Issue 7 Excellence in oncology

Developing an effective
biomarker strategy

Free
Thinking
Excellence in oncology
Developing an effective biomarker strategy
Oncology is arguably the most exciting area
of medicine in which to be working today.
Biomarkers and companion diagnostics offer
incredibly valuable predictive power, which is
of benefit to payers, physicians and patients.
Payers are able to demonstrate that the
treatment they are paying for will be of
maximum value. Physicians feel confident that
they are offering an effective drug, which is at
the cutting-edge of medicine. And patients
clearly benefit from a treatment programme
that reduces the risk of unnecessary toxicities
and offers them better outcomes.
Manufacturers with an innovator drug now in development will
usually search for a suitable biomarker to launch alongside the drug.
It is critical that manufacturers develop an effective launch/
marketing strategy for their biomarker in order to maximise uptake
of their oncology brand.

But biomarker testing means manufacturers need to consider a

wider stakeholder mix in developing a strategy - the oncologist who
is treating the patient, the healthcare professional performing the
biopsy (which might be a surgeon, interventional radiologist, or
other specialist depending on the cancer type) and the pathologist
who will conduct and interpret (or outsource) the biomarker tests
ordered by the oncologist.
The accepted protocol for use of a companion diagnostic
appropriate to the manufacturers brand will need to be effectively
understood. But biomarker testing logistical flows can vary by
market, therapy area, geographical region and even at the local
hospital level.

Our free thinker

Tom Winter, Director
Tom Winter is a Director at Research Partnership, having joined
the graduate programme in 2003. He is a trusted partner to many
of RPs global US-based clients and has presented at major
international conferences, most recently at PBIRG in Naples,
Florida in 2013. He is an expert in market understanding, device
testing, early communication development and patient insight
mining.Tom has also worked across a variety of therapy areas;
most recently oncology, diabetes, cardiovascular disease,
neurology and HCV.

researchpartnership.com
Issue 7 Excellence in oncology
Developing an effective
biomarker strategy

Biomarker testing means the stakeholder mix broadens

Oncologist/Treating HCP HCP who performs biopsy Pathologist Patient

Order biomarker / Extract tissue for biopsy Conducts (and / or Will need to pay for test
companion diagnostic tests using variety of methods outsources) biomarker tests in self-pay markets
Often know little about test ordered by oncologist
processes, or what platforms Usually passive role, unlikely
are used to make treatment
Use results to guide recommendations
treatment

A strategy based on understanding
In developing an effective strategy, research is required in order to
understand:
How tests are selected and prioritised
How biopsies are carried out amount of tissue, methods or there are suggestions that other markers will determine likelihood of
used, HCPs involved
The role of the pathologist in biomarker testing
Objective 1:
Understand selection and prioritisation of tests
Even though they may be given recommendations advising them to
do otherwise, oncologists may decide to carry out tests sequentially,
according to clinical or prevalence factors, rather than undertake
simultaneous testing, in an attempt to save time and money. For
example, the College of American Pathologists recommends that all
NSCLC patients are tested for EGFR and ALK irrespective of whether
or not the patient is a smoker, their age, race or sex. However, some
physicians will order the tests sequentially: EGFR first, as it is more
prevalent, then ALK if the results of the EGFR test are unable to guide
treatment decisions. Because it is well known that EGFR mutations
are found more commonly in non-smokers than smokers, some
physicians use the patients smoking status to decide whether or not
to test for EGFR. Consequently, if your biomarker has a low prevalence
prevalence, you may need to convince the oncologist of the value of
simultaneous testing. National/regional guidelines may influence the
oncologist but may not be relied upon in determining actual behaviour.
If the test is for a rare tumour type or biomarker with a low
incidence, then it may not be possible for the test to be undertaken
in the hospital. If this is the case, the biomarker test will need to be
outsourced, which means that it will take longer and may cost
more. The oncologist may be keen to start treatment immediately,
so he may be unwilling to wait for test results to come back if
outsourced. This means that some brands may become 2nd line
treatments by default, even though they may be more suited than
the 1st line prescribed option.

Case study
Developing a strategy to encourage widespread biomarker testing

Research Partnership has conducted
many studies on biomarker testing to
address some of the issues posed. Here is
an example of a recent project undertaken
for a new product, which demonstrated
significant OS benefit in patients who
expressed the biomarker, but where
biomarker testing was not widely used.
The solution
We chose to conduct in-depth interviews
(IDIs) and dyad (duo) interviews in the US,
France, Germany, UK and Japan. The IDIs
were undertaken with oncologists, HCPs
taking biopsies and pathologists, to drill
down into the processes used. Dyads
were undertaken with oncologists and
pathologists in order to understand
different perspectives/viewpoints and
offered an environment where the
oncologist and pathologist could challenge
each other regarding the process. This
helped us and the client manufacturer
identify where barriers or problems lay
and enabled them to consider practical
solutions and communication techniques
which could result in a shift in
perception / behaviour.
The output
Using the findings from this research, the
client manufacturer was able to profile the
physicians who were and werent testing.
Our results showed that testing profiles
depended on hospital setting, for example
if oncologists were in academic centres or
non-academic centres, level of comfort
managing the side effects of the product,
exposure to peers who were testing, and
their belief in the efficacy of the drug.
We were also able to identify the
roadblocks/issues for each stakeholder:
Issue 7 Excellence in oncology
Developing an effective
biomarker strategy

Increasing numbers of biomarkers for a tumour type means more demand on tissue sample

Is tissue collected sufficient for multiple tests?

Can more be collected Can a patient be rebiopsied

at initial biopsy? to get more?
HCP who
performs biopsy Is this possible? What is the risk?

Does the HCP know to do this? Will patients agree?

In self-pay markets, cost of testing becomes a major factor, as the
patient becomes the reluctant payer. In many emerging markets, the
focus is on treating diseases with present symptoms, rather than on
diagnostic testing and prevention. The patient might not understand
the importance of the test and might refuse to pay for it. The doctor,
who is often time poor, may not spend the time trying to educate
the patient or change their mind. Roche identified this as a barrier
for Herceptin in Asian markets and consequently came up with a
strategy to offer HER-2 FISH testing free of charge.
Objective 2:
Understand how the biopsy is carried out
The increasing number of biomarkers for a tumour type means that
there is more demand on tissue sample. This is particularly true of
IHC tests, where pathologists have reported running out of tissue.
The amount required will depend on the type and quantity of tests
being done. The physician undertaking the biopsy may be reluctant
to remove too much tissue for fear of causing too much damage.
The volume of tissue collected will depend on the technique being
used some yield less tissue than others.
Its important for the manufacturer to understand the whole biopsy
process. Questions which need to be addressed will include:
Who performs the biopsy?
What interaction does the HCP performing the biopsy have
with the pathologist and oncologist? Is there a feedback
process on quality / amount of tissue?
How is the process monitored?
What methods are used and how much tissue is collected?
Are there regulations governing the amount of tissue which
can be taken?
Can more tissue be collected at the initial biopsy? If so,
what does this involve?
Interestingly, according to studies we have undertaken, we have
found that pathologists who test less think they would have

continued over

Roadblocks for HCP taking tissue
We found that the physician was
concerned about taking too much tissue
and didnt understand that with new
biomarkers there was a greater demand on
the tissue samples. They were defensive
when challenged and blamed the biopsy
process.These insights highlighted the
need for the manufacturer to communicate
using the right tone and acknowledge the
challenges the HCP was facing. It also
identified the need to find new ways of
collecting more tissue.
Roadblocks for Pathologists
The survey revealed that whilst some
pathologists were proactively testing, the
majority were not. This highlighted that
there was a need either to get oncologists
requesting more tests or to build other
paths for more proactive testing ie. via
the pathologist.
Roadblocks for Oncologists
Our survey revealed that oncologists often
used clinical markers of the patient to
prioritise testing and would make an
educated guess. Even those who said
they were testing were often cycling
through options and only testing when
necessary (ie if others not found to
be present).
In conclusion
The findings highlighted the need for the
manufacturer to provide clinical evidence
of patient types who may have the
biomarker and communicate the need for
upfront simultaneous testing in order to
maximise the likelihood of positive
outcomes for the patient.

28
Issue 6 Excellence in oncology
Developing an effective
biomarker strategy
sufficient tissue for more; those who test more tend to run out.
In some cases where more tissue is required to run another round of
tests, a biopsy may have to be carried out again. However, there is a
risk associated with biopsying and therefore this increases the level
of risk of damage to the patient, who may refuse, particularly if the
process is more invasive and uncomfortable, or if the healthcare
market requires them to pay for it themselves.
The alternative is to use archived tissue in the next round of testing
if it is available. However, there is debate around whether or not this
is as useful for testing, and pathologists show varying degrees of
preference for fresh versus archival tissue for different types of
biomarker tests. If archival tissue is used, the manufacturer needs
to ask - where does it get stored? Who is responsible for it and
who pays for storage?
Objective 3:
Understand the role of the pathologist
Typically, the pathologist plays a passive role in biomarker testing,
conducting tests as ordered by the pathologist, interpreting those
tests and providing the results to the oncologist. However in some
markets and hospitals there is either a desire or the potential for the
pathologist to have more involvement / responsibility in selecting
tests that are run and how they are carried out. This could be
important for manufacturers whose biomarkers are not prioritised by
the oncologist or for indications where many tests need to be carried
out. In order to develop an effective biomarker strategy,
Contact us
We would be delighted to support your research needs in oncology. If you would like to know more,
or just have a question, please feel free to contact us.
US
Tom Winter Angela Duffy
tomw@researchpartnership.com
+44 20 80695010
Harriet Kozak
harrietk@researchpartnership.com
+1 215 6829203
Our global offices
manufacturers need to understand the role of the pathologist and
their needs throughout the testing process:
How proactive is the pathologist in running that
particular test?
What platforms are used?
Will the tests need to be outsourced?
Should test kits be provided or will the tests be done
manually in a lab?
How should pathologist be trained / accredited?
If the pathologist is willing or able to be more proactive, they may
be more supportive of simultaneous testing, where it could be
beneficial. They may have greater influence in deciding how much
tissue is collected, and so giving pathologists a voice in this respect
may be critical if tissue is likely to run out by the time a particular test is
conducted. Pathologists also evaluate different assays for biomarkers,
and may make decisions as to which should be outsourced versus
which should be conducted in-house. If conducted in-house, then
proper training will be required to ensure that the pathologists are able
to interpret the test results accurately, which is particularly important
for more subjective tests that are conducted via IHC.
Manufacturers also need to consider how they should offer the
tests in practice: would pathologists prefer test kits, which offer the
advantage of speed, or the assay reagents, which offer the
advantage of flexibility?
Europe
angelad@researchpartnership.com
+44 20 80695003
Asia and Emerging Markets
Marc Yates
marcy@researchpartnership.com
+44 1984 623115
About us
Research Partnership is one of the largest independent healthcare
market research and consulting agencies in the world. Trusted
partner to the global pharmaceutical industry, we use our expertise
and experience to deliver intelligent, tailor-made solutions.
We provide strategic recommendations that go beyond research,
helping our clients to answer their fundamental business challenges.
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