Supporting Information
Derivation of Empirical Conversion Formulae
A conversion formula was constructed using the weight-only BSA estimating equation (24,
25). Conversion equations were also derived empirically from OZGROW doses. Each dose
within a dose range was standardized by adjusting it for any systematic change in dose with
age or weight as determined by linear regression. These adjusted mg/m 2/week doses were
than used to derive adjusted mg/kg/week doses and thus plot relationships between fixed
mg/m2/week doses and mg/kg/week doses for each dose range.
All doses in the Training Set were used to derive empirical conversion equations. In regards
to the linear relationship between mg/kg/week dose and age for fixed mg/m2/week dose it
was found that the adjusted slopes calculated for each 1 mg/m2/week increment from 2 to
10mg/m2/week were linearly related to dose; specifically it was found that
𝑆𝑙𝑜𝑝𝑒𝑘𝑔 = −0.0011(𝐷𝑜𝑠𝑒𝑚2 ) − 0.0014
In addition to slope, a linear relationship requires an intercept value, in this case a dose
estimate at 0 years of age. It was observed that the ratio of the per m2 dose to the per kg
dose projected back to 0 years of age, that is, the dose intercept was essentially constant
with a weighted mean value of 20.4 m2/kg. Thus, for any particular fixed mg/m2/week dose
the mg/kg/week intercept value will be 𝐷𝑜𝑠𝑒𝑚2 ⁄20.4.
Thus, the mg/kg/week dose for a given mg/m2/week dose and age can be estimated as
𝐷𝑜𝑠𝑒𝑘𝑔 =
𝐷𝑜𝑠𝑒𝑚2
+ (−0.0011(𝐷𝑜𝑠𝑒𝑚2 ) − 0.0014)𝐴𝑔𝑒𝑌𝑒𝑎𝑟𝑠
20.4
To convert a per kg dose to a per m2 dose this formula can be rearranged to give,
𝐷𝑜𝑠𝑒𝑚2 =
1000𝐷𝑜𝑠𝑒𝑘𝑔 + 1.4𝐴𝑔𝑒𝑌𝑒𝑎𝑟𝑠
49.0 − 1.1𝐴𝑔𝑒𝑌𝑒𝑎𝑟𝑠
With respect to the power relationship between mg/kg/week dose and weight for fixed
mg/m2/week dose it was found that both the exponent (decreasing) and the multiplication
term (increasing) were both linearly related to an increasing dose in mg/m2/week such that,
𝐷𝑜𝑠𝑒𝑘𝑔 = (0.114𝐷𝑜𝑠𝑒𝑚2 − 0.0546)𝑊𝑡𝑘𝑔
(−0.0039𝐷𝑜𝑠𝑒 2 −0.3046)
𝑚
Over the range of doses tested, 2 to 10mg/m2/week, the exponent term varied only
marginally from -0.311 to -0.344, increasing slightly the steepness of trajectory for the most
negative exponent to approximately 10kg weight which thereafter this small difference was
maintained. The multiplication term represents the equivalent mg/kg/week dose at a weight
of 1kg and not surprisingly increases with mg/m2/week dose. The above formula cannot be
simply rearranged to convert mg/kg/week doses to mg/m2/week doses. However, as the
exponent term does not vary greatly, if the mean exponent value, -0.328, is used, an
approximate conversion, below, can be found.
𝐷𝑜𝑠𝑒𝑚2 =
1
(5000𝐷𝑜𝑠𝑒𝑘𝑔 𝑊𝑡𝑘𝑔 0.328 + 273)
572
Supporting Information Figure. Doses (pre 2008) for the indications of GH deficiency
(GHD), short stature and slow growth (SSSG), and Turner syndrome (TS) in mg/m 2/week
and mg/kg/week plotted
Table 1. Examples of changes in mean first year GH dose and response to treatment for different starting weights. Compared to published
mean responses from Bakker et al.(26) and predicted responses from Ranke et al.(29, 30) at equivalent starting ages and other relevant
parameters.
