In 2010, new data about the safety of recombinant human growth hormone (rhGH) resulted in warnings and subsequent pronouncements by the US Food and Drug Administration (FDA) and its European counterpart [the European Medicines Agency (EMA)] regarding its use in children and adolescents as an elective treatment for short stature. However, opinions about these new data are divergent: the FDA did not change the label of the drug and experts have argued for further research on the safety of rhGH. In this situation of an evolving scientific controversy, it is unclear how questions about benefit and risk are communicated to patients and their parents. Social biases and misperceptions about the deleterious effects of short stature and the benefits of added height influence decisions to prescribe rhGH and may affect discussions of the warnings by regulators. Fully supporting a model of shared decision-making involving children and adolescents requires sharing risk-benefit information, including evolving information from drug regulators, with patients and parents.

Keywords:
Growth hormone, Safety, Short stature, Children, Informed consent
1.
Rosenfeld RG, Cohen P, Robison LL, Bercu BB, Clayton P, Hoffman AR, et al: Long-term surveillance of growth hormone therapy. J Clin Endocrinol Metab 2012;97:68–72.
2.
Food and Drug Administration: Drug safety communication. Recombinant human growth hormone (somatropin): ongoing safety review – possible increased risk of death. December 22, 2010. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm237969.htm (accessed December 4, 2012).
3.
Carel JC, Ecosse E, Landier F, Meguellati-Hakkas D, Kaguelidou F, Rey G, et al: Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study. J Clin Endocrinol Metab 2012;97:416–425.
4.
Food and Drug Administration: Drug safety communication: safety review update of recombinant human growth hormone (somatropin) and possible increased risk of death. August 4, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm265865.htm.
5.
European Medicines Agency: European medicines agency confirms positive benefit-risk balance of somatropin-containing medicines. December 15, 2011 (last updated April 23, 2012). http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/public_health_alerts/2011/12/human_pha_detail_000048.jsp&mid=WC0b01ac058001d126 (accessed December 4, 2012).
6.
Sävendahl L, Maes M, Albertsson-Wikland K, Borgström B, Carel JC, Henrard S, et al: Long-term mortality and causes of death in isolated GHD, ISS, and SGA patients treated with recombinant growth hormone during childhood in Belgium, the Netherlands, and Sweden: preliminary report of 3 countries participating in the EU SAGhE study. J Clin Endocrinol Metab 2012;97:E213–E217.
7.
Malozowski S: Reports of increased mortality and GH: will this affect current clinical practice? J Clin Endocrinol Metab 2012;97:380–383.
8.
Lantos J, Siegler M, Cuttler L: Ethical issues in growth hormone therapy. JAMA 1989;261:1020–1024.
9.
Eisenberg N, Roth K, Bryniarski KA, Murray E: Sex differences in the relationship of height to children’s actual and attributed social and cognitive competencies. Sex Roles 1984;11:719–734.
10.
Martel LF, Biller H: Stature and stigma: the biopsychosocial development of short males. Lexington, Lexington Books, 1987.
11.
Jackson LA, Ervin KS: Height stereotypes of women and men: the liabilities of shortness for both sexes. J Soc Psychol 1992;132:433–445.
12.
Clopper R, Mazur T, Ellis A, Michael P: Height and children’s stereotypes; in Stabler B, Underwood L (eds): Growth, stature, and adaptation. Chapel Hill, University of North Carolina at Chapel Hill, 1994, pp 7–18.
13.
Cuttler L, Marinova D, Mercer MB, Connors A, Meehan R, Silvers JB: Patient, physician, and consumer drivers: referrals for short stature and access to specialty drugs. Med Care 2009;47:858–865.
14.
Silvers JB, Marinova D, Mercer MB, Connors A, Cuttler L: A national study of physician recommendations to initiate and discontinue growth hormone for short stature. Pediatrics 2010;126:468–476.
15.
Sandberg DE, Bukowski WM, Fung CM, Noll RB: Height and social adjustment: are extremes a cause for concern and action? Pediatrics 2004;114:744–750.
16.
Sandberg DE, Colsman M: Growth hormone treatment of short stature: status of the quality of life rationale. Horm Res 2005;63:275–283.
17.
Sandberg D, Michael P: Psychosocial stresses related to short stature: does their presence imply psychiatric dysfunction? In Drotar D (ed): Assessing Pediatric Health-Related Quality of Life and Functional Status: Implications for Research. Mahwah, Lawrence Erlbaum Associates, 1998, pp 287–312.
18.
Voss LD, Mulligan J: Bullying in school: are short pupils at risk? Questionnaire study in a cohort. Br Med J 2000;320:612–613.
