Medical Science Liaison Compliance

Medical Science Liaisons Roles: Enigma and Dilemma

By Jane Chin, Ph.D. This article supersedes Medical Science Liaison: Examining the Role, Revisited, originally published in Medical Science Liaison Quarterly, Volume I Number 4, Winter 2004. First update published in Fall 2006. Second update published in Winter 2009.

When I first wrote this article in 2004, originally titled “Medical Science Liaison: Examining the Role, Revisited” I was a senior medical liaison at a pharmaceutical company. At around the same time, I was interviewed by Medical Meetings magazine for “Breaking the Silence: Medical Science Liaisons Stand Up for Their Integrity.”

The atmosphere was charged and the sentiment telling - abuses of the credibility MSLs have with influential thought leaders are catching up with some pharma companies.  Medical science liaisons across the industry were glad someone was talking and at least raising questions that they raised only in private.

A Medical Science Liaison on National TV

I was not the egregious one: during the summer of 2003, David Franklin’s face was plastered on television nationwide in a Dateline NBC interview that promises sensational crackdown of Pharma’s corruption and deception.  I was at a scientific meeting when the interview happened and received voicemails from MSLs, excited about the coverage.  Thank goodness for a three-hour time difference. I called my husband from the East Coast and asked him to record the segment. The interview transcript (along with the picture of David Franklin’s face) had been on NBC’s website, under “Drug giant accused of false claims”.  As of February 21, 2009, this article may be accessed at http://www.msnbc.msn.com/id/3079883/ .

Now, years later and many hundreds of millions of penalty dollars from questionable sales- and marketing practices, are pharmaceutical companies finally doing the "right" thing, at least where MSL roles are concerned?

My observation is that MSL directors are trying, and while their efforts still parallel the hardships of spawning salmon swimming upstream, at least they are getting more nods of sympathy from upper management.

Figure Below: Screen capture (as of February 2009) of Dateline NBC’s website archive on former MSL and whistleblower David Franklin.  During the airing of the broadcast, Franklin was employed at Boston Scientific.  In 2004, Pfizer, which had acquired Warner-Lambert and the company’s lawsuit around the Neurontin case, settled the lawsuit.  Franklin was awarded $26.6 Million as part of the settlement.

Moment of Truth Assessment for MSL Directors

Medical science liaison Directors may conduct this assessment to gauge whether the program’s MSL activities may pass the litmus test (and especially the “Dateline NBC test”) of compliance:

Intent of Field-Medical Involvement

Is the intent of greater MSL involvement in the field closely related to sales and marketing objectives?  Are MSLs’ performance tied in any way to sales performance?

• Overtly - for example, the sales team are rewarded on total sales including off-label sales of the company’s drug, and sales representatives are using their area MSLs to “grow the market” in unapproved indications (off-label promotion).

• Covertly - for example, your sales and marketing directors play golf with the CEO on weekends and as a result, you are facing an executive-driven pressure to engage your MSLs in increased and risky crossfunctional collaborations.  You are asked to make your MSLs help the company’s sales reps to “even the playing field”.

Reach and Frequency Directives

Are your MSLs demanded to "target the right doctors with the right message at the right frequency", but the definition of the “right doctors” are based on the commercial teams’ definition and driven by prescribing behavior rather than based on a broad, medical science definition of “thought leadership”?

• Caveat - it may make sense to ask MSLs to have at least some interaction with a physician in order to build any new relationship.

• However - if MSLs are calling on 200 “thought leaders” you may need to explain how you’re defining thought leaders and whether these include a high percentage of high prescribers.

• Additionally – the MSL’s thought leader relationship may have reached a steady state where the MSL is able to maintain a significant rapport via telephone and email communication that supplement an occasional – rather than frequent – face-to-face visit.

Whose Quota are These, Anyway?

Are the imposed quotas on field-medical activities in any way linked to an intent to gain a sales-based return on investment (ROI) for the MSL program?

• Caveat – I have found most interesting our industry’s creativeness to “relaunch” the same thing under a different name. In the case of MSL value and metrics, executives have shied away from using the term return on investment (ROI).  Yet many executives have simply adopted safer sounding names to mean the same thing.  Hence, we hear about the return on science (ROS) or return on education (ROE).  The reality is that ROS or ROE can still be tied to risky field medical behaviors.

