Background: Despite the developments of recombinant growth hormone (rhGH) treatment and the benefits in long-term clinical health outcomes, evidence has shown that many children with growth hormone deficiency (GHD) still fail to achieve their target adult height. Suboptimal outcomes have been largely attributed to treatment non-adherence. Methods: A search of 11 electronic databases was undertaken to identify relevant articles, published in English, between 1985 and 2018. Additional search strategies included hand-searching topic review articles to identify eligible studies. Articles were screened against the inclusion eligibility criteria and data on sample characteristics, study design, outcomes, and key findings was extracted. The results were narratively synthesised and categorised using the COM-B theoretical framework. Results: Twenty-one full-text articles were assessed for eligibility, of which 6 articles met the inclusion criteria. The prevalence of non-adherence in the included studies varied from 7 to 71%. Potentially modifiable factors associated with rhGH non-adherence were categorised within the COM-B framework; key factors included: a lack of knowledge and understanding of the condition and treatment, discomfort and pain associated with injections, and the quality of the healthcare professional-patient relationship. Conclusion: This review highlights the scope of the adherence problem evident amongst the paediatric GHD population and in addition presents the wide range of potentially modifiable factors that explain this health-related behaviour.

1.
Acerini
C
,
Albanese
A
,
Casey
A
,
Denvir
L
,
Jones
J
,
Mathew
V
, et al.
Initiating growth hormone therapy for children and adolescents
.
Br J Nurs
.
2012
Oct
;
21
(
18
):
1091
7
.
[PubMed]
0966-0461
2.
Rosenfeld
RG
,
Bakker
B
.
Compliance and persistence in pediatric and adult patients receiving growth hormone therapy
.
Endocr Pract
.
2008
Mar
;
14
(
2
):
143
54
. Available from:
[PubMed]
1530-891X
3.
Cutfield
WS
,
Derraik
JG
,
Gunn
AJ
,
Reid
K
,
Delany
T
,
Robinson
E
, et al.
Non-compliance with growth hormone treatment in children is common and impairs linear growth
.
PLoS One
.
2011
Jan
;
6
(
1
):
e16223
.
[PubMed]
1932-6203
4.
Fisher
BG
,
Acerini
CL
.
Understanding the growth hormone therapy adherence paradigm: a systematic review
.
Horm Res Paediatr
.
2013
;
79
(
4
):
189
96
.
[PubMed]
1663-2818
5.
Polak
M
,
Blair
J
,
Kotnik
P
,
Pournara
E
,
Pedersen
BT
,
Rohrer
TR
.
Early growth hormone treatment start in childhood growth hormone deficiency improves near adult height: analysis from NordiNet® International Outcome Study
.
Eur J Endocrinol
.
2017
Nov
;
177
(
5
):
421
9
.
[PubMed]
0804-4643
6.
Reiter
EO
,
Price
DA
,
Wilton
P
,
Albertsson-Wikland
K
,
Ranke
MB
.
Effect of growth hormone (GH) treatment on the near-final height of 1258 patients with idiopathic GH deficiency: analysis of a large international database
.
J Clin Endocrinol Metab
.
2006
Jun
;
91
(
6
):
2047
54
.
[PubMed]
0021-972X
7.
Haverkamp
F
,
Gasteyger
C
.
A review of biopsychosocial strategies to prevent and overcome early-recognized poor adherence in growth hormone therapy of children
.
J Med Econ
.
2011
;
14
(
4
):
448
57
.
[PubMed]
1369-6998
8.
Horne
R
. (
2006
).
Compliance, adherence, and concordance: implications for asthma treatment.
Journal.chestnet.org. Retrieved from http://journal.chestnet.org/article/S0012-3692(15)32958-5/abstract
9.
Vrijens
B
,
De Geest
S
,
Hughes
DA
,
Przemyslaw
K
,
Demonceau
J
,
Ruppar
T
, et al.;
ABC Project Team
.
A new taxonomy for describing and defining adherence to medications
.
Br J Clin Pharmacol
.
2012
May
;
73
(
5
):
691
705
.
[PubMed]
0306-5251
10.
Smith
SL
,
Hindmarsh
PC
,
Brook
CG
.
Compliance with growth hormone treatment—are they getting it?
Arch Dis Child
.
1993
Jan
;
68
(
1
):
91
3
. Available from:
[PubMed]
0003-9888
11.
Haverkamp
,
F.
,
Johansson
,
L.
,
Dumas
,
H.
,
Langham
,
S.
,
Tauber
,
M.
,
Veimo
,
D.
, &
Chiarelli
,
F.
(
2008
).
Observations of nonadherence to recombinant human growth hormone therapy in clinical practice.
Clinical Therapeutics, 30(2), 307–316.
12.
Hartmann
K
,
Ittner
J
,
Müller-Rossberg
E
,
Schönau
E
,
Stephan
R
,
Ullrich
KP
, et al.
Growth hormone treatment adherence in prepubertal and pubertal children with different growth disorders
.
Horm Res Paediatr
.
2013
;
80
(
1
):
1
5
.
