Medical Affairs Focus

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Tag Archives: Proactivity

Topic 40: BREAKING: Court Rules FDA Cannot Prevent Truthful Off-label Promotion

In a court case that may have huge implications for pharma, a federal district judge in Manhattan ruled that the FDA cannot prevent a company from conducting off-label promotion if the promotion is truthful and scientifically accurate.

This ruling stems from the Amarin case that we discussed HERE.  In that case, Amarin argued that the precedent set by the Caronia case (which we discussed HERE) allowed them to promote off-label if the information shared was truthful and not misleading.  The FDA argued that the Caronia ruling was specific to those circumstances only and did not apply to Amarin.  Judge Engelmayer wrote in today’s ruling that “…A fair reading of that decision refutes the F.D.A.’s view that the Second Circuit’s ruling was limited to the facts of Caronia’s particular case.”

While this only currently applies to the circuit in question, it is a clear precedent that will need to be addressed if the FDA intends to retain its current regulatory approach to off-label promotion.  The FDA has not stated whether it intends to appeal but it did not appeal the Caronia ruling, a decision some pundits felt was made to avoid having a broader precedent set for allowing truthful off-label promotion.

This is an ongoing story but it could have some major implications for pharma and medical affairs.  Stay tuned to this space for more developments as they occur.

Any comments or thoughts on today’s news?  Click here to share them.

Topic 38 – FDA Comments on Off-label Dissemination – Did it just tip its hand on upcoming off-label policy?

Have you had the opportunity to follow the Amarin lawsuit against the FDA?  If not, a quick recap:

 Amarin is literally a fish-oil salesman – they have fish-oil pills that are already FDA approved for the treatment of very high levels of triglycerides.  They had conducted clinical trials to expand their label to patients with lower levels of high triglycerides.  The FDA rejected their application.  Amarin decided it wanted to share the results of those studies anyway since they were positive and sued the FDA for the right to share its data on off-label use.

The interesting part comes from the FDA response letter.  Putting aside their primary concern that Amarin failed to work with them before suing them, the letter signed by Janet Woodcock went on to layout the condition in which Amarin (or for that matter any pharam company) can share off-label data.

First, the letter reiterated what we already know and have discussed: the reprint exemption to off label communication – distribute reprints from peer-reviewed journals, avoid some simple issues like highlighting only the “good” passages, and you are in the clear.

But then the letter goes on to say that Amarin can also write up and distribute its own summary of the results of their trial if the write up:

  • Remains factual and does not omit material information or introduce bias
  • Includes full data for each treatment group
  • States that the current label does not approve of the use
  • States that the impact on the off-label use has not been determined
  • Shares data about other, known similar studies that may have different results
  • Any financial or affiliation biases between the firm and the people who conducted the study

They go on to add that to protect against being misleading the company should:

  • Provide a copy of the current Package Insert
  • Provide a copy of any relevant reprints
  • Discuss these topics in an educational or scientific setting and not as a part of a promotional discussion or attached to promotional materials
  • Discussions should be conducted by persons with the appropriate background or training to accurately communicate scientific information

While that is still a lot of hurdles, that is a long way from reprints only.  And while these are NOT an official policy now, I think this is telegraphing what we should expect to see in the upcoming policies.

I particularly like the final bullet point which makes it clear that these topics need to be discussed by roles that sound very much like MSLs.

To speculate, if the FDA were to allow establish this as the policy, it would surely free up MA to proactively share both off label and label supportive information.  That would be a big improvement for some MA organizations that deny all proactive sharing of off-label information.

You can find the letter HERE.  The juicy bits begin on page 8.

What do you think?  Click here to leave a comment.

Topic 36 – Off-Label Promotion Prosecution is Changing – and Medical Affairs Should Benefit

Normal disclaimer: I am not a lawyer just a lay observer.

I was at the 3rd Annual World Congress Summit on the Evolving Role of Medical Affairs.  As in the last two years, one of the highlights is the presentation by a representative of the OIG and US States Attorney on Off-Label Promotion.

Usually this is an opportunity for them to remind us that pharma is not allowed to promote off label, trot out examples of people who were prosecuted for off-label promotions (which are almost exclusively Sales and Marketing examples, not MA examples) and then encourage us to snitch on our organizations if we think we see this behavior.

