The role of growth hormone device optimization in patient-reported outcomes: real-world evidence from South Korea

Figures & data

Figure 1. The conceptual model used to identify factors associated with GH device preference GH, growth hormone; GHD, growth hormone deficiency

Table 1. Patient and caregiver/LAR demographics

Patients (N = 94)
Age (years), mean (SD)	11.0 (2.0)
Child^a, n (%)	47 (50.0)
Adolescent^b, n (%)	47 (50.0)
Sex, n (%)
Male	34 (36.2)
Female	60 (63.8)
Duration of treatment (years), mean (SD)	2.2 (1.6)
Diagnosis, n (%)
More severe condition	21 (22.3)
Growth hormone deficiency	7 (7.4)
Small for gestational age	13 (13.8)
Noonan syndrome	1 (1.1)
Less severe condition	73 (77.7)
Idiopathic short stature	50 (53.2)
Familial short stature	12 (12.8)
Precocious puberty	8 (8.5)
Others^c	3 (3.2)
No family history of GH disorders, n (%)	94 (100.0)
Height at diagnosis (cm), mean (SD)	124.4 (17.1)
Height SDS at diagnosis, mean (SD)	−1.0 (1.3)
Weight at diagnosis (kg), mean (SD)	27.3 (10.3)
Weight SDS at diagnosis, mean (SD)	−0.6 (1.1)
Height at the point of the survey (cm), mean (SD)	141.3 (13.8)
Height SDS at the point of the survey, mean (SD)	−0.4 (0.9)
Weight at the point of the survey (kg), mean (SD)	37.6 (11.3)
Weight SDS at the point of the survey, mean (SD)	−0.2 (0.8)
Injection administrator, n (%)
Patient	8 (8.5)
Caregiver/LAR	86 (91.5)
Last device used before Norditropin NordiFlex®, n (%)
Norditropin® NordiLet®	86 (91.5)
Others^d	8 (8.5)
Duration of use of Norditropin NordiFlex® at the point of survey (weeks), mean (SD)	17.1 (5.8)
No. of injections missed in a typical month, n (%)
<3 times	86 (91.5)
3–5 times	6 (6.4)
>5 times	2 (2.1)
Caregivers/LARs (N = 94)
Age (years), mean (SD)	43.8 (4.0)
Sex, n (%)
Male	5 (5.3)
Female	89 (94.7)
Highest academic qualification, n (%)
High School	6 (6.4)
University or college	36 (38.3)
Other	10 (10.6)
Preferred not to answer	42 (44.7)
Annual household income in KRW, n (%)
<50 million	9 (9.6)
50 million to <70 million	14 (14.6)
70 million or more	16 (16.7)
Preferred not to answer	55 (57.3)

^aAge ≤11 years for girls and age ≤12 years for boys, ^bAge >11 years for girls and age >12 years for boys, ^cIncludes hypothyroidism, failure to thrive and constitutional delay of growth and puberty, ^dPrefilled Eutropin®, Growtropin® II, Saizen® Easypod®, Genotropin® GoQuick®

GH, growth hormone; KRW, South Korean won; LAR, legally authorized representative; SD, standard deviation; SDS, standard deviation score.

Figure 2. Primary and secondary outcomes: GH device preference, satisfaction, perceived ease of use and missing fewer injections (N = 94) GH, growth hormone

Table 2. Bivariate associations between patient and caregiver/LAR characteristics and preference for Norditropin NordiFlex®

