Electronic PatientReported Outcomes: Following FDA guidance from a Vendor Perspective Jennifer Ross,

1
Electronic Patient-Reported Outcomes Following
FDA guidance from a Vendor Perspective Jennifer
Ross, MS, M.Phil.Ed. Ellen Shea, RN
Overview
Key Points

• Sponsors often utilize vendors for the planning
  implementation of their trials
• Sponsors vendors are required to meet FDA
  requirements when implementing (Electronic
  Patient-Reported Outcomes) ePRO in a trial
• Meeting these expectations can be challenging
  across the pharmaceutical industry
• ePRO use in clinical trials requires careful
  planning execution
• Trials can face serious consequences throughout
  the FDA the product development approval
  processes when FDA expectations are not satisfied
• FDA released a Draft Guidance to assist industry
  in communicating their perspective on how they
  evaluate ePRO-use for efficacy endpoints in
  clinical trials for support claims made in
  approved product labeling

• It is important for both sponsors vendors to
  meet FDA requirements when implementing ePRO in a
  trial
• There are different regulations that need to be
  followed when utilizing electronic means for the
  collection of PRO data
• Sponsors should plan carefully to ensure FDA
  regulatory requirements are met for sponsor
  investigator record keeping, maintenance,
  access when using ePRO
• Vendors should become involved early in the
  planning process of clinical trials when
  implementing ePRO
• Vendors should have maintain Standard
  Operating Procedures surrounding ePRO system
  development, implementation maintenance
• Sponsors vendors should be familiar in FDA
  regulations document pertaining to use of ePRO
  (see FDA ePRO reference documents below)
• Sponsors vendors should be able to recognize
  critical issues, the associated consequences
  how to avoid handle them

Objectives

• To acknowledge the benefits associated with the
  implementation of ePRO
• To provide an overview of important
  considerations sponsors vendors need to address
  in order to meet FDA expectations during the
  planning implementation phases when using ePROs
  in clinical trials
• To bring attention to the key potential issues
  that may arise when implementing ePRO systems for
  both sponsors vendors
• To recognize the consequences that can result
  from these potential issues
• To propose recommendations ways to avoid these
  critical issues following the FDA guidance as a
  vendor or when using a vendor

FDA ePRO reference documents

• Guidance for industry patient-reported outcomes
  measures use in medical product development to
  support labeling claims draft guidance
• Draft guidance for industry Computerized Systems
  Used in Clinical Trials
• Guidance for industry Part 11 (21 CFR 11),
  Electronic Records Electronic SignaturesScope
  Application
• Principal record keeping requirements for
  clinical investigators sponsors21 CFR
  312.50, 312.58, 312.62, 312.68, 812.140, 812.145

Benefits of ePRO
Selected References

• Higher patient compliance vs. paper
• Better data quality accuracy for study results
  
• Patient experience is more consistent than with
  paper
• Eliminates memory recall (Parking Lot Syndrome)
• Provides accurate time date stamped
  information
• Prevents missing data
• Reduces errors within the data
• Can handle complex skip patterns
• Reduces effort error involved in the data
  entry of PRO data from paper
• Able to implement sophisticated designs that can
  ensure valid patient responses
• Eliminates additional information patients may
  write in the margins
• Eliminates burden of deciphering patient hand
  writing
• Eliminates out of range or ambiguous data
• Real-time electronic reports can be available
  via the web
• Outbound calling option can be available

i. Identify Concepts Develop Conceptual
Framework Identify concepts domains that are
important to patients. Determine intended
population research application. Hypothesize
expected relationships among concepts.

• Coons, SJ, Gwanltney, CJ, Hays R, Lundy, JL,
  Sloan, JA, Revicki, DA, Lenderking, WR, Cella, D
  Bascg, E. Recommendations on Evidence Needed to
  Support Measurement Equivalence between
  Electronic Paper-based Patient-Reported Outcome
  (PRO) Measures ISPOR ePRO Good Research
  Practices Task Force Report
• Gwaltney, CJ, Shields, AL Shiffman S (2008).
  Equivalence of electronic paper-and-pencil
  administration of patient-reported outcome
  measures a meta-analytic review. Value in
  Health, 11 (2), 322-323.
• Patrick, DL, Burke, LB, Powers, JH, Scott, JA,
  Rock, EP, Dawisha, S, ONeill, R Kennedy, DL
  (2007). Patient-Reported Outcomes to Support
  Medical Product Labeling Claims FDA Perspective.
  Value in Health, 10 (2), 125-137.
• Revicki, DA, Gnanasakthy, A Weinfurt, K
  (2007). Documenting the rationale psychometric
  characteristics of patient reported outcomes for
  labeling promotional claims the PRO Evidence
  Dossier. Quality of Life Research, 16 (4),
  717-723.
• Sloan, JA, Halyard, MY, Frost, MH, Dueck, AC,
  Teschendorf, B, Rothman, ML, the Mayo/FDA
  Patient-Reported Outcomes Consensus Meeting
  Group, (2007). The Mayo Clinic Manuscript Series
  Relative to the Discussion, Dissemination,
  Operationalization of the Food Drug
  Administration Guidance on Patient-Reported
  Outcomes. Value in Health, 10 (2), 59-63.
• Wiklund, I (2004). Assessment of
  patient-reported outcomes in clinical trials the
  example of health-related quality of life.
  Fundamental Clinical Pharmacology, 18 (3),
  351-363.
• Willke, RJ, Burke LB Erickson P (2004).
  Measuring treatment impact a review of
  patient-reported outcomes other efficacy
  endpoints in approved product labels. Controlled
  Clinical Trials, 25 (6), 535-552.

Figure 1. The PRO instrument development
modification process.
(from the FDA PRO guidance for industry)
ii. Create Instrument Generate items. Choose
administration method, recall period, response
scales. Draft instructions. Format
instrument. Draft procedures for scoring
administration. Pilot test draft instrument.
Refine instrument procedures.
iv. Modify Instrument Change concepts
measured, populations studied, research
application, instrumentation, or method of
administration.
iii. Assess Measurement Properties Assess score
reliability, validity, ability to detect
change. Evaluate administrative respondent
burden. Add, delete, or revise items. Identify
meaningful differences in scores. Finalize
instrument formats, scoring, procedures,
training materials.