Drug, Device Industries Seek Fewer Limits on Off-Label Communications

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By Bronwyn Mixter

The drug and medical device industries want the FDA to allow them to give more information to payers and health-care professionals about off-label, or unapproved, uses of their products to help them make decisions.

In comments to the Food and Drug Administration, industry groups said payers and health-care professionals want more information about the safety, effectiveness and value of treatments and while the labeling provides important treatment information, it doesn’t provide information that is learned about treatments over time. But consumer groups told the agency they are against loosening the FDA’s restrictions on off-label communications because doing so would put patients at risk. The industries were responding to a memorandum the FDA released in January laying out the issues. Comments were due April 19 (Docket No. FDA-2016-N-1149).

The drug and device industries have been pushing the FDA to clarify its policy on medical product communications for a long time. Under long-standing policy at the FDA, companies can be subject to criminal prosecution and civil liability if they promote their products for uses the FDA hasn’t specifically approved. Industry has criticized the policy as unduly restrictive and claims it infringes manufacturers’ free speech rights. President Donald Trump’s nominee to head the FDA, Scott Gottlieb, has indicated he would consider relaxing the restrictions on off-label communications.

Patients Should Come First

“We are all here to serve the patient, and to do what is in the patient’s best interest. So if there is a difference of view between industry and patient groups, those differences really need to be worked out keeping the patient at the center of the discussion,” Bradley Merrill Thompson, a Washington-based health-care attorney with Epstein Becker & Green PC, told Bloomberg BNA in a May 1 email. Thompson also is a Bloomberg BNA advisory board member.

Thompson said he “would encourage the industry groups and patient groups to get together and talk about this, and sort it through to determine exactly what the core difference is. If there is an approach that would best serve patients, that approach should win out.”

“That said, not every patient group truly represents all patients. And indeed, sometimes differences of opinion are not really based on intellectual differences regarding facts, but a lack of trust,” Thompson said. “If the issue is trust, then industry needs to work to figure out how to build up that trust.”

Deborah M. Shelton, a partner in the FDA Practice Group of McCarter & English in Washington, also told Bloomberg BNA in an email “the advocacy around product communications is far more nuanced than approved v. unapproved uses.” She said there are really three categories of information that aren’t found in FDA-approved labeling:

  •  communications with payers, including information about a pipeline product (unapproved product or unapproved use of an approved product);
  •  communications with health-care professionals about information on an approved use that isn’t explicitly included in the FDA-approved labeling; and
  •  communications with health-care professionals about an unapproved use.

“While from a purely First Amendment perspective, the three buckets are on more of equal footing, from the standpoint of implementation and associated policy there seems to be a general recognition among all stakeholders of the need to more immediately prioritize the first two categories in order to create the certainty that has been sought for many years,” Shelton said. “The third category—communications with health-care professionals about an unapproved medically accepted alternative use—is important, but many seem to recognize that it may take longer to implement.” Shelton also is a Bloomberg BNA advisory board member.

FDA Commissioner Nominee’s Views

Scott Gottlieb, the nominee for FDA commissioner, seems to support the idea of loosening off-label communications restrictions.

On April 27, the Senate Health, Education, Labor and Pensions Committee approved Gottlieb’s nomination. His nomination now goes to the full Senate for consideration.

Prior to the committee’s vote, Sen. Elizabeth Warren (D-Mass.) asked Gottlieb in her questions for the record whether medical product companies should be given greater latitude to promote their products for unapproved indications.

Gottlieb said in his response he believes “that patients and physicians make the best decisions when they have access to as much truthful, non-misleading, scientifically-based information as possible. Toward these same ends, FDA has consistently acknowledged that there is some public health benefit of allowing certain non-promotional communication about truthful, non-misleading, clinical data that is not already incorporated into FDA-approved product labeling.”

In separate answers to Sen. Patty Murray’s (D-Wash.) questions on off-label communications, Gottlieb said that if he is confirmed he “will commit to working with FDA’s professional staff to get up to speed on the agency’s latest thinking and actions on these matters, and providing clarity to manufacturers, payers, providers, and patients about acceptable truthful and non-misleading communications related to clinical data not already incorporated in a label.”

Reform Needed

The FDA needs to reform its current approach to regulating communications between manufacturers and health-care providers and payers, the Biotechnology Innovation Organization said in comments on the FDA’s memorandum.

BIO said the FDA’s off-label communication policies haven’t been changed in the last several decades and the policies need to be updated to align with the Constitution and “to inform the increasing complexity of healthcare models and population health management.”