[PubMed]
1663-2818
13.
Medicines adherence: involving patients in decisions about prescribed medicines and supporting adherence | Guidance and guidelines | NICE. (
2009
). Retrieved from https://www.nice.org.uk/guidance/cg76
14.
Norgren
S
. (
2009
).
Adherence remains a challenge for patients receiving growth hormone therapy.
Europepmc.org. Retrieved from http://europepmc.org/abstract/med/19550391
15.
Mohseni
S
,
Heydari
Z
,
Qorbani
M
,
Radfar
M
.
Adherence to growth hormone therapy in children and its potential barriers
.
J Pediatr Endocrinol Metab
.
2018
Jan
;
31
(
1
):
13
20
.
[PubMed]
0334-018X
16.
Osterberg
L
,
Blaschke
T
.
Adherence to medication
.
N Engl J Med
.
2005
Aug
;
353
(
5
):
487
97
.
[PubMed]
0028-4793
17.
Kapoor
RR
,
Burke
SA
,
Sparrow
SE
,
Hughes
IA
,
Dunger
DB
,
Ong
KK
, et al.
Monitoring of concordance in growth hormone therapy
.
Arch Dis Child
.
2008
Feb
;
93
(
2
):
147
8
.
[PubMed]
0003-9888
18.
Desrosiers
P
,
O’Brien
F
. (
2005
).
Patient outcomes in the GHMonitor: the effect of delivery device on compliance and growth.
Europepmc.org. Retrieved from http://europepmc.org/abstract/med/16456500
19.
Kirk
J
.
Indications for growth hormone therapy in children
.
Arch Dis Child
.
2012
Jan
;
97
(
1
):
63
8
.
[PubMed]
0003-9888
20.
Jackson
C
,
Eliasson
L
,
Barber
N
,
Weinman
J.
Applying COM-B to medication adherence.
The European Health Psychologist
2014
, 16(1), 7-17. 2
21.
Higgins
JP
,
Green
S
, editors
. (
2008
).
Cochrane Handbook for Systematic Reviews of Interventions.
Chichester, UK: John Wiley & Sons, Ltd. 0712184
22.
Liberati
A
,
Altman
D
. (
2009
).
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
Annals of Internal. Retrieved from http://annals.org/article.aspx?articleid =744698
23.
Human growth hormone (somatropin) for the treatment of growth failure in children | Guidance and guidelines | NICE. (
2010
). Retrieved from https://www.nice.org.uk/guidance/ta188
24.
Bagnasco
F
,
Di Iorgi
N
,
Roveda
A
,
Gallizia
A
,
Haupt
R
,
Maghnie
M
;
Adherence Investigators Group *
.
Prevalence and correlates of adherence in children and adolescents treated with growth hormone: a multicenter italian study
.
Endocr Pract
.
2017
Aug
;
23
(
8
):
929
41
.
[PubMed]
1530-891X
25.
Ergur
AT
,
Gunes
SO
,
Bahceci
O
. (
2017
)
The adherence to growth hormone therapy in children with growth hormone deficiency.
Hormone research in paediatrics, 88(1), 311-311: P2-857. Retrieved from https://www.karger.com/Article/Pdf/481424
26.
Farfel
A
,
Shalitin
S
,
Koren-Morag
N
. (
2017
).
Long-term adherence to growth hormone therapy in a large health maintenance organization cohort.
Hormone Research in Paediatrics, 88(1), 491-492: P3-826. Retrieved from https://www.karger.com/Article/Pdf/ 481424
27.
Sayarifard
F
,
Imcheh
FB
,
Badri
S
,
Faghihi
T
,
Qorbani
M
,
Radfar
M
.
Growth Hormone Utilization Review in a Pediatric Primary Care Setting
.
J Res Pharm Pract
.
2017
Jan-Mar
;
6
(
1
):
40
3
.
[PubMed]
2319-9644
28.
Hughes
,
I. P.
,
Harris
,
M.
,
Choong
,
C. S.
,
Ambler
,
G.
,
Cutfield
,
W.
,
Hofman
,
P.
, … Australasian Paediatric Endocrine Group (APEG). (
2012
). Growth hormone regimens in Australia: analysis of the first 3 years of treatment for idiopathic growth hormone deficiency and idiopathic short stature. Clinical Endocrinology, 77(1), 62–71. . 2011.04230.x
29.
De Pedro
S
,
Murillo
M
,
Salinas
I
,
Granada
ML
,
Martinez
M
,
Puig-Domingo
M
, et al.
Variability in adherence to rhGH treatment: socioeconomic causes and effect on children’s growth
.
Growth Horm IGF Res
.
2016
Feb
;
26
:
32
5
. Available from:
[PubMed]
1096-6374
30.
Kremidas
D
,
Wisniewski
T
,
Divino
VM
,
Bala
K
,
Olsen
M
,
Germak
J
, et al.
Administration burden associated with recombinant human growth hormone treatment: perspectives of patients and caregivers
.
J Pediatr Nurs
.
2013
Jan
;
28
(
1
):
55
63
.
