How 21st Century Cures could change communications between biopharma, providers, & patients
It’s never a good thing to receive a fax from the FDA’s Office of Prescription Drug Promotion (OPDP), formerly known as DDMAC (Division of Drug Marketing, Advertising and Communication). But it’s something that happens to almost every drug manufacturer at least once.
In November 2010, Celgene received a letter from the OPDP via fax, explaining that a white paper that Celgene distributed during an American Society of Clinical Oncology (ASCO) meeting about a month earlier was in violation of specific FDA promotional regulations. Apparently an OPDP representative had approached Celgene’s exhibit booth during ASCO and picked up a copy of the paper.
There were several violations, according to OPDP, but one that stood out, according to the FDA reviewers, was that the paper “broadened the indication” for Abraxane (paclitaxel), which at that time was indicated for the secondary treatment of metastatic breast cancer (MBC).
Broadening the indication
So how did Celgene broaden the indication? The paper cited a phase II, randomized study in which first-line treatment of women with MBC increased progression-free survival. The paper also cited data from well-designed trials highlighting the use of Abraxane for treatment of other types of cancer (e.g., non-small cell lung cancer or NSCLC) for which Abraxane was still under investigation.
The problem was not that the statements in the paper weren’t true based on solid, evidence-based data, but rather that they mentioned uses of Abraxane that were considered off-label.
In addition, Celgene violated a key FDA regulation: “Promotion of an investigational new drug is prohibited under FDA regulations at 21 CFR 312.7(a), which states that, “A sponsor or investigator, or any person acting on behalf of a sponsor or investigator, shall not represent in a promotional context that an investigational new drug is safe or effective for the purposes for which it is under investigation or otherwise promote the drug.”
The ramifications for Celgene, as well as their medical communications agency, were not pleasant. But regulators had caught them in the act of distributing off-label information in a promotional context at a medical meeting where physicians who make treatment decisions had access to their messaging.
Since then, Abraxane has been approved for treatment of advanced NSCLC; however, Celgene reps were not able to communicate that information to patients at the time, because it was not yet part of the approved label.
The 21st Century Cures Act and off-label promotion
Many would argue that suppressing Celgene’s ability to communicate evidence-based information about Abraxane may have cost some patients their lives. In fact, that argument has become a crucial part of the sweeping new healthcare bill making its way through Congress right now—the 21st Century Cures Act.
This ambitious proposed legislation is a 400-plus page document with a lot of working parts, but the overall goal, according to the House Energy and Commerce Committee, chaired by Reps. Fred Upton (R-MI) and Diana DeGette (D-CO), is to “accelerate the discovery, development and delivery of life saving and life improving therapies and transform the quest for faster cures.”
There are two provisions in the 21st Century Cures Act that deal with expanding drug makers’ ability to communicate with greater latitude: Section 2101 covers “Facilitating Dissemination of Healthcare Economic Information, and Section 2102 covers “Facilitating Responsible Communication of Scientific and Medical Developments.”
Our focus in this piece is on Section 2102, and what supporters hope to gain if this provision is approved as part of the final bill (assuming that the bill does, indeed, pass).
Just how potentially groundbreaking are these provisions? Sung Hee Choe, Director at Avalere Health, a Washington, D.C.-based healthcare advisory company, says, “They represent a loosening of restrictions that should give drug makers more leeway, but the language is fairly modest. Some think that lawmakers could have gone further.”
The Medical Information Working Group
Even before the committee introduced 21st Century Cures in April 2014, the Medical Information Working Group (MIWG) had petitioned the FDA several times to take actions to clarify its regulations and policies with respect to off-label promotion. MIWG is an informal coalition of drug companies focused on “issues related to the federal government’s regulation of truthful, non-misleading, scientifically substantiated manufacturer communications about new, or off-label, uses of approved drugs and approved/cleared medical devices.”
Since 2008, the MIWG, which includes Allergan, Bayer Healthcare, Boehringer Ingelheim, Eli Lilly, Genentech, GSK, Johnson & Johnson, Novartis, Novo Nordisk, Pfizer, Purdue, and Sanofi, has been prodding the FDA to clarify and reconsider its policies around various types of communication—first by submitting comments to the FDA on draft guidance regarding distribution of scientific and medical journal articles and reference texts, and later through two Citizen’s Petitions, once in 2011 and again in 2013.
According to Choe, “It was the actions of the MIWG that really put this issue at the forefront, and now there is a groundswell of activity around evidence communications.”
However, there was also another event that accelerated demand for broader communications regulations. On December 3, 2012, the Second Circuit issued a decision in United States v. Caronia, which upheld the First Amendment rights of a former sales rep for Orphan Medical. When accused of off-label detailing, Alfred Caronia mounted a defense based on the principle of free speech and his right to communicate relevant and truthful data.
And eventually, he won.
The threshold for truth
FDA approval is based on data from two, placebo-controlled, randomized studies that are deemed well designed by the agency; however, many consider that threshold too restrictive. A source who works closely with the MIWG but requested anonymity told BioPharma Dive, “We are not of the view that truthful speech is related only to data from placebo-controlled, randomized clinical trials. “
MIWG is of the view that there is a range of scientific information that should qualify as “truthful,” including meta-analyses, retrospective studies and pharmacoeconomic data. While the source concedes that the MIWG “has not yet tried to define the outer limits of truthfulness,” the group strongly believes that suppression of relevant, truthful, "off-label" information is ultimately harmful to patients. At the same time, they also are emphatic that before communicating off-label information, whoever is sharing the content must fully disclose that the content is off-label.
So what happens if off-label information becomes allowable in promotional settings? That’s difficult to say at this point, but there are a lot of people who are watching closely, including those who collaborate with drug makers to create medical communications materials.
The agency perspective
Eric Malter, Founding Partner and CEO of MDC, a programmatic healthcare advertising and communications agency in New York City, has been in medical communications for 40 years. And he knows what it’s like to receive a DDMAC letter.
According to Malter, “Assuming that healthcare communicators strictly adhere to the “truthful” and fully disclosed provisions of the 21st Century Cures Act, it is my opinion that this legislation can only enhance our ability to communicate and ultimately be of benefit to healthcare providers and patients alike.”
But can providing off-label messages really change physicians’ approach to decision-making? Malter thinks so. "In the words of a famous former clothing retailer, an educated consumer is our best customer," he said. "In this case, a well-educated healthcare provider is our best opportunity to ensure that the full potential of certain drug entities is realized, at the discretion of a provider armed with the maximum amount of knowledge."
- United States Congress The 21st Century Cures Act