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Tag Archives: Compliance

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.

Topic 33: Significant Future Risk of Naming and Shaming in Clinical Trial Results Posting

The Problem

We have talked a lot about big data on this blog, and that’s because it’s a game changer.

As evidence, did you see this article in the NEJM? It’s a research analysis in which they pulled the entire ClinicalTrials.gov database and analyzed it to determine who has been publishing summarized clinical trials results as required by FDAAA from 2007. This analysis was done by cardiologists at Duke, and what got the headlines was that only 38% of completed studies had their data posted as required by the law.

However, dig a little deeper and with more of our focus and you can learn some interesting things about the biopharma industry. Of all the 13,300 (all numbers rough for discussion purposes) completed clinical trials analyzed, 66% were industry sponsored or roughly 8700 trials. Only 5100 of the 13,300 completed clinical trials reported any results, and of 3600 of those 5100 reporting trials, or 71%, were industry trials. So, in a world of terrible compliance, industry was punching above its weight. That still leaves some 5100 industry trials with not results posted despite the law.

BUT, you say, isn’t there some exception for holding back results until after FDA approval/rejection. Yes, a company can file a certificate which allows it to delay posting results in that circumstances. Of the 5100 completed industry trials missing data only 2000 certificates were filed – leaving 3100 or 36% of all industry trials unreported or uncertified per the law.

This is where big data and company reputation risk raises its ugly head. There are big data sources already out there that read all the data from ClinicalTrials.gov. With today’s big data tools it is a straight forward exercise to determine which industry company sponsored which trial and whether it reported/certified per the law. They will also know which products have failed to report/certify if the products are approved. It is not long from now that some reporter will put this together and produce a list of the “best and worst biopharma companies for publishing results” – some uncharitable media outlets (and which ones are charitable to biopharma) may even imply sinister intent at “denying their legal obligation to share this data – what are they hiding.”

Implications for Medical Affairs and Clinical Development

There is a unique opportunity to head this potential distraction off at the pass. We don’t want our MA field team’s spending time justifying why the company is not posting data.

While maintaining ClinicalTrials.gov is generally the responsibility of the CD in most organizations, MA has a strong vested interest to ensuring that the company is bullet proof in this area. MA and CD need to collaborate to make sure that data is posted or the certificates are filed. A process audit to confirm that the processes are in place and are working, as well as verifying that the company does not have any missing posting or filings, is a small bit of work that can save a huge amount of distraction for the entire organization in the future.

What has been your experience in this area? Leave a comment

Topic 24: Highlights of Day 1 of the Medical and Scientific Communications 2013 Forum

As I mentioned earlier, I am attending the DIA MSC meeting in Pheonix, AZ this week.  The MSC has increased value this year because they have added a track specifically focused on MSLs.  Through the hard work of the MSL Track Chair people Rebecca Vermeulen and Ramineh Zoka, as well as the hard work of all the presenters the MSL Track has had a terrific first day.

DISCLAIMER:  My focus is on interesting information, I did not try to take verbatim notes and will not try to assign comments to a particular speaker.  Any mistakes are mine alone.

In no particular order, some of things are found interesting included:

–  A pill is poison unless the right information is wrapped around it.

–  ACA

  • Because of the passage of the ACA and the Supreme Court upholding the law, Rx spending is expected to increase 4.7% more than is the law had not passed
  • With the ACA’s introduction of roughly 20 million newly insured people in 2014, the US market will become the fastest growing pharmaceutical market in the world

–  Tax Deductibility for Marketing and Sales expenses in Biopharma

  • Some talk about eliminating this to increase tax revenue
  • Proposed 3 times in the last year but killed each time
  • NOT at all clear whether MA would be considered marketing under tax law
  • If passed, likely to see major cuts needed to balance budgets in these areas

