Bioequivalence and Bioavailability Forum

Simulation settings: 2,500 studies with 16 subjects
  Sampling every 5 minutes up to 2 × tmax of R (2.50 h),
  exponentially increasing intervals to tlast (16 h) = 38 samples:
    0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70,
    75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135,
    140, 145, 150 min, 3.5, 4, 5.5, 7, 9.5, 12.5, 16 h.
  Seven formulations
  L  = lower limit: tmax = 1.000 h, ka = 2.190 / h, t½,a = 19.0 min
  T1 = fastest    : tmax = 1.125 h, ka = 1.822 / h, t½,a = 22.8 min
  T2 = fast       : tmax = 1.188 h, ka = 1.672 / h, t½,a = 24.9 min
  R  = Reference  : tmax = 1.250 h, ka = 1.539 / h, t½,a = 27.0 min
  T3 = slow       : tmax = 1.316 h, ka = 1.417 / h, t½,a = 29.4 min
  T4 = slowest    : tmax = 1.389 h, ka = 1.296 / h, t½,a = 32.1 min
  U  = upper limit: tmax = 1.562 h, ka = 1.065 / h, t½,a = 39.0 min

Simulation results:
  L = lower limit
    Median  : 1.0833 h (Bias: +0.0833 h, Range: 0.7500 - 1.4583 h)
    HL      : 1.1146 h (Bias: +0.1146 h, Range: 0.8333 - 1.4583 h)
    Skewness: +0.4452
  T1 = fastest
    Median  : 1.2083 h (Bias: +0.0833 h, Range: 0.8750 - 1.6250 h)
    HL      : 1.2500 h (Bias: +0.1250 h, Range: 0.9167 - 1.5833 h)
    Skewness: +0.4093
  T2 = fast
    Median  : 1.2917 h (Bias: +0.1042 h, Range: 0.9167 - 1.7917 h)
    HL      : 1.3125 h (Bias: +0.1250 h, Range: 0.9583 - 1.6667 h)
    Skewness: +0.3858
  R  = Reference
    Median  : 1.3333 h (Bias: +0.0833 h, Range: 1.0000 - 1.7917 h)
    HL      : 1.3750 h (Bias: +0.1250 h, Range: 1.0417 - 1.7500 h)
    Skewness: +0.3505
  T3 = slow
    Median  : 1.4167 h (Bias: +0.1009 h, Range: 1.0000 - 1.8750 h)
    HL      : 1.4375 h (Bias: +0.1217 h, Range: 1.1250 - 1.7500 h)
    Skewness: +0.2960
  T4 = slowest
    Median  : 1.5000 h (Bias: +0.1111 h, Range: 1.1250 - 2.0000 h)
    HL      : 1.5208 h (Bias: +0.1319 h, Range: 1.1250 - 1.9583 h)
    Skewness: +0.2594
  U = upper limit
    Median  : 1.6667 h (Bias: +0.1042 h, Range: 1.2500 - 2.2500 h)
    HL      : 1.6771 h (Bias: +0.1146 h, Range: 1.3333 - 2.1250 h)
    Skewness: +0.0878
  HL: Hodges-Lehmann estimate

Comparisons:
  According to the guidance (based on medians)
  passed ‘±20% criterion’ (80.00-125.00%)
    L  = lower limit: 52.1%
    T1 = fastest    : 80.9%
    T2 = fast       : 90.4%
    T3 = slow       : 91.2%
    T3 = slowest    : 84.8%
    U  = upper limit: 57.0%

  Heretic alternative (based on Hodges-Lehmann estimates)
  passed ‘±20% criterion’ (80.00-125.00%)
    L  = lower limit: 53.2%
    T1 = fastest    : 87.2%
    T2 = fast       : 94.9%
    T3 = slow       : 95.2%
    T3 = slowest    : 89.5%
    U  = upper limit: 61.1%