The Practical Art of
Endpoint Selection:
Industry Perspectives
A View from the Pharma Industry
of the FDA Guidance on PROs
Glenn A. Phillips, Ph.D.
Director Health Economics & Outcomes Research
Sunovion Pharmaceuticals
The opinions and information
presented today are that of this
presenter and do not reflect the
opinions or position of Sunovion
Pharmaceuticals.
Endpoint Selection
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In many ways endpoint selection in clinical trials
for drug development is set
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Historical precedence for what is used and accepted
Secondary endpoints may provide some opportunity
to utilize new tools
The 2006 draft Guidance to Industry on Patient
Reported Outcome (PRO) measures created a
new or perhaps renewed interest in the
development and inclusion of PROs
Why does it matter to us
 This
is important for many stakeholders:
Patients may better understand the expected effect of a
medication and may be able to self identify as needing a
particular treatment
 Prescribers may be able to target patients who have specific
needs based on reported PRO efficacy and be able to assess
the impact of a treatment for any given patient
 Payers may recognize how a new treatment is distinct from
existing treatments and make appropriate formulary decisions
 Regulators may better understand the efficacy of new
medications by identifying how patients are impacted
 Pharmaceutical companies may better focus medications by
identifying the outcomes that patients report and may gain a
competitive advantage by targeting specific symptoms that are
not well treated.

 To
provide the right treatment to the right patient.
What are we doing about it
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Development of PROs has become a part of
drug development
Some companies have developed internal
groups that lead the development of PROs
Talking with regulators about the inclusion of
PROs in clinical trials and negotiating how they
can be used and to what end
Identifying vendors who can develop PROs
A word about vendors

The vendors who develop PROs to meet the Guidance,
undertake a very specialized set of tasks

Interviewing patients, whether individually or in focus groups
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Qualitatively analyzing data from the interview process
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Constructing a PRO based on the patient’s words
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Refining the PRO based on testing the measure

Developing the endpoint model and fitting the measure into a
conceptual framework

These are not the tasks of just any CRO a certain level of
understanding and experience are necessary to do this well

Academic partners/vendors can provide a level of expertise
that many non-academic vendors might not be able to
provide.
What are some key activities

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Developing relationships with vendors and other
measure developers
Internal training on PRO development

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Working with stakeholders to define the measure to be
developed
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Specifically to reinforce necessary timelines
Internal stakeholders: trial design, inclusion/exclusion criteria,
endpoint model and conceptual framework
External stakeholders: endpoints of interest to the community,
acceptance of those proposed
Working with regulatory affairs to complete the
necessary dossier to have a PRO evaluated
What resources are required
 Money:
not an inexpensive activity
 Time!


No longer can a new measure be made up and put
into a trial in a matter of weeks
Timeline for development of a new measure 12 to 24
months depending on many factors

Disease state, specific outcome, breadth of outcome,
understanding of the outcome of interests
 People

who can manage the development
Obtain the appropriate input, work with and
understand what the vendor is doing, prepare the
dossier
ePRO
 Electronic
PROs provide easier mechanisms for
collecting PRO data, but require special
considerations

What format was the measure developed in and can it
easily be transferred to ePRO

At minimum a cross validation will need to be completed to
show an ePRO is equivalent if the measure was not initially
in electronic format

Will ePRO technology be easily used by the population of
interest

This is an even more specialized group of vendors
Qualification Process for Drug
Development Tools
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“Qualification is a conclusion that within the stated
context of use, the results of assessment with a DDT can
be relied upon to have a specific interpretation and
application in drug development and regulatory decisionmaking.”
Not about DDTs “submitted as part of a regulatory
application for a specific drug development program.”

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Described as being developed in “pre-competitive space”
PROs approved through this mechanism will be made publicly
available
Qualification Process for Drug
Development Tools
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So this is outside the development process of new drugs, as a
person who works in pharma the impact of this on my work
becomes a bit dubious.
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To the extent that consortia are set up to develop measures it is
important for us to be involved and aware of these activities,
however:
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Please don’t hear this as not caring about the measures, I believe
almost every area of health care needs to improve the measures used
The speed at which these types of development efforts move, tend to
make us less interested in the short term
Initially the fit-for-purpose of any given measure developed in this way
will be questionable for any given study or development program
Finally, waiting for measures developed through the qualification
process might dampen the enthusiasm for utilizing PROs.
Thank You
Discussion and Questions


What PROs are being approved at this time?
What about other types of measures will they
begin to see this type of scrutiny?

A level of scrutiny that is arguably much tougher
than has been previously applied to measures,
PRO or not.