FDA's Off-Label Communication Changes Should Start With Payers – PhRMA

FDA could relax its constraints on off-label communications by biopharmaceutical manufacturers in stages, starting with allowing broader discussions with payers and other groups making coverage decisions, the Pharmaceutical Research and Manufacturers of American and Biotechnology Innovation Organization are suggesting.

“All of this change doesn’t have to occur all at once. We think it’s useful to think about a possible step-wise approach to some of the regulatory change that would be called for,” PhRMA VP and Senior Counsel Jeffrey Francer said during a Sept. 15 webinar hosted by GHC Life Sciences.

PhRMA and BIO recently began a renewed push for disseminating drug information to health care professionals and payers by releasing a set of principles aimed at spurring the release of regulations from FDA that would enable the practice. (Also see "Off-Label Communication Principles From PhRMA, BIO Aim For Reg Changes" - Pink Sheet, 27 Jul, 2016.)

Francer suggested FDA could start the process by aiming first at the “low-hanging fruit” – circumstances that lend themselves to change in the near term. He noted there is already solid consensus that broader communications between payers and manufacturers is needed and could be accomplished without risk of misleading the data recipients.

“There seems to be almost unanimous recognition that there should be a clear safe harbor for communications between companies and payers and other population health decision makers – in other words, not individual prescribers but those who are making coverage decisions or recommendations that would be applicable to a whole population,” Francer said.

Communications could focus on pharmacoeconomic data and on “sharing clinical trial information prior to approval so that the insurance companies can understand the scope of the potential population, which is critical for their modeling, as well as what they think the treatment is going to do,” Francer explained.

Francer noted that Congress endorsed broader pharmacoeconomic discussions between manufacturers and payers in the 1997 FDA Modernization Act. But manufacturers have been wary about taking advantage of the opportunity offered by FDAMA Sec. 114 because FDA has not issued guidance clarifying what would be appropriate under the provision. (Also see "Comparative Rx Economic Claims Without Head-to-Head Trials Risky – J&J’s Jimenez" - Pink Sheet, 22 Apr, 2015.)

Avoiding Coverage Surprises

As to pre-approval discussions, “we’ve heard from the payer community that they want more information, especially about unapproved drugs that are in the pipeline, earlier than before,” he said. “And they want companies to present the information “proactively,” not necessarily following “an explicit request for information.”

Pre-approval discussions could offer payers the opportunity to offer advance “guidance” on how a drug might be received by payers, Express Scripts Chief Medical Officer Steve Miller said.

Payers “especially don’t want to be surprised when new drugs are approved that can be breakthroughs, and I point to the hepatitis C drugs as the prime example here,” Francer explained.

In such situations, “coverage decisions may be delayed or payers may have difficulty fitting these new drugs within their model,” he noted. Payers were surprised by the high price of Gilead Sciences Inc.’s Sovaldi (sofosbuvir) when it launched in late 2013. Because they were unprepared to manage the cost, many limited coverage of the drug to sicker patients first.

“Earlier communication…would make the whole system more efficient,” Francer said. He also suggested that pre-approval communication could lead to cost savings through the creation of value-based contracts. ”

“Given that payers are extremely sophisticated consumers of health care data and they are telling us they want this communication, this really should be a ‘no brainer’ to FDA and HHS,” Francer maintained. “We believe FDA can and should make these changes in a very short term, especially given the sophistication of these audiences and the relatively low risk of sharing information.”

PBM Wants To Offer Pricing 'Guidance'

Pre-approval discussions could offer payers the opportunity to offer advance “guidance” on how a drug might be received by payers, Express Scripts Holding Co. Chief Medical Officer Steve Miller said in an interview.

“We could offer pharma the following: You look at [a market opportunity] from your drug’s perspective and you say, ‘How much, for instance, can society afford for a [non-alcoholic steatohepatitis] NASH product?’ We have the perspective of the payer who’s got to pay for the new NASH drug and the new cancer drug and the new hepatitis drug. And so we want to share with them what we know will be the market’s receptivity.”

He also suggested payers would have “given the hepatitis companies different guidance” on pricing their drugs. “Would that have changed their pricing? I don’t know. But would that have been helpful in the discussion? Probably.”

Discussing Outcomes Based on Real-World Data

A second phase in reforming FDA’s communications policies could involve allowing discussions with health care professionals about drug benefits that are “consistent” with the approved indication and are supported by data such as real-world evidence, Francer said.

For example, he pointed to evidence that the use of statins reduces cardiovascular disease. “You might do an analysis based on payer records or health care records of the long-term effectiveness of statin in decreasing heart attacks or other cardiovascular events,” he explained.

“In this way, we’re not talking about the traditional type of ‘off-label’ use. But you are talking about sharing data that are literally off the label. And you might also be talking about data that don’t meet the FDA’s standards of getting on the label,” which calls for conducting randomized clinical trials.

“The fact of the matter is the standard for adding information to the labeling and adding to an approval is the ‘substantial evidence standard’. And there’s a different standard for communication, which is the truthful and non-misleading standard,” Francer maintained.

He added “FDA is already committed to taking a look at the use of real world evidence for regulatory decision making within the PDUFA VI agreement.” (Also see "FDA To Join The 'Real World' Under PDUFA VI" - Pink Sheet, 15 Jul, 2016.)

Public Meeting Focusing On Most Challenging Area

Francer suggested that action by FDA on payer communications and use of real-world data should not wait until after it holds a public hearing on off label communications in November. (Also see "Off-Label Debate Between FDA, Industry To Formally Begin After Election" - Pink Sheet, 31 Aug, 2016.)

In fact, Francer suggested that the meeting appears to be focused on a potentially more difficult area to address – communication of information to prescribers on what are more clearly off-label uses.

Communications to prescribers on “medically accepted alternative uses” would be a third step in redefining FDA’s communications policies, he said.

Alternative uses would include those “that are different from the approved indication but are medically accepted in that they may be in federal recognized [clinical] compendia or recognized clinical practice guidelines and they may even be the standard of care – some of the oncology drugs are the standard of care in ways that are outside their labeling.”

“We believe that additional sharing of this information can help patients by providing responsible information to health care professionals.” Although this may not be accomplished in the short term, “sooner or later FDA is going to have to grapple with the First Amendment decisions … that plainly allow for the truthful, non-misleading communication about this kind of information,” Francer said.