When Do Doctors Discount Clinical Trial Results?

by Jonathan J. Darrow

A research study reported today in the New England Journal of Medicine found that physicians are able to discriminate between clinical trials with high levels of rigor versus those with low levels of rigor, as well as between clinical trials that are funded by industry and those that are funded by the government.

The randomized study analyzed the responses of 269 physicians who were presented with hypothetical abstracts of clinical trial findings for three hypothetical drugs.  Abstracts were deliberately crafted to reflect three levels of clinical trial rigor (low, medium, and high), and three types of funding disclosure (no disclosure, National Institutes of Health funding, and pharmaceutical industry funding), yielding 27 abstract types.

The major finding of the study was that physicians are less willing “to believe and act on trial findings, independent of the trial’s quality,” if the trial is funded by industry.  That industry funding led to a decrease in perceived credibility, even for large and well-designed trials, concerned the study authors, who felt that “[t]he methodologic rigor of a trial, not its funding disclosure, should be a primary determinant of its credibility.”

The full article citation is: Aaron S. Kesselheim et al., A Randomized Study of How Physicians Interpret Research Funding Disclosures, 367(12) New Eng. J. Med. 1119 (Sept. 20, 2012). Available here.

[Editorial Note: And within the et al. is Chris Robertson, a former Petrie-Flom Academic Fellow, current prof at University of Arizona, and future guest blogger here at Bill of Health!]

Intellectual Property in Investment Agreements: More “Teeth” for Foreign Investors’ IP Rights, Less for Access to Medicines

By Adriana Benedict

Last week, Public Citizen published a Health GAP analysis entitled “Leaked TPP Investment Chapter Presents a Grave Threat to Access to Medicines,” in which Professor Brook Baker explains four ways in which access to medicines is compromised by the USTR’s leaked investment chapter proposal for the Trans-Pacific Partnership Agreement.  The problematic provisions he identifies — inclusion of intellectual property (IP) in the definition of “investment”, ambiguous scope of minimum standards of treatment, inadequate exceptions and limitations for public interest measures, and performance requirement limitations preventing development of local and sustainable production—are not new, but have been included either implicitly or explicitly in countless bilateral investment treaties (BITs) (including the U.S. Model BIT) and the investment chapters of free trade agreements (FTAs) (including virtually all US FTAs and the proposed EU-India FTA).  Such inclusion gives more “teeth” to foreign investors’ IP rights, but what of access to medicines?

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Is FDA’s 2013 Budget At Risk?

By Patrick O’Leary

Back in February, President Obama’s FY 2013 budget authorized $4.5 billion for the Food and Drug Administration (FDA), about $2 billion of which was to come from user fees, the fees paid by regulated industry under a variety of schemes including the Prescription Drug User Fee Act (PDUFA), the Medical Device User Fee Act (MDUFA) and newly-created programs for generic drugs and biosimilars. As of today, FDA’s ability to collect and use these fees is in question, endangering vital agency activities including drug and device premarket review.

The threat to FDA user fees crystallized on September 14, when the Office of Management and Budget released its Report Pursuant to the Sequestration Transparency Act of 2012, explaining what may happen if Congress fails to reach an accord on the federal budget as required by the Budget Control Act of 2011 (BCA). Such a failure would trigger sequestration resulting in an 8.2% reduction in non-exempt, non-defense discretionary funding. On pages 79-80, the report indicates that $3.873 billion of FDA’s budget for 2013 is considered eligible for sequestration. According to analysis by the Alliance For a Stronger FDA, this indicates that major user fee programs have been included as sequestration-eligible funds. According to the OMB report, the FDA budget would be reduced under sequestration by around $318 million.

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Tobacco Labeling and the Ethics of Persuasion

by Nadia N. Sawicki

The D.C. Circuit’s recent decision vacating the FDA’s graphic labeling requirements has prompted a flood of valuable commentary about compelled speech doctrine, including Richard Epstein’s, below.  While analysis of the First Amendment issues is important, I view the R.J. Reynolds case instead as an example of how emphasis on formal legal arguments may detract attention from the underlying source of public opposition.

My current research focuses on the state’s use of emotionally-gripping graphic imagery in medical and public health contexts. I focus on two examples – the “fear appeal,” exemplified by the FDA’s graphic tobacco labeling requirements; and appeals to positive emotions, such as maternal bonding, exemplified by state laws requiring that women view ultrasound images and hear the heartbeat of their own fetus before consenting to an abortion.

Both types of appeals to emotion have faced constitutional challenges – as violations of First Amendment compelled speech doctrine, or imposition of undue burdens on reproductive liberty interests.   But these formalistic constitutional tests do not, in my opinion, get at the heart of the public’s concern about government persuasion using emotional imagery.  Few contemporary commentators are willing to challenge requirements for scientifically valid textual warnings. Rather, it is the use of images – diseased lungs, cadavers, fetal heartbeats – that strikes a chord of concern among many critics.  Whether designed to inspire fear, love, or disgust, the government’s use of these images to persuade seems to run counter to the principles of democratic discourse.

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New Product Liability Regime for Stem Cell Products?

By Hyeongsu Park

In May 2012, Health Canada granted market authorization for Prochymal. This decision is the world’s first regulatory approval of a stem cell drug (as well as the first therapy for acute graft-vs-host disease, a serious complication of bone marrow transplantation that kills up to 80% of children affected). Like Prochymal, many stem cell products have exciting therapeutic potential, such as bone regeneration and cartilage formation. And the global stem cell product market is estimated to reach $6.6 billion by 2016. However, side-effects remain unknown, and the regulations for such products are largely non-existent. So what should happen if a patient gets hurt?

Stephen R. Munzer (UCLA School of Law) discusses this question in his latest article in the Boston University Journal of Science and Technology Law, and recommends that qualified strict liability should govern product liability for stem cell products. Read More

FDA Law: More Statutes Than Regulations?

By Katie Booth

The FDA Law Blog has just published a semi-serious study by Kurt Karst on the growth of Title 21 of the United States Code (“USC”) compared to Title 21 of the Code of Federal Regulations (“CFR”) over the past twelve years. Title 21 governs food and drug law. Karst used the PDFs of the USC and CFR available on the Government Printing Office website to compare the number of pages in the USC and CFR from year-to-year. A graph of his results is available on Karst’s post, “The Obesity Epidemic: FDA’s Growing Waistline!

Unsurprisingly, Title 21 of both the USC and the CFR grew in length between 1999 and 2011. More interestingly, however, the USC grew by 50% while the CFR grew by only 10%. If the purpose of regulations is to interpret and flesh out statutes, common sense would suggest that food and drug regulations would grow at a greater rate than food and drug laws (or at least at the same rate). Karst’s explanation for his findings is that the “FDA has been issuing far fewer regulations, and instead, has been implementing the law through guidance and other policy documents.”

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Generic Drugs: Grabbing a Bigger Slice

by Jonathan J. Darrow

The expiration of the patent on $11-billion-per-year Lipitor® (atorvastatin calcium) last November received wide media attention and was eagerly greeted by consumers, reflecting public excitement that seems to have not yet dissipated.  In the following months, prices “plunged from about $175 a month for Lipitor to about $15 for generics,” according to a recent article in the New York Times. At times it felt as if legions of consumer Davids had triumphed over a corporate Goliath.

Although the public’s euphoria over the availability of cheaper generic versions of drugs is an understandable cause for celebration, price decreases in themselves should not be mistaken for net gains to society.  The societal gains represented by new drugs, to the extent there are any gains at all, come from the new therapeutic benefits that those drugs offer to patients. The entrance of generic competition, on the other hand, merely represents a shift of wealth from one unit of society (originator manufacturers) to another (patients, and also generic drug companies and insurers).

While individual consumers may care little about “net gains to society,” policy-makers should care: If there are no net gains to society from the high prices preceding patent expiration, then perhaps the patent system should be abolished entirely.  That option, however, has not been a serious topic of discussion in the United States since the 1870s. Instead of debating the underlying issues, however, the public’s attention is focused on what is easiest to see: When can I pay less?  One has to wonder, however, what the innovative landscape would look like if more attention were paid to baking a bigger pie, rather than celebrating the newfound ability to grab a bigger slice.

Making Sense of Tobacco Regulation: The First and Fifth Amendment Challenges

[posted on behalf of Richard Epstein]

The entire question of the FDA’s tobacco regulation is likely to spur extended commentary, given the split of opinions between the D.C. Circuit, which knocked out the packaging labels by a divided vote in RJ Reynolds v. FDA, and the earlier decision in the Sixth Circuit, that sustained the regulation.  The packaging regulations have to be resolved once and for all on a national level, so the case will go up even, I think, if the D.C. Circuit decides to follow the Sixth Circuit in an en bank opinion.  So what then should be done?

The issue is one that I have approached before.  In the interests of full disclosure, I am a fierce opponent of smoking, who worked in from the mid-1980s into the early 1990s as a consultant for the tobacco lawyers on tort liability issues.  After that time, I worked on a number of other issues, in some instances taking positions adverse to the industry.  This particular post is done solely and wholly on my own.

In thinking about this case, much of the doctrinal dispute revolved around the much mooted  Central Hudson test used in too many First Amendment Cases.

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