Table 3.

Baseline ePIRS quartile ranking predicts likelihood of advancing HY status.

	ePIRS quartile	Number in quartile	Quartile value (Score, Baseline)	Within group hazard ratio (HR) compared to PD quartile I (95% CI for HR)	z	Pr (>|z|)	Hazard ratio (HR) compared to controls (95% CI for HR)
	Controls	186	Median = 2	Controls I derivation reference group
A: Derivation Sample (N = 380)	I	111	≤2				5.3 (1.7–16.3)***
	II	85	3–6	2.03 (1.00–4.11)	1.97	0.049	10.7 (3.7–31.5)****
	III	78	7–10	3.34 (1.71–6.54)***	3.52	0.00043	17.7 (6.2–51.0)****
	IV	76	≥11	8.28 (4.48–15.29)****	6.75	<0.00001	44.1 (15.9–122.2)****
B: IPD Sample (N = 79)	I (Ref)	86	Derivation sample de-novo quartile I reference group (Modified)
	I	25	≤2	1.90 (0.51–7.02)	0.96	0.34	9.7 (1.9–48.4)**
	II	18	3–6	2.52 (0.68–9.29)	1.38	0.17	12.7 (2.6–63.6)***
	III	21	7–10	2.53 (0.68–9.47)	1.38	0.17	13.2 (2.6–67.3)***
	IV	14	≥11	16.18 (6.34–41.23)****	5.83	<0.00001	88.0 (23.2–333.5)****
C: GPD Sample (N = 141)	I (Ref)	111	Derivation sample de-novo quartile I reference group				5.3 (1.7–16.3)***
	I	20	≤2	2.81 (0.56–14.06)	1.26	0.21	21.6 (2.5–185.3)***
	II	29	3–6	0.94 (0.11–7.87)	−0.056	0.96	7.4 (0.6–95.1)
	III	43	7–10	3.84 (1.15–12.83)	2.19	0.029	28.5 (4.7–174.1)***
	IV	60	≥11	13.26 (5.13–34.28)****	5.34	<0.00001	103.2 (18.7–569.9)****

Progression to HY ≥ 3, by quartile, compared to healthy controls (right-most columns) and compared to Quartile I. Reference Quartile I values in all cases are taken from the de-novo sample. A: Significant, and progressive impact of quartile on risk development of HY ≥ 3 is noted in the de-novo PD derivation sample. B: In the IPD validation sample, ePIRS scores in the fourth quartile (≥11) were associated with a significantly higher likelihood of progression to HY ≥ 3. C: In the GPD cohort, once again membership in Quartile 4 confers a higher risk of progression to HY ≥ 3 compared to de-novo subjects with ePIRS scores ≤ 2.

**p ≤ 0.01, ***p ≤ 0.005, ****p ≤ 0.0001.