United States: Five Important Themes To Watch In The Reform Of FDA's Off-Label Communications Policy

As we've previously reported, FDA has recently been forced to reexamine its legal position and enforcement policies related to drug and device manufacturers' off-label communications. Although the Agency has for years resisted calls to loosen its long-standing prohibitions on the off-label promotion of unapproved products, it has simultaneously recognized that truthful and non-misleading scientific or medical information coming from manufacturers about their own drug, biologic, and device products plays an important role in the U.S. health care system. This has especially been true in a climate where individual products are becoming more complex; precision medicine approaches to treating disease are gaining ground in clinical practice; and the health system is evolving into one more focused on outcomes and value-based arrangements between entities. The expansion of First Amendment commercial speech principles by the courts over the past decade and lawsuits against FDA also have pushed the Agency to move towards the potential reform of its existing off-label policies.

FDA recently held a highly anticipated public hearing to allow different stakeholders to express their distinct viewpoints regarding the appropriate regulatory approach to manufacturers' communications about off-label uses for their marketed products. Over the course of those two days, the panel of FDA officials convened for the event (as well as those of us in attendance or watching via webcast) heard perspectives from representatives of drug and device manufacturers, health care professionals, patients and caregivers, patient advocacy groups, research institutions, insurers and other payors. Although the presentations and discussions raised many more questions than it provided answers, we took away 5 recurring themes from this hearing on off-label communications.

Our "Top 5 Themes" of the Off-Label Hearing

  1. Different Rules Are Needed for Different Circumstances. Companies and trade groups argued that FDA cannot maintain a "one-size-fits-all" policy for two main reasons – not all communications are created equal, and not all products have the same risks associated with off-label use. For example, medical device manufacturers advocated for their own policy approach in light of the training and ongoing technical support they provide to users of complex medical devices. Stakeholders asked the Agency to delineate the permissible scope of each particular type of communication and to define those "safe harbors" clearly and with sufficient detail to eliminate the uncertainty that currently abounds when it comes to certain types of truthful and non-misleading scientific exchange. Allowing manufacturers to engage in narrowly defined communications that are put into proper context with appropriate disclaimers, certifications, or other protections in place (like the current framework for providing off-label reprints to health care professionals) seemed to have numerous supporters. Other suggested approaches included the development of an adverse event reporting system for off-label uses only.
  2. Off-Label Information Should Be Shared with Health Plans and Payors. Manufacturer entities, as well as health plans and payors who also addressed the panel, urged FDA to create a safe harbor that would permit product developers to share information with payors about their products before approval, while a new or supplemental application is undergoing FDA review. Harms to patients can accrue when an insurer does not have enough clinical data to make a coverage decision about a medically accepted off-label use for a product, because often the product manufacturer is the best source of such clinical information given its comprehensive monitoring of its product's risks and benefits. Representatives of both manufacturers and health plans pointed out that health plans and payors are extremely sophisticated recipients of data and information, and as such would be appropriate recipients of off-label information.
  3. Lack of Drug Development Specific to Vulnerable Populations Encourages Off-Label Uses, and Increased Communication Would Protect Those Patients. Many off-label uses for approved products are a consequence of the lack of drugs developed specifically for pediatric populations or for certain rare disease indications. A patient advocacy group explained that pediatric cancer patients routinely receive off-label treatments with drugs, biologics, and medical devices because no cancer treatment is specifically approved by FDA for pediatric use. And physicians pointed out that many drugs are useful in treating ophthalmological diseases and conditions, even though FDA has not approved such indications, and cutting off the flow of scientific data to treating physicians will restrict the ability of doctors to provide effective treatments. Clinicians and other practitioners treating these uniquely vulnerable populations desire easy access to relevant, legitimate data about risks and alternative dosing regimens, which, again, product manufacturers may be in the best position to provide. However, the participants making this argument agreed that manufacturers must be required to provide some certification or statement about the degree of reliability of such data.
  4. Adverse Events Associated with Off-Label Uses May Be Tempered with More Off-Label Communications. As FDA Commissioner Califf noted in his remarks at the start of the hearing, off-label uses are typically associated with more adverse events than approved uses for the same drug. Patients as well as some patient advocacy groups strongly opposed any loosening of off-label communication rules, in part due to these increased safety risks and specific examples of serious patient harms or death as a consequence of an unapproved use. Other patient advocacy groups, however, argued that off-label communications should be permitted to expand legitimate treatment options but with certain patient protections, such as informed consent from the patient and the existence of sufficient literature supporting the off-label treatment's safety and effectiveness. The unanswerable question underpinning these arguments is: Would there be fewer, or less serious, adverse experiences associated with off-label use if clinicians were better informed about the parameters of an off-label use.
  5. Off-Label Communications Are Valuable in Precision Medicine. The advancement and success of precision medicine – where knowledge of disease subtypes and a patient's specific genetic and metabolic profile is used to tailor treatment towards the best possible outcome – could be directly impacted by manufacturers' ability to share information with other health care stakeholders. Developers of genetic tests and screening devices explained that new evidence and uses for those tests are constantly being published in the medical literature and such evidence should be available to guide clinicians when they are making treatment or dosing decisions for patients.

Persons who may want to watch the archived webcast of the event or review the eventual transcript can access those materials on FDA's website here.

This informal hearing was the beginning of an information-gathering phase for FDA, which will continue through January 9, 2017 – it is accepting written comments on the topic until that date and we recommend that all affected stakeholders submit their feedback to the Agency (Docket Number FDA-2016-N-1149). It remains to be seen what actions FDA will take in response to the increasing public pressure to reform its policies related to off-label communications.

Will FDA proceed in a stepwise fashion, as urged by some members of industry, to permit certain communications with payors first, then move on to more complicated and controversial circumstances? Will the Agency immediately issue a draft guidance to explain how it is going to integrate First Amendment concerns into its policies on manufacturer communications? While we don't yet know which approach FDA will take, rest assured that we will be watching FDA's next steps closely and will report back on any future developments in this area.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

In association with
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Check to state you have read and
agree to our Terms and Conditions

Terms & Conditions and Privacy Statement

Mondaq.com (the Website) is owned and managed by Mondaq Ltd and as a user you are granted a non-exclusive, revocable license to access the Website under its terms and conditions of use. Your use of the Website constitutes your agreement to the following terms and conditions of use. Mondaq Ltd may terminate your use of the Website if you are in breach of these terms and conditions or if Mondaq Ltd decides to terminate your license of use for whatever reason.

Use of www.mondaq.com

You may use the Website but are required to register as a user if you wish to read the full text of the content and articles available (the Content). You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these terms & conditions or with the prior written consent of Mondaq Ltd. You may not use electronic or other means to extract details or information about Mondaq.com’s content, users or contributors in order to offer them any services or products which compete directly or indirectly with Mondaq Ltd’s services and products.


Mondaq Ltd and/or its respective suppliers make no representations about the suitability of the information contained in the documents and related graphics published on this server for any purpose. All such documents and related graphics are provided "as is" without warranty of any kind. Mondaq Ltd and/or its respective suppliers hereby disclaim all warranties and conditions with regard to this information, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Mondaq Ltd and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use or performance of information available from this server.

The documents and related graphics published on this server could include technical inaccuracies or typographical errors. Changes are periodically added to the information herein. Mondaq Ltd and/or its respective suppliers may make improvements and/or changes in the product(s) and/or the program(s) described herein at any time.


Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:

  • To allow you to personalize the Mondaq websites you are visiting.
  • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our information providers who provide information free for your use.

Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.

If you do not want us to provide your name and email address you may opt out by clicking here .

If you do not wish to receive any future announcements of products and services offered by Mondaq by clicking here .

Information Collection and Use

We require site users to register with Mondaq (and its affiliate sites) to view the free information on the site. We also collect information from our users at several different points on the websites: this is so that we can customise the sites according to individual usage, provide 'session-aware' functionality, and ensure that content is acquired and developed appropriately. This gives us an overall picture of our user profiles, which in turn shows to our Editorial Contributors the type of person they are reaching by posting articles on Mondaq (and its affiliate sites) – meaning more free content for registered users.

We are only able to provide the material on the Mondaq (and its affiliate sites) site free to site visitors because we can pass on information about the pages that users are viewing and the personal information users provide to us (e.g. email addresses) to reputable contributing firms such as law firms who author those pages. We do not sell or rent information to anyone else other than the authors of those pages, who may change from time to time. Should you wish us not to disclose your details to any of these parties, please tick the box above or tick the box marked "Opt out of Registration Information Disclosure" on the Your Profile page. We and our author organisations may only contact you via email or other means if you allow us to do so. Users can opt out of contact when they register on the site, or send an email to unsubscribe@mondaq.com with “no disclosure” in the subject heading

Mondaq News Alerts

In order to receive Mondaq News Alerts, users have to complete a separate registration form. This is a personalised service where users choose regions and topics of interest and we send it only to those users who have requested it. Users can stop receiving these Alerts by going to the Mondaq News Alerts page and deselecting all interest areas. In the same way users can amend their personal preferences to add or remove subject areas.


A cookie is a small text file written to a user’s hard drive that contains an identifying user number. The cookies do not contain any personal information about users. We use the cookie so users do not have to log in every time they use the service and the cookie will automatically expire if you do not visit the Mondaq website (or its affiliate sites) for 12 months. We also use the cookie to personalise a user's experience of the site (for example to show information specific to a user's region). As the Mondaq sites are fully personalised and cookies are essential to its core technology the site will function unpredictably with browsers that do not support cookies - or where cookies are disabled (in these circumstances we advise you to attempt to locate the information you require elsewhere on the web). However if you are concerned about the presence of a Mondaq cookie on your machine you can also choose to expire the cookie immediately (remove it) by selecting the 'Log Off' menu option as the last thing you do when you use the site.

Some of our business partners may use cookies on our site (for example, advertisers). However, we have no access to or control over these cookies and we are not aware of any at present that do so.

Log Files

We use IP addresses to analyse trends, administer the site, track movement, and gather broad demographic information for aggregate use. IP addresses are not linked to personally identifiable information.


This web site contains links to other sites. Please be aware that Mondaq (or its affiliate sites) are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of these third party sites. This privacy statement applies solely to information collected by this Web site.

Surveys & Contests

From time-to-time our site requests information from users via surveys or contests. Participation in these surveys or contests is completely voluntary and the user therefore has a choice whether or not to disclose any information requested. Information requested may include contact information (such as name and delivery address), and demographic information (such as postcode, age level). Contact information will be used to notify the winners and award prizes. Survey information will be used for purposes of monitoring or improving the functionality of the site.


If a user elects to use our referral service for informing a friend about our site, we ask them for the friend’s name and email address. Mondaq stores this information and may contact the friend to invite them to register with Mondaq, but they will not be contacted more than once. The friend may contact Mondaq to request the removal of this information from our database.


This website takes every reasonable precaution to protect our users’ information. When users submit sensitive information via the website, your information is protected using firewalls and other security technology. If you have any questions about the security at our website, you can send an email to webmaster@mondaq.com.

Correcting/Updating Personal Information

If a user’s personally identifiable information changes (such as postcode), or if a user no longer desires our service, we will endeavour to provide a way to correct, update or remove that user’s personal data provided to us. This can usually be done at the “Your Profile” page or by sending an email to EditorialAdvisor@mondaq.com.

Notification of Changes

If we decide to change our Terms & Conditions or Privacy Policy, we will post those changes on our site so our users are always aware of what information we collect, how we use it, and under what circumstances, if any, we disclose it. If at any point we decide to use personally identifiable information in a manner different from that stated at the time it was collected, we will notify users by way of an email. Users will have a choice as to whether or not we use their information in this different manner. We will use information in accordance with the privacy policy under which the information was collected.

How to contact Mondaq

You can contact us with comments or queries at enquiries@mondaq.com.

If for some reason you believe Mondaq Ltd. has not adhered to these principles, please notify us by e-mail at problems@mondaq.com and we will use commercially reasonable efforts to determine and correct the problem promptly.