FDA Drug Amendments: Still a good fit at fifty?

Fifty years ago on Wednesday, President Kennedy signed into law the US Food and Drug Amendments. The amendments radically overhauled the way in which manufacturers brought drugs to market. Most importantly, the amendments instituted the four-phase review process and the requirement that manufacturers get informed consent from people receiving experimental drugs. If the past fifty years is any indication, though, its unlikely that FDA’s current regulations are well suited to deal with the changing context of medicine, including clinical trials of stem-cell therapies forecasted with the Nobel Prize Committee’s awarding of their prize in Physiology or Medicine earlier this week.

The amendments’ supporters had good intentions and the regulations have had positive effects overall. Yet the US government is still trying to redress many of their negative consequences. The rules have proven to be outmoded for new circumstances that policymakers did not have in mind when they created the amendments five decades ago.

The four-phase review process requires that manufacturers apply to the FDA and submit drugs for agency review three times—at least. One consequence of the four-phase review system is that it extended the time until consumers could access new therapies. This can seem a small price to pay to assure that drugs are safe and effective, a phrase that has become the slogan for the Amendments. People with new, fast-moving diseases, however, have seen the delay as a death sentence. For example, sociologist Steven Epstein has written extensively and carefully about the response to drug delays in the 1980s and 1990s among the HIV/AIDS activist community. The FDA has responded with changes, such as a fast-track approval system, but these shifts tend to come only in response to dire crises.

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FDA’s New Dance with Big Pharma: Are Patients the Band?

Efthimios Parasidis

One week prior to the Supreme Court’s landmark ruling in the health care cases, Democrats and Republicans overwhelmingly voted in favor of health-related legislation (387-5 House; 96-1 Senate).  Industry and HHS were quick to congratulate our elected officials on a triumphant bipartisan achievement, while the FDA enthusiastically welcomed its latest collaboration with Big Pharma.  Lobby groups boasted of their ability to “craft” legislation with FDA and praised the “unprecedented level of public input” into the new law.

We should all be concerned.

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NEJM: Cutting Family Planning in Texas (and more)

Our friends over at the New England Journal of Medicine just alerted us to a new perspectives piece addressing the impact of cutting family planning funds in Texas (the piece was also picked up by Politico).  The authors interviewed 56 leaders of organizations throughout the state that provided reproductive health services using public funding before cuts went into effect, and what they found was disturbing:

  • Most clinics have restricted access to the most effective contraceptive methods because of their higher up-front costs (choosing pills over IUDs or subdermal implants).
  • Clinics have started to turn away those who canot pay, when previously their visits would have been covered by public funds, and women who can pay the newly instated fees are choosing less effective methods and fewer tests to save money.
  • A number of clinics have lost their exemption from Texas’ law requiring parental consent for teens under 18 who seek contraceptives.

Overall, the authors conclude that laws intended to defund Planned Parenthood in an attempt to limit access to abortion (even though federal and state funding cannot be used for abortion anyway) have resulted in policies limiting women’s access to range of preventative reproductive health services and screenings.

Alta Charo weighs in via a NEJM podcast, discussing the future of reproductive health care for women in the US, particularly in light of upcoming elections (as well as the article we discussed last week on conscientious action, and other general issues in reproductive health policy).  Take a listen!

And one more NEJM plug for now: our Bill of Health blogger Kevin Outterson also has a podcast online discussing the record-breaking settlements of pharmaceutical fraud cases and the need for further regulation.

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.