title: Development of a Symptom-Based Patient-Reported Outcome Instrument for Functional Dyspepsia: A Preliminary Conceptual Model and an Evaluation of the Adequacy of Existing Instruments.
abstract: The aim was to document, from the perspective of the empirical literature, the primary symptoms of functional dyspepsia (FD), evaluate the extent to which existing questionnaires target those symptoms, and, finally, identify any missing evidence that would impact the questionnaires' use in regulated clinical trials to assess treatment efficacy claims intended for product labeling.
  
  
  
  A literature review was conducted to identify the primary symptoms of FD and existing symptom-based FD patient-reported outcome (PRO) instruments. Following a database search, abstracts were screened and articles were retrieved for review. The primary symptoms of FD were organized into a conceptual model and the PRO instruments were evaluated for conceptual coverage as well as compared against evidentiary requirements presented in the FDA's PRO Guidance for Industry.
  
  
  
  Fifty-six articles and 16 instruments assessing FD symptoms were reviewed. Concepts listed in the Rome III criteria for FD (n = 7), those assessed by existing FD instruments (n = 34), and symptoms reported by patients in published qualitative research (n = 6) were summarized in the FD conceptual model. Except for vomiting, all of the identified symptoms from the published qualitative research reports were also specified in the Rome III criteria. Only three of the 16 instruments, the Dyspepsia Symptom Severity Index (DSSI), Nepean Dyspepsia Index (NDI), and Short-Form Nepean Dyspepsia Index (SF-NDI), measure all seven FD symptoms defined by the Rome III criteria. Among these three, each utilizes a 2-week recall period and 5-point Likert-type scale, and had evidence of patient involvement in development. Despite their coverage, when these instruments were evaluated in light of regulatory expectations, several issues jeopardized their potential qualification for substantiation of a labeling claim.
  
  
  
  No existing PRO instruments that measured all seven symptoms adhered to the regulatory principles necessary to support product labeling. As such, the development of a new FD symptom PRO instrument is supported.
authors.affiliation: Adelphi Values, Boston, MA, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Taylor
authors.affiliation: Study Endpoints, Ironwood Pharmaceuticals, Inc., 301 Binney Street, Cambridge, MA, 02142, USA. DReasner@IronwoodPharma.com.
authors.forename: David S
authors.initials: DS
authors.lastname: Reasner
authors.affiliation: Allergan plc., Jersey City, NJ, USA.
authors.forename: Robyn T
authors.initials: RT
authors.lastname: Carson
authors.affiliation: Pfizer, Collegeville, PA, USA.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Deal
authors.affiliation: Adelphi Values, Boston, MA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Foley
authors.affiliation: Adelphi Values, Boston, MA, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Iovin
authors.affiliation: Outcometrix, Tucson, AZ, USA.
authors.forename: J Jason
authors.initials: JJ
authors.lastname: Lundy
authors.affiliation: Adelphi Values, Boston, MA, USA.
authors.forename: Farrah
authors.initials: F
authors.lastname: Pompilus
authors.affiliation: Adelphi Values, Boston, MA, USA.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Shields
authors.affiliation: Shire, Zug, Switzerland.
authors.forename: Debra G
authors.initials: DG
authors.lastname: Silberg
mesh_terms: D004415:Dyspepsia / Q000150:complications*; D006801:Humans; D000071066:Patient Reported Outcome Measures; D036301:Qualitative Research; D011795:Surveys and Questionnaires; D016896:Treatment Outcome