Factors Related to Treatment Non-Adherence Among Caregivers of Pediatric and Adolescent Growth Hormone Deficiency Patients in Japan

Figures & data

Table 1 Treatment Adherence and Caregiver, Patient, and Treatment Characteristics

n (%)	All caregivers (n=112)	Poor adherence caregivers^a(n=36)	Moderate to good adherence caregivers^b(n=76)	p-value
Caregiver characteristics
Adherence level
Poor adherence	36 (32.1)	36 (100.0)	-	-
Moderate adherence	44 (39.3)	-	44 (57.9)	-
Good adherence	32 (28.6)	-	32 (42.1)	-
Caregiver gender
Male	51 (45.5)	17 (47.2)	34 (44.7)	0.805
Female	61 (54.5)	19 (52.8)	42 (55.3)
Caregiver age
20–29	3 (2.7)	2 (5.6)	1 (1.3)	0.194
30–39	49 (43.8)	23 (63.9)	26 (34.2)	0.003
40–49	47 (42.0)	8 (22.2)	39 (51.3)	0.004
50 or older	13 (11.6)	3 (8.3)	10 (13.2)	0.457
Number of children under age 18 living at home
1 child	22 (19.6)	8 (22.2)	14 (18.4)	0.636
2 children	61 (54.5)	18 (50.0)	43 (56.6)	0.514
3 or more children	29 (25.9)	10 (27.8)	19 (25.0)	0.754
Gender of primary caregiver
Male	34 (30.4)	16 (44.4)	18 (23.7)	0.026
Female	78 (69.6)	20 (55.6)	58 (76.3)
Employment status of primary caregiver
Full-time / part-time	86 (76.8)	32 (88.9)	54 (71.1)	0.037
Not currently working	26 (23.2)	4 (11.1)	22 (28.9)
Highest educational attainment of primary caregiver
Middle school	5 (4.5)	1 (2.8)	4 (5.3)	0.552
High school	15 (13.4)	5 (13.9)	10 (13.2)	0.916
Vocational / short-term college	28 (25.0)	6 (16.7)	22 (28.9)	0.161
University / college	43 (38.4)	12 (33.3)	31 (40.8)	0.449
Graduate school	19 (17.0)	10 (27.8)	9 (11.8)	0.036
Prefer not to answer	2 (1.8)	2 (5.6)	0 (0.0)	0.038
Annual household income
Less than 5 million JPY	22 (19.6)	5 (13.9)	17 (22.4)	0.292
5 million JPY to <10 million JPY	49 (43.8)	14 (38.9)	35 (46.1)	0.475
10 million JPY or more	31 (27.7)	14 (38.9)	17 (22.4)	0.068
Prefer not to answer	10 (8.9)	3 (8.3)	7 (9.2)	0.879
Patient characteristics
Patient gender
Male	74 (66.1)	23 (63.9)	51 (67.1)	0.737
Female	38 (33.9)	13 (36.1)	25 (32.9)
School age
Pre-elementary school	33 (29.5)	16 (44.4)	17 (22.4)	0.017
1st to 3rd year elementary school	36 (32.1)	8 (22.2)	28 (36.8)	0.122
4th to 6th year elementary school	27 (24.1)	8 (22.2)	19 (25)	0.748
Middle school	16 (14.3)	4 (11.1)	12 (15.8)	0.509
Treatment characteristics
Primary facility type
Hospital	71 (63.4)	19 (52.8)	52 (68.4)	0.109
Clinic	41 (36.6)	17 (47.2)	24 (31.6)
Primary department treated by
Pediatrics	90 (80.4)	32 (88.9)	58 (76.3)	0.118
Diabetes/metabolic/endocrinology	14 (12.5)	2 (5.6)	12 (15.8)	0.126
Internal medicine	5 (4.5)	2 (5.6)	3 (3.9)	0.700
Other	1 (0.9)	0 (0)	1 (1.3)	0.489
Do not know	2 (1.8)	0 (0)	2 (2.6)	0.326

Note: ^aPoor adherence is defined as an MMAS-8 score of < 6.0 points. ^bModerate to good adherence is defined as an MMAS-8 score of 6.0 to 8.0 points.

Table 2 Treatment Adherence and Health Literacy Among Caregivers Based on HLS-14

Mean (SD)	All caregivers (n=112)	Poor adherence caregivers^a(n=36)	Moderate to good adherence caregivers^b(n=76)	p-value
Overall	50.1±7.3	49.3±6.5	50.5±7.7	0.421
Functional health literacy	17.6±5.0	15.6±5.3	18.6±4.7	0.003
Communicative health literacy	18.8±3.5	19.2±4.0	18.6±3.3	0.374
Critical health literacy	13.7±2.8	14.4±2.9	13.3±2.8	0.049

Note: ^aPoor adherence is defined as an MMAS-8 score of <6.0 points. ^bModerate to good adherence is defined as an MMAS-8 score of 6.0 to 8.0 points.

Table 3 Treatment Adherence and Satisfaction Concerning Treatment

Those that selected 4 (“Satisfied”) or 5 (“Very satisfied”) on a 5-point Likert scale, n (%)	All caregivers (n=112)	Poor adherence caregivers^a(n=36)	Moderate to good adherence caregivers^b(n=76)	p-value
Satisfaction concerning treatment
Consultation time	80 (71.4)	28 (77.8)	52 (68.4)	0.306
Treatment options	86 (76.8)	24 (66.7)	62 (81.6)	0.081
Drug treatment used	84 (75.0)	24 (66.7)	60 (78.9)	0.161
Device used (injection device)	83 (74.1)	27 (75.0)	56 (73.7)	0.882
Treatment efficacy (at improving stature)	77 (68.8)	26 (72.2)	51 (67.1)	0.585
Treatment safety (side effects and pain)	68 (60.7)	20 (55.6)	48 (63.2)	0.442
Communication with physicians	86 (76.8)	28 (77.8)	58 (76.3)	0.864
Communication with nurses and pharmacists	78 (69.6)	25 (69.4)	53 (69.7)	0.975
Physical and mental burden of patient related to treatment	60 (53.6)	17 (47.2)	43 (56.6)	0.354
Physical and mental burden of caregiver related to treatment	55 (49.1)	18 (50.0)	37 (48.7)	0.897
Cost of rhGH treatment	74 (66.1)	23 (63.9)	51 (67.1)	0.737

Note: ^aPoor adherence is defined as MMAS-8 score <6.0 points. ^bModerate to good adherence is defined as an MMAS-8 score of 6.0 to 8.0 points.

Table 4 Treatment Adherence and Opinions Concerning Treatment

Those that selected 4 (“Agree”) or 5 (“Agree with a lot”) on a 5-point Likert scale, n (%)	All caregivers (n=112)	Poor adherence caregivers^a(n=36)	Moderate to good adherence caregivers^b(n=76)	p-value
Opinions concerning treatment
If growth hormone therapy is not administered as directed, then the desired effect cannot be achieved	50 (44.6)	16 (44.4)	34 (44.7)	0.977
Physicians should check for non-adherence (missed or unintentional injections) during consultations	49 (43.8)	17 (47.2)	32 (42.1)	0.610
Caregivers should report non-adherence (missed or unintentional injections) during consultations	62 (55.4)	18 (50.0)	44 (57.9)	0.433
Caregivers should keep records of growth hormone injections	65 (58.0)	22 (61.1)	43 (56.6)	0.650
Physicians should review caregiver’s record of growth hormone injections	54 (48.2)	20 (55.6)	34 (44.7)	0.285
Caregivers should decide in advance when to give growth hormone injections and adhere to it	67 (59.8)	21 (58.3)	46 (60.5)	0.825
Physicians should take the initiative in providing information about the disease and its treatment	66 (58.9)	23 (63.9)	43 (56.6)	0.463
Caregivers should get informed about the disease/therapy as needed	66 (58.9)	23 (63.9)	43 (56.6)	0.463
I gather information sufficiently about the disease and its treatment	48 (42.9)	16 (44.4)	32 (42.1)	0.815
I have sufficient understanding of the disease/therapy in practice	55 (49.1)	19 (52.8)	36 (47.4)	0.593
Drugs/devices (injectors) should be determined by the physician	53 (47.3)	19 (52.8)	34 (44.7)	0.426
Drugs/devices (injectors) should be selected by the caregiver	26 (23.2)	12 (33.3)	14 (18.4)	0.081
Doctors, pharmacists, or nurses should ask caregivers about any problems with the drug/device (injector) used	64 (57.1)	22 (61.1)	42 (55.3)	0.559
Caregivers should consult about any problems related to the drug/device (injector) used	61 (54.5)	20 (55.6)	41 (53.9)	0.873
Physicians should ask caregivers about their desire to change the drug/device (injector) used	48 (42.9)	19 (52.8)	29 (38.2)	0.144
Caregivers should consult with physicians about changing the drug/device (injector) used	51 (45.5)	18 (50.0)	33 (43.4)	0.514
Missing an injection once or twice a month is not a problem	44 (39.3)	20 (55.6)	24 (31.6)	0.015
Intentionally skipping an injection once or twice a month is not a problem	22 (19.6)	12 (33.3)	10 (13.2)	0.012

Note: ^aPoor adherence is defined as MMAS-8 score <6.0 points. ^bModerate to good adherence is defined as an MMAS-8 score of 6.0 to 8.0 points.

