title: Patient-reported outcomes to assess the efficacy of extended-release guaifenesin for the treatment of acute respiratory tract infection symptoms.
abstract: BACKGROUND
  Guaifenesin is a component of medicines used to improve symptoms associated with upper respiratory tract infections. Patient-reported outcome instruments are valuable for evaluating symptom improvements; however, a validated tool to assess efficacy of mucoactive drugs does not exist. We compared the efficacy of extended-release guaifenesin with placebo for treatment of symptoms of upper respiratory tract infection using subjective efficacy assessments in a pilot study and confirmed precision of assessments in a validation study.
  
  
  METHODS
  The pilot study was a randomized, double-blind study where patients were dosed with either 1200 mg extended-release guaifenesin (n = 188) or placebo (n = 190), every 12 hours for 7 days. Efficacy was assessed using subjective measures including the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and the Wisconsin Upper Respiratory Symptom Survey. End-of-study assessments were completed by patients and investigator. The validation study consisted of two phases. In Phase I, subjects completed interviews to gather evidence to support the content validity of the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and Patient's End-of-Treatment Assessment. Phase II examined the psychometric properties of assessments evaluated in Phase I of the validation study using data from the pilot study.
  
  
  RESULTS
  Subjective measures of efficacy at Day 4 showed the most prominent difference between treatment groups, in favor of guaifenesin. The 8-symptom related questions (SUM8) in the Daily Cough and Phlegm Diary, analyzed as a composite score appeared to be the strongest candidate endpoint for further evaluation. Results from the interviews in Phase I supported the content of the assessments which were validated during Phase II. Treatments were well tolerated.
  
  
  CONCLUSIONS
  Results from the clinical pilot and validation studies showed that the SUM8 diary scores were robust and reliable for use as efficacy endpoints in studies of mucoactive drugs.
  
  
  BACKGROUND
  The study was registered with clinicaltrials.gov (NCT01046136).
authors.affiliation: H2A Associates, LLC, 3350 SW 27th Ave, Miami, FL 33133, USA. Helmut@H2A-Associates.com
authors.forename: Helmut
authors.initials: H
authors.lastname: Albrecht
authors.forename: Margaret
authors.initials: M
authors.lastname: Vernon
authors.forename: Gail
authors.initials: G
authors.lastname: Solomon
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004311:Double-Blind Method; D005100:Expectorants / Q000008:administration & dosage; D005260:Female; D006140:Guaifenesin / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015995:Prevalence; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D005100:Expectorants; D006140:Guaifenesin