Adult leg length is particularly sensitive to environmental factors and diet in early childhood because that is the period of most rapid leg growth. Trunk growth is faster than leg growth after infancy and before puberty, and may be associated with the effects of serious illness and parental separation because of the child's growing sensitivity to stressful circumstances, as well as the result of the biological effects of illness.

This document was developed to enable greater consistency in the practice, application, and documentation of Model‐Informed Drug Discovery and Development (MID3) across the pharmaceutical industry. A collection of “good practice” recommendations are assembled here in order to minimize the heterogeneity in both the quality and content of MID3 implementation and documentation. The three major objectives of this white paper are to: i) inform company decision makers how the strategic integration of MID3 can benefit R&D efficiency; ii) provide MID3 analysts with sufficient material to enhance the planning, rigor, and consistency of the application of MID3; and iii) provide regulatory authorities with substrate to develop MID3 related and/or MID3 enabled guidelines.

The role of modeling and simulation (M&S) in the design and interpretation of phase III studies, from break out session 4 of the European Medicines Agency (EMA)/European Federation of Pharmaceutical Industries and Associations (EFPIA) M&S workshop, was divided into themes illustrated with case studies (Table 1): (1) M&S being conducted to support the design of confirmatory trials; (2) longitudinal model‐based test as primary inferential analysis (biosimilarity and disease progression trials); (3) assessment of benefit–risk ratio, approval and labeling of an unstudied dose or dosing regimen, and development of future regulatory guidance. CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e27; doi:; advance online publication 27 February 2013

#65 Background: Breast cancer survival appears to be improved by pre-diagnostic use of hormone therapy (HT), but it is unclear from existing studies whether this is attributable to a direct beneficial effect of HT or because HT use encourages the development of certain tumor types with better prognosis. It is therefore important to examine whether the association between HT use and survival still remains after adequate adjustment for tumor characteristics.
 Methods: The California Teachers Study is an ongoing prospective study of female public school teachers and administrators. These analyses included 2,783 postmenopausal women whose use of HT was known and who were diagnosed with an incident primary invasive breast cancer after joining the cohort in 1995-96 and followed until death or the end of 2005. Incident cancers and tumor characteristics were ascertained through annual linkage with the statewide California Cancer Registry. Deaths were ascertained through annual linkage with the California state mortality files, the Social Security Administration Death Master File and the National Death Index. HT and other covariates were self-reported on the baseline questionnaire. We estimated the relative risk (RR) of breast cancer death stratifying by age in years, and using age in days from breast cancer diagnosis as the time scale (censoring deaths from other causes).
 Results: During the follow-up period, 159 (5.7%) women died of breast cancer. In unadjusted analysis, former and current HT use, specifically current estrogen-progestin (EP) use (RR=0.37; 0.24-0.57) but also current unopposed estrogen (E) use (RR=0.64; 0.43-0.95), was significantly associated with reduced breast cancer mortality, compared with no HT use. In multivariable analysis, taking into account race, body mass index, smoking history, lifetime physical activity, and co-morbidities, the risk estimates were somewhat attenuated (EP RR=0.40; 0.26-0.63 and E RR=0.67; 0.44-1.00). After additional adjustment for tumor characteristics (stage at diagnosis, estrogen receptor status, number of positive lymph nodes, grade and tumor size) and treatment received (surgery type and radiation) the risk estimates were considerably attenuated (EP RR=0.53; 0.33-0.84 and E RR=0.82; 0.53-1.27).
 Conclusion: Use of EP before diagnosis was associated with a reduced risk of death due to breast cancer. Use of E was also associated with reduced breast cancer mortality, although the association was not statistically significant after adjustment for indicators of general health, characteristics of the tumor and treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 65.

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