title: Fibroid interventions: reducing symptoms today and tomorrow: extending generalizability by using a comprehensive cohort design with a randomized controlled trial.
abstract: BACKGROUND
  Uterine fibroids are an important source of morbidity for reproductive-aged women. Despite an increasing number of alternatives, hysterectomies account for about 75% of all fibroid interventional treatments. Evidence is lacking to help women and their health care providers decide among alternatives to hysterectomy. Fibroid Interventions: Reducing Symptoms Today and Tomorrow (NCT00995878, clinicaltrials.gov) is a randomized controlled trial to compare the safety, efficacy, and economics of 2 minimally invasive alternatives to hysterectomy: uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery. Although randomized trials provide the highest level of evidence, they have been difficult to conduct in the United States for interventional fibroid treatments. Thus, contemporaneously recruiting women declining randomization may have value as an alternative strategy for comparative effectiveness research.
  
  
  OBJECTIVE
  We sought to compare baseline characteristics of randomized participants with nonrandomized participants meeting the same enrollment criteria and to determine whether combining the 2 cohorts in a comprehensive cohort design would be useful for analysis.
  
  
  METHODS
  Premenopausal women with symptomatic uterine fibroids seeking interventional therapy at 3 US academic medical centers were randomized (1:1) in 2 strata based on calculated uterine volume (<700 and ≥700 cc(3)) to undergo embolization or focused ultrasound surgery. Women who met the same inclusion criteria but declined randomization were offered enrollment in a parallel cohort. Both cohorts were followed up for a maximum of 36 months after treatment. The measures addressed in this report were baseline demographics, symptoms, fibroid and uterine characteristics, and scores on validated quality-of-life measures.
  
  
  RESULTS
  Of 723 women screened, 57 were randomized and 49 underwent treatment (27 with focused ultrasound and 22 with embolization). Seven of the 8 women randomized but not treated were assigned to embolization. Of 34 women in the parallel cohort, 16 elected focused ultrasound and 18 elected embolization. Compared with nonrandomized participants, randomized participants had higher mean body mass index (28.7 vs 25.3 kg/m(2); P = .01) and were more likely to be gravid (77% vs 47%; P = .003) and smokers (42% vs 12%; P = .003). Age, race, uterine volume, number of fibroids, and baseline validated measures of general and disease-specific quality of life, pain, depression, and sexual function did not differ between the groups. When we performed a comprehensive cohort analysis and analyzed by treatment arm, the only baseline difference observed was a higher median McGill Pain Score among women undergoing focused ultrasound (10.5 vs 6; P = .03); a similar but nonsignificant trend was seen in visual analog scale scores for pain (median, 39.0 vs 24.0; P = .06).
  
  
  CONCLUSIONS
  Using a comprehensive cohort analysis of study data could result in additional power and greater generalizability if results are adjusted for baseline differences.
authors.affiliation: Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN; Department of Obstetrics and Gynecology, Women Health Hospital, Assiut University, Assiut, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: AbdElmagied
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Vaughan
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Weaver
authors.affiliation: Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN.
authors.forename: Shannon K
authors.initials: SK
authors.lastname: Laughlin-Tommaso
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN.
authors.forename: Gina K
authors.initials: GK
authors.lastname: Hesley
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN.
authors.forename: David A
authors.initials: DA
authors.lastname: Woodrum
authors.affiliation: Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, CA.
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Jacoby
authors.affiliation: Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Kohi
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, Durham, NC.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Price
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, Durham, NC.
authors.forename: Angel
authors.initials: A
authors.lastname: Nieves
authors.affiliation: Department of Radiology, Duke University, Durham, NC.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Miller
authors.affiliation: Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN; Division of Health Care Policy and Research, Mayo Clinic, Rochester, MN.
authors.forename: Bijan J
authors.initials: BJ
authors.lastname: Borah
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN.
authors.forename: Krzysztof R
authors.initials: KR
authors.lastname: Gorny
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, Durham, NC.
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Leppert
authors.affiliation: Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Lemens
authors.affiliation: Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN. Electronic address: stewart.elizabeth@mayo.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Stewart
mesh_terms: D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D020073:Gravidity; D006801:Humans; D007889:Leiomyoma / Q000628:therapy*; D010147:Pain Measurement; D012907:Smoking / Q000453:epidemiology; D014464:Ultrasonic Therapy; D055357:Uterine Artery Embolization; D014594:Uterine Neoplasms / Q000628:therapy*
keywords: focused ultrasound; leiomyomas; study design; uterine artery embolization; uterine fibroids