Current Indications for Growth Hormone Therapy

Description

Growth hormone (GH) has been used therapeutically for over 50 years. Since the development of a nearly unlimited supply of recombinant human GH in the mid-1980s, children with less severe GH deficiency can also profit from GH replacement therapy. Careful and accurate diagnosis and specific dosing, both essential to ensure normal height development, require the clinician to understand the finer points of clinical trials, to acquire quality evidence and assess the benefits of therapeutic intervention. Furthermore, genetic and environmental factors influencing GH sensitivity and responsiveness need to be taken into account. In this second edition all these aspects are covered in depth. Clinical examination, detailed auxological measurements, bone age assessment, molecular analysis and neuro-radiological evaluation as well as an adaptive strategy of dosing focusing on a patient‘s individual responsiveness are discussed in detail. This volume of Endocrine Development is essential reading for pediatric endocrinologists, pediatricians and clinical nurse specialists involved in GH therapy.

Informations

• Publié par: S. Karger AG
• Date de parution: 02 juin 2010
• Nombre de lectures: 0
• EAN13: 9783805591959
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Current Indications for Growth Hormone Therapy
2nd, revised edition
Endocrine Development
Vol. 18
Series Editor
P.-E. Mullis     Bern
 
Current Indications for Growth Hormone Therapy
2nd, revised edition
Volume Editor
Peter C. Hindmarsh     London
5 figures and 18 tables, 2010
Endocrine Development
Founded 1999 by Martin O. Savage, London
_________________________
Prof. Peter C. Hindmarsh Developmental Endocrinology Research Unit Institute of Child Health London, UK
Library of Congress Cataloging-in-Publication Data
Current indications for growth hormone therapy / volume editor, Peter C. Hindmarsh. –– 2nd, rev. ed.
p.;cm. –– (Endocrine development, ISSN 1421-7082 ;v. 18)
Includes bibliographical references and indexes.
ISBN 978-3-8055-9194-2 (hard cover: alk. paper)
1. Somatotropin-Therapeutic use. I. Hindmarsh, P. C. (Peter C.) II. Series: Endocrine development, v. 18.1421-7082 ;
[DNLM: 1. Growth Disorders––drug therapy. 2. Hormone Replacement Therapy––methods. 3. Human Growth Hormone––deficiency. 4. Human Growth Hormone––therapeutic use. W1 EN3635 v.18 2010/WK550 C976 2010]
RM291.2.S6C87 2010
615'.363––dc22
2010003907
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents® and PubMed/ MEDLINE.
Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book 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.
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 change 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.
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.
© Copyright 2010 by S. Karger AG, P.O. Box, CH-4009 Basel (Switzerland)
www.karger.com
Printed in Switzerland on acid–free and non–aging paper (ISO 9706) by Reinhardt Druck, Basel
ISSN 1421–7082
ISBN 978–3–8055–9194–2
 
Contents
Preface
Hindmarsh, P.C. (London)
Clinical Trials: Planning and Analysis
Farewell, V.T. (Cambridge); Cook, R.J. (Waterloo, Ont.)
The Evidence Base for Growth Hormone Effectiveness in Children
Kelnar, C.J.H. (Edinburgh)
Safety of Recombinant Human Growth Hormone
Carel, J.-C. (Paris); Butler, G. (London)
Diagnosis of Growth Hormone Deficiency
Webb, E.A.; Dattani, M.T. (London)
Biological Determinants of Responsiveness to Growth Hormone: Pharmacogenomics and Personalized Medicine
Mullis, P.-E. (Bern)
Clinical Considerations in Using Growth Hormone Therapy in Growth Hormone Deficiency
Ranke, M.B. (Tübingen)
Current Indications for Growth Hormone Therapy for Children and Adolescents
Richmond, E. (San José); Rogol, A.D. (Indianapolis, Ind./Charlottesville, Va.)
GH Use in the Transition of Adolescence to Adulthood
Mauras, N. (Jacksonville, Fla.)
Author Index
Subject Index
 
