title: The effect of adjusting for baseline hypoglycemia when analyzing hypoglycemia data: a systematic analysis of 15 diabetes clinical trials.
abstract: BACKGROUND
  Baseline hypoglycemia rates are generally not collected or included as a covariate in statistical models used for analyzing hypoglycemia data. The objective of the present study was to examine the effect of adjusting for baseline hypoglycemia on estimation efficiency and statistical power.
  
  
  METHODS
  A post hoc analysis of data from 15 insulin trials, including patients with type 1 diabetes mellitus (T1DM) (n=210), previously insulin-treated type 2 diabetes mellitus (T2DM) (n=1,511), or T2DM and previously insulin-naive (n=1,075). Hypoglycemic episodes were analyzed with a negative binomial regression model.
  
  
  RESULTS
  Baseline nocturnal hypoglycemia rate was significantly correlated with post-baseline nocturnal hypoglycemia rate in previously insulin-treated patients with T1DM and T2DM (correlation range, 0.37-0.63; P<0.001). Adjusting for baseline hypoglycemia resulted in a reduction in the SE for negative binomial regression for previously insulin-treated patients with T1DM and T2DM (range, 2.2-11.8%) and increased statistical power. Modeling of lengthening the lead-in period increases the correlation between baseline and post-baseline hypoglycemia event rate and statistical power.
  
  
  CONCLUSIONS
  Baseline hypoglycemia rate is significantly correlated with post-baseline hypoglycemia rate for patients with diabetes treated with insulin prior to randomization. The length of the lead-in period can impact correlations between baseline and post-baseline data, and adjustment for baseline hypoglycemia may improve the estimation efficiency for hypoglycemia data analyses in clinical trials.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285, USA. luo_junxiang@lilly.com
authors.forename: Junxiang
authors.initials: J
authors.lastname: Luo
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Jacober
authors.forename: Melvin J
authors.initials: MJ
authors.lastname: Prince
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Carey
authors.forename: Yongming
authors.initials: Y
authors.lastname: Qu
mesh_terms: D000328:Adult; D000368:Aged; D002940:Circadian Rhythm; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012890:Sleep; D013997:Time Factors
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin