Background
Methods
Data collection and study population
Definition of health-related and socio-demographic variables
Assessment of medicine use
Data processing
Quality control
Statistical analysis
Results
Prevalence and determinants of off-label use
Children with drug use (n = 8,899) | Children with off-label medicine use of ≥ 1 preparation (n = 3,610) | Children with excl. in-label medicine use (n = 4.334) | Children with excl. not-attributable medicine use (n = 955) | Children with off-label vs. excl. in-label medicine use (n = 7,808) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
n | % | 95% CI | % | 95% CI | % | 95% CI | % | 95% CI | OR | 95% CI | p-value | |
Total | 8,899 | 50.8 | (49.5-52.2) | 40.2 | (38.8-41.5) | 48.7 | (47.3-50.2) | 11.1 | (10.3-12.0) | |||
Sex | .015 | |||||||||||
Boys | 4,362 | 48.7 | (47.2-50.3) | 41.4 | (39.7-43.1) | 46.2 | (44.5-47.9) | 12.4 | (11.3-13.6) | 1.13 | (1.03-1.25) | |
Girls | 4,537 | 53.1 | (51.5-54.7) | 38.9 | (37.1-38.8) | 51.2 | (49.3-53.2) | 9.8 | (8.9-10.9) | 1(Referenz) | ||
Age group | < .001 | |||||||||||
0 - 2 years | 2,089 | 74.9 | (72.9-76.9) | 42.4 | (39.8-45.1) | 53.1 | (50.3-55.9) | 4.5 | (3.5-5.8) | 1.45 | (1.24-1.69) | |
3 - 6 years | 1,939 | 51.1 | (48.8-53.3) | 48.7 | (46.1-51.4) | 39.7 | (37.2-42.2) | 11.6 | (10.0-13.4) | 2.08 | (1.79-2.41) | |
7 - 10 years | 1,718 | 42.6 | (40.4-44.8) | 41.3 | (38.9-43.8) | 45.7 | (43.3-48.1) | 13.0 | (11.4-14.8) | 1.52 | 1.31-1.78) | |
11 - 13 years | 1,289 | 42.4 | (40.1-44.7) | 36.9 | (34.0-40.0) | 46.5 | (43.1-49.8) | 16.6 | (14.3-19.2) | 1.36 | (1.15-1.60) | |
14 - 17 years | 1,864 | 50.7 | (49.5-52.2) | 32.5 | (30.2-34.8) | 56.1 | (53.6-58.8) | 11.4 | (9.9-13.1) | 1(Referenz) | ||
Region | .355 | |||||||||||
East | 2,881 | 51.7 | (49.2-54.2) | 40.3 | (38.3-42.4) | 50.1 | (47.9-52.2) | 9.6 | (8.7-10.7) | 1.06 | (0.93-1-19) | |
West | 6,018 | 50.7 | (49.2-52.2) | 40.1 | (38.5-41.7) | 48.5 | (46.8-50.2) | 11.4 | (10.5-12.4) | 1(Referenz) | ||
Urbanity | .022 | |||||||||||
Rural area | 1,985 | 50.5 | (47.8-53.1) | 36.5 | (33.4-39.8) | 54.5 | (51.0-58.0) | 8.9 | (7.1-11.1) | 0.83 | (0.69-1.00) | |
Small city | 2,314 | 50.9 | (48.3-53.5) | 42.0 | (39.0-45.0) | 47.3 | (44.6-49.6) | 10.8 | (9.3-12.4) | 1.10 | (0.92-1.30) | |
Medium-sized city | 2,561 | 50.7 | (48.2-53.3) | 41.6 | (39.4-43.8) | 47.3 | (45.2-49.4) | 11.1 | (10.0-12.4) | 1.07 | (0.91-1.24) | |
Large city | 2,039 | 51.2 | (48.4-53.9) | 39.1 | (36.8-41.5) | 47.9 | (45.1-50.8) | 12.9 | (11.2-14.9) | 1(Referenz) | ||
Migrant background | .954 | |||||||||||
Yes | 1,071 | 41.4 | (38.8-44.2) | 35.8 | (32.6-39.1) | 44.1 | (40.5-47.8) | 20.1 | (17.5-22.9) | 0.99 | (0.82-1.21) | |
No | 7,788 | 52.8 | (51.5-54.1) | 40.9 | (39.4-42.3) | 49.5 | (48.0-51.1) | 9.6 | (8.8-10.4) | 1(Referenz) | ||
