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

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 257-280-Disorders of Vitamin D Metabolism & Action
Basic/Translational
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-263
Yuval Eisenberg*1, Arfana Akbar2, Buvana Manickam3, Hiba Mohiuddin1, Subhash C Kukreja4 and Elena Barengolts5
1University of Illinois at Chicago, College of Medicine, Chicago, IL, 2Jesse Brown VAMC, Chicago, IL, 3University of Illinois, Chicago, Chicago, IL, 4Univ of Illlinois, Chicago, IL, 5University of Illinois College of Medicine, Chicago, IL
Objective:To assess broader applicability of results of ongoing randomized clinical trial (RCT) of vitamin D supplementation in prediabetes by comparing African American men (AAM) excluded to those included, along with determination of the trial’s effectiveness vs efficacy continuum.

Methods: We performed retrospective chart review to compare subjects excluded (OUT) to those included (IN) in RCT. The main inclusion criteria were hemoglobin A1C (A1C) 5.7-6.9%, body mass index (BMI) 28-39kg/m2, 25-hydroxyvitamin D (25OHD) 5-29ng/ml, and the main exclusions were known T2DM, and serious disease that may interfere with participation or increase risk of side effects. Evaluation of effectiveness vs efficacy of the trial was performed using Pragmatic-Explanatory Contiuum Indicator Summary (PRECIS)1 tool completion for all 10 domains on a 10 point scale, by 16 endocrinology section members after discussion of the trial methodology. Scores near 0 favor efficacy research (i.e. ideal environment) while scores near 10 favor effectiveness research (i.e. practical setting)2.

Results: Subjects (n=356) had the same demographics (mean [SD]): AAM, Age 59[10] years. The OUT (n=178) vs IN (n=178) group had lower A1C (%) 5.8[0.5] vs 6.1[0.2], p<0.01. The level of 25OHD was similar (ng/ml) 15.2[5.5] vs 14.3[5.1], p=0.88.  There was significant difference for LDL(mg/dl) 97.3 [31.2] vs 111.9 [27], HDL (mg/dl) 51.3[13.9] vs 44.6[10.1], and Charlson Index3 2.8[1.6] vs 2.2[1.13] for OUT and IN groups respectively.  There were no differences for other measures: eGFR, cholesterol, triglycerides, proportion of HTN, DJD, CVD (including MI, stroke, PVD, and CHF), cancer (all combined), and psychiatric problems (including PTSD, depression, schizophrenia, and substance abuse). Subgroup analysis of subjects with A1C 5.7-6.9% (OUT n=105, IN n=178) showed significantly more cancer and less psychiatric disease and thiazide diuretic use for OUT vs IN.  PRECIS data for all 16 participants (mean [SD]) was 7.7[0.67].

Discussion:Our analysis shows that RCT, an accepted gold standard for evidence-based advice, has clinically relevant limitations. Although the notion exists that RCT involves highly selected patients, the comparison of included and excluded subjects is rarely done or reported in the literature. RCT vary in their pragmatism which is important for physicians to understand regarding limitations of generalizing results to patients seen in clinical practice.

Conclusion: Patients included and excluded from this RCT differ by several important clinical characteristics. Advice based on the evidence from this RCT may not be applicable to all patients with the same demographics and disease seen in a clinical practice, although study design favors pragmatic applicability.

(1) Thorpe et al., A pragmatic–explanatory continuum indicator summary(PRECIS): a tool to help trial designers, J Clin Epidemiol 2009, 62(5):464–475.(2) Bratton et al., The value of the pragmatic-explanatorycontinuum indicator summary wheel in anongoing study: the bullous pemphigoid steroidsand tetracyclines study, Trials 2012, 13:50. (3) Charlson et al., A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83.

Nothing to Disclose: YE, AA, BM, HM, SCK, EB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported in part by Merit Review grant from the Department of Veterans Affairs awarded to EB and NIH grant # UL1RR029879 awarded to CCTS at UIC.