• However - MSL directors are now using more quality-based markers including thought leader satisfaction surveys to communicate value to stakeholders, and customer satisfaction still can gain upper management’s delight.  Additionally, programs are focusing on total outcomes, which would minimize the risk of isolating individual MSLs’ apparent “poorer” performance that is inherent in some geography (for example, a MSL working in New York City versus a MSL responsible for the entire West Coast).

Answering these simple questions may be the first step to assess your own organization’s risk level in field-medical science activities.

Why MSL Roles Remain an Enigma

The medical science liaison profession remains an enigma, and most MSLs will admit that they cannot readily answer the everyday question “what do you do for work?”

This enigma is perpetuated by what MSL profession lacks:

• no standard job description (though we all have some idea what MSLs do)

• no standard eligibility criteria (though we tend to agree on basic criteria)

• no standard performance metric (this is where companies fall on old habits)

• no standard regulatory guidelines (this is where old habits may get risky)

"Being in the MSL world since early inception, I have seen the field evolve from 'what do you do and how do you differ from my sales person' to 'I have never been an MSL but I know what you do and, by the way, I'll tell you how to do your job'. The job is getting tougher to do and there are lots of challenges, not the least of which are the FDA and their focus on our profession. This makes it even more critical to attract, hire and retain the right people, which are in dire shortage." Feedback from an editorial board member, Medical Science Liaison Quarterly, Volume II Number 4 Winter 2004.

Lack of Guidance Driven by Industry and Governing Bodies

Even PhRMA, the industry's official organization has no guidelines of conduct for a professional sector that is rapidly expanding.  Back in 2004 when Alan Holmes presided, I have written PhRMA asking for an organizational opinion or guidance on the activities of MSLs.  I was directed to the PhRMA code - I think; the email response was extremely cryptic, suggesting that the responder did not understand my query.

In 2009, more industry documents and regulatory guidelines have either directly or indirectly addressed the activities of medical science liaison professionals, but these documents reiterate the general role of the MSL without clearly outlining ethical standards or codes of conduct.  The MSL’s code of conduct within his or her organization remains at the discretion of that organization.

Even as many MSL programs have standard operating procedures governing both daily activities of the medical science liaison (including circumstances that warrant such activity) as well as delineating contact protocols with other functions like sales and marketing, the MSL role appears to be left up to the interpretation and more importantly – a multi-layered intent of industry executives.  The benefit of a written rule of engagement is the ability for the MSL to point to a document when confronted with a questionable request instead of explaining why the MSL wasn’t refusing to be a team player by not visiting a “really important doctor.”

How “Safe” is Organizing MSL Programs Under Medical Affairs?

Some may believe that MSLs are an extension of the pharmaceutical company's medical director.  While most lawyers and compliance officers will feel more comfortable to see the company organize their medical science liaisons under the medical affairs umbrella, I am not convinced that this is as safe a haven as many would believe.

A memorable example is a global pharmaceutical company’s MD-trained medical director who made a speech at the company’s national sales meeting.  In dramatic fashion, he began his speech with, “I am here not to bash {competitor drug} - but TO BURY IT!”  After receiving thunderous applause from the company audience, the medical director proceeded to describe a head-to-head study that most MSLs working with that drug avoided discussing because of an underwhelming difference in response rate between the company drug and a competitor drug.  Yet the medical director related the results in a way that is best described as “spinning the data” – portraying a bigger difference than there actually was.  This medical director did what the sales and marketing directors expected him to do.  If this was the conduct of the company’s medical affairs director, then the fate of this medical director’s “extension” – the MSLs – would face similar pressures from the company’s sales and marketing teams.

Let us assume that the MSL director is an ethical and politically perceptive individual who keeps her team out of trouble while appearing friendly to all internal stakeholders.  If the director heads a program funded by commercial entities, then the funding department would be expected to exert some influence in the activities of the program and in turn, rightly demand a return on its investment.  Even if the program is funded by “medical affairs” - and the FDA never mandated that MSL programs be placed under medical affairs - companies may still retain sales-driven incentives from MSL activities, which render this a purely cosmetic organization.