–  Sunshine Act

  • Already happening for 16 companies under CIA’s
  • For a taste of the info that will be available, see this link
  • New PhRMA/Coalition formed to educate public about wave of new disclosure information coming called National Dialog for Healthcare Innovation

–  Caronia Ruling (you knew I would have to get something in here about this)

  • No one knows when it will be law of the land but likely 5 to 10 years
  • Old standard of safe – what is on the label
  • New standard will be – information that a reasonable consumer would not find misleading
  • New standard is current FTC standard for all advertisement
  • Data will be king, but not just data submitted to FDA
  • For time being, continue like no change

–  History of MSL Role

  • First MSLs started 40 years ago
  • Up John created role and actually trademarked the name MSL
  • Part of the sales teams – scientific sales

–  MSL Facts of Interest

  • Most MSLs manage between 25 and 49 KOLs
  • 32% of companies surveyed (n~60+) intend to grow MSL team
  • Only 11% intend to shrink MSL teams

–  Value of MSLs by Physicians

  • Surveys showed physicians do NOT value frequency, they value:
    • Accessibility
    • Responsiveness
    • Knowledge
    • Up to date information
    • Do NOT want to meet with MSLs if:
      • Only have old or out of date information
      • Feel they are biased
      • Have nothing new to tell them

–  Diagnostic MSLs

  • Specific MSL group focused on uptake of diagnostics
  • Big challenge – to use a diagnostic, they need the diagnostic platform – often millions of dollars
  • Thus broader array of people involved in decision beyond just HCP, including:
    • Bench Tech
    • Lab Managers
    • Pathologists
    • Administration
    • Opens questions about right regulatory regime for non-HCPs

–  CIA Driven Changes

  • CIAs require standards and documentation
  • Documentation increasingly taking the form of customer relationship management systems specifically for MA
  • Most common system by show of hands in the room: Veeva running on Salesforce.com
  • To be effective, this type of system needs to:
    • Track interactions
    • Manage content
    • Link the two
    • Key pitfalls
      • Privacy, especially for global systems given EU requirements
      • Complexity

Obviously, this is merely a few key concepts from the day but it should give you some flavor of the type of discussions and the focus of the meeting.  Overall I would say the tone was very positive, given the challenges MSLs face in their highly regulated environment.  Everyone at the meeting was confident that MSLs value was high and these challenges could be met.  Look forward to tomorrow.

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.

Topic 23: Key Implications for MA Leaders in the New Sunshine Act Rules

In previous posts this week I have broken down the key provisions of Sunshine Act rules.  Now I want to provide my thoughts on what this means for MA leaders and their teams.

Owning the Correction Process

Everyone who conveys something of value to a physician within biopharma will need to understand these rules and their part of tracking them.  This is a new administrative burden for many parts of biopharma.

BUT, there is one specific work activity that I want to address before I jump into implementation concerns.  When all this data is compiled and sent to CMS, the physicians will have a yearly chance to review it and offer corrections.  These corrections will need to be reviewed and discussed with the company.

So the big operational question is – Who is going to take point on that correction interaction?  Are we going to expect that the physician try to contact different functional areas within the company directly with their questions?  That may not be reasonable since the reported values will not make it clear who is responsible within the biropharma.

I am going to suggest that someone needs to take clear ownership of this responsibility and in the case of KOLs it should be MA.  MA should be responsible for serving as the point of contact for KOLs with these issues and driving the issues to resolution.  Non-KOL physicians should be handled by an administrative group in finance, but KOLs really need to handled carefully if we do not want to damage our relationships.

Overall Sunshine Implementation

To prepare for the Sunshine Act, MA needs to ensure the following:

  1. Internal systems are being built to properly capture this information
  2. MA personnel and specifically MSLs are receiving proper training to understand how and when to report this information
  3. A physician education program is developed and MA’s role in executing the physician program is clearly defined

I will highlight each of these elements and discuss related key Sunshine Act rules.

