What makes Bob Temple so endearing (and his opinions so enduring) is his blunt truth telling. Alas, he is often the Cassandra of White Oak.
Recently Temple stated his belief that regulations on product promotion should not impede companies from rebutting findings from comparative effectiveness research involving their products.
This may not sound like a big deal – but it’s a clarion call for those who understand the imperative to systematically and scientifically counter the counter-detailing efforts coming thanks to the tens of millions of tax dollars earmarked for such efforts by the Patient Protection and Affordable Care Act (PPACA).
According to the Pink Sheet, “The subject of asymmetry in the reporting and commenting on CER findings has been a key point of discussion for NPC as CER has taken on a more visible role within the health care debate. Some suggest manufacturers of products subject to CER might have difficulty discussing the findings of the research given FDA restraints on commercial speech.”
Speaking at the February 9th conference, Asymmetry in the Ability to Communicate CER Findings: Ethics and Issues for Informed Decision Making (hosted by the National Pharmaceutical Council and cosponsored by the National Health Council and WellPoint), Temple said there is “no FDA view … that drug companies are condemned to silence about their products outside of formal promotion or perhaps published articles. If there’s something published that seems wrong, is based on poorly designed meta-analysis and so on, I don’t see any impediment to answer that and companies do answer that all the time."
Indeed, Bob seemed surprised and displeased that industry has sat by while the grand poobahs of comparative effectiveness share their questionable conclusions.
According to Dr. Temple, “A recent example might be newspaper assertions that antidepressants have no long-term benefit and really don’t work. This has been published repeatedly, and I’d like to see a rebuttal from the people who make antidepressants, because I think the published reports … are wrong. [FDA] may get around to rebutting, but somebody else might want to, and I don’t think there is any impediment to doing that."
Pedal to the metal? Not so fast. Bob qualified his remarks by saying (appropriately) that companies should be mindful of how FDA regulates speech when (and if) they decide to rebut wrong or misleading information from a comparative effectiveness research (whether or not it’s government-funded). “It is clear to me that a sponsor could correct or dispute a CER statement by a payer, or even the government, as long as the correction was not itself promotional."
And there’s the rub. Just what does “promotional” mean – and who is to judge?
Temple gives a good example of how to avoid such a problem:
“In recent months, we’ve seen companies disagree publically with meta-analyses, with epidemiologic conclusions they considered unsupported on methodologic grounds, and that’s OK, although making their own [conclusions] probably would not be."
In other words, it’s not “promotional” to point out a comparative effectiveness study’s design flaws and, therefore, the errors of its conclusions. If such an approach is “compliant,” it opens up tremendous opportunity in countering so-called “academic” detailing.
Or does it? Temple’s is a powerful voice inside the FDA – but it is only one voice. If Secretary Sebelius’ interference in the agency’s Plan B decision is any indication – might not his view be similarly overturned by the mandarins in the Humphrey Building? After all, the comparative effectiveness studies under debate are funded by PPACA and fielded by the Agency for Healthcare Research and Quality (AHRQ). And, to put it bluntly, the current administration has not looked kindly on those who question either its philosophical motives or legislative methods. Industry is deemed guilty until proven guilty. The current modus operandi seems to follow Franz Kafka’s statement that, “My guiding principle is this: Guilt is never to be doubted.”
Which brings us back to the question, what does promotional mean?
A recent paper by Coleen Klasmeier (a former FDA attorney and currently the head of Sidley Austin’s FDA regulatory practice), addresses this issue head on. She points out that “The FDA approach is one of delicate balance – of forbidding off-label promotion without undue incursion into the ability of physicians to obtain information about off-label uses from manufacturers.”
This issue of “undue incursion” seems to dovetail nicely with Bob Temple’s notion of focusing on design flaws and incorrect conclusions. But what of intent?
Well – intent is in the eyes of the beholder. Where one person might see a robust discussion of study design, another might see promotional intent. The foundational problem, as Klasmeier eloquently points out, is the FDA’s reliance on “multifactorial tests rather than bright-line standards.”
Plainly stated, regulators at the FDA (and particularly those who must address thorny First Amendment issues) embrace ambiguity over predictability. It gives them almost limitless power. Industry, on the other hand, wants and needs an evidence-based regulatory framework that provides predictable standards for their communications efforts. Bright lines. Predictability is power in pursuit of the public health. Minus such an effort, we get the troubling example of Par Pharmaceuticals.
In a pending First Amendment suit against the FDA, Par contends the government is criminalizing it’s speech to healthcare professionals about the on-label use of its appetite suppressant Megace ES (megestrol acetate) in settings where doctors prescribe the drug for both approved and unapproved uses.
Par’s complaint, filed Oct. 14 in the U.S. District Court for the District of Columbia, seeks a preliminary injunction against government enforcement of FDA labeling regulations on the grounds they are harming Par’s First Amendment rights by chilling protected speech.
Par’s suit states that physicians more frequently prescribe the drug to treat wasting in non-AIDS geriatric and cancer patients and that the majority of prescriptions for the drug are for off-label uses.
Par also seeks a declaratory judgment that it may speak about the approved use to physicians who could prescribe it for that use, even if they are more likely to prescribe the drug for off-label uses.
“Common sense dictates that the government cannot justify censoring a broad swath of truthful and valuable speech regarding lawful activity out of a desire to prevent other lawful activity,” a memorandum in support of the motion for preliminary injunction states. “And it is absurd to think that the government may imprison a person for engaging in truthful speech about a lawful activity that the government itself subsidizes.”
At issue in Par’s suit are provisions in the Food, Drug, and Cosmetic Act concerning “intended use” of a drug and misbranding.
“If a manufacturer speaks about the on-label use of its drug in a setting where the manufacturer knows that physicians prescribe the drug off-label, the government interprets the FDA’s ‘intended use’ regulations to deem the manufacture to be expressing an ‘objective intent’ that physicians prescribe the drug off-label,” Par’s memorandum states.
In a press release announcing the suit Par said it hoped to “elicit tailored and constitutionally permissible regulatory guidance to ensure that physicians may be kept abreast of valuable, on-label information about prescription drugs to aid in their provision of quality and informed patient care.”
Atlas was permitted the opinion that he was at liberty, if he wished, to drop the Earth and creep away; but this opinion was all that he was permitted. – Franz Kafka
If a company can be challenged when it discusses strictly on-label uses of a product, how much more convoluted, challenging and intimidating will it be to challenge a government-funded and government-detailed comparative effectiveness study?
Disputing comparative effectiveness studies – or any research for that matter -- need not fall into the chasm of promotion (off-label or otherwise). To lump scientific discourse into this slippery silo is to court both agency action and political attention. Alas, as Klasmeier writes, “The off-label problem reflects the accretion of administrative interpretations over the years.”
“Accretion” – otherwise known as mission creep.
Klasmeier continues, “… the commercialization of an investigational new drug is not to be construed to interfere with a manufacturer’s entitlement to engage in scientific exchange.”
And isn’t debating the flaws of a research study scientific exchange -- even if (and especially when) such exchanges raise questions about conclusions that are contrary to any given company’s marketing and sales objectives? How does the issue of intent play into compliance when legitimate scientific exchanges also impact promotional considerations?
On which side should regulators err?
The answer is as easy as it is difficult – regulators should err on the side of the public health. And perhaps the best precedent is FDAMA Section 401, which expressly permits companies to provide reprints of peer-reviewed medical journal articles on off-label studies (as long as they have a pending supplemental application with the agency).
But – as a word to the wise – let’s remember the astute observation of William Blake that, “A truth that’s told with bad intent, beats all the lies you can invent.”