In other words, MSL programs placed under medical affairs or R&D are not necessarily "safer" or "more ethical" than those under sales and/or marketing. Programs placed under medical affairs tend to be farther removed from the pressures of sales and marketing, but a program placed under medical affairs can easily assume a sales-like mentality, where MSLs are expected to conduct at least 10 educational programs per quarter, make 3 calls per day, and "help out sales colleagues to convert difficult accounts, access no-see doctors, and grow the market with high-decile physicians."

MSL Role: Substantive or Symbolic?

Regulatory scrutiny has focused on the direct- and indirect drivers on MSLs’ activities.

Therefore, companies should realize that the symbol (what function the MSL program reports to, what advanced degrees MSLs hold) does not matter as much as the substance (what MSLs are actually expected to do, who applies the greatest pressures on MSL objectives) when it comes to evaluating activity drivers.

In fact, the well-publicized Neurontin® case (against Parke-Davis/Warner Lambert/Pfizer) was an example of the MSL program serving as one facet of a multi-pronged off-label sales strategy. Allegations of corrupt sales and marketing practices were coupled with an abuse of trust between MSLs with advanced degrees (Franklin was a PhD and alleged that he was coached to misrepresent his experiences in cardiovascular medicine) and physicians.

Even then, is the firewall purely symbolic, or are there teeth to a separation of science and sales?

In the past, many MSL program managers and directors have encouraged or required MSLs to "work with sales reps" to demonstrate program value to the key internal stakeholders: sales and marketing.  Many of these activities may be completely legitimate (for example, if a rep's physician was unsatisfied with the response s/he received from a standard or tailored medical information query and demanded to speak with a field-based medical personnel,) but these activities were vulnerable to abuse of the MSL role.

Expanding MSL Programs: Encouraging or Concerning?

Up until the PhRMA Code revision of 2009, most companies have curbed or cut back joint calls between MSLs and sales representatives.  Many companies have reallocated research- and educational program funding from sales or marketing to medical affairs or even third-party vendors (particularly in medical education / CME programs).  The first wave of response to compliance by MSL programs has been the reduction of risky internal collaborative behaviors and separation of research and educational funding from any illegal incentives.

“The critical issue for MSLs in the future is to provide our internal and external customers the appropriate medical and scientific information in order to improve patient care and maximize the value of our product portfolio. The value of our activities must be outcome driven and clearly recognizable to a broadening base of stakeholders. The job of the MSL has become increasingly more difficult as the MSL role has expanded beyond the traditional MSL/Academic KOL relationship to include scientific discussions with managed markets, medical associations, and regulatory agencies." Feedback from an editorial board member, Medical Science Liaison Quarterly, Volume II Number 4 Winter 2004.

With the 2009 PhRMA code revision, where the field-sales activities become increasingly restrictive, and coupled with the continual wave of physicians and institutions shutting their offices to sales representatives, the industry has responded with an expansion of MSL programs.  Many medical affairs executives anticipate a re-emergence of pressures for crossfunctional collaboration, as MSLs may now need to compensate for an increasing barrier faced by sales representatives to physicians.

In other words, the “same old” crossfunctional conflicts will become relevant in medical affairs again in 2009, only these conflicts will be amplified in today’s uncertain times, with higher barriers to engage with physicians, steeper competition amongst pharmaceutical companies, and harsher financial realities of operating in a cost-cutting environment.

The expansion of MSL programs at first glance appeared to be a trend worthy of celebration.  However, I feel more concerned than encouraged for one simple fact: most company executives still cannot clearly justify the MSL role’s existence in an objective, independently contributing way to the long-term valuation of the company. The intangible deliverables of the MSL program and qualitative metrics ("impact" or "value") of an MSL's contribution to the organizational bottom-line remains this profession's Achilles' heel.

A Matter of Culture and Self Examination

The role of the MSL can no longer be ill-defined or enigmatic.  The nature of MSL value as a function of interactions with internal stakeholders and external stakeholders can no longer be in limbo while the cadre of industry consultants tries to help management figure out the metrics dilemma.

Perhaps we may not discover ideal metrics for a very long time, but pharma companies’ risk of doing business are increasing every year.  Hundreds of millions of dollars have been paid in off-label prosecution lawsuits across the pharmaceutical industry since 2004, when Pfizer settled the Neurontin case.  Hundreds of millions of dollars more may be at stake.  Most small companies will not survive penalties of this magnitude.