19.
Downie AB, Mulligan J, McCaughey ES, Stratford RJ, Betts PR, Voss LD: Psychological response to growth hormone treatment in short normal children. Arch Dis Child 1996;75:32–35.
20.
Theunissen NC, Kamp GA, Koopman HM, Zwinderman KA, Vogels T, Wit JM: Quality of life and self-esteem in children treated for idiopathic short stature. J Pediatr 2002;140:507–515.
21.
Ross JL, Sandberg DE, Rose SR, Leschek EW, Baron J, Chipman JJ, et al: Psychological adaptation in children with idiopathic short stature treated with growth hormone or placebo. J Clin Endocrinol Metab 2004;89:4873–4878.
22.
Hunt L, Hazen RA, Sandberg DE: Perceived versus measured height. Which is the stronger predictor of psychosocial functioning? Horm Res 2000;53:129–138.
23.
Theunissen NC, Kamp GA, Koopman HM, Zwinderman KA, Vogels T, Wit JM: Quality of life and self-esteem in children treated for idiopathic short stature. J Pediatr 2002;140:507–515.
24.
Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Endocrinologic and metabolic drugs advisory committee meeting. June 10, 2003. http://www.fda.gov/ohrms/dockets/ac/03/transcripts/3957T1.htm (accessed December 4, 2012).
25.
Sandberg DE, Brook AE, Campos SP: Short stature: a psychosocial burden requiring growth hormone therapy? Pediatrics 1994;94:832–840.
26.
Zimet GD, Cutler M, Litvene M, Dahms W, Owens R, Cuttler L: Psychological adjustment of children evaluated for short stature: a preliminary report. J Dev Behav Pediatr 1995;16:264–270.
27.
Voss LD: Is short stature a problem? The psychological view. Eur J Endocrinol 2006;155(suppl 1):S39–S45.
28.
Lee JM, Appugliese D, Coleman SM, Kaciroti N, Corwyn RF, Bradley RH, et al: Short stature in a population-based cohort: social, emotional, and behavioral functioning. Pediatrics 2009;124:903–910.
29.
Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, et al: 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. J Clin Endocrinol Metab 2008;93:4210–4217.
30.
Sperling MA: Long-term therapy with growth hormone: Bringing sagacity to SAGhE. J Clin Endocrinol Metab 2012;97:81–83.
31.
Salvatori R: Growth and development: growth hormone therapy – is it worth the risk? Nat Rev Endocrinol 2012;8:259–260.
32.
Office for Human Research Protections (OHRP), Office for Protection from Research Risks. Tips on informed consent. 1993. http://www.hhs.gov/ohrp/policy/ictips.html (accessed December 5, 2012).
33.
Braddock III CH, Edwards KA, Hasenberg NM, Laidley TL, Levinson W: Informed decision making in outpatient practice: time to get back to basics. JAMA 1999;282:2313–2320.
34.
Mazur DJ, Merz JF: How older patients’ treatment preferences are influenced by disclosures about therapeutic uncertainty: surgery versus expectant management for localized prostate cancer. J Am Geriatr Soc 1996;44:934–937.
35.
Fallowfield L: Offering choice of surgical treatment to women with breast cancer. Patient Educ Couns 1997;30:209–214.
36.
Collins ED, Kerrigan CL, Anglade P: Surgical treatment of early breast cancer: what would surgeons choose for themselves? Eff Clin Pract 1999;2:149–151.
37.
Wallace C, Leask J, Trevena LJ: Effects of a web based decision aid on parental attitudes to MMR vaccination: a before and after study. BMJ 2006;332:146–149.
38.
Gomes T, Juurlink DN, Moore I, Maguire JL, Mamdani MM: The impact of federal warnings on publically funded desmopressin utilization among children in Ontario. J Pediatr Urol 2012;8:249–253.
39.
Olfson M, Marcus SC, Druss BG: Effects of Food and Drug Administration warnings on antidepressant use in a national sample. Arch Gen Psychiatry 2008;65:94–101.
40.
Richmond E, Rogol AD: Current indications for growth hormone therapy for children and adolescents. Endocr Dev 2010;18:92–108.
41.
Klein AV: The first subsequent entry biologic authorized for market in Canada: the story of Omnitrope, a recombinant human growth hormone. Biologicals 2011;39:278–281.
42.
Franklin SL, Geffner ME: Growth hormone: the expansion of available products and indications. Pediatr Clin North Am 2011;58:1141–1165.
43.
American Academy of Pediatrics, Committee on Bioethics: Informed consent, parental permission, and assent in pediatric practice. Pediatrics 1995;95:314–317.
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2013
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