Category | Factor | Values Considered in Simulations |
---|---|---|

GFR decline | Mean long-term slope | −1.5, -3.25, or −5 ml/min per 1.73 m^{2} |

SD of long-term slope | 3.0, 3.5, 4.0, or 4.5 ml/min per year/1.73 m^{2} | |

Correlation of slope and intercept | −0.03^{a} | |

Slope skewness | Slight negative skewness (generalized log γ shape parameter=3)^{a} | |

Autocorrelation | 0 | |

Size of residuals | Residual variance=0.67×expected GFR (low variability) or 0.817×expected GFR (moderate variability)^{a} | |

Acute effect | Mean acute effect | −2.5, −1.25, 0, +1.25, or 2.5 ml/min per 1.73 m^{2} at baseline GFR=42.5 ml/min per 1.73 m^{2} |

Attenuation of initial acute effect | Linear to 15 ml/min per 1.73 m^{2} or no attenuation | |

Variability of acute effect | Acute effect SD=1 ml/min per 1.73 m^{2} | |

Long-term treatment effect | Type of long-term treatment effect | Proportional, uniform or intermediate^{b} |

Size of long-term treatment effect | 0% or 25%, reduction in the slope for a subject with an average long-term slope in the absence of treatment | |

Death and ESKD | Death rate per year | 0.03375–0.00025×expected GFR (ranges from 0.030 at GFR=15 to 0.01125 at GFR=90 ml/min per 1.73 m^{2})^{a} |

GFR level associated with onset of ESKD | Uniformly distributed between 6 and 15 ml/min per 1.73 m^{2} | |

Design and conduct | Accrual period and total follow-up | Short: 1 yr accrual and 1.5 yr further follow-up |

Medium: 1.5 yr accrual and 2.5 yr further follow-up | ||

Long: 2 yr accrual and 4 yr further follow-up | ||

Measurement frequency | Months 3, 6, and every 6 mo thereafter | |

Mean baseline GFR | 27.5, 42.5, or 67.5 ml/min per 1.73 m^{2} | |

No. of baseline GFRs | 2 | |

Permanent loss to follow-up rate | 2%/yr | |

Intermittent missing GFRs | 5% |

↵a See supplement to reference 8 for additional details.

↵b Under the proportional effect model, the distribution of chronic GFR slopes in the treatment group were generated by simulating the slope of the i

^{th}patient as*β*_{i}×{(1−k)1[*β*_{i}<0]+1[*β*_{i}≥0]}, where*β*_{i}denotes the slope the patient would have had without the treatment, k is the proportional reduction due to the treatment among patients whose GFR would have declined without the treatment, and 1[*β*_{i}<0] and 1[*β*_{i}≥0] are 0–1 indicator variables for negative and non-negative slopes, respectively. Thus the proportional effect model assumes the treatment reduces the magnitude of the slope by 100×k percent among patients whose slope would have been negative without the treatment but has no effect on patients whose slope would have been ≥0 without the treatment. Under the uniform treatment effect model the chronic GFR slopes in the treatment group were generated as*β*_{i}−k×mean(*β*_{i}) where mean(*β*_{i}) is the mean chronic slope without the treatment. Under the intermediate treatment effect model, the chronic slopes in the treatment group were generated as [*β*_{i}−(k/2)×mean(*β*_{i})]+[*β*_{i}×{[1−(k/2)]1[*β*_{i}<0]+1[*β*_{i}≥0]}].