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 In many ways endpoint selection in clinical trials for drug development is set 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precedence for what is used and accepted Secondary endpoints may provide some opportunity to utilize new tools The 2006 draft Guidance to Industry on Patient Reported Outcome (PRO) measures created a new or perhaps renewed interest in the development and inclusion of PROs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 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 Qualitatively analyzing data from the interview process Constructing a PRO based on the patient’s words 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 Developing relationships with vendors and other measure developers Internal training on PRO development Specifically to reinforce necessary timelines Working with stakeholders to define the measure to be developed 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 “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 decision- making.” Not about DDTs “submitted as part of a regulatory application for a specific drug development program.” Described as being developed in “pre-competitive space” PROs approved through this mechanism will be made publicly available

Qualification Process for Drug Development Tools 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. 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 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: 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.