Instead of swimming upstream to find the elusive magic bullet metric, perhaps our industry can all agree that no objective metrics currently exist that satisfies the true value of MSL programs.  A MSL program's proactive or reactive approach to current events relating to the MSL role can be indicative of the director's management philosophy, or in a larger scale, indicative of the company's culture.

Most pharmaceutical company web sites post value statements that seem more idealistic than realistic, with a strong focus of "doing the right thing" and conducting business ethically. No company states that “our mission is to make sales at all costs, or at least whatever is necessary for me to get my bonus,” yet actual employee practices tell a different story of some executives’ true mission.

In the past, many of us have been waiting for the FDA to step in and make a sweeping regulatory overhaul to the MSL function within healthcare.  The real question is, can we afford to keep waiting for a train that may never come? The time has come for MSL programs and compliance officers to periodically conduct internal audits and informal "self-examination" on activities and objectives.  It now looks like the golden age of regulating industry’s conduct is upon the pharmaceutical industry and us as its constituents. 

Dissemination of Off-Label Information, Safe Harbors, and Conduct of Medical Science Liaisons

Jane Chin, Ph.D. President, Medical Science Liaison Institute.

This article deconstructs a widespread notion of "safe harbor" in discussing off-label information, and present three critical issues in compliance as identified by medical science liaisons (MSLs).

Quest for “Safe Harbor”

Where, if anywhere, does the law ascribe ‘safe harbor’ surrounding verbal and written dissemination of off-label use for a drug? Based on the general activities of medical science liaisons, the motivation behind the question should be obvious.  Dissecting the origins of the term “safe harbor” is an ugly process to wade through, as I and an attorney colleague discovered, because each section required you to look up another legal document ("This sentence is valid unless circumstances as described in Section 553" – and section 553 will lead you to another section, and so on), but compliance officers and attorneys are probably used to this.

We found that under United States Code Title 21 Food and Drugs, Chapter 9, Subchapter V, Part D, Section 360aaa (amended by FDAMA's Section 551), "Requirements for dissemination of treatment information on drugs or devices" contains a safeguard to disseminate written information when the manufacturer fulfills certain requirements to enable distribution of information that is not in the approved labeling of the drug. These requirements have an exception described under Section 557 "Rules of Construction":

(a) "UNSOLICITED REQUEST. – Nothing in section 551 shall be construed as prohibiting a manufacturer from disseminating information in response to an unsolicited request from a health care practitioner."

Notice that this is not specific to the type of dissemination - i.e. - written or oral.

The FDAMA Effect

Before FDAMA (FDA Modernization Act of 1997), drug makers could not disseminate off-label information without risking prosecution based on violation of Food, Drug, and Cosmetics Act. Section 551 resides under 401 "Dissemination of Information on New Uses." Circumstances where drug makers may disseminate information on new (off-label) use of a drug are where the companies:

1. Submit a sNDA

2. Do not disseminate false or misleading information

3. Conduct the clinical work embodied by disseminated material

4. Submit the copy of materials to the FDA at least 60 days prior to dissemination

5. Include prominent disclaimer of off-label, unapproved use

Where “Safe Harbor” is Not

Ironically, the term "safe harbor" is not found in FDAMA document. Through a series of guidance drafts, the term "safe harbor" came to represent very specific circumstances through which information may be disseminated from drug makers to healthcare practitioners. Herein lies the safeguards through which companies may disseminate off-label information, unfortunately defined as a "safe harbor." I say "unfortunately", because the term has given some constituents the perception that "safe harbor" is as general or safe as it actually is.

"Safe harbor" is implied in Chapter 1 Food and Drug Administration, Department of Health and Human Services (HHS) Part 99.1 Scope:

(a)    This part applies to the dissemination of information on human drugs, including biologics, and devices where the information to be disseminated.

(b)    This part does not apply to a manufacturer's dissemination of information that responds to a health care practitioner's unsolicited request.

Again, this does not specify method of dissemination - i.e. - written or verbal, nor does it specify all the rules that the manufacturer must fulfill to disseminate written information.

This leads to the first critical issue: 

There is NO "Safe Harbor" special to Medical Science Liaisons in Off-Label Information Dissemination.

(Tip for Compliance officers and corporate attorneys: your MSL director would like you to sear the above truth onto the consciousness of every commercial executive who is 100% convinced otherwise.)