	Preference for NordiFlex®^a (n = 53)	No difference or preference for previous device^b (n = 41)	p-value
Patients
Age (years), mean (SD)	11.0 (1.6)	11.0 (2.5)	0.994
Child^c, n (%)	30 (63.8)	17 (36.2)	0.112
Adolescent^d, n (%)	23 (48.9)	24 (51.1)
Sex, n (%)			0.612
Male	18 (52.9)	16 (47.1)
Female	35 (58.3)	25 (41.7)
Duration of treatment (years), mean (SD)	2.5 (1.8)	1.8 (1.2)	0.040
Diagnosis, n (%)			0.038^f
More severe condition	16 (76.2)	5 (23.8)
Growth hormone deficiency	6 (85.7)	1 (14.3)
Small for gestational age	9 (69.2)	4 (30.8)
Noonan syndrome	1 (100.0)	0 (0.0)
Less severe condition	37 (50.7)	36 (49.3)
Idiopathic short stature	21 (42.0)	29 (58.0)
Familial short stature	9 (75.0)	3 (25.0)
Precocious puberty	7 (87.5)	1 (12.5)
Others^e	0 (0.0)	3 (100.0)
No family history of GH disorders, n (%)	53 (56.4)	41 (43.6)	N/A
Height at diagnosis (cm), mean (SD)	121.8 (15.8)	127.7 (18.4)	0.094
Height SDS at diagnosis, mean (SD)	−1.2 (1.3)	−0.8 (1.3)	0.167
Weight at diagnosis (kg), mean (SD)	25.8 (8.9)	29.4 (11.6)	0.093
Weight SDS at diagnosis, mean (SD)	−0.7 (1.3)	−0.5 (0.9)	0.427
Height at the point of the survey (cm), mean (SD)	140.2 (11.7)	142.6 (16.2)	0.414
Height SDS at the point of the survey, mean (SD)	−0.6 (0.9)	−0.2 (0.9)	0.067
Weight at the point of the survey (kg), mean (SD)	36.9 (10.3)	38.5 (12.6)	0.479
Weight SDS at the point of the survey, mean (SD)	−0.3 (0.9)	−0.2 (0.8)	0.514
Injection administrator, n (%)			0.715
Patient	5 (62.5)	3 (37.5)
Caregiver/LAR	48 (55.8)	38 (44.2)
Last device used before Norditropin NordiFlex®, n (%)			0.064^h
Norditropin® NordiLet®	46 (53.5)	40 (46.5)
Others^g	7 (87.5)	1 (12.5)
Duration of use of Norditropin NordiFlex® at the point of survey (weeks), mean (SD)	16.6 (5.6)	17.7 (6.1)	0.372
Caregivers/LARs
Age (years), mean (SD)	43.5 (4.2)	44.2 (3.8)	0.380
Sex, n (%)			0.867
Male	3 (60.0)	2 (40.0)
Female	50 (56.2)	39 (43.8)
Highest academic qualification, n (%)			0.325
High School	5 (83.3)	1 (16.7)
University or college	22 (61.1)	14 (38.9)
Other	4 (40.0)	6 (60.0)
Preferred not to answer	22 (52.4)	20 (47.6)
Annual household income in KRW, n (%)			0.583
<50 million	6 (66.7)	3 (33.3)
50 million to <70 million	7 (50.0)	7 (50.0)
70 million or more	7 (43.8)	9 (56.3)
Preferred not to answer	33 (60.0)	22 (44.0)

^aStandardized score of preference toward NordiFlex® >0, ^bStandardized score of preference toward NordiFlex® ≤0, ^cAge ≤11 years for girls and age ≤12 years for boys, ^dAge >11 years for girls and age >12 years for boys, ^eIncludes hypothyroidism, failure to thrive and constitutional delay of growth and puberty, ^fp-value for comparison between ‘more severe condition’ and ‘less severe condition’, ^gPrefilled Eutropin®, Growtropin® II, Saizen® Easypod®, Genotropin® GoQuick®, ^hp-value for comparison between ‘Norditropin® NordiLet®’ and ‘Others’

GH, growth hormone; KRW, South Korean won; LAR, legally authorized representative; SD, standard deviation; SDS, standard deviation score.

Figure 3. Associations between domains of subjective benefits and preference for (A), satisfaction with (B), perceived ease of use (C), and self-reported adherence (D) with Norditropin NordiFlex®

Table 3. Bivariate associations between patient and caregiver/LAR characteristics and satisfaction with Norditropin NordiFlex®