[PubMed]
0882-5963
31.
Lass
N
,
Reinehr
T
.
Low Treatment Adherence in Pubertal Children Treated with Thyroxin or Growth Hormone
.
Horm Res Paediatr
.
2015
;
84
(
4
):
240
7
.
[PubMed]
1663-2818
32.
Aydın
BK
,
Aycan
Z
,
Şıklar
Z
,
Berberoğlu
M
,
Öcal
G
,
Çetinkaya
S
, et al.
Adherence to growth hormone therapy: results of a multicenter study
.
Endocr Pract
.
2014
Jan
;
20
(
1
):
46
51
.
[PubMed]
1530-891X
33.
Bozzola
M
,
Pagani
S
,
Iughetti
L
,
Maffeis
C
,
Bozzola
E
,
Meazza
C
.
Adherence to growth hormone therapy: a practical approach
.
Horm Res Paediatr
.
2014
;
81
(
5
):
331
5
.
[PubMed]
1663-2818
34.
Drosatou
C
,
Karachaliou
F
,
Vlachopapadopoulou
EA
,
Petrou
V
,
Kaloumenou
E
,
Michalakos
S
. (
2014
).
Assessment of Compliance with GH Therapy.
ESPE Abstracts (2014) 82 P-D-3-1-818. Retrieved from http://abstracts.eurospe.org/hrp/0082/hrp0082p3-d1-818.htm
35.
Miller
BS
,
Rotenstein
D
,
Deeb
LC
,
Germak
J
,
Wisniewski
T
.
Persistence with growth hormone therapy in pediatric patients
.
Am J Pharm Benefits
.
2014
;
6
(
1
).1945-4481
36.
Oyarzabal
M
,
Aliaga
M
,
Chueca
M
,
Echarte
G
,
Ulied
A
. (
1998
).
Multicentre survey on compliance with growth hormone therapy: what can be improved?
Acta Paediatrica (Oslo, Norway : 1992), 87(4), 387–391. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/ 9628292
37.
Leiberman
E
,
Pilpel
D
,
Carel
CA
,
Levi
E
,
Zadik
Z
.
Coping and satisfaction with growth hormone treatment among short-stature children
.
Horm Res
.
1993
;
40
(
4
):
128
35
.
[PubMed]
0301-0163
38.
Gács
G
,
Hosszu
E
.
The effect of socio-economic conditions on the time of diagnosis and compliance during treatment in growth hormone deficiency
.
Acta Paediatr Hung
.
1991
;
31
(
2
):
215
21
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1867888
[PubMed]
0231-441X
39.
Michie
S
,
van Stralen
MM
,
West
R
.
The behaviour change wheel: a new method for characterising and designing behaviour change interventions
.
Implement Sci
.
2011
Apr
;
6
(
1
):
42
.
[PubMed]
1748-5908
40.
National Institutes of Health (NIH) Quality Assessment tool for Observational Cohort and Cross Sectional Studies. Retrieved from https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
41.
Dumas
H
,
Panayiotopoulos
P
,
Parker
D
,
Pongpairochana
V
.
Understanding and meeting the needs of those using growth hormone injection devices
.
BMC Endocr Disord
.
2006
Oct
;
6
(
1
):
5
.
[PubMed]
1472-6823
42.
Ahmed
SF
,
Smith
WA
,
Blamires
C
.
Facilitating and understanding the family’s choice of injection device for growth hormone therapy by using conjoint analysis
.
Arch Dis Child
.
2008
Feb
;
93
(
2
):
110
4
.
[PubMed]
0003-9888
43.
Brod
M
,
Højbjerre
L
,
Alolga
SL
,
Beck
JF
,
Wilkinson
L
,
Rasmussen
MH
. (
2017
).
Understanding Treatment Burden for Children Treated for Growth Hormone Deficiency.
The Patient - Patient-Centered Outcomes Research, 10(5), 653–666.
44.
van Dongen
,
N.
, &
Kaptein
,
A.
(
2012
). Parents’ views on growth hormone treatment for their children: psychosocial issues. Patient Preference and Adherence, 6, 547. . S33157
45.
Marini
,
M. G.
,
Chesi
,
P.
,
Mazzanti
,
L.
,
Guazzarotti
,
L.
,
Toni
,
T. D.
,
Salerno
,
M. C.
, … Sacchetti, C. (
2016
). Stories of experiences of care for growth hormone deficiency: the CRESCERE project. Future Science OA, 2(1), fso.15.82.
46.
Garfield
S
,
Clifford
S
,
Eliasson
L
,
Barber
N
,
Willson
A
.
Suitability of measures of self-reported medication adherence for routine clinical use: a systematic review
.
BMC Med Res Methodol
.
2011
Nov
;
11
(
1
):
149
.
[PubMed]
1471-2288
47.
McDonald
HP
,
Garg
AX
,
Haynes
RB
.
Interventions to enhance patient adherence to medication prescriptions: scientific review
.
JAMA
.
2002
Dec
;
288
(
22
):
2868
79
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12472329
[PubMed]
0098-7484
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.