Ultimately, the thrust of this exercise is to demonstrate that no where in the statues (laws) does a statement exist that allows medical science liaison activities to be governed differently than those of a pharmaceutical sales representative. In the eyes of the regulators, job title or compensation structure makes no difference in how the activities of a pharmaceutical company employee are regulated. If a pharmaceutical employee works within the boundaries specified by what is collectively identified as "safe harbor," the company is safe. If the employee's actions fall outside the box, it's fair game. This does not mean it's illegal per se. The company may just need to argue its case in court.

Promotional constituents who still think that medical science liaisons are protected by safe harbor and thus can talk all the off-label information they want are harboring dangerous beliefs. Many sales representatives, for instance, have brought their medical liaisons into physicians' offices and have either seeded off-label discussions or blatantly started conversations as "Dr. Smith, this is MSL Hannah. MSL Hannah, why don't you tell Dr. Smith about {off-label use of drug}?" 

This brings us to a second critical issue:

Compliance Programs are Useless Without Enforcement at Both the Corporate Level and Field Level.

Since the OIG published its final guidance in May 2003 issue of the Federal Register (Volume 68, Number 86) and recommended establishment of a compliance program, pharmaceutical companies have formed committees and initiatives toward such programs. However, establishing programs and enforcing compliance guidelines both at the corporate level and in the field are not mutually inclusive. Some medical liaisons have related that their interactions with commercial constituents have not changed, and heads of these constituents are leaving the medical liaisons to direct "proper interaction" with sales representatives during a physician meeting.

What Effective Compliance Really Requires

While forming compliance programs is as encouraging as organizing medical liaison groups under medical affairs as opposed to under sales and/or marketing, I believe that symbolic compliance is as useless as symbolic firewalls where liaison programs are concerned.

Putting everyone through compliance training is a nice first step, but the metrics of success in a compliance program is not whether everyone has passed a test or completed a course, but by direct- or indirect risk reduction indicators in the field. This is not about what companies organize and how they organize their groups, but ultimately whether companies are following through with their "compliance strategies" and executing on those strategies. 

This premise directs the third critical issue, which is:

Effective Compliance Requires Leadership, Not Lip-Service.

The term "empowerment" has become a fad, a nice sounding term that signifies nothing. Is "leadership" becoming such a term in the medical science liaison profession? How liaison directors and managers lead their programs in the coming years will show whether management is truly leading or paying lip service to their liaisons. Many liaisons will admit to joining companies they believe to have the culture and infrastructure to allow them to "appropriately perform their duties." Most if not all companies' mission or value statements contain words like "ethics" and "integrity." Yet liaisons are running into managers and directors who lend no support when they raise concerns about their companies' business practices, and even label their liaisons as trouble makers or uncooperative.

When a liaison sees risky business practices, it is the liaison's responsibility as an ethical professional to speak up and communicate this to their managers. Imagine my chagrin when an attorney shared his advice for liaisons: "Unless you're asked to participate in o illegal activities, keep your mouth shut if you want to keep your job." The attorney's clients are those who had opened their mouths and were retaliated by their management. His advice may be practical, but keeping silent won't do much for ensuring appropriate use of the liaison role or for improving the image of the pharmaceutical industry. This also further illustrates the systemic problem of poor leadership at the management level.

A medical science liaison's cause for concern may not always be indicators of risk or liability. Yet how a manager or director handles these concerns reveals whether he or she is a leader who examines the root cause of these concerns or a figurehead who administrates. Should improper pressures come from powerful internal constituents, a leader is willing to be held accountable for changes in communications or expectations between the liaison group and internal constituents. Employees follow leaders, not administrators.

At the heart of this technically oriented business are relationships. Medical science liaisons have long been told that their responsibilities are to cultivate relationships – both with external customers and with internal colleagues. Medical science liaisons' internal colleagues may fare as well by proactively cultivating relationships with their medical liaisons, not to use liaisons for sales purposes or "as a nice gift to the ego of an important physician," but to understand how the liaison role contributes to the organization and how liaison teams serve distinct and equally vital functions for the organization. What the field-based science liaison role becomes in these next few years should not be shaped by government regulators, but by industry's medical liaisons, managers, directors, and senior management.