Missing | 40 | |||||||||||
Social status | .157 | |||||||||||
Low | 2,249 | 47.1 | (45.0-49.2) | 39.1 | (36.6-41.7) | 47.0 | (44.4-49.7) | 13.9 | (12.1-15.8) | 0.91 | (0.78-1.07) | |
Middle | 4,083 | 51.2 | (49.7-52.7) | 39.9 | (37.9-41.9) | 50.4 | (48.3-52.5) | 9.7 | (8.6-10.8) | 0.90 | (0.80-1.00) | |
High | 2,403 | 55.1 | (53.0-57.3) | 42.5 | (40.4-44.7) | 47.6 | (45.4-49.8) | 9.9 | (8.5-11.4) | 1(Referenz) | ||
Missing | 164 | |||||||||||
Parents’ rated subjective health status | < .001 | |||||||||||
Excellent | 3,261 | 47.2 | (45.4-48.9) | 38.2 | (36.1-40.3) | 51.7 | (49.6-53.8) | 10.1 | (9.1-11.2) | 0.71 | (0.58-0.88) | |
Good | 4,840 | 52.1 | (50.6-62.9) | 41.2 | (39.4-42.9) | 47.1 | (45.3-49.0) | 11.7 | (10.5-13.0) | 0.89 | (0.73-1.07) | |
Moderate/Bad/Very Bad | 798 | 60.0 | (49.5-52.2) | 41.7 | (37.9-45.6) | 46.7 | (42.8-50.7) | 11.6 | (9.3-14.3) | 1(Referenz) |
Spectrum of off-label use
Drug use categories | Origin of medicines (n = 12,587*) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Prescribed | OTC | Other sources | |||||||
n | % | 95% CI | n | % | 95% CI | n | % | 95% CI | |
Off-label medicine use
|
2,344
|
29.9
|
(28.9-30.9)
|
925
|
30.3
|
(28.7-31.9)
|
515
|
30.6
|
(28.5-32.9)
|
➢ Indication | 376 | 4.8 | (4.3-5.2) | 106 | 3.5 | (2.9-4.2) | 56 | 3.3 | (2.6-4.3) |
➢ Age | 326 | 4.2 | (3.7-4.6) | 100 | 3.3 | (2.7-4.0) | 45 | 2.7 | (2.0-3.6) |
➢ Under-dosing | 1,263 | 16.1 | (15.3-16.9) | 590 | 19.3 | (18.0-20.8) | 339 | 20.2 | (18.3-22.2) |
➢ Over-dosing | 379 | 4.8 | (4.4-5.3) | 129 | 4.2 | (3.6-5.0) | 75 | 4.5 | (3.6-5.6) |
In-label medicine use
|
5,508
|
70.1
|
(69.1-71.1)
|
2,129
|
69.7
|
(68.1-71.3)
|
1,166
|
69.4
|
(67.1-71.5)
|
ATC-class | Off-label use | In-label use | Total | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Indication | Age | Over-dosing | Under-dosing | ||||||||
n | % | n | % | n | % | n | % | n | % | n | |
Total
|
541
|
4.3
|
476
|
3.8%
|
583
|
4.6
|
2,202
|
17.4
|
8,865
|
70.0
|
12,667
|
A00 ALIMENTARY TRACT and METABOLISM
|
140
|
4.8
|
113
|
3.9%
|
86
|
2.9
|
654
|
22.4
|
1,933
|
66.1
|
2,926
|
A01 Stomatological preparations | 47 | 2.8 | 80 | 4.7% | 41 | 2.4 | 308 | 18.2 | 1215 | 71.9 | 1691 |
A03 Antispasmodic and anticholinergic agents and propulsives | 6 | 4.7 | 3 | 2.4 | 8 | 6.3 | 18 | 14.2 | 92 | 72.4 | 127 |
A07 Antidiarrheals. Intestinal Antiinflammatory/Antiinfektive Agents | 5 | 4.9 | 7 | 6.8 | 6 | 5.8 | 11 | 10.7 | 74 | 71.8 | 103 |
A11 Vitamins | 35 | 5.1 | 10 | 1.4 | 18 | 2.6 | 218 | 31.5 | 411 | 59.4 | 692 |
A12 Mineral Supplements | 42 | 22.5 | 4 | 2.1 | 6 | 3.2 | 84 | 44.9 | 51 | 27.3 | 187 |
A14 Anabolic Agents for Systemic Use | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 100 | 2 |
B00 BLOOD and BLOOD FORMING ORGANS
|
0
|
0
|
4
|
5.5
|
