challenges of heterogeneity for the growing global trend in “risk-based regulation” across many industries, and I’ve been procrastinating that, too, I think, largely because it requires me first to provide the reader with a précis of the heterogeneity problem. All of this is annoying, because there are lots of things that build on that central thesis that I’d like to write about, if only I could get over this strange aversion.

Enter physician-scientist David Shaywitz, whose overly kind piece yesterday in the Pharma & Healthcare section of Forbes.com, Personalized Regulation: More Than Just Personalized Medicine — And Urgently Required, highlights my work and, essentially, Up Goers it for me. It of course doesn’t cover all of the points I make in the paper, and in other ways it extends my thesis beyond what I defend in the paper, but it gives readers the gist. Thank you, David! (Let this also serve as supplemental answers to hiring committee questions about “What does your work have to do with the law?” and “Aren’t you ‘just’ a bioethicist whose work has no relevance for health or administrative law?”)

And now, with that out of the way, in my next post I’ll feel free to apply the heterogeneity problem to this question I was asked on Twitter. I can almost guarantee you that it will be my first and last post about football.

[Cross-posted at The Faculty Lounge]

Twitter Round-Up (1/13-1/19)

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By Casey Thomson
The flu, gun control, and legal action against the FDA – all amongst our Twitter feeds this past week. Read on for more:
  • Frank Pasquale (@FrankPasquale) retweeted a link to the FDA’s current legal trouble concerning their failure to disclose antibiotic resistance data. The Government Accountability Project (GAP) is accusing the FDA of violating the freedom of information law, failing to release data on antibiotic drug usage within the meat industry in order to, as they claim, protect industry secrets. This failure takes special significance when considering that, according to GAP, “80% of all antibiotics sold in the US are utilized by the meat industry.” (1/14)
  • Michelle Meyer (@MichelleNMeyer) retweeted an article in the Health Affairs Blog concerning how to improve the Learning Healthcare System (LHS), which adapts data into knowledge that directs evidence-based practice and health system change. Specifically, the U.S. Department of Veterans Affairs is developing two approaches, namely Point-of-Care Research (“a method of performing clinical trials within the daily practicalities of the [health-care system] (with the intent of advancing these systems to LHS)”), and the Collaborative Research to Enhance and Advance Transformation and Excellence (strengthening health services research, which analyzes the factors regarding the obtainment of care). (1/14)
  • Arthur Caplan (@ArthurCaplan) reported on the American College of Physicians’ new recommendation that all healthcare providers receive the influenza vaccine for this particularly harsh flu season, in addition to other listed immunizations. (1/15)
  • Frank Pasquale (@FrankPasquale) additionally added a post on the inequality of the 2012-2013 flu outbreak – namely, the disproportionate number of lower-income individuals who are contracting the illness. The article noted the results of a study which found that while the majority of efforts for vaccinations occur in more wealthy neighborhoods, covering poorer neighborhoods with vaccine care early benefits the wealthier neighborhoods more so than if such vaccinations were delayed. (1/16)
  • Arthur Caplan (@ArthurCaplan) also shared a link to an examination into New York’s newly passed major gun control law, which addressed gun control ownership of those with mental illness. Caplan dissolved claims that the new measures were “draconian,” noting that such practices of reporting individuals that may pose concern for the safety of others have already been in practice but that these new policies make the process of reporting a legal imperative, and simpler.
  • Daniel Goldberg (@prof_goldberg) shared an article on SAGE Journals about the experience of gender within the healthcare science environment, specifically looking at the subtle practices of masculinist actions taking place that may remain unnoticed or unchallenged. The report is based on the discussed experiences of healthcare scientists with men in healthcare science laboratories. (1/16)
  • Alex Smith (@AlexSmithMD) linked to an article on an intervention for “post-hospital syndrome”, commonly known as the Acute Care for Elders (ACE) Unit. The intervention, while evidence-based and already in place in many hospital locations, may be overlooked by practitioners or healthcare authors. This unit works to reduce the effects that often derive largely from the “allostatic and psychological stress” accumulated during a hospital stay. (1/18)
  • Frank Pasquale (@FrankPasquale) posted a report on bias in reporting on breast cancer clinical trials. The study found that “nearly one-third of reports on large, randomized studies over-emphasize some benefits of therapy,” in addition to providing “insufficient attention or discussion of treatment side effects.” Considering that such reports factor prominently in how doctors decide to pursue treatment and therapy for patients, this misreporting leaves many doctors unaware of the true consequences of tested treatments – and may cause them to decide plans for treatment that they would not otherwise pursue. (1/19)

Note: As mentioned in previous posts, retweeting should not be considered as an endorsement of or agreement with the content of the original tweet.