Table 5 Exploratory Factor Analysis: Treatment Satisfaction

Category	Item	Factor 1	Factor 2	Factor 3
Satisfaction with drug / device used	Drug treatment used	0.90	0.13	0.32
	Device used (injection device)	0.70	0.28	0.29
Satisfaction with degree of physical and mental burden related to treatment	Physical and mental burden of patient related to treatment	0.13	0.97	0.18
	Physical and mental burden of caregiver related to treatment	0.28	0.58	0.34
Satisfaction with communication with healthcare professionals	Communication with physicians	0.29	0.23	0.80
	Communication with nurses and pharmacists	0.39	0.28	0.72

Notes: Shaded boxes indicate items within each factor with loading factors greater than 0.5. Three factors were identified: Factor 1 which has a strong association with satisfaction with the drug / device used, Factor 2 which has a strong association with satisfaction with degree of physical and mental burden related to treatment, and Factor 3 which has a strong association with satisfaction with communication with healthcare professionals. These three factors were used in the K-Means clustering analysis.

Table 6 K-Means Cluster Analysis: Treatment Satisfaction

Category	Cluster 1 “Burdened” (n=27)	Cluster 2 “Satisfied” (n=24)	Cluster 3 “Drug / device focused” (n=32)	Cluster 4 “Communication focused” (n=29)
Satisfaction with drug / device used	0.465	0.813	−0.851	−0.167
Satisfaction with degree of physical and mental burden	−1.164	1.067	0.400	−0.243
Satisfaction with communication with healthcare professionals	0.611	0.490	0.281	−1.285
Moderate to good adherence, n (%)^a	19 (70.4)	21 (87.5)	16 (50.0)	20 (69.0)

Note: ^aModerate to good adherence is defined as an MMAS-8 score of 6.0 to 8.0 points.

Table 7 Exploratory Factor Analysis: Opinions Related to Treatment

Category	Item	Factor1	Factor2	Factor3
Importance of treatment management	Caregivers should keep records of growth hormone injections	0.86	0.20	0.22
	Caregivers should get informed about the disease/therapy as needed	0.73	0.30	0.35
	Caregivers should report non-adherence (missed or unintentional injections) during consultations	0.72	0.18	0.28
	Caregivers should decide in advance when to give growth hormone injections and adhere to it	0.65	0.23	0.33
Importance of consultation concerning drug / device used	Caregivers should consult about any problems related to the drug/device (injector) used	0.21	0.82	0.29
	Caregivers should consult with physicians about changing the drug/device (injector) used	0.24	0.76	0.11
Importance of treatment info gathering and understanding	I gather information sufficiently about the disease and its treatment	0.33	0.18	0.80
	I have sufficient understanding of the disease/therapy in practice	0.40	0.29	0.68

Notes: Shaded boxes indicate items within each factor with loading factors greater than 0.5. Three factors were identified: Factor 1 which has a strong association with items related to importance of treatment management, Factor 2 which has a strong association with items related to importance of consultation cornering their drug / device, and Factor 3 which has a strong association with items relates to the importance of info gathering and understanding. These three factors were used in the K-Means clustering analysis.

Table 8 K-Means Cluster Analysis: Opinions Related to Treatment

	Cluster 1 “Involved” (n=36)	Cluster 2 “Managed” (n=32)	Cluster 3 “Mismanaged” (n=14)	Cluster 4 “Uninvolved” (n=30)
Importance of treatment management	0.463	0.760	−1.564	−0.636
Importance of consultation concerning drug / device used	0.186	0.380	0.890	−1.044
Importance of treatment info gathering and understanding	0.967	−0.513	−0.098	−0.567
Moderate to good adherence, n (%)^a	23 (63.9)	23 (71.9)	8 (57.1)	22 (73.3)

Note: ^aModerate to good adherence is defined as an MMAS-8 score of 6.0 to 8.0 points.