Preface
This is the second edition of ‘Current Indications for Growth Hormone Therapy’. Since the first edition there has been a dramatic increase in our understanding of various aspects of the growth hormone system particularly from the molecular standpoint. To keep the reader up dated on this we have revised the chapter on the diagnosis of growth hormone deficiency and introduced a new chapter on the impact of molecular variants of the growth hormone receptor on the growth response to growth hormone therapy. Understanding the evidence base for the use of growth hormone remains the cornerstone of this book hence the chapter by Chris Kelner on the evidence base and the statistical reasoning behind trial design by Vern Farewell. These chapters are important in understanding the comments made in the clinical applications chapters which consider longer term data on growth hormone usage which it has to be said has produced mixed results that warrant more detailed trials in the future.
It is 50 years since the description of the first use of growth hormone therapy in the New England Journal of Medicine , so it is timely for us to review where we are in that field and it was highly appropriate that Michael Ranke took the task of reviewing this area for us. Finally, we need to be mindful that our patients do grow up and need long-term follow-up under adult endocrinologists and Nelly Mauras provides us with a view on what we should be doing during this important phase of development.
Inevitably, medicine will face many challenges in the field of quality care as we go forward over the next 10 years. We know that growth hormone is effective in a number of situations so our focus will now shift towards demonstrating that such interventions actually benefit the patient and/or society. We start this discussion in this book but this is only a first attempt at a complex area that we will all need to engage in as responsible clinicians.
Peter C. Hindmarsh , London, UK
Chapter 1
Hindmarsh PC (ed): Current Indications for Growth Hormone Therapy, ed 2, revised. Endocr Dev. Basel, Karger, 2010, vol 18, pp 1-22
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Clinical Trials: Planning and Analysis
Vernon T. Farewell a Richard J. Cook b
a MRC Biostatistics Unit, Institute of Public Health, Cambridge, Cambridge, UK and b Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ont., Canada
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Abstract
With specific reference to studies of growth hormone therapies, this chapter re-examines some basic principles in clinical research and considers some of the more complex aspects of trial design. The statistical structure which underpins trial design is characterized with specific attention given to samples size, subgroup analyses, multicentre trials and the role and implementation of randomization. Topics related to outcomes in studies of growth hormone therapy are discussed, including the possible value of surrogate responses, longitudinal outcomes and their analysis, and multiple outcomes. Additional design issues addressed are multiarmed trials, factorial designs and study monitoring. Brief comments are offered on the interpretation of negative trials and on non-inferiority trials.
Copyright © 2010 S. Karger AG, Basel
Introduction
The randomized clinical trial is widely regarded as the optimal study design by which to investigate and communicate the utility of new treatments. Randomized trials control for confounders, facilitate causal inferences, and generate unbiased estimates of treatment effect for the relevant patient population. The classic form of a clinical trial involves a group of patients at a clinical research centre who agree to be randomly assigned to one of two treatments. After a relatively short period of follow-up, the ‘outcome’ of the treatment is available for enough individuals that a comparison can be made as to the relative effectiveness of the two treatments.
Many factors conspire to make this classic picture unrealistic, but the advantages of this randomized clinical trial design cannot be ignored. Indeed this simplistic design discussed above serves as a paradigm with which more complex clinical study designs should be compared. Investigations which involve growth hormone therapy present some specific challenges to the classic paradigm. The purpose of this chapter is to re-examine some basic principles of clinical research, consider some of the more complex aspects of trial design, and make specific references to how these pertain to studies of growth hormone therapies.
Statistical Structure for Planning of Trials
General Remarks
The primary aim of a clinical trial is to provide a convincing answer to an important question regarding a therapeutic intervention. A trial which cannot do this is both a waste of resources and, in our view, unethical. Therefore, these aims must be kept clearly in mind when deciding whether to initiate a trial. Whether these aims are fulfilled will depend on the choice of treatments, outcome measures, patient populations, and a variety of other concerns, including, of course, whether there is in fact an underlying effect of therapy.
Much of the planning of a clinical trial is based on the statistical significance test that is to be carried out upon completion of the trial to determine whether convincing evidence of a difference between the treatments under study has emerged. We focus here on the case of a trial comparing an experimental treatment to a standard control intervention. This will usually, although not alway