Medical Science Liaison (MSL) and KOL Regulatory Compliance

June 2011

MSL-KOL Engagement:
Ensuring Compliance
A FirstWord ExpertViews Report

MSL-KOL Engagement: Ensuring Compliance

Report Title: MSL-KOL Engagement: Ensuring Compliance
Published June 2011
© Copyright 2011 Doctor’s Guide Publishing Limited

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Contents
Executive summary .............................................................................................. 1

Evolution of the MSL role....................................................................................... 2

What do MSLs do? .......................................................................................... 4

Education versus promotion ............................................................................. 6

US regulations governing MSLs .............................................................................. 8

US rules on off-label promotion ........................................................................ 8

EU rules on off-label promotion ........................................................................ 9

Off-label marketing cases .................................................................................... 11

A growing concern........................................................................................ 13

Off-label prescribing ..................................................................................... 15

The clinician’s perspective .......................................................................... 17

Off-label strategies ....................................................................................... 17

Corporate integrity agreements ............................................................................ 19

Increased scope of CIAs ................................................................................ 19

Standard operating procedures............................................................................. 22

Firewalling................................................................................................ 23

Clarification .............................................................................................. 23

What SOPs should address ......................................................................... 26

Globalisation............................................................................................. 27

MSL training ...................................................................................................... 28

Frequency of training ................................................................................. 30

Tracking and reporting systems............................................................................ 31

June 2011 i

All Contents Copyright © 2011 Doctor's Guide Publishing Limited. All Rights Reserved


Technological advances .............................................................................. 32

Compensation and metrics................................................................................... 34

Quantitative metrics .................................................................................. 34

Qualitative metrics..................................................................................... 35

Case study 1: mid-size pharmaceutical company..................................................... 36

Case study 2: medical device company.................................................................. 38

Board considerations........................................................................................... 40

Enforcement policies ........................................................................................... 42

Enforcement policy in the UK ......................................................................... 42

Enforcement policy in the US.......................................................................... 43

Individual responsibility .............................................................................. 44

Acknowledgements ............................................................................................. 47

ii June 2011



Executive summary
Medical science liaisons (MSLs) are the healthcare consulting professionals at the
vanguard of a new way of engaging with physicians. But while rising numbers of them are
being hired to educate researchers and prescribers about a company’s products they
often find themselves treading a thin and contentious line when those products are known
to be used off-label. Physicians want to talk about these uses and companies have an
interest in sharing the latest scientific information, which can leave MSLs with the difficult
question of how to apply the broad policy that forbids off-label promotion in virtually
every market in the world.
How do companies ensure MSLs always act appropriately to requests for information
about off-label uses and, more importantly, how do they ensure those actions are seen to
be appropriate?
How do they prevent MSLs from acting as sales reps in another guise, thus risking the
integrity of the entire profession before it has had time to fulfill its potential in modern
pharmaceutical practice?

These questions, and others, are answered in a rare look at the practice of off-label
promotion, its regulation on both sides of the Atlantic, and how companies are responding
to enforcement measures, particularly in the US, where a de facto policy of limited rule-
making and broad enforcement by threat of criminal prosecution is forcing companies to
examine their compliance policies.

The true extent of off-label promotion is not known but in the US, where whistleblowers
are both protected and incentivised to provide evidence against their employers, cases
are increasingly being tried and settled at levels that can no longer be regarded as just a
cost of business. In September 2009, Pfizer paid $2.3 billion to settle charges that it
improperly promoted four products. This trumped the $1.4 billion Eli Lilly had been forced
to pay earlier that year for marketing Zyprexa to patients who do not have the drug’s two
approved indications, for schizophrenia and bipolar disorder.

If fines and the threat of a corporate integrity agreement (CIA) are not sufficient impetus
to get compliance procedures in order, there is also the risk that individual executives will
be held to account.

June 2011 1



of care is changing and evolving, how policy might be changing individuals’ roles within
the delivery of healthcare, whether it be in radiology or cardiology, or in monitoring, and
so on. This is really responding to the value we’ve seen from these interactions in terms
of providing us with new insights into healthcare and how we can respond with solutions
to improve the delivery of care and patient outcomes.”

