Non-Compliance with Growth Hormone Treatment in Children Is Common and Impairs Linear Growth Wayne S. Cutfield1,2*, Jose´ G. B. Derraik1, Alistair J. Gunn 3 , Kyle Reid4, Theresa Delany1, Elizabeth Robinson5, Paul L. Hofman1,2 1 Liggins Institute, University of Auckland, Auckland, New Zealand, 2 National Research Centre for Growth and Development, University of Auckland, Auckland, New Zealand, 3 Departments of Physiology and Paediatrics, University of Auckland, Auckland, New Zealand, 4 Pharmaceutical Management Agency of New Zealand (PHARMAC), Wellington, New Zealand, 5 Department of Epidemiology and Biostatistics, University of Auckland, Auckland, New Zealand Abstract Background: GH therapy requires daily injections over many years and compliance can be difficult to sustain. As growth hormone (GH) is expensive, non-compliance is likely to lead to suboptimal growth, at considerable cost. Thus, we aimed to assess the compliance rate of children and adolescents with GH treatment in New Zealand. Methods: This was a national survey of GH compliance, in which all children receiving government-funded GH for a four- month interval were included. Compliance was defined as $85% adherence (no more than one missed dose a week on average) to prescribed treatment. Compliance was determined based on two parameters: either the number of GH vials requested (GHreq) by the family or the number of empty GH vials returned (GHret). Data are presented as mean 6 SEM. Findings: 177 patients were receiving GH in the study period, aged 12.160.6 years. The rate of returned vials, but not number of vials requested, was positively associated with HVSDS (p,0.05), such that patients with good compliance had significantly greater linear growth over the study period (p,0.05). GHret was therefore used for subsequent analyses. 66% of patients were non-compliant, and this outcome was not affected by sex, age or clinical diagnosis. However, Maori ethnicity was associated with a lower rate of compliance. Interpretation: An objective assessment of compliance such as returned vials is much more reliable than compliance based on parental or patient based information. Non-compliance with GH treatment is common, and associated with reduced linear growth. Non-compliance should be considered in all patients with apparently suboptimal response to GH treatment. Citation: Cutfield WS, Derraik JGB, Gunn AJ, Reid K, Delany T, et al. (2011) Non-Compliance with Growth Hormone Treatment in Children Is Common and Impairs Linear Growth. PLoS ONE 6(1): e16223. doi:10.1371/journal.pone.0016223 Editor: Maria Castro, University of California Los Angeles, and Cedars-Sinai Medical Center, United States of America Received August 24, 2010; Accepted December 15, 2010; Published January 31, 2011 Copyright: 2011 Cutfield et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was funded by PHARMAC (the pharmaceutical purchasing division of New Zealand’s Ministry of Health) who assisted with data collection. However, PHARMAC had no role on the analysis, decision to publish, or preparation of the manuscript. Note that, as a government agency, PHARMAC is completely independent of the pharmaceutical industry. Competing Interests: The authors have declared that no competing interests exist. * E-mail: w.cutfield@auckland.ac.nz Introduction Non-compliance with prescribed drug treatments is widespread [1]. Key factors include discomfort (e.g. associated with daily injections) [2], long-term treatment [3], complexity of treatment regimens, age, individual and family dynamics, as well as patient or family’s understanding of treatment benefits and consequences of non-compliance [3,4]. These principles suggest that children administered growth hormone (GH) as a daily subcutaneous injection for many years are at risk of treatment non-compliance. GH treatment is very expensive; the annual cost for a 30 kg child has been estimated as US$ 15,000 to US$ 20,000 per annum, while the annual costs of treating adolescents to maximize adult height can reach US$ 50,000 [5]. Thus, non-compliance with treatment must lead to appreciable waste of funding; it is presumed that it would also impair long-term linear growth [6,7], but there are few objective data. In this study we examined compliance with GH treatment and its effect on linear growth over a single four-month period in a complete national cohort of New Zealand children and adoles- cents. In view of the reliance of previous studies on self-report or prescription data [6–11], we contrasted a caregiver-reported measure of GH utilisation with an objective measure (number of GH vials returned during the interval). Materials and Methods Review with the Multiregion Ethics Committee (Wellington, New Zealand) determined that ethics approval of this compre- hensive audit was not required. This study was an unbiased, anonymized national survey of GH compliance in all New Zealand children and adolescents receiving publically-funded GH in a single four-month interval in 2007. All patients receive monthly allocations of GH based upon surface area dosing. Each month, the caregivers of the patients are contacted by phone to determine how many residual vials of GH the family have, and thus how many vials are required for the coming month (GHreq). For the duration of this review, caregivers PLoS ONE | www.plosone.org 1 January 2011 | Volume 6 | Issue 1 | e16223