Mitigating Compliance Risk and Off-Label Promotion Prosecutions and OIG Scrutiny of Medical Science Liaison Activities

June 2007 Industry Conference Report by Tanya Douglas-Holland MD. (Medical Science Liaison with a Specialty Pharmaceutical Company. This report has been submitted as part of MSL Institute's "Press Pass" to the conference.)

In today’s current environment of off-label drug usage, many companies walk a thin line between following regulatory guidelines and meeting business objectives.  The Center for Business Intelligence’s 8th Annual Conference, “Guidelines for Disseminating Off-Label Information,” provided industry professionals with an opportunity to:

• hear from governing bodies and review the current regulatory landscape as it relates to off-label activity

• receive guidance on which program standards, structures, and monitoring should be in place to ensure compliance; and

• evaluate their current programs to ensure they are meeting the requirements of off-label dissemination. This report highlights the major points of the meeting.

Disclaimer: The content of this article is based on the information presented by conference speakers, and does not necessarily represent the positions or personal opinions of Dr. Holland, Dr. Holland’s employer,  or MSL Institute.

Latest Developments in Off-Label Prosecution

Overall, there is significant active enforcement taking place. Since January of 1992, there have been over 100 major health care fraud settlements with an estimated $5.3 billion dollars paid by pharmaceutical companies.  It is reported that there are approximately 120 prosecutors working on healthcare fraud alone, and since 1992, 57% of recovery efforts involved pharmaceuticals.

The increasing devotion of governmental resources to recovery suggests that there is an on-going problem within the pharmaceutical industry.  The “Schering-Plough Case” is one of the most recent examples involving off-label promotion.  Schering-Plough was accused of giving false, misleading information about Temodar® at a booth during a national oncology scientific meeting; it was alleged that Temodar® was being promoted off-label for broader treatment of brain and metastatic cancers, and Intron A was improperly promoted off-label for superficial bladder cancer and Hepatitis C.

A warning letter was drafted by FDA and sent to Schering-Plough in 2001; in August of 2006, Schering-Plough Corporation was sentenced and agreed to pay a total of $435,000,000 to resolve criminal charges and civil liabilities in connection with these illegal sales and marketing practices.

Mitigating the Risk of Private Lawsuits for Off-Label Uses

The term off-label was defined as “for uses or treatment regimens (dosing, combinations) or patient populations not included in the approved labeling.”   Furthermore, it was emphasized that it is important to understand the distinction between “off-label promotion” and “off-label education.”  These terms were delineated in the following manner:

• off-label promotion  markets claims for a product regarding a clinical use not in labeling **Off-label promotion creates new legal risks and potential liability to consumers and third-party payors.

• off-label education  disseminates medical literature (or underwrites continuing education) on information not in the label.

It is not always clear what is legal and what is not; judges and juries will conflate (i.e. merge into one) off-label education and off-label promotion and have a hard time making the distinction.  Examples of the types of evidence used in off-label promotion cases include:

• company awareness of the risks of off-label promotion (what did you know and when did you know it?)

• training and activities of marketing professionals and sales representatives

• non-promotional educational activities

• interactions with regulators on approval, labeling, & marketing

• documents – call notes, labeling, financial, marketing, etc.

As a result of the ambiguity surrounding off-label promotion and education, there is no real way to ELIMINATE the risks of private lawsuits – they will happen.

The number #1 way to REDUCE the risk of a private lawsuit is to NOT ENGAGE IN OFF-LABEL PROMOTION.  The following 6 considerations were offered to cope with unclear legal standards:

1. Assess what is known about the effectiveness of the off-label use -- What is the totality of clinical evidence?

2. Assess the potential commercial benefits from proposed off-label activities

3. Assess the health risks from off-label use -- Does the use involve additional adverse events?

4. Assess product liability risks

5. Assess marketing risks -- Will sales representatives be involved and can they be properly trained and controlled?

6. Assess other legal risks -- Is the product reimbursed by the government?

It is important for industry professionals to understand the foundation for off-label information lawsuits and reduce their risk. When the government comes looking, it is important for organizations to willingly provide any requested information; problems arise when there are attempts to destroy or conceal documents.

For example, had Schering-Plough been truthful and upfront, damages may have been less.  Voluntary disclosures could potentially result in non-prosecution.  Governmental agencies want companies to have compliance programs that work.  Corporate Integrity Agreements (CIAs) serve as examples of what the government expects and can be used as the “gold standard” for developing good compliance programs. 