3
|
4.1
|
17
|
23.3
|
49
|
67.1
|
73
|
C00 CARDIOVASKULAR SYSTEM
|
3
|
5.2
|
11
|
19.0
|
3
|
5.2
|
22
|
37.9
|
19
|
32.8
|
58
|
C01 Cardic Therapy | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 30.0 | 7 | 70.0 | 10 |
C05 Vasoprotectives | 1 | 4.0 | 0 | 0 | 1 | 4.0 | 17 | 68.0 | 6 | 24.0 | 25 |
C07 Beta Blocking Agents | 1 | 10.0 | 7 | 70.0 | 0 | 0 | 1 | 10.0 | 1 | 10.0 | 10 |
D00 DERMATOLOGICALS
|
69
|
4.4
|
42
|
2.7
|
30
|
1.9
|
344
|
21.8
|
1,094
|
69.3
|
1579
|
D01 Antifungals for Dermatological Use | 7 | 6.1 | 1 | 0.9 | 5 | 4.3 | 21 | 18.3 | 81 | 70.4 | 115 |
D02 Emollients and Protectives | 4 | 1.6 | 4 | 1.6 | 4 | 1.6 | 29 | 11.9 | 203 | 83.2 | 244 |
D03 Preparations for Treatment of Wounds and Ulcers | 17 | 5.3 | 2 | 0.6 | 0 | 0 | 3 | 0.9 | 297 | 93.1 | 319 |
D04 Antipruritics. incl. Antihistamines. Anesthetics etc. | 1 | 0.6 | 1 | 0.6 | 1 | 0.6 | 46 | 28.6 | 112 | 69.6 | 161 |
D06 Antibiotics and Chemotherapeutics for Dermatological Use | 10 | 11.6 | 1 | 1.2 | 2 | 2.3 | 49 | 57.0 | 24 | 27.9 | 86 |
D07 Corticosteroids. Dermatological Preparations | 23 | 10.2 | 15 | 6.6 | 13 | 5.8 | 95 | 42.0 | 80 | 35.4 | 226 |
D10 Anti-Akne Preparations | 2 | 1.8 | 0 | 0 | 1 | 0.9 | 28 | 25.5 | 79 | 71.8 | 110 |
D11 Other Dermatological Preparations | 4 | 1.8 | 16 | 7.4 | 3 | 1.4 | 69 | 31.8 | 125 | 57.6 | 217 |
G00 GENITO URINARY SYSTEM and SEX HORMONES
|
52
|
10.5
|
2
|
0.4
|
4
|
0.8
|
8
|
1.6
|
431
|
86.7
|
497
|
G03 Sex Hormones and Modulators of the Genital System | 48 | 10.6 | 1 | 0.2 | 3 | 0.7 | 2 | 0.4 | 398 | 88.1 | 452 |
H00 SYSTEMIC HORMONAL PREPARATIONS. excl. SEX HORMONES and INSULINS
|
6
|
2.0
|
0
|
0
|
7
|
2.4
|
29
|
9.8
|
253
|
85.8
|
2,,95
|
H03 Thyroid Therapy | 1 | 0.4 | 0 | 0 | 5 | 2.0 | 28 | 11.4 | 212 | 86.2 | 246 |
J00 ANTIINFECTIVES for SYSTEMIC USE
|
25
|
6.7
|
5
|
1.3
|
21
|
5.6
|
71
|
19.0
|
252
|
67.4
|
374
|
J01 Antibiotics for Systemic Use | 25 | 7.5 | 4 | 1.2 | 21 | 6.3 | 71 | 21.3 | 212 | 63.7 | 333 |
L00 ANTINEOPLASTIC and IMMUNMODULATING AGENTS
|
8
|
9.4
|
7
|
8.2
|
5
|
5.9
|
24
|
28.2
|
41
|
48.2
|
85
|
L03 Immunostimulants | 8 | 11.3 | 6 | 8.5 | 4 | 5.6 | 23 | 32.4 | 30 | 42.3 | 71 |
M00 MUSCULO-SKELETAL SYSTEM
|
11
|
2.0
|
31
|
5.6
|
8
|
1.5
|
47
|
8.5
|
454
|
82.4
|
551
|
M01 Antiinflammatory and Antirheumatic Products | 2 | 0.8 | 16 | 6.4 | 6 | 2.4 | 26 | 10.4 | 200 | 80.0 | 250 |
M02 Topical Products for Joint and Muscular Pain | 7 | 2.5 | 14 | 5.0 | 1 | 0.4 | 16 | 5.7 | 242 | 86.4 | 280 |
N00 NERVOUS SYSTEM
|
28
|
2.6
|
43
|
3.9
|
11
|
1.0
|
93
|
8.5
|
921
|
84.0
|
1,096
|
N02 Analgesics | 11 | 1.4 | 30 | 3.9 | 5 | 0.6 | 66 | 8.5 | 664 | 85.6 | 776 |
N06 Psychoanaleptics | 7 | 3.8 | 2 | 1.1 | 0 | 0.0 | 9 | 4.9 | 167 | 90.3 | 185 |
R00 RESPIRATORY SYSTEM
|
94
|
2.4
|
202
|
5.2
|
334
|
8.6
|