But this year was different.  This year we were all introduced to an important new term – Off-label Plus.  What does Off-label Plus mean?  It’s how they refer to cases that they are willing to prosecute.  In light of the Caronia ruling (an overview of which you can find here, with subsequent commentary here and here), they are no longer willing to base cases on simply promoting off label (assuming the test laid out in Caronia that the off-label information presented is from a credible, unbiased source, like a “real” journal, and the presentation is not misleading).  Instead, they are only willing to go after cases where there is Off-Label Plus something else, like Kickbacks or Fraud of some type.

In my opinion this is huge for medical affairs – most medical affairs organizations are unwilling to proactively share even an article published in the NEJM if it is off-label out of fear of being accused of promoting off-label.  Instead we wait to be asked, since responding to a question is not promotion.  I think the fear of promotion is now unjustified.

The simple reality is that even before Caronia no medical affairs employee has ever been prosecuted for simply providing accurate, non-misleading off-label information.  Caronia  was a sales guy, not medical affairs. The only example that the prosecutor could cite of an MA employee being prosecuted was a device company where the medical affairs lead used speaking fees as a kick backs.   Now that Caronia is out there, I think the risk is even lower.

Just like our treatments, all of medical affairs is a risk / benefit.  If we wanted zero risk, we would not have medical affairs or sales or marketing for that matter.  Instead we reduce our risks through the use of strong processes and a compliance function to ensure those processes remain in place.  It is my assertion that providing credible, non-misleading peer-reviewed published off-label data pro-actively is no longer a major risk, assuming there are procedures in place to avoid all the other “Plus” activities.

I don’t expect this to change overnight, but some organizations are going to start operating this way and when the sky does not fall, all medical affairs organizations will be operating this way – my guess is within 5 years.  And this is all for the best – its good for HCPs because they will have the latest information, its good for patients because their HCPs will be well informed and its good for medical affairs because it allows us to do our jobs even better than today.

What do you think?  Leave a comment by clicking here.

Caronia Legal Discussion

For those of you who can’t get enough discussion about the Caronia case and its impact on off label promotion, Law Journal TV has done a panel discussion about it.  Worth a watch but mostly confirms what we have been discussing here.

Update: Caronia and Off Label Promotion – The Beat Goes On

At a recent CBI compliance conference in DC, Tom Abrams, director of the Office of Prescription Drug Promotion (OPDP) in the Center for Drug Evaluation and Research (CDER) basically said that as far as his agency was concerned nothing was going to change in their enforcement of off-label promotion.  His rationale is, in my non-legal opinion, in the vein of “it depends on what the definition of ‘is’ is”.  I think OPDP has chosen to see what they want to see in the ruling, but regardless they are not changing their approach or tactics.

Take a look at his full statement below:

The government has determined not to seek further review of the Second Circuit’s decision in United States v. Caronia, No. 09-5006-cr (2d Cir.).  FDA does not believe that the Caronia decision will significantly affect the agency’s enforcement of the drug misbranding provisions of the Food, Drug, and Cosmetic Act (FD&C Act).

In 2009, Alfred Caronia was convicted of conspiring to distribute a misbranded drug in violation of the FD&C Act.  A divided panel of the Second Circuit held that the jury instructions erroneously permitted, and that the government’s argument encouraged, the jury to treat speech promoting unapproved (off-label) uses of an FDA-approved drug as a criminal offense in and of itself.  The court of appeals did not address the constitutionality of the theory of liability on which the government had defended the conviction:  namely, that the promotion of a drug for an unapproved use may be relied on as evidence that the unapproved use is an intended one, and a drug that lacks adequate directions for its intended uses is misbranded.

Because the court did not address the constitutionality of a prosecution resting on that theory, and because the court also acknowledged that the First Amendment does not preclude an enforcement action based on speech regarding unapproved uses that is false or misleading, the Second Circuit’s decision does not bar the government from continuing to enforce the misbranding provisions of the FD&C Act, including through criminal prosecution where appropriate, in cases involving off-label promotion.  More generally, the decision does not strike down any provision of the FD&C Act or its implementing regulations, nor does it find a conflict between the Act’s misbranding provisions and the First Amendment or call into question the validity of the Act’s drug approval framework.

Bottom line, they are sticking with the belief that while anyone has the “right” to promote off-label, doing so ultimately leads to misbranding which is in violation of the FD&C act.  How you square this with the Second Circuit’s ruling that there is protection for promoting off-label as long as the information provided is true will be an argument that will, no doubt, end up back in court.  I’m not a lawyer but I thought my rights trump your laws.

But for now off-label promotion remains open to OPDP enforcement.

What are your thoughts?

h/t PharmaExec Blog

Update: Off Label Free Speech Ruling Left Unchallenged at Appeals Level

As I discussed here, a recent ruling by the Second Circuit Appeals Court provided a new legal foundation for off-label promotion on free-speech grounds.  As the law currently stands in the Second Circuit, as long as the speech is “truthful” it is protected by the First Amendment and thus open to anyone.  Sales reps and MSLs in Ney York, Conn. and Vermont have one less thing to worry about.

Many, myself included, assumed that the FDA would ask for a re-hearing in the Second Circuit, but that date has come and gone without such a request.  You can read about it here.

At this point the FDA can go two ways – they can ignore the ruling and let it stand for the Second Circuit, which may result in a set of haphazard interpretations over time as different Circuit Counts rule differently, or it can appeal the ruling the Supreme Count.  Assuming the Supreme Court would agree to hear the case, appealing it to them could result in a ruling that the Second Circuit ruling should be the law of the land.

So the FDA is left with a choice – take what it has and accept that the off-label promotion rules may gradually crumble or risk those rules completely by appealing to the Supremes.  They have until mid-March (or until mid-May if they wish to extend their timeline) to make that decision.  I will continue to fill you in when I learn more – watch this space!!

Topic19: MA Impact of the Caronia Ruling

As most of you know, the Caronia Ruling by the Second Circuit Court of Appeals found that a pharma rep was within his 1st Amendment rights to discuss off label use of his company’s drugs, assuming that those discussions were truthful.  This went off like a rifle shot within the pharma world with all sorts of discussions, you can read some of them here, here and here.

It is very likely that this ruling will be appealed to the full Second Circuit, and/or directly to the Supreme Court.  But there are reasons to believe that the Supremes may be open this interpretation given their past rulings on similar subjects.  Regardless, until this is settled it only applies to the Second Circuit so unless you are a pharma company only doing business in the Second Circuit in and around New York, you can’t make much change.

BUT, what if this becomes the new law of the land?  What does it mean for Medical Affairs?  That’s what I want to explore in this blog post.

The most obvious impact it has is on all the current focus we place on “proactivity”.  I have discussed this topic in detail here, here, and here.  I bemoaned the unclear state of the current regs here. Now we are imagining a world where the issue of proactivity has to be seen in a completely different light.  MA avoided proactively discussing off-label data on our products because proactivity implied promotion and it is (or in our scenario was) illegal to promote off label.  Under this scenario that thinking would be wrong.  Replaced, potentially, with a focus on “truthfulness”.

Now, for MA at least, this is an expectation we are more than willing to meet.  In the past MA has typically thought of any peer reviewed study as truthful but some of the commentators are suggesting that the definition might become the same one that they use for the FTC.  The FTC definition id focused on “…competent, reliable scientific evidence supporting the claims you are making…” so it may not require a peer reviewed journal publication.  The one caveat, however, is that if you conduct a test and find that the content being shared is misleading to 20% or more of the targeted consumers, than it is not considered truthful.  In general, then, although peer reviewed journals would not be a requirement, it would represent a fairly safe harbor to avoid the risk of sounding misleading.

So, in the future world we are imagining, our field force of MSLs would be free to go out to HCPs armed with peer reviewed journal articles, and introduce the HCP to that article and then proceed to have a scientific exchange about the results, assuming they stick to findings documented in that or other peer reviewed articles.

Scientifically speaking, this frees MSLs to have very wide ranging discussions with HCPs at their initiation and allows for much greater control over the type of discussions that we have with the HCPs.  It will allow MSLs to show much greater value to the organization by allowing the targeting of discussions that are the most meaningful to our products.  And if you think is hard to hire MSLs today, watch out.  With that increase in value will come greater investment in both MSLs and in Investigator Initiated Studies and P4 studies that will now be seen as more valuable as well.

What do you think?  Do you think it we will see the end of proactivity restrictions in the next three years?  Leave your comments above.

QuickNote: Off Label Promotion Ruled OK by US District Court

In a ruling with huge potential impact on MA as well as commercial functions, the Court of Appeals for the Second Circuit in Manhattan has overturned a conviction of a salesperson who was promoting the off-label use of a product! This 2-1 ruling goes against years of court rulings stating that pharma does not have the right to promote off-label.  In fact,  in the past month GSK has been fined $3 billion for off-label promotion and J&J fined $181 million for off label promotion.