Education versus promotion

There is a thin line between educating healthcare professionals (HCPs) about a product
and promoting it, and nowhere is that line more apparent than when a product is known
to have off-label uses that HCPs want to talk about and companies have an interest in
encouraging. While the rules surrounding off-label promotion are clear (see below), the
question of how companies should apply the broad commandment that forbids it to the
daily routine of interacting with HCPs can often be a difficult one for MSLs and their
managers.

“While there are strict codes of conduct they don’t
really have specific guidance for MSLs or the
MSL-type role,” he says. “Because it is a
relatively new role within the pharmaceutical
industry, there is still lack of clarity on the
appropriate non-promotional activities of MSLs.
Companies have to individually create their own
guidelines on MSL activities.”

Macgregor spells out the ambiguity in Europe. “While there are strict codes of conduct
they don’t really have specific guidance for MSLs or the MSL-type role,” he says. “Because
it is a relatively new role within the pharmaceutical industry, there is still lack of clarity on
the appropriate non-promotional activities of MSLs. Companies have to individually create
their own guidelines on MSL activities.”

6 June 2011



The clinician’s perspective

The practice is so widespread in some areas that doctors are calling for cost-effective
trials to be conducted on common off-label uses of drugs. The Alliance of Speciality
Medicine, which includes the American Society of Cataract and Refractive Surgery, wants
the FDA to help drug companies design such trials. The move was apparently prompted
when companies stopped issuing drug samples to cataract surgeons due to concerns
about charges of off-label promotion. Dr Daniel S. Durrie, refractive surgery section editor
of Ocular Surgery News (OSN), says, “I hope the FDA itself does not block the ability of
the companies willing to do new studies and get FDA approval. We should be able to
develop a system that is good for the clinicians and provides specific data on surgical
outcomes.” 16

Off-label strategies

In April 2011, the Public Library of Science (PloS) Medicine published a retrospective
analysis of 41 complaints into off-label promotion arising from 55 whistleblowers from
January 1996 to October 2010. The idea, say the authors, was to get a broader picture of
the practice, which “can be used to develop new regulatory strategies aimed at effective
oversight of off-label marketing.” 17

The results, shown in Figure 5, indicate three main non-mutually exclusive goals of
promoting drugs off-label. The most obvious, in 85 percent of cases, was to expand a
drug’s use into unapproved indications. Another was to expand use into unapproved
disease subtypes, for example, antidepressants approved for adults being promoted to
paediatricians. A third was to promote unapproved, typically higher, dosing strategies.

The authors also identified four non-mutually exclusive types of marketing to achieve
these goals: prescriber-related practices such as financial incentives and free samples;
internal practices such as sales quotas that could only be met if the sales force promoted
off-label drug use; payer-related practices such as discussions with prescribers about
ways to ensure insurance reimbursement for off-label prescriptions; and consumer-

16
http://www.osnsupersite.com/view.aspx?rid=81827
17
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000431

June 2011 17



Standard operating procedures
Interactions between MSLs and HCPs have always been a legal minefield because the
potential for promoting an unapproved product is always present. But the increased scope
of recent CIAs, coupled with higher penalties, has significantly enhanced the need for
board members, via compliance officers, to know that MSL teams are conducting
themselves appropriately at all times.

It doesn’t help that while there are regulations in all countries banning off-label
promotion, as well as ever-stricter industry codes of practice, there are no specific
regulations for MSLs. “The compliance guidance provided by the government can be
interpreted in different ways by different companies. This is why having SOPs is really
helpful,” says Dale Kummerle, director of medical education of MSLs at Bristol-Myers
Squibb. “It gives clear guidance to MSLs and to the organisation as to how the
government guidance is defined. This gives a certain peace of mind that you are working
within a framework that has been approved and that you’re not doing anything risky.”

“We have SOPs for clinical research, medical
information, so why not have them for MSL
activity?” asks Dr Zlata Caric, managing director
of Lener Medical Consulting. “I know a few
companies working on developing SOPs but this
is a new development and I expect others to
follow.”

Accordingly, we are starting to see more SOPs to stratify the procedures a company
endorses with respect to MSL conduct. “We have SOPs for clinical research, medical
information, so why not have them for MSL activity?” asks Dr Zlata Caric, managing
director of Lener Medical Consulting. “I know a few companies working on developing
SOPs but this is a new development and I expect others to follow.”

22 June 2011



Compensation and metrics
With increased emphasis on building and maintaining long-term relationships with KOLs,
the MSL role must be based on fair metrics to evaluate performances and reward
appropriately. “Well, we all know what the sales metrics are, and the MSLs metrics are
none of them. Simple as that. If you are talking about the MSLs’ role as being scientific,
then we are talking about clinical trials, we are talking about publications, we are talking
about scientific exchange, and those should be the metrics,” says the “keeper of SOPs”
who asked to remain anonymous.

Quantitative metrics

The metrics should be concrete and reachable goals that apply to each MSL’s activities. 24
Some of the common metrics used to measure MSL performance are:

x Number of investigator-initiated trials (IITs) submitted

x Number of KOLs visited

x Age and depth of relationship with KOLs

x Number of articles/publications authored

x Number of scientific/educational speeches delivered

x Customer feedback

“The main metrics MSLs are measured on are the number of IITs submitted, and the
number of KOL visits,” says Dr Dyer. “Another is identifying and building new KOL
relationships. Other activities include developing product labels, building scientific
collateral information and training sales reps. These activities can be monitored on a
monthly, quarterly or yearly basis.

“Companies need to make sure MSLs are also evaluated on the basis of compliance. If the
company has a pre-existing certification or compliance-training programme in place, then
it’s almost always a yearly evaluation. But I’ve worked for a number of companies that

24
Cutting Edge Information-How to Compensate a Winning MSL Team-http://www.cuttingedgeinfo.com/news-
events/press-releases/successful-medical-science-liaison-compensation/

34 June 2011



wet age-related macular degeneration, in March 2011. This effectively leaves UK
opthamologists with little alternative than to use cancer drug Avastin, which has only
been authorised for colorectal, lung and breast cancer. This alleged violation of European
rules has not been tested in the courts but it is reflected in calls from the 2010 Belgian EU
Council Presidency for greater clarity on off-label use across the union. In its background
report on innovation for a ministerial conference in September 2010, off-label use was
described as an undefined area in which coordination is lacking at European level. 26

Enforcement policy in the US

“The risk/reward calculus is skewed dramatically
in favour of settlement when a loss would
jeopardise the firm’s viability by forfeiting
government reimbursement for its products,”
says John Osborn, former executive vice-
president and general counsel of Cephalon.

Off-label promotion is more hotly debated in the US, where there are higher penalties for
non-compliance and more exposure of wrongdoing via the False Claims Act, which creates
financial incentives for whistleblowers. There is also legal friction when trying to square
the ban with the First Amendment right to free speech. However, legal arguments based
on free speech have carried less weight since a 1998 revision to a rule issued by the OIG
that expanded its authority to exclude drug manufacturers from receiving federal health
reimbursement if they are found to have engaged in significant financial or other
impropriety. Even though the OIG has said it did not expect this expanded rule to result
in manufacturers being convicted and subject to mandatory exclusion, the risk alone was
enough to alter a company’s defenses. “The risk/reward calculus is skewed dramatically
in favour of settlement when a loss would jeopardise the firm’s viability by forfeiting

26
http://www.lifesciences.nautadutilh.com/Off-label_-_Final_version_article_-_Extended_edition.pdf

June 2011 43



Acknowledgements
FirstWord would like to acknowledge Dr Samuel Dyer, CEO of Medical Science Liaison
World (www.mslworld.com) as the co-author of this study. FirstWord would also like to
thank the following participants for their time and insights:

Drew Macgregor, medical operations manager, Bristol-Myers Squibb Europe

Lode Dewulf, vice-president of global medical affairs, UCB

Dr Robin Winter-Sperry, president and CEO, Scientific Advantage

Kevin Appareti, global director of MSLs, Philips Healthcare

Dale Kummerle, director, medical education, Bristol-Myers Squibb

Dr Zlata Caric, president, Lener Medical Consulting

Dr Eric Silfen, chief medical officer, Philips Healthcare

Yanis Saradjian, director of consulting, Cutting Edge Information

June 2011 47


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