Payers and health-care professionals want more information about the safety, effectiveness and value of treatments, and biopharmaceutical companies often have the most detailed and up-to-date information about their products, BIO said. While a product’s label provides important treatment information, it doesn’t provide information learned about a treatment over time, the group said.

The label also generally includes information that is most relevant to the FDA’s review of the product’s efficacy and safety, but payers and health-care professionals also are interested in scientific information about how the treatment works on patient subpopulations and how it compares to the current standard of care, BIO said.

First Amendment Issues

The FDA’s memorandum “inappropriately proposes to restrict important speech about unapproved uses of medical products that could be beneficial to both healthcare professionals and the patients that they serve,” the Pharmaceutical Research and Manufacturers of America (PhRMA) said.

“The First Amendment permits FDA to restrict speech only as a last resort, and places the burden squarely on FDA to support any restrictions on speech,” PhRMA said. But the FDA’s positions in the memorandum don’t meet this burden because there are less restrictive ways to address the agency’s regulatory concerns on off-label communications.

In July 2016, PhRMA and BIO jointly published principles for the responsible sharing of truthful and nonmisleading information about medicines with health-care professionals and payers.

PhRMA said the principles balance the FDA’s role in evaluating the safety and efficacy of new drugs and new indications with the need for insurers and health-care professionals to be fully educated about treatment options. Specifically, the PhRMA-BIO principles state that:

  •  communications should be based on analyses using scientifically and statistically sound methodologies;
  •  communications should clearly disclose appropriate contextual information to ensure that the recipient has all of the material necessary to make an informed assessment about the quality of the information presented; and
  •  communications should accurately represent the data on which they are based and should be tailored to the sophistication level of the intended audience.
PhRMA said that “at a minimum, FDA should allow manufacturers to communicate, subject to the three above concepts, about unapproved uses of FDA-approved medicines that are medically accepted.”

Medical Devices

The Advanced Medical Technology Association (AdvaMed) said device makers need to be able to communicate with health-care providers about their products.

Truthful and nonmisleading communications about unapproved uses of cleared medical devices “support clinical decision making and the delivery of timely, quality and efficient healthcare as well as facilitate research to support new advances in healthcare,” AdvaMed said.

“An FDA policy that permits such communications would not undermine the agency’s interest in the development of robust scientific data on safety and effectiveness, particularly in light of payor and value-driven healthcare requirements,” AdvaMed said.

Using medical devices usually requires substantial discussion between medical device manufacturers and health-care professionals, AdvaMed said. Manufacturers often provide training and technical support on medical devices for physicians to ensure they are using the device safely and effectively.

AdvaMed also said the health-care community needs timely information about new technologies, which can help patients who suffer from conditions that don’t already have a treatment.

The FDA shouldn’t “discourage or harm the flow of such critical exchange between manufacturers and healthcare professionals using their products,” AdvaMed said.

Opposition to Loosening Restrictions

Consumer groups, however, said they don’t want looser restrictions on off-label communications.

The USA Patient Network said in comments to the FDA that loosening the restrictions “would be extremely problematic” and isn’t in the best interest of patients.

“Patients already aren’t fully aware of what FDA approval does and doesn’t mean. Most patients don’t know that drugs are approved for specific use or that adverse event rates are higher for off label use,” the network said. Patients and prescribers “often are both operating under assumption that FDA approval means safe for all uses.”

The USA Patient Network said “instead of easing existing restrictions on off label use communications, FDA should provide training in medical schools to explain the risks of off-label uses, teaching them that it often means there is no solid evidence that the benefits outweigh the risks of that off-label indication.”

Additionally, the consumer group Public Citizen said the FDA should “strengthen, not loosen, its restrictions on promotion of drugs and medical devices for unapproved uses.”

“When an unproven assertion of safety and effectiveness is relied on, the resulting harm may be severe,” Public Citizen said.

Public Citizen also said the First Amendment doesn’t support the industry’s request to lower the restrictions on off-label promotion. The group said if off-label communications were fully protected by the First Amendment, it would imply that a manufacturer could market a drug with no approval at all.

“Such a result would overturn the carefully constructed, decades-old regulatory structure that governs pharmaceuticals, which is premised on the FDA’s expertise in determining whether to permit marketing only of drugs that manufacturers have proven to be safe and effective for their intended use,” the consumer group said.

Consumer Reports also said in comments that it opposes “any promotion of unapproved uses of medications and medical devices.”

To contact the reporter on this story: Bronwyn Mixter in Washington at bmixter@bna.com

To contact the editor responsible for this story: Brian Broderick at bbroderick@bna.com

For More Information

The FDA's memorandum is at http://src.bna.com/lv5.

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