The Practical Art of Endpoint Selection: Industry Perspectives

1. 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

2. The opinions and information presented today are that of this presenter and do not reflect the opinions or position of Sunovion Pharmaceuticals.

3. 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for what is used and accepted • Secondary endpoints may provide some opportunity to utilize new tools • The 2006 draft Guidance to Industry on Patient Reported Outcome (PRO) measures created a new or perhaps renewed interest in the development and inclusion of PROs

4. 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.

5. 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

6. 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.

7. 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

8. 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

9. 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

10. 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

11. 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.

12. Thank YouDiscussion 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.