Role of Office of Inspector General’s (OIG) in Monitoring Off-Label Activity and Promotion

The OIG has become increasingly concerned with illegal off-label promotion.  Because Medicare Part D is one of industry’s “new largest customers” and has significant subpoena power, OIG is concerned about anything that may raise the cost of the pharmaceuticals they pay for.  They have begun taking a more active approach in investigating violations surrounding off-label promotion.  Last year, the OIG identified the following areas where they will assist in regulatory monitoring and reviewing of off-label cases:

Information Requests for information relating to off-label uses of a product

• Is there an internal tracking process?

• Is there documentation in an inquiry database?

• Are reports sent to a compliance officer on apparent off-label request activity in the field?

Charitable Contributions

• Are there processes and procedures in place? What are the approval criteria to determine the level of contribution provided?

• What is the budget source?  Is it coming from marketing?

• Is there a requirement for disclosures by the recipient of funding?

• Are there ROI analyses surrounding contributions

Educational Sponsorship Activities, including grants for independent third-party medical education programs (e.g. Accredited CME)

• Is there a compliance officer review?

•  Excluding scholarships, are sponsorship arrangements made to a specific individual?

• Were oral or written arrangements made prior to submission of written application?

• Are there appropriate financial disclosures?

Educational “Programs” including exhibits, advisory boards, and speaker trainings

• Are there criteria in place to identify and select participating health care professionals?

• Is there a tracking/monitoring system in place?

• What is the budget funding source?

Employee Compensation

• Are there financial incentives to motivate sales and marketing personnel to engage in improper promotional sales activities?

• In what manner do medical personnel (including MSLs) participate in meetings/events with health care professionals (both alone and/or with sales force)? What role do these medical personnel play at these meetings?

Medical Science Liaisons (MSL)

• There is much suspicion from OIG on the role of a MSL and their activities. 

• What guidelines are in place for MSLs working in investigator-initiated studies?

Importance of Integrating Federal Trade Commission (FTC) Guidelines into a Corporate Compliance program

The FTC has evolved to become the government’s “watchdog” over competitive and marketing practices that impact consumers.  Regulations, laws, and initiatives by the FTC touch upon many industries.  The role of the FTC is twofold; it seeks to 1) prevent deceptive or unfair acts and practices, and 2) prevent unfair methods of competition (antitrust).  Ultimately, the FTC seeks to maintain the integrity of the marketplace.

The FTC is interested in “off-label” use, and as a result, the health care and pharmaceutical industries are under the microscope of FTC.   While the Food and Drug Administration’s (FDA) focuses primarily on prescription drugs and biologic products, the FTC focuses on over-the-counter drugs, foods, and dietary supplements.  However, both agencies work in concert to protect consumers from deceptive claims.  In the future, areas of particular concern to the FTC as it relates to “off-label” information include advertising & marketing, privacy, retail practices, and international efforts.  The FTC is also very concerned about “non-adult marketing” as well as advertising in Spanish.

Dissemination of Off-Label Information within Frameworks of Current Case Laws, FDA Rules, and Company Policies

Although the Washington Legal Foundation (WLF) vs. Henney court decision ruled CME guidance and Section 401 of FDAMA are “safe harbors,” the FDA can use dissemination of reprints or medical text as evidence in enforcement action of unapproved intended use.  Thus, while the FDA does not intend to restrict the dissemination of scientific information, 21 CFR 312.7 does restrict promotional claims of safety or effectiveness of a drug in uses for which it is under investigation. Furthermore, this regulation precludes commercialization of a drug before it is approved for commercial distribution.  Although there are existing challenges for defining promotional materials, companies and individuals should strive to balance and minimize risks.

The following recommendations are offered as “Compliance Program Essentials:”

• Clear guidelines to all employees concerning when, if, and how dissemination of off-label information could be appropriate;

• Routine monitoring and auditing procedures to ensure policies and guidelines are being followed;

• Internal review processes to ensure all materials are scientifically sound and not false or misleading;

• Coordinated efforts across multiple disciplines to see the “big picture” with regard to the universe of possible off-label concerns. 

It is important to note that policies regarding dissemination of off-label information are NOT limited to sales forces; off-label rules are also applicable to MSLs, clinical, and R&D personnel as well.