	More satisfied with NordiFlex®^a (n = 53)	No difference or more satisfied with previous device^b (n = 41)	p-value
Patients
Age (years), mean (SD)	11.0 (1.8)	11.0 (2.4)	0.928
Child^c, n (%)	28 (59.6)	19 (40.4)	0.242
Adolescent^d, n (%)	25 (53.2)	22 (46.8)
Sex, n (%)			0.612
Male	18 (52.9)	16 (47.1)
Female	35 (58.3)	25 (41.7)
Duration of treatment (years), mean (SD)	2.5 (1.8)	1.8 (1.2)	0.030
Diagnosis, n (%)			0.010^f
More severe condition	17 (81.0)	4 (19.1)
Growth hormone deficiency	6 (85.7)	1 (14.3)
Small for gestational age	10 (76.9)	3 (23.1)
Noonan syndrome	1 (100.0)	0 (0.0)
Less severe condition	36 (49.3)	37 (50.7)
Idiopathic short stature	22 (44.0)	28 (56.0)
Familial short stature	8 (66.7)	4 (33.3)
Precocious puberty	6 (75.0)	2 (25.0)
Others^e	0 (0.0)	3 (100.0)
No family history of GH disorders, n (%)	53 (56.4)	41 (43.6)	N/A
Height at diagnosis (cm), mean (SD)	121.7 (16.0)	127.8 (18.2)	0.152
Height SDS at diagnosis, mean (SD)	−1.2 (1.3)	−0.8 (1.4)	0.186
Weight at diagnosis (kg), mean (SD)	25.7 (8.9)	29.4 (11.6)	0.092
Weight SDS at diagnosis, mean (SD)	−0.7 (1.3)	−0.5 (0.9)	0.467
Height at the point of the survey (cm), mean (SD)	140.5 (12.4)	142.2 (15.5)	0.560
Height SDS at the point of the survey, mean (SD)	−0.5 (0.9)	−0.3 (0.9)	0.220
Weight at the point of the survey (kg), mean (SD)	37.2 (10.5)	38.1 (12.4)	0.723
Weight SDS at the point of the survey, mean (SD)	−0.2 (0.9)	−0.2 (0.8)	0.979
Injection administrator, n (%)			0.715
Patient	5 (62.5)	3 (37.5)
Caregiver/LAR	48 (55.8)	38 (44.2)
Last device used before Norditropin NordiFlex®, n (%)			0.064^h
Norditropin® NordiLet®	46 (53.5)	40 (46.5)
Others^g	7 (87.5)	1 (12.5)
Duration of use of NordiFlex® at the point of survey (weeks), mean (SD)	16.3 (5.5)	18.2 (6.0)	0.112
Caregivers/LARs
Age (years), mean (SD)	43.6 (4.2)	44.0 (3.8)	0.604
Sex, n (%)			0.867
Male	3 (60.0)	2 (40.0)
Female	50 (56.2)	39 (43.8)
Highest academic qualification, n (%)			0.325
High School	5 (83.3)	1 (16.7)
University or college	22 (61.1)	14 (38.9)
Other	4 (40.0)	6 (60.0)
Preferred not to answer	22 (52.4)	20 (47.6)
Annual household income in KRW, n (%)			0.851
<50 million	5 (55.6)	4 (44.4)
50 million to <70 million	7 (50.0)	7 (50.0)
70 million or more	8 (50.0)	8 (50.0)
Preferred not to answer	33 (60.0)	22 (40.0)

^aStandardized score of satisfaction with NordiFlex® >0, ^bStandardized score of satisfaction with NordiFlex® ≤0, ^cAge ≤11 years for girls and age ≤12 years for boys, ^dAge >11 years for girls and age >12 years for boys, ^eIncludes hypothyroidism, failure to thrive and constitutional delay of growth and puberty, ^fp-value for comparison between ‘more severe condition’ and ‘less severe condition’, ^gPrefilled Eutropin®, Growtropin® II, Saizen® Easypod®, Genotropin® GoQuick®, ^hp-value for comparison between ‘Norditropin® NordiLet®’ and ‘Others’

GH, growth hormone; KRW, South Korean won; LAR, legally authorized representative; SD, standard deviation; SDS, standard deviation score.

Table 4. Bivariate associations between patient and caregiver/LAR characteristics and perceived ease of use with Norditropin NordiFlex®