786
|
20.2
|
2477
|
63.6
|
3,893
|
R01 Nasal Preparations | 13 | 1.3 | 55 | 5.5 | 18 | 1.8 | 60 | 6.1 | 845 | 85.3 | 991 |
R02 Throat Preparations | 2 | 1.3 | 2 | 1.3 | 13 | 8.7 | 9 | 6.0 | 124 | 82.7 | 150 |
R03 Anti-Asthmatics | 20 | 3.5 | 46 | 8.0 | 16 | 2.8 | 72 | 12.6 | 419 | 73.1 | 573 |
R04 Chest Ointments. Inhalatives | 3 | 1.0 | 35 | 11.3 | 0 | 0.0 | 108 | 34.7 | 165 | 53.1 | 311 |
R05 Cough and Cold Preparations | 42 | 2.6 | 54 | 3.3 | 278 | 16.9 | 476 | 28.9 | 797 | 48.4 | 1647 |
R06 Antihistamines for Systemic Use | 13 | 6.1 | 10 | 4.7 | 9 | 4.2 | 60 | 28.3 | 120 | 56.6 | 212 |
S00 SENSORY ORGANS
|
20
|
10.0
|
2
|
1.0
|
10
|
5.0
|
60
|
30.0
|
108
|
54.0
|
200
|
S01 Ophthalmologicals | 19 | 13.4 | 2 | 1.4 | 2 | 1.4 | 47 | 33.1 | 72 | 50.7 | 142 |
S02 Otologicals | 1 | 1.9 | 0 | 0 | 7 | 13.5 | 11 | 21.2 | 33 | 63.5 | 52 |
V00 VARIOUS
|
5
|
2.3
|
1
|
0.5
|
6
|
2.8
|
23
|
10.6
|
183
|
83.9
|
218
|
V03 All Other Therapeutic Products | 3 | 3.0 | 0 | 0 | 4 | 4.0 | 18 | 18.2 | 74 | 74.7 | 99 |
V06 General Nutrients | 0 | 0 | 1 | 2.0 | 2 | 4.0 | 5 | 10.0 | 42 | 84.0 | 50 |
Z00 HOMOEOPATHICS
|
80
|
10.0
|
11
|
1.4
|
55
|
6.9
|
23
|
2.9
|
631
|
78.9
|
800
|
ATC-class | 0-2 years | 3-6 years | 7-10 years | 11-13 years | 14-17 years |
---|---|---|---|---|---|
n (%) | n (%) | n (%) | n (%) | n (%) | |
A00 Alimentary tract and metabolism
| 328 (21.3) | 255 (49.5) | 172 (50.0) | 108 (47.8) | 130 (43.0) |
B00 Blood and blood forming organs
| 2 (13.3) | 1 (14.3) | 2 (50.0) | 10 (52.6) | 9 (32.1) |
C00 Cardiovascular system
| 3 (100) | 2 (40.0) | 9 (64.3) | 9 (90.0) | 16 (61.5) |
D00 Dermatologicals
| 102 (26.6) | 106 (30.1) | 110 (31.0) | 75 (37.1) | 92 (32.1) |
G00 Genito urinary system and sex hormones
| 4 (66.7) | 1 (10.0) | 6 (50.0) | 2 (25.0) | 53 (11.5) |
H00 Systemic hormon. preparations excl. sex hormones and insulins
| 3 (14.3) | 11 (19.3) | 7 (13.7) | 7 (9.5) | 14 (15.2) |
J00 Antiinfectives for systemic use
| 29 (32.2) | 41 (36.6) | 18 (30.5) | 15 (31.9) | 19 (28.8) |
L00 Antineoplastic and immunmodulating agents
| 7 (70.0) | 16 (57.1) | 8 (42.1) | 6 (42.9) | 7 (50.0) |
M00 Musculo-skeletal system
| 13 (25.5) | 17 (23.3) | 18 (16.8) | 21 (18.9) | 28 (13.4) |
N00 Nervous system
| 20 (12.7) | 21 (20.2) | 51 (25.5) | 39 (16.5) | 44 (11.1) |
P00 Antiparasitic products insecticides and repellents
| 1 (33.3) | 1 (20.0) | 1 (14.3) | 0 | |
R00 Respiratory system
| 356 (39.1) | 493 (40.4) | 288 (35.7) | 146 (30.7) | 133 (27.7) |
S00 Sensory organs
| 30 (56.6) | 30 (42.3) | 13 (61.9) | 11 (36.7) | 8 (32.0) |
V00 Various
| 16 (16.3) | 6 (25.0) | 7 (16.7) | 1 (5.6) | 5 (13.9) |
Z00 Homoeopathics
| 41 (23.2) | 47 (20.3) | 37 (19.2) | 22 (20.6) | 22 (23.9) |
TOTAL n = 12,667
| 954 (27.1) | 1048 (37.3) | 747 (33.5) | 473 (29.8) | 580 (23.0) |