The Value of A Qualified Outcome Measure Janet Woodcock, M.D.

Transcription

1 The Value of A Qualified Outcome Measure Janet Woodcock, M.D. The Critical Path Institute (CPI) Multiple Sclerosis Outcome Assessments Consortium (MSAOC) 1 April 2013 White Oak 1

2 Overview of Workshop Create an interactive scientific dialogue between FDA and the MSOAC scientists regarding ongoing efforts with FDA, the European Medical Association (EMA), the Critical Path Institute (CPI), and the National Multiple Sclerosis (MS) Society. Describe the state-of-the-art disability measures for MS Identify the limitations of the existing measures Explore options for analyzing existing clinical trial data. Develop new therapeutic and data standards for assessing outcomes in clinical trials of MS therapies Draft a plan for collecting, standardizing, and analyzing data from MS studies with the goal of qualifying a new clinician-reported outcome measure of disability for use in future MS trials. 2

3 Value of an Accepted Disease Measure Broadly accepted measure can stimulate development in the field Eliminate second guessing during development and review process about validity or meaning of measure Often can contain more information than single domain type endpoints Consensus development--experts and patients-increases value and acceptance 3

4 Potential Contributions of MSOAC There is potentially great value to new MS measures as we move into an era of multiple effective drugs for MS. An endpoint with improved ability to evaluate different types of treatment effects may aid us in discriminating among the effects of various drugs There are a number of aspects of neurological impairment not well evaluated by existing, well-established measures. A new endpoint or endpoints that can be publicly available to all sponsors and can measure the treatment effects on these aspects will be valuable information to patients and prescribers. This is a task of substantial size, so can best be accomplished when the entire MS community comes together to work toward this end. This includes investigators, industry and patient organizations. While the qualification process for a new endpoint measure is not a requirement, it is the most efficient path towards creating new endpoint measures that both the medical community and FDA can feel comfortable relying on, and will make it available for use in upcoming drug development programs.

5 Evidentiary Standards There are not generally accepted evidentiary standards for new endpoints FDA does not have all the wisdom with regard to development of these standards! Every endpoint has tradeoffs between difficulty of development and confidence in the information relayed Community should have input on tradeoffs 5

6 Substantial Evidence and Measurement A claim of treatment benefit must be supported by substantial evidence Adequate and well-controlled studies [21 CFR ] Well-defined and reliable assessments Measures are well-defined and reliable when Empiric evidence demonstrates that the score quantifies the concept of interest in the targeted context of use The concept of interest measured by the score and defined by the endpoint in the clinical trial context of use determines the appropriate labeling or advertising claim The context of use includes the targeted purpose and circumstances of measurement FDA reviews whether the available data support the use of the measure in the context defined by the clinical studies that provide evidence of treatment benefit 6

7 Use of Composite Endpoints A single score is not likely able to capture everything we need to know to conclude that a treatment has benefit In the 1990 s, FDA adopted the ACR composite endpoint for rheumatoid arthritis This EP had all sorts of measures combined into a responder score Not methodologically ideal, but it worked It is easy to imagine a combination of one or more measures from each of the following groups for MS: A daily symptom/function PRO measure A functional assessment completed in the clinic A biomarker

8 Other Benefits of Consortium Possibility to draft guidance on conduct of trials using new measure Possibility to participate in development of data standards for MS trials Possibility to contribute to international harmonization of standards (EMA participating in workshop) 8

9 EMA FDA Communication. EMA and FDA are having telephone discussions about the COA qualification process Aim to harmonize submission templates during both the Advice and Consultation as well as the Review Stages E.g., both use the same process for all COA PROs, ClinROs, ObsROs Under our MOU, EMA and FDA can have discussions about specific COA qualification projects that are under concurrent review by the two agencies and we encourage concurrent submissions. EMA and FDA are encouraging applicants that include new COAs as endpoints in applications to also seek qualification of the new measure independent of the action on the new drug.