The evidence base for growth hormone effectiveness in children

Clinical medicine is a holistic attempt to provide the best care for patients. A clinician's knowledge may be biased (belief vs. knowledge), families' and patients' expectations may be unrealistic, and a 'worthwhile' outcome may be difficult to define. New evidence, which may or may not be of high quality and may or may not be rigorously evaluated by the clinician's own critical review, is then added to a set of prior beliefs to influence prescribing practice. Applying evidence to inform high-quality patient care is not straightforward. Methodological difficulties with many studies of childhood growth include underpowered studies, predicted or projected height comparisons, historical control groups, selection bias and variable treatment protocols. Many growth studies are reported based on 'predicted adult height' or other surrogate markers - even final height is not a validated proxy for psychological contentment or 'quality of life' (QoL). Because you can measure something (or think you can) does not in itself make it important and clinically relevant. Sometimes what is most important is most difficult to measure, and even when it can be, statistical significance is not the same as a clinically relevant difference. Making someone taller, even if achievable, is not an end in itself. What outcomes do we (and patients) consider clinically important and relevant? In growth hormone (GH) therapy studies should it be final height, height at or through puberty, psychological benefit (short vs. long term) or QoL improvement? How do these relate to safety issues and risks of harm? The limitations of growth screening, GH testing and our lack of information on, and understanding of, clinically relevant outcomes in response to GH therapy are discussed in these contexts.