FDA Reprimands Genentech for “Drastically Overstat[ing] the Efficacy of Tarceva”

by Jonathan J. Darrow

On October 3, 2012, the FDA’s Division of Professional Drug Promotion issued an untitled letter to Genentech in connection with its cancer drug Tarceva.  Tarceva (erlotinib) was approved in 2004 for the treatment of non-small cell lung cancer, and has since been approved, in combination with Gemzar (gemcitabine), for the treatment of pancreatic cancer. Its approval letter reported a tumor response that was 9 times greater with Tarceva than with placebo (0.9% in placebo versus 8.9% in Tarceva), but relatively modest improvements in 1-year survival rates: approximately 8 of 10 patients on placebo did not survive 1 year, while about 7 of 10 patients on Tarceva did not survive (see page 6, line 102 of the approval letter).  A 2005 New York Times article was less than enthusiastic about Tarceva’s efficacy, noting that it (along with several other cancer drugs that were new at the time) “help[s] most patients only marginally . . . .”  Despite its modest efficacy, Tarceva was reported in the same New York Times article to cost almost $31,000 per year.  A number of patents are listed in the FDA’s Orange Book as covering Tarceva until 2020.

The recent untitled letter accused Genentech’s promotional materials of misleadingly indicating that Tarceva in combination with gemcitabine extended overall survival by 3.7 months in comparison with gemcitabine alone, when the actual increase in survival was only about 12 days.  The FDA characterized the discrepancy as “drastically overstat[ing] the efficacy of Tarceva.”  (The figure of 3.7 months was derived, according to the FDA, “from a retrospective, exploratory subgroup analysis that does not provide substantial evidence to support the efficacy claims cited . . . .”). In addition, the front cover of one of the promotional materials in question contained an image of an hourglass positioned on its side, presented with the claim: “Extending survival for moments that matter.”  Although the claim with its associated image may be literally true (“moments” is left undefined), the FDA characterized the image and claim as “drastically overstat[ing] the overall survival benefit for patients” because it “strongly suggests that time is standing still for the cancer patient because of Tarceva therapy.”  The FDA noted a number of other instances of misleading overstatement of efficacy or minimization of risk.

The October 3 Tarceva letter brings to 23 the total number of Drug Marketing and Advertising Warning Letters (and untitled letters) listed by the FDA’s Office of Drug Promotion as having been sent this year.

NIH + NFL = PHLR

By Scott Burris, JD

The National Football League has given the National Institutes of Health $30 million for research on traumatic brain injury. There is much we don’t know about the causes, effects, prevention and treatment of sports-related brain injury – but that doesn’t mean that we should put all our eggs into the basket of biomedical research. Since Washington state pioneered its youth-sports brain injury prevention model-law in 2009, 40 states have passed laws setting out rules aimed at the problem (We’re tracking these on LawAtlas, the new PHLR policy surveillance portal). Most of these laws work by promoting identification of concussions, regulating the athlete’s return to play, and educating parents and coaches.

To put it another way, the nation, through a majority of its state legislatures, has embarked on a major initiative to reduce sports-related injuries. Tens of millions of people will be affected in some way – athletes, parents and coaches. Limited school-based resources will be consumed to comply with these laws. And, most importantly, people worried about the problem will, to some extent, rely on implementation of these laws to protect student athletes.

If this public health intervention were a drug or a new technique for changing behavior, its efficacy would be rigorously tested by government-funded research. Why should things be different because this possibly magic bullet happens to be based in the law? So far, the CDC has funded implementation case studies of youth sports concussion laws in Washington and Massachusetts. PHLR is funding a more in-depth study in Washington, with results expected next year.

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Using the Taxing Power for Public Health

By Scott Burris

In a Perspective in this week’s New England Journal of Medicine, Michelle Mello and Glenn Cohen, both professors at Harvard, write about the prospects for using the constitutional Taxing Power to adopt innovative laws to advance public health objectives.  Cueing off the Supreme Court’s decision in the Affordable Care Act litigation, Mello — who is also a member of PHLR’s Methods Core — and Cohen write that the Court appears to have opened the door for “more targeted, assertive interventions to promote public health” under the Taxing Power than Congress has previously pursued. “For example, instead of merely taxing tobacco sales, the federal government could require individuals to pay a tax penalty unless they declare that they haven’t used tobacco products during the year. It could give a tax credit to people who submit documentation that their bodymass index is in the normal range or has decreased during the year or to diabetic persons who document that their glycated hemoglobin levels are controlled. It could tax individuals who fail to purchase gym memberships. …These strategies depart from traditional uses of taxes by targeting omissions and noncommercial activities that are important drivers of chronic disease.”  Read the full article online at the New England Journal of Medicine online.

Early Warning on Heroin and Syringe Exchange?

By Scott Burris

It’s hard to believe that after all these years, all the evidence, and all the reductions in HIV among injection drug users, we still only have 15 states that explicitly authorize syringe exchange programs (SEPs). (See LawAtlas for an interactive map.)  CDC estimates we still have around 4,000 new cases a year by injection, so that’s reason enough to keep the SEPs we have open and start new ones where drug users are not now being reached.

Now another factor could be in play. Harm reductionists are reporting an upsurge in SEP users in places where efforts to crack down on illicit pill use have started to bite.  A lot of these users are reportedly young, under 25, and at serious risk of getting HIV or HCV.

So far we only have anecdotal reports. It could be coincidence, or overblown.  But we should be worried: there is nothing strange about pharmaceutical opioid users moving on to heroin when pills get scarce. It would be prudent as a matter of health policy to make sure that syringe access services are available in every community where opioid users are injecting, and to make sure these programs have surge capacity.  That’s prudent policy: here on planet earth we are cutting health budgets and, I fear, ignoring the effect of pill control on heroin use.

All this reminds us how important it is to be closely evaluating the consequences of new laws and policies that are intended to reduce illicit pill use.  Their success in reducing consumption is only part of the picture: the ultimate issue of concern is that we protect the health of people who are using until they can reach a safer place in their lives.

Quality Control on the Back-End via the ACA and on the Front-End via Tort Litigation

By Vickie J. Williams

I am back after a brief hiatus for the Jewish holidays. L’Shanah Tova to all my readers who have just celebrated the Jewish New Year.

The first Monday in October is, of course, a special day for all of us legal eagles–the Supreme Court is back in session. The other significant thing about October 1 for those interested in health law is that hospitals will now be fined if too many of their Medicare patients are readmitted within 30 days of discharge due to complications. As reported by the Associated Press, this is part of the Affordable Care Act’s push to incentivize quality improvement while trying to save taxpayers money. Right now, admissions for only three medical conditions are subject to the penalty: heart attacks, heart failure and pneumonia. Penalties are held to a maximum of 1% of the hospital’s Medicare payments for now, but will rise to a maximum of 3% of Medicare payments over several years. This attempt to control quality of care on the back-end constitutes a marked contrast with the way reimbursement policy has worked over the last several decades to discourage hospitals from keeping patients in beds for “social” reasons, such as having nobody to care for them at home if they are discharged. Many Medicare hospital readmissions are due to non-compliant behavior by fragile patients with few resources to help them once they leave the hospital, something that is not really subject to the hospital’s control, and says nothing about the hospital’s quality of care for the patient. For decades, Medicare payment policy, which generally pays hospitals the same amount for caring for a patient regardless of how long he or she is in the hospital, has encouraged speedy discharges. This is touted as a way to save costs. Apparently, the new policy on payments for readmission is an acknowledgement that there is both a financial and a human cost to treating medically and socially fragile people in the express lanes of health care. It remains to be seen whether the penalties result in better quality care, or significant savings, but surely they will result in increased work for hospital social workers and discharge planners. Read More

Soda Industry Sues to Block NYC Ban on Sugar-Sweetened Beverage Sales

By Rebecca Haffajee

Sure enough, last Friday the American Beverage Association and others, represented by Latham & Watkins, sued to block Mayor Bloomberg’s ban on the sale of sugar-sweetened beverages larger than 16 oz at certain NYC vendors. The suit, filed in the NY Supreme Court, asserts that the Mayor bypassed the proper legislative process for governing NYC, instead imposing the ban by executive fiat. The petition cites the many proposals considered and rejected by the NY City Council and NY State Legislature with respect to sugar-sweetened beverage (e.g., excise taxes, restrictions on the use of food stamps, warning labels, and product placement rules) as evidence that the legislature has chosen not to act to restrict sales in this sphere. The petition also claims that the scope of the Dept. of Health (DOH) action here is unprecedented, despite the fact that the DOH banned the use of trans fats in foods and required calorie postings at enumerated food service establishments.

Several specific causes of action are alleged by the soda industry, including:

  • that the New York City Charter, in it’s general language, does not delegate the necessary enumerated powers to the DOH to implement such a ban;
  • that even if authority to enact the ban has been delegated by the legislative branch to the executive branch, such delegation is unconstitutional as in violation of the separation-of-powers doctrine (i.e., the legislature cannot cede its fundamental policy-making responsibility to an administrative agency); and
  • that the ban fails to pass rational basis review given it’s arbitrary features that are unrelated to it’s stated purpose (e.g., cutoff at 16 oz size, exclusion of alcohol, and application to certain food establishments but not grocery or conveniences stores).

The plaintiffs request that the court enjoin and permanently restrain the ban.  They also want a decision by Dec. 15, 2012, so that affected businesses can avoid expending funds to comply with the law (set to take effect March 12, 2013). A response from the DOH will be forthcoming before an eagerly awaited court decision. A Cleveland Judge recently sided with the city when it sued the State of Ohio for trying to preempt its regulation of trans fats. Cleveland, the Judge ruled, was within its powers under the State constitution. But this most recent soda ban challenge applies to a different state’s legislative scheme, and a finding in favor of the plaintiffs could render Major Bloomberg’s “War on Fat” via other initiatives also susceptible to challenge.

Reporting Information about Clinical Trial Data: Passing the Torch from HHS to the FDA

By Leslie Francis

In 2007, motivated by concerns that pharmaceutical companies were not sharing negative data about what had been learned in clinical trials, Congress established enhanced reporting requirements.

A series of articles published in January 2012 in the British Medical Journal demonstrates that data reporting remains deeply problematic, especially for industry-sponsored trials. (The articles can be found here and are very much worth reading).

A posting Sept. 26 in the Federal Register indicates that the Secretary of HHS has delegated authority to to oversee the reporting process to the FDA.  Whether this signals improved monitoring of clinical trial data submissions remains to be seen.  One can only hope.

Call for Papers – Petrie-Flom Center Annual Conference: The Food and Drug Administration in the 21st Century

We are pleased to announce plans for our annual conference, this year entitled: “The Food and Drug Administration in the 21st Century.”  This one and a half day event will take place Friday and Saturday, May 3-4, 2013, at Harvard Law School in Cambridge, Massachusetts. For details on the event and the call for proposals, see the Call for Papers/Presentations. Abstracts are due no later than December 10, 2012.

Good news and bad news about gun laws, mental illness and violence — Part 2

This is Part 2 in a three-part series on gun laws, mental illness and violence in the United States. Read Part 1.

By Jeffrey Swanson, PhD

It is hard to find good news in our nation’s gun violence statistics, but here’s this: If somebody shoots you today, your chances of survival are about 83 percent — up from 78 percent just ten years ago.  The improving survival rate for gunshot victims has helped nudge the national homicide rate down by about half a percentage point since 2001. Of course, the cloud behind that silver lining is that more people are actually getting shot. The CDC recorded almost 600,000 injuries caused by assault with a firearm in the past decade, as the combined rate of fatal and nonfatal gun assault injuries rose from about 18 to about 21 per hundred thousand.

Now for the bad news: When the shooter and the victim happen to be the same person, the odds of survival and death are reversed: 8 out of 10 die. Suicide attempts with a gun almost always succeed, because they are almost always aimed at the brain at close range, and there is seldom anyone around to call 911.

For those who “get lucky,” surviving a gunshot to the head can be a pyrrhic victory.  We all cheered Gabrielle Giffords’ courageous walk across the stage at the Democratic National Convention, but let’s face it: Her physical appearance was as much a reminder of what she has lost as it was a testimony to the miracles that timely neurosurgery can perform. Most survivors of gunshot injuries — whether self- or other-inflicted — don’t look like much like Gabby Giffords and they tend to have fewer supportive friends. They are often disadvantaged young people who struggle to recover in places where hope runs thin. Could better gun laws, better enforced, prevent their plight?  Perhaps they could, but only as a small piece of complex sociological puzzle.

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Would you rather medical school train your PCP to have good hands or a good bedside manner?

Last week NPR covered a story highlighting how medical education is morphing in order to adapt to the unmet demand for primary care physicians driven (at least in part) by the increased access to primary care that will be ushered in under the ACA.  It may be surprising to some to learn that many of the most prestigious medical schools like Johns Hopkins and Harvard do not have a primary care program; however, as reported by NPR, medical schools may soon rethink this hole in their curriculum in the face of changing demands upon the health care system and its accompanying incentives for young physicians to enter primary care.   Mount Sinai School of Medicine is leading the way in this regard by launching a new department of family medicine in June.

Intuitively, changing the medical education system to produce more primary care physicians will further goals of the ACA by increasing access to primary care, and therefore improving overall public health and diminishing cost by decreasing emergency room care for conditions that could have been treated less expensively or avoided altogether by increasing access to preventative services.  These are the arguments we’ve heard repeatedly by the champions of the ACA and by the Obama administration, particularly through its vision for the Prevention and Public Health Fund which was intended to bolster the pipeline of primary care physicians before being gutted earlier this year.

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