	Perceived NordiFlex®^a to be easier to use (n = 43)	No difference or perceived previous device^b to be easier to use (n = 51)	p-value
Patients
Age (years), mean (SD)	10.9 (1.6)	11.0 (2.4)	0.884
Child^c, n (%)	25 (53.2)	22 (46.8)	0.147
Adolescent^d, n (%)	18 (38.3)	29 (61.7)
Sex, n (%)
Male	16 (47.1)	18 (52.9)	0.847
Female	27 (45.0)	33 (55.0)
Duration of treatment (years), mean (SD)	2.6 (2.0)	1.9 (1.2)	0.030
Diagnosis, n (%)			0.029^e
More severe condition	14 (66.7)	7 (33.3)
Growth hormone deficiency	4 (57.1)	3 (42.9)
Small for gestational age	9 (69.2)	4 (30.8)
Noonan syndrome	1 (100.0)	0 (0.0)
Less severe condition	29 (39.7)	44 (60.3)
Idiopathic short stature	18 (36.0)	32 (64.0)
Familial short stature	7 (58.3)	5 (41.7)
Precocious puberty	4 (50.0)	4 (50.0)
Others^f	0 (0.0)	3 (100.0)
No family history of GH disorders, n (%)	43 (45.7)	51 (54.3)	N/A
Height at diagnosis (cm), mean (SD)	121.7 (16.1)	126.7 (17.8)	0.159
Height SDS at diagnosis, mean (SD)	−1.1 (1.4)	−0.9 (1.2)	0.484
Weight at diagnosis (kg), mean (SD)	25.6 (9.0)	28.8 (11.1)	0.133
Weight SDS at diagnosis, mean (SD)	−0.7 (1.4)	−0.6 (0.9)	0.673
Height at the point of the survey (cm), mean (SD)	140.4 (11.3)	142.0 (15.7)	0.568
Height SDS at the point of the survey, mean (SD)	−0.5 (1.0)	−0.4 (0.9)	0.516
Weight at the point of the survey (kg), mean (SD)	37.0 (10.3)	38.1 (12.2)	0.657
Weight SDS at the point of the survey, mean (SD)	−0.2 (1.0)	−0.2 (0.8)	0.862
Injection administrator, n (%)			0.625
Patient	3 (37.5)	5 (62.5)
Caregiver/LAR	40 (46.5)	46 (53.5)
Last device used before Norditropin NordiFlex®, n (%)			0.082^h
NordiLet®	37 (43.0)	49 (57.0)
Others^g	6 (75.0)	2 (25.0)
Duration of use of NordiFlex® at the point of survey (weeks), mean (SD)	16.4 (5.3)	17.7 (6.2)	0.300
Caregivers/LARs
Age (years), mean (SD)	43.7 (4.5)	43.9 (3.6)	0.823
Sex, n (%)			0.511
Male	3 (60.0)	2 (40.0)
Female	40 (44.9)	49 (55.1)
Highest academic qualification, n (%)			0.714
High School	4 (66.7)	2 (33.3)
University or college	17 (47.2)	19 (52.8)
Other	4 (40.0)	6 (60.0)
Preferred not to answer	18 (42.9)	24 (57.1)
Annual household income in KRW, n (%)			0.499
<50 million	6 (66.7)	3 (33.3)
50 million to <70 million	5 (35.7)	9 (64.3)
70 million or more	8 (50.0)	8 (50.0)
Preferred not to answer	24 (43.6)	31 (56.4)

^aStandardized score of satisfaction with NordiFlex® >0, ^bStandardized score of satisfaction with NordiFlex® ≤0, ^cAge ≤11 years for girls and age ≤12 years for boys, ^dAge >11 years for girls and age >12 years for boys, ^ep-value for comparison between ‘more severe condition’ and ‘less severe condition’, ^fIncludes hypothyroidism, failure to thrive and constitutional delay of growth and puberty, ^gPrefilled Eutropin®, Growtropin® II, Saizen® Easypod®, Genotropin® GoQuick®, ^hp-value for comparison between ‘Norditropin® NordiLet®’ and ‘Others’

GH, growth hormone; KRW, South Korean won; LAR, legally authorized representative; SD, standard deviation; SDS, standard deviation score.

Table 5. Bivariate associations between patient and caregiver/LAR characteristics and self-reported adherence with Norditropin NordiFlex®

