Understanding the Growth Hormone Therapy Adherence Paradigm: A Systematic Review

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Abstract

Introduction: Growth hormone (GH) therapy is used to treat a variety of growth disorders in childhood/adolescence. Its efficacy is thought to be dependent on patients' adherence to their treatment regimen. Methods: PubMed was searched using the keywords ‘growth hormone', ‘child'[Mesh], ‘adolescent'[Mesh], and ‘patient compliance'[Mesh]. Results: Most studies of adherence to paediatric GH therapy have used either issued/encashed GH prescriptions or questionnaires. Estimates of prevalence of non-adherence vary from 5-82%, depending on the methods and definitions used. Different studies have variously demonstrated an association (or lack thereof) between adherence and age, socioeconomic status, treatment duration, injection device used and injection-giver. A number of interventions have been proposed to improve adherence, including offering a choice of injection device, but none are supported by trials. Poor adherence is associated with reduced height velocity and likely increased economic costs; evidence for other effects is circumstantial. Conclusion: Adherence to paediatric GH therapy is suboptimal, which may partially explain why the mean final height attained is below that of the general population. Analysis of the causes of non-adherence is complicated by conflicting evidence from different studies. Multifactorial interventions are most likely to be successful in improving adherence. We make recommendations for further research.

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Most cited references 53

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Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop.

P. Cohen, A Rogol, C L Deal … (2008)

Our objective was to summarize important advances in the management of children with idiopathic short stature (ISS). Participants were 32 invited leaders in the field. Evidence was obtained by extensive literature review and from clinical experience. Participants reviewed discussion summaries, voted, and reached a majority decision on each document section. ISS is defined auxologically by a height below -2 sd score (SDS) without findings of disease as evident by a complete evaluation by a pediatric endocrinologist including stimulated GH levels. Magnetic resonance imaging is not necessary in patients with ISS. ISS may be a risk factor for psychosocial problems, but true psychopathology is rare. In the United States and seven other countries, the regulatory authorities approved GH treatment (at doses up to 53 microg/kg.d) for children shorter than -2.25 SDS, whereas in other countries, lower cutoffs are proposed. Aromatase inhibition increases predicted adult height in males with ISS, but adult-height data are not available. Psychological counseling is worthwhile to consider instead of or as an adjunct to hormone treatment. The predicted height may be inaccurate and is not an absolute criterion for GH treatment decisions. The shorter the child, the more consideration should be given to GH. Successful first-year response to GH treatment includes an increase in height SDS of more than 0.3-0.5. The mean increase in adult height in children with ISS attributable to GH therapy (average duration of 4-7 yr) is 3.5-7.5 cm. Responses are highly variable. IGF-I levels may be helpful in assessing compliance and GH sensitivity; levels that are consistently elevated (>2.5 SDS) should prompt consideration of GH dose reduction. GH therapy for children with ISS has a similar safety profile to other GH indications.

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The Brief Medication Questionnaire: a tool for screening patient adherence and barriers to adherence.

B L Svarstad, B A Chewning, B L Sleath … (1999)

Self-report tools for monitoring adherence can be useful in identifying patients who need assistance with their medications, assessing patient concerns, and evaluating new programs. The aim of this study is to test the validity of the Brief Medication Questionnaire (BMQ), a new self-report tool for screening adherence and barriers to adherence. The tool includes a 5-item Regimen Screen that asks patients how they took each medication in the past week, a 2-item Belief Screen that asks about drug effects and bothersome features, and a 2-item Recall Screen about potential difficulties remembering. Validity was assessed in 20 patients using the Medication Events Monitoring System (MEMS). Results varied by type of non-adherence, with the Regimen and Belief Screens having 80-100% sensitivity for "repeat" non-adherence and the Recall Screen having 90% sensitivity for "sporadic" non-adherence. The BMQ appears more sensitive than existing tools and may be useful in identifying and diagnosing adherence problems.

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The assessment of refill compliance using pharmacy records: Methods, validity, and applications

Allan V Prochazka, John F. Steiner (1997)

The refill records of computerized pharmacy systems are used increasingly as a source of compliance information. We reviewed the English-language literature to develop a typology of methods for assessing refill compliance (RC), to describe the epidemiology of compliance in obtaining medications, to identify studies that attempted to validate RC measures, to describe clinical features that predicted RC, and to describe the uses of RC measures in epidemiologic and health services research. In most of the 41 studies reviewed, patients obtained less medication than prescribed; gaps in treatment were common. Of the studies that assessed the validity of RC measures, most found significant associations between RC and other compliance measures, as well as measures of drug presence (e.g., serum drug levels) or physiologic drug effects. Refill compliance was generally not correlated with demographic characteristics of study populations, was higher among drugs with fewer daily doses, and was inconsistently associated with the total number of drugs prescribed. We conclude that, though some methodologic problems require further study, RC measures can be a useful source of compliance information in population-based studies when direct measurement of medication consumption is not feasible.

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Author and article information

Journal

Journal ID (publisher-id): HRP

Journal ID (nlm-ta): Horm Res Paediatr

Journal ID (doi): 10.1159/issn.1663-2818

Title: Hormone Research in Paediatrics

Publisher: S. Karger AG

ISSN (Print): 1663-2818

ISSN (Electronic): 1663-2826

Publication date Subscription-year: 2013

Publication date (Print): May 2013

Publication date (Electronic): 29 April 2013

Volume: 79

Issue: 4

Pages: 189-196

Affiliations

^aDepartment of Paediatrics, University of Cambridge, and ^bThe Weston Centre, Institute of Metabolic Science, Cambridge University Hospitals Foundation NHS Trust, Cambridge, UK

Author notes

*Benjamin G. Fisher, Department of Paediatrics, University of Cambridge, Box 116, Level 8, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ (UK), E-Mail ben.fisher@cantab.net

Article

Publisher ID: 350251 Other ID: Horm Res Paediatr 2013;79:189-196

DOI: 10.1159/000350251

PubMed ID: 23635797

SO-VID: b8b4d489-574b-400d-82e9-ce38e6af51e4

License:

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.

History

Date received : 13 November 2012

Date accepted : 25 February 2013

Page count

Tables: 3, Pages: 8

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