1. Internal Systems Developed for Sunshine Reporting

This is one area that MA probably has the least control.  These should already be underway and hopefully MA has already had a fair amount of say.  If MA is part of the stakeholder group that is reviewing these systems, I would ask the following questions based on my reading of the Sunshine Act rules:

  • Will the system cover all payments, even those related to OTC or other non-pharma products?
  • Is the company going to report in a consolidated fashion or separately by subsidiary/JV?
  • Is the organization going to add context statements to payments?  If so, which ones and when?
  • How many products will be associated with each payment?  Rules allow up to 5
  • Are we prepared to track corrections and resubmit within the 15 day window after corrections are due?

2. MA Personnel Training on Sunshine Reporting

There is a fair amount of nuance in the Sunshine Act reporting rules.  It is critical that training is developed that make the following clear to MA staff:

  1. Overall Payments
    • If value is provided to a physician but not at the request of the physician, it still needs to be reported.
    • Waived fees – of a physician suggests it is donated to a charity on their behalf it will still be tracked, unless they truly waive their fee without obligation to the company
    • All payments need to be coded by category – training is needed on the definition and difference (eg. travel vs. meals)
  2. Food
    • If a group meal is provided where the value is greater than $10 per person, each physician that actually partakes of the meal must be tracked
    • Unless the food provided at a large event, in which case it does not have to tracked
  3. Indirect Payments
    • Value provided to a third party but expected to be delivered to a physician must be tracked under the physician’s name
    • Value provided to an institution with the intention that it will go to a physician even if that physician is unnamed must be tracked (eg. providing funding to a teaching hospital for research grants will have to be tracked to the recipient physician)
    • Blinded payments to physicians for market research do not need to be tracked
  4. CME Programs
    • Accredited programs are exempt from reporting only if no names of speakers or even specific criteria for speaker selection is provided and the manufacturer does not pay the speakers directly
    • General subsidies for CME tuition does not have to be tracked
  5. Patient Education
    • Patient education materials and items are excluded from being tracked

3. Educating Physicians and Especially KOLs

It is vital that our KOLs are aware of the rules so that we can avoid confusion and bad feelings.  Some key elements of the rules that I believe every physician/KOL should know:

  1. General Rules of the Road
    • All value provided greater than $10 must now be reported, or multiple smaller transactions that add up to $100 in one year
    • All data is tracked and submitted yearly
    • Physician must register with CMS website to gain access to the data in their name
    • After registration, physician will receive notification when data is posted yearly about them
    • Physician will have 45 days after notifications to review data
    • Physician will go onto CMS website and enter any corrections they think are necessary
    • Manufacturer has 15 days to review the corrections submitted and accept or reject
    • If the manufacturer rejects the correction, the manufacturer and the physician are expected to negotiate and reach consensus
    • If consensus is not reached, the manufacturer value number is used but it is marked as “in dispute”
  2. Nuance of Value Tracking
    • Value tracked will include OTC and other non-pharma products from the company
    • If value is provided to a physician but not at the request of the physician, it still needs to be reported.
    • Value contributed to charity in their name will still be reported – eg. primary research honoraria donated to a cause is still considered value provided and will not be coded as charity contribution but as primary research honoraria
    • Tracking pierces the outsourcing veil – if a manufacturer pays a CRO and the CRO pays the physician, it tracks as the manufacturer paying the physicians
    • Reporting on research payments and value may be delayed for up to 4 years or until FDA approval, so do not be surprised if some clinical trial payments do not show up on the yearly total.  Similarly don’t be surprised to see multiple year’s worth of payments show up in one year after FDA approval, but they will be labeled with the year actually worked.

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.