Definition of a Medical Science Liaison (MSL) Role and Evaluation of MSL Risk Tolerance Level

The ultimate role of a MSL is to “provide scientific and educational information to health care professionals (HCPs).”  Appropriate activities encompassed in this role include:

• Maintaining long-term scientific contact with critical thought leaders;

• Providing the company with competitive intelligence and disease treatment trends;

• Managing investigator initiated trials (IIT);

• Supporting on-label discussions with in-depth knowledge;

• Communicating additional information regarding marketed drugs in an unbiased manner; and

• Providing scientific support at conferences.

MSLs occupy a middle-ground between sales/marketing and medical communications/ medical affairs.  The FDA does not recognize MSLs as a “special class” and both OIG and the DOJ monitor the role of MSLs as it relates to healthcare compliance.  MSLs are prohibited from promoting off-label uses of products and disseminating medical/scientific information that is false or lacking fair balance.  The risk of MSLs becoming “off-label sales representatives” is real; thus it is crucial for MSLs and others to evaluate their tolerance level.

Areas of concern with relevant questions to consider when assessing companies’ risk when deploying MSLs may include:

TONE AT THE TOP

• What is the real message being given to MSLs by management, not just from compliance? (RED flags include the use of “subtle” i.e. non-written guidance to MSLs as well as job descriptions that are either vague or at odds with day-to-day activity)

• How is the MSL department organized and managed?

INTERACTIONS WITH SALES & MARKETING REPRESENTATIVES

• What is the policy on joint presentations and meetings?

• What is the frequency of sales representative presence at KOL meetings

VOLUME OF ACTIVITY

• What is the number of presentations, number of HCPs in audience, and potential magnitude of impact and perception by outside reviewer?

IIT PROGRAM

• What are the criteria for selection of studies and funding?

• What is the involvement of MSLs?

• How is follow-up conducted?

MULTIPLE THERAPEUTIC AREAS

• Are there multiple policies and processes for MSLs?

BONA FIDE SERVICES AND FAIR MARKET VALUE

• Is there assurance that all studies and services provided by HCPs are valid and payments are consistent and represent fair market value (i.e. speakers, advisory panels, clinical trials)?

PUBLICATIONS

• Is ghost writing taking place? (Yes = RED flag)

• Is there full disclosure in all publications of investigator/authors relationships to company?

MARKETING PLANS AND MSL ANNUAL PLAN

• Is off-label promotion laid out as a Brand goal and reflect activity by MSLs? (Yes = RED flag)

PROACTIVE VS. REACTIVE BEHAVIOR

• Are medical information requests unsolicited or can there be involvement by sales representatives?

• Is “probing for prescribing” involved? (Yes = RED Flag)

FORMULARY/OUTCOMES PRESENTATIONS

• Are MSLs doing off-label presentations to larger groups? If so, who is the audience and who reviews the presentation to ensure it is fair and balanced?

TREND ANALYSIS OF MSL AND MEDICAL INFORMATION REQUEST ACTIVITY

• Is there monitoring of incoming requests for origin, type of question asked, answers given, method of response (letter vs. MSL visit)?

KOL LOCAL AND REGIONAL KOL PROGRAMS – HOW ARE THEY DEFINED AND MANAGED

• Are there multiple levels (e.g. tier 1, 2, 3) and if so what are the criteria?

DOCUMENT MANAGEMENT

• Is there a robust system for managing all information and requests including decisions and sign-offs?

TOTALITY OF SPENDING

• Are you linked into the company’s process to track all payments made to HCPs?

Conclusion

Over the past decade, the climate in which industry professionals operate has changed significantly.  One presenter from the conference had this to say: “WE SHOULD BE SCARED IN INDUSTRY.”

Despite the fluctuating industry landscape, there are existing roadmaps which can help MSLs and other industry professionals navigate the seemingly treacherous terrain.  Corporate Integrity Agreements offer an opportunity to learn from mistakes and are excellent guides that can be used to create effective compliance programs.

When evaluating dissemination of off-label information, MSLs should remember that enforcement is based “on the message, not the messenger.”  It is important for MSLs to thoroughly understand our role, and we should continuously evaluate and minimize risks.  Proper training, appropriate tracking & monitoring are crucial to ensuring an environment of compliance and integrity.