OZGROW Data
Bakker et
Ranke Prediction Models(29, 30)
al.
2008(26)1
Indication Starting Starting
mg/m2/wk
mg/kg/wk
GV2
GV4 (Ratio)3 GV4,5 (Ratio)3 GV4-Fixed
GV4-0.30
2
2
3
6
(Gender) Weight
Age
Dose
Dose
(Ratio)
Dose
mg/kg/wk7
2
3
3
3
(Years)
(Ratio)
(Ratio)
(Ratio)
(Ratio)3
GHD8
10kg
2.61
3.98 (1.00)
0.177 (1.00) 12.33 (1.00) 11.88 (1.00)
11.87 (1.00) 11.87 (1.00)
12.73 (1.00)
(Male)
20kg
7.36
4.37 (1.10)
0.162 (0.92) 9.98 (0.81)
10.10 (0.85)
10.69 (0.90) 10.83 (0.91)
11.69 (0.92)
30kg
10.83
4.61 (1.16)
0.143 (0.81) 8.75 (0.71)
9.08 (0.76)
9.50 (0.80)
9.85 (0.83)
10.70 (0.84)
GHD8
10kg
2.89
4.14 (1.00)
0.187 (1.00) 11.38 (1.00) 11.90 (1.00)
11.88 (1.00) 11.88 (1.00)
12.64 (1.00)
(Female) 20kg
7.20
4.57 (1.10)
0.169 (0.91) 8.93 (0.79)
10.15 (0.85)
10.85 (0.91) 11.02 (0.93)
11.78 (0.93)
30kg
10.23
4.71 (1.14)
0.154 (0.82) 7.56 (0.67)
9.05 (0.76)
9.80 (0.82) 10.11 (0.85)
10.88 (0.86)
SSSG9
10kg
3.24
4.52 (1.00)
0.205 (1.00) 10.01 (1.00) 10.77 (1.00)
8.30 (1.00)
8.30 (1.00)
8.37 (1.00)
(Male)
20kg
8.40
4.76 (1.05)
0.186 (0.90) 7.52 (0.75)
8.72 (0.81)
6.91 (0.83)
6.92 (0.83)
6.99 (0.83)
30kg
12.20
4.93 (1.09)
0.171 (0.83) 7.15 (0.71)
8.00 (0.74)
5.85 (0.70)
5.87 (0.71)
5.94 (0.71)
SSSG9
10kg
3.42
4.64 (1.00)
0.212 (1.00) 10.09 (1.00) 10.05 (1.00)
8.16 (1.00)
8.16 (1.00)
8.23 (1.00)
(Female) 20kg
8.96
5.16 (1.11)
0.200 (0.95) 7.54 (0.75)
8.46 (0.84)
6.91 (0.85)
6.92 (0.85)
6.98 (0.85)
30kg
12.18
5.46 (1.18)
0.194 (0.91) 7.28 (0.72)
8.36 (0.83)
6.04 (0.74)
6.05 (0.74)
6.12 (0.74)
1. For constant mean dose of 0.3 mg/kg/wk.
2. Means from linear or polynomial regressions of data.
3. Ratio to the value at 10kg starting weight or equivalent starting age.
4. GV: Growth velocity (cm/year) in first year of GH treatment.
5. Dose (mg/kg/wk) listed for “OZGROW Data” used in calculations.
6. Dose (mg/kg/wk) at 10kg retained for calculations at 20kg and 30kg.
7. Dose of 0.30 mg/kg/wk used for all calculations to allow comparison with Bakker et al.(26).
8. Compared to the IGHD (idiopathic GHD) cohort of Bakker et al. (26) or GHD cohort of Ranke et al. (29).
9. Compared to the ISS (idiopathic short stature) cohort of Bakker et al. (26) and Ranke et al.(30).