Topic 19 – EU Considering Major Change in P4 Trials

A new position paper has been floated by the European Commission Health and Consumer Directorate-General that may have HUGE impacts on the way P4 trails are conducted in the EU (and the rest of the world).  My take on it is below:

Stemming from the new EU regulations around pharmacovigilance, the EU is also considering the role of post-marketing efficacy studies (PAES).  In a position paper seeking feedback, found here, the EU lays out its perspective that the new PV legislation also refers to the possibility of requiring the market authorization holder to develop PAES to complement the efficacy data used to grant marketing authority.  That power is granted where “concerns relating to some aspects of the efficacy of the medicinal product are identified and can be resolved only after the medicinal product has been marketed.”

Regulatory Purpose

The position paper goes on to lay out the regulatory purpose of PAES and suggest that after the results of a required PAES were provided to the regulatory agencies, they would be free revisit the authorization decision and determine if “…the marketing authorization should be maintained as granted, varied or even withdrawn on the basis of the new data resulting from the study.”

While regulatory agencies have always been free to revisit their decisions, this approach seems to imply that they are obligated to reconsider their decision after the required PAES.  This makes thoroughly changes the role of the non-PV focused P4 trial from today’s approach to a much more high-stake trial.  Under this approach, these types of P4 trials would have much higher risk and would likely need to be treated much more like we treat P3 studies.  This means a likely significant increase in cost for these trials.

Efficacy vs. Effectiveness

The next section of the position paper focuses on the question of efficacy vs. effectiveness.  The paper comes down clearly on the side of efficacy.  Again, this could be a major change for P4 trials, many of which are focused on developing real-world effectiveness data to provide support for reimbursement decision makers.  This change may also force a significant revisiting of the P4 approach followed today.  Additional P4 trials may be needed if the mandated trials focus on efficacy and cannot be tasked with also considering effectiveness.  This will have a significant impact on time and budget as well.

Situations Where PAES May Be Required

The paper then proposes a set of 7 situations where PAES may be required.  They are:

Situation Where PAES May Be Required Comment
1.   Studies aimed at determining clinical outcome following initial assessment based on surrogate endpoints This type seems very logical.  If surrogate end points were used to get authorization, then a study may be required investigating the underlying endpoint sought.  But, this may significantly add to the cost of using surrogate endpoints for approval, since surrogates are sometimes used because of the time (and cost) of gathering data on the underlying endpoints.
2.   Studies on combinations with other medicinal products Acknowledging that testing for authorization can only cover a limited range of combinations, P4 trials may be required to test additional combinations.
3.   Studies in sub-populations Given the limitations on the number of sub-populations, additional sub-populations may be required to be tested.
4.   Studies in the context of the European standard of care If the trial uses subjects primarily from outside of the EU, the EU may request additional information from patients treated within the EU.  This would negate any cost savings a company might hope to garner by working in other markets.
5.   Studies linked to a change in the understanding of the standard of care for the disease and/or the pharmacology of the medicinal product This is a scary one.  It proposes that if the standard of care for a disease had changed, the authorization holder may be required to develop new efficacy data addressing the new standard of care.  This could result in a never-ending need for new efficacy trials – a major change in way we think of authorized products.
6.   Studies aimed at determining the long-term efficacy of a medicinal product This is one of the “traditional” reasons for P4 is long-term analysis.  Difference is focus on efficacy instead of effectiveness.
7.   Studies in everyday medical practice The proposals suggests that these would be required when “…there is clear evidence that the benefits of the medicinal product underdiscussion as shown by randomised controlled clinical trials might be significantly affected by

the real-life conditions of use.”  This seems to open the door for any misgivings or concerns by the regulatory authorities to result in the requirements for a trial – and when they get results they will be obliged to revisit the approval.

Final Thoughts

While this is still in proposal stage, the direction is clear.  PAES is going to become a new tool for regulators who have efficacy concerns about both new approved and legacy products to address their concerns.  It is likely to have a significant impact on the cost, risk and structure of Medical Affairs if it comes into effect.

I urge you if you have comments to follow the process found in the document to express them.  I will be doing so.

What are your thoughts?  Am I overreacting? Please leave a comment.

h/t PharmExecBlog