	Missed fewer injections with NordiFlex®^a (n = 14)	No difference or missed fewer injections with previous device^b (n = 80)	p-value
Patients
Age of patient (years), mean (SD)	10.2 (1.3)	11.1 (2.1)	0.103
Child^c, n (%)	12 (25.5)	35 (74.5)	0.008
Adolescent^d, n (%)	2 (4.3)	45 (95.7)
Sex of patient, n (%)			0.969
Male	5 (14.7)	29 (85.3)
Female	9 (15.0)	51 (85.0)
Duration of treatment (years), mean (SD)	2.8 (2.2)	2.1 (1.5)	0.135
Diagnosis, n (%)			0.007^e
More severe condition	7 (33.3)	14 (66.7)
Growth hormone deficiency	3 (42.9)	4 (57.1)
Small for gestational age	4 (30.8)	9 (69.2)
Noonan syndrome	0 (0.0)	1 (100.0)
Less severe condition	7 (9.6)	66 (90.4)
Idiopathic short stature	4 (8.0)	46 (92.0)
Familial short stature	3 (25.0)	9 (75.0)
Precocious puberty	0 (0.0)	8 (100.0)
Others^f	0 (0.0)	3 (100.0)
No family history of GH disorders, n (%)	14 (14.9)	80 (85.1)	N/A
Height at diagnosis (cm), mean (SD)	112.4 (15.8)	126.5 (16.6)	0.004
Height SDS at diagnosis, mean (SD)	−1.6 (1.6)	−0.9 (1.3)	0.076
Weight at diagnosis (kg), mean (SD)	21.4 (8.5)	28.4 (10.3)	0.018
Weight SDS at diagnosis, mean (SD)	−0.9 (1.8)	−0.6 (1.0)	0.391
Height at the point of the survey (cm), mean (SD)	132.9 (8.0)	142.7 (14.1)	0.014
Height SDS at the point of the survey, mean (SD)	−0.9 (0.8)	−0.3 (0.9)	0.027
Weight at the point of the survey (kg), mean (SD)	32.3 (9.8)	38.5 (11.4)	0.059
Weight SDS at the point of the survey, mean (SD)	−0.4 (1.0)	−0.2 (0.8)	0.340
Injection administrator, n (%)
Patient	0 (0.0)	8 (100.0)	0.216
Caregiver/LAR	14 (16.3)	72 (83.7)
Last device used before Norditropin NordiFlex®, n (%)			<0.001^h
Norditropin® NordiLet®	8 (9.3)	78 (90.7)
Others^g	6 (75.0)	2 (25.0)
Duration of use of NordiFlex® at the point of the survey (weeks), mean (SD)	14.3 (6.2)	17.6 (5.6)	0.045
No. of injections missed in a typical month, n (%)			0.465
<3 times	14 (16.3)	72 (83.7)
3 to 5 times	0 (0.0)	6 (100.0)
>5 times	0 (0.0)	2 (100.0)
Caregivers/LARs
Age (years), mean (SD)	43.6 (5.2)	43.8 (3.8)	0.894
Sex, n (%)			0.742
Male	1 (20.0)	4 (80.0)
Female	13 (14.6)	76 (85.4)
Highest qualification, n (%)			0.011
High School	3 (50.0)	3 (50.0)
University or college	6 (16.7)	30 (83.3)
Others	3 (30.0)	7 (70.0)
Prefer not to answer	2 (4.8)	40 (95.2)
Annual household income in KRW, n (%)			0.052
<50 million	4 (44.4)	5 (55.6)
50 million to <70 million	1 (7.1)	13 (92.9)
70 million or more	3 (18.8)	13 (81.3)
Preferred not to answer	6 (10.9)	49 (89.1)

^aStandardized score of satisfaction with NordiFlex® >0, ^bStandardized score of satisfaction with NordiFlex® ≤0, ^cAge ≤11 years for girls and age ≤12 years for boys, ^dAge >11 years for girls and age >12 years for boys, ^ep-value for comparison between ‘more severe condition’ and ‘less severe condition’, ^fIncludes hypothyroidism, failure to thrive and constitutional delay of growth and puberty, ^gPrefilled Eutropin®, Growtropin® II, Saizen® Easypod®, Genotropin® GoQuick®, ^hp-value for comparison between ‘Norditropin® NordiLet®’ and ‘Others’

GH, growth hormone; KRW, South Korean won; LAR, legally authorized representative; SD, standard deviation; SDS, standard deviation score.

Figure 4. Forest plots of mean (95% CI) standardized scores of subjective benefits of GH device features categorized by domain: self-efficacy (A), ease of use (B), minimal disruption of daily life (C), and positive feelings about injection (D)

Data availability statement

The data that support the findings of this study are available on request from the corresponding author (WYC). The data contain information that could compromise research participant privacy/consent are therefore not publicly available.