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.

Art Caplan on Grace Lee

Unfortunately, these stories are like deja vu.  In his most recent MSNBC commentary, Art Caplan emphasizes that we all have the right to refuse medical care, even if others disagree and even if it means death.  Here’s his take:

Opinion: Daughter has right to die against parents’ wishes

When your time comes to die, you probably hope that you will be surrounded by loving family members and friends who will support you and help you leave this earth at peace with one another. Sadly, for 28 year-old SungEun Grace Lee, who is dying in a Long Island hospital, that is not happening.

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Upcoming Event: Harvard Med School Public Forum

PRESCRIBING MEDICATION TO END LIFE

THURSDAY, OCTOBER 25, 2012 4:00 – 6:00 PM

Harvard Medical School Carl W. Walter Amphitheater Tosteson Medical Education Center 260 Longwood Avenue, Boston

Should a physician licensed in Massachusetts–at the request of a capable, terminally ill, adult patient (meeting certain conditions)–be allowed to prescribe medication that could end that person’s life?  The answers to this ballot question are just two: yes or no. The questions, though, are countless.

PANELISTS

Lachlan Forrow, MD, Chair, Massachusetts Expert Panel on End of Life Care

Carol Powers, JD, President, Community Voices in Medical Ethics, Inc.

Ellen Weinstein, JD, Assistant General Counsel, Boston Medical Center

Marcia Angell, MD, Signer, Initiative Petition for MA Death With Dignity Act

MODERATORS

Robert Truog, MD, Professor of Medical Ethics, Anesthesiology, & Pediatrics, HMS

Christine Mitchell, RN, Associate Director, Clinical Ethics, Harvard Medical School

Sponsored by the HMS Division of Medical Ethics

Rationing, Irrelevant Utilities, and Inter vs. Intrapersonal distribution

This blog post was prompted by discussions with Frances Kamm, Jonathan Wolff,  and others after a great presentation Jonathan gave on the Valuation of Life and Health in Government Policies.

To return to an issue I have discussed briefly in other work, the question is how we should count very small gains in health for large numbers of people, a sub-set of the aggregation problem.  As I put the problem in a footnote in my Article Beyond Best Interests, 96 Minn. L. Rev. 1187 (2012):

Utilitarians typically aggregate small harms to many people and count the sum. See, e.g., John Rawls, A Theory of Justice 23-24 (1971) (discussing the societal balance of present and future gains against present and future losses). The deontologist Frances Kamm has instead suggested that not all harms and benefits are equal, under what she calls the “Principle of Irrelevant Utility”: Suppose two almost identical individuals A and B are mortally ill and we have only enough serum to save one, but because of tiny differences in how much serum they need if we save A there will be enough serum left over to also cure person C’s sore throat, but if we save B there will not be. Kamm argues that it would be unjust in this circumstance to allocate the serum to A rather than B on this basis as opposed to holding a straight lottery between the two. If the sore throat is not enough to justify giving A preference over B when everything is equal, says Kamm, it is an “irrelevant utility” such that even if we could save not only C’s sore throat but a million such sore throats, for example, it would not matter; the utility bonus is irrelevant and therefore even aggregated in large quantities cannot count. Quite different, she claims, would be a case where in fact the serum enables us to save C’s leg, which would be a relevant utility. See F.M. Kamm, Morality, Mortality: Death and Whom to Save from It 144-63 (1993); Frances M. Kamm, To Whom?, 24 Hasting Ctr. Rep. 29, 31-32 (1994).

On the other hand, this principle may have counter-intuitive implications. To use an example suggested by John Broome, the National Health Service (the U.K.’s universal health care system) gives out millions of analgesics for headaches; at some level, due to health care rationing and fixed budgets, that means that someone’s life will not be saved.  John Broome, All Goods are Relevant, in WHO, Summary Measures of Population Health: Concepts, Ethics, Measurement and Applications 727, 727-28 (Christopher J.L. Murray et al. eds., 2002).

What came up over dinner, and I thought was particularly interesting, was the following question:

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Symposium: Freedom of Choice at the End of Life, Nov. 16

By Nadia N. Sawicki

New York Law School’s Justice Action Center is hosting a symposium on elder law on Friday, November 16, titled “Freedom of Choice at the End of Life: Patients’ Rights in a Shifting Legal and Political Landscape.”   A number of Bill of Health bloggers (myself included) will be speaking at this event, which will address topics including legal and practical impediments to honoring end-of-life wishes, the practicalities of drafting and using advance planning tools, pain management and palliative care, futility, and ethical dilemmas in end-of-life care.  You can register here.

Conscientious Actions and Refusals

Great new Perspectives piece by Lisa Harris out in NEJM on the need to recognize that conscience can compel action, not only refusals to provide certain types of care (including abortion).  Elizabeth Sepper makes a similar argument in her forthcoming article in the Virginia Law Review.

First,  let me just say that I couldn’t agree more – it is essential to recognize both sides of the coin.  As I’ve argued elsewhere, both ought to be respected and protected, to a point, but the issues raised by conscientious refusal versus conscientious action are distinct in some important ways.  The primary problem with refusals is that they can burden patients by creating barriers to care, if not managed appropriately.  On the other hand, conscientious action would make care available to patients – and what could be wrong with that?

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Art Caplan in The Lancet: Death by Refusal to be Turned

Our blogger Art Caplan has a fascinating new piece in The Lancet today about an elderly patient who refused to be turned in his hospital bed and died from the ensuing bed sores/infection.  Art’s conclusions emphasize both patient autonomy and preserving the ability of health care professionals to provide care in humane and safe conditions.  In the meantime, he asks a number of important questions about this patient’s decision:

Could Harold or any other patient deny care considered basic and standard? If he asked not to be turned could he also demand that the heat be turned off in his room? Could he refuse to let anyone touch him at all? Could a patient demand no elevation of his bed? No taking of vital signs? And without a clear policy about a request not to turn, were the hospital staff exposing themselves to a good deal of bureaucratic and regulatory grief when Harold died?

 and

Harold seems to have been well within his legal rights to refuse turning. But would a hospital or a nursing home be within their rights to refuse him admission if what he wants is well outside the standard of care? Should all health-care institutions have a policy on turning? Although such requests are rare, the turmoil they cause is enormous. Should “not turning” be offered as an option in circumstances akin to those governing the ending of dialysis, ventilator support, resuscitation, and chemotherapy? Should turning be a topic of discussion as part of writing an advanced directive? If so, what support ought to be given to health-care providers involved in a case where a competent patient insists on not being turned?

What do you think?