Evaluating the therapeutic procedures

Once the study procedures are demarcated, component analysis proceeds by evaluating the therapeutic procedures and non-therapeutic procedures according to separate moral rules. Therapeutic procedures must meet the requirement of clinical equipoise, that is, they must be consistent with competent medical care (Weijer & Miller, 2004). As

described above, some of the therapeutic procedures of the NIH growth hormone study— including the blood and urine tests, body measurements, tests of growth and bone

maturