title: Similarities and differences between patients included and excluded from a randomized clinical trial of vitamin D supplementation for improving glucose tolerance in prediabetes: interpreting broader applicability.
abstract: BACKGROUND
  Randomized Clinical Trial (RCT) designs range from highly selective resulting in lack of external validity to more inclusive, requiring large sample sizes to observe significant results. Few publications, however, have compared excluded to enrolled participants. We aimed to assess our trial's design based on the effectiveness versus efficacy continuum using the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool and to compare included and excluded patients.
  
  
  METHODS
  Fifteen members of endocrinology section completed PRECIS for DIVA (D-Vitamin Intervention in VA) trial; an RCT evaluating vitamin D supplementation in improving dysglycemia in patients with prediabetes. Retrospective chart review compared subjects excluded (OUT) to those included (IN) in RCT. Student's t and Chi-square tests were used to compare continuous and categorical variables. Additionally, multiple logistic regression was completed.
  
  
  RESULTS
  PRECIS scores were nearly universally pragmatic. 178 patients enrolled in DIVA trial were compared with 178 randomly selected patients excluded from study involvement. There was no significant difference between IN and OUT for the majority of the continuous and all of the categorical variables. Multivariate logistic regression identified only the A1c, HDL and Charlson Index as significant predictors of a participant's inclusion or exclusion. There was higher HDL (51.3(13.9) versus 44.6(10.1), P = 0.001) and Charlson Index (2.85(1.6) versus 2.2(1.17), P = 0.001) for OUT versus IN groups. Subanalysis of excluded patients in A1c range 5.7 to 6.9, had lower BMI (30.7(3.4) versus 32(2.7), P = 0.002) but higher HDL (mg/l: 49.7(11.8) versus 44.6(10.1), P = 0.001) and Charlson index (2.85(1.6) versus 2.2(1.17), P = 0.001) than included participants. Additionally, there was a trend towards higher rates of cancer (22.9% versus 12.9%, P = 0.033) but less psychiatric problems (56.2% versus 72.5%, P = 0.026) and thiazide diuretic use (18.1% versus 29.8%, P = 0.034).
  
  
  CONCLUSIONS
  DIVA trial design appears to favor broad clinical applicability. The majority of objectively compared variables did not different between patients included and excluded from this RCT. Advice based on the evidence from this RCT may be applicable to a larger group of patients than those fitting inclusion/exclusion criteria alone.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01375660 (registered 15 June 2011).
authors.affiliation: Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, 1819 West Polk Street, Chicago, IL, 60612, USA. eisenbe1@uic.edu.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Eisenberg
authors.affiliation: Department of Medicine, Section of Endocrinology, Jesse Brown VA Medical Center, 820 South Damen Avenue, Chicago, IL, 60612, USA. Hiba.noora@gmail.com.
authors.forename: Hiba
authors.initials: H
authors.lastname: Mohiuddin
authors.affiliation: Department of Medicine, Section of Endocrinology, Jesse Brown VA Medical Center, 820 South Damen Avenue, Chicago, IL, 60612, USA. Karthikdoc9@gmail.com.
authors.forename: Karthik
authors.initials: K
authors.lastname: Cherukupally
authors.affiliation: Department of Medicine, Section of Endocrinology, Jesse Brown VA Medical Center, 820 South Damen Avenue, Chicago, IL, 60612, USA. Hzaidi1988@gmail.com.
authors.forename: Hassan
authors.initials: H
authors.lastname: Zaidi
authors.affiliation: Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, 1819 West Polk Street, Chicago, IL, 60612, USA. skukreja@uic.edu.
authors.forename: Subhash
authors.initials: S
authors.lastname: Kukreja
authors.affiliation: Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, 1819 West Polk Street, Chicago, IL, 60612, USA. eibareng@uic.edu.|Department of Medicine, Section of Endocrinology, Jesse Brown VA Medical Center, 820 South Damen Avenue, Chicago, IL, 60612, USA. eibareng@uic.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Barengolts
mesh_terms: D001741:Black or African American; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D016009:Chi-Square Distribution; D002985:Clinical Protocols; D015897:Comorbidity; D019587:Dietary Supplements; D004872:Ergocalciferols / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D011236:Prediabetic State / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004872:Ergocalciferols; D006442:Glycated Hemoglobin; D014807:Vitamin D; C517652:hemoglobin A1c protein, human; C104450:25-hydroxyvitamin D