Clearly, new legal ground is being broken here.  BUT, if urge caution.  This is one ruling that contradicts years of previous rulings.  It may serve as grounds for kicking this up to the Supreme Court, but until clear legal direction is given I would not be changing any policies.

Take a look at the article here and the actual ruling here.

Topic7: Coordinating MA and Commercial

A reader asks:  “Given the importance of consistent communication to the healthcare community, my company is seeking to better coordinate commercial and MA messaging.  What is the best approach for doing this?”

Thanks for the question.   The answer is: Very Carefully!  My sense is that your commercial function is driving this requirement.  I infer this from your question because you use the term “messaging” which is generally a marketing term.  Let’s remember that the purpose of marketing is promotional – promoting the sale and safe use of our products.  Since it is promotional, their communications are limited to on-label information.  If their communications go beyond the label, they are promoting off-label.  We all know this is against the law.

MA is allowed to discuss off label topics only under very specific circumstances – when they receive an unsolicited request.  MA is allowed to have some proactive discussions which are educational and non-promotional about related non-label topics depending on the rules of each organization.  See a detailed discussion of this here.

So, marketing is promotional and MA is non-promotional.  What “messaging” can a promotional and non-promotional functions share?  Conservative organizations would argue that any messaging topics that support the promotional needs of commercial is, by definition, not an acceptable topic for non-promotional MA.  But, many organizations would agree that promotional topics can focus on the product and its competitive positioning; while there can be related non-promotional topics such as the underlying disease state.

Most organizations that allow some coordination between promotional and non-promotional topics understand that this is a risk.  To avoid the risk of MA appearing as a promotional entity, most companies expect the coordination will go one way only:  from MA to commercial.  The theory is that MA is going to be educating the market regardless and the commercial function is just becoming aware of what MA is doing.

Going the other way, from commercial to MA, runs the risk of appearing as though MA is part of the promotional machinery.

So, reader, be careful.  Processes and systems must be put in place to ensure that the coordination is going the right way only.  Otherwise, you run the risk of a future whistleblower pulling out a document showing that MA has become a promotional resource.

For example, there need to be clear firewalls between the way MA is measured and the way commercial is measured on the effectiveness of their communication efforts.  We have discussed MA measurements here.  Commercial measures of effectiveness should be much more related to sales and penetration.

Thanks for the question!

If you have a question, please email me or leave it in the comments!

Topic1: Proactivity- Impact of Decreased Proactivity

Given the ambiguity of the regulations, most organizations are reducing the degree of proactivity to ensure that they remain within compliance.  Going to the left on the MA Spectrum of Proactivity.   However, decreasing the degree of proactivity carries risks of its own.

Failing to Meet Obligations as Partners in Science

The most pressing risk associated with limiting the proactivity of MA outreach is that information that would have been useful to the HCPs does not get into their hands.  While HCPs have the obligation to maintain their own knowledge, the reality is that there is so much information available that many HCPs cannot possibly keep up with everything, especially physicians that treat a range of disease states.  They rely on many expert groups, including associations, practice standard setting bodies, journals and, yes, pharmaceutical companies to help point out information they may not have found on their own.  Pharma companies often employ some of the leading experts on the disease state where they focus their research and have a positive perspective to share with the community.

Confusion Among HCPs

Given that many HCPs have traditionally relied on pharma as one of their sources for alerting them to new scientific information, the sudden halting of this support would normally be disruptive.  But, even more challenging is the fact that this change will be unclear to the HCPs as different pharma companies set different policies.   A pharma company that recently reduced its degree of proactivity surveyed some HCPs it would have normally interacted, and found a strong sense of betrayal by those HCPs that the organization had discontinued this support and an equally strong sense of confusion about why this support would be discontinued.   Most HCPs surveyed said they would not replace proactive interaction with direct contact to the pharma companies because, to paraphrase one response, they don’t know what they don’t know to ask about.

Closing Thoughts

Every company needs to weigh risk and benefits with any decision it makes.  Unfortunately, when it comes to proactivity many organizations have lately been focused entirely on risk.  Even with the ambiguity noted in a previous post there appears to be room for some form of proactivity.  And, HCPs are expecting it.  For MA to achieve their goals, they need to work with their organizations to ensure that the benefit/risk is being considered in full before any changes are made.

What do you think?  Leave a comment below.

Legal Note:  All information and interpretations presented are only the opinion of the author(s) who are not lawyers. And, even if we were lawyers, given the wide range of interpretations of the current regulations you would still need to get the input from your own compliance organization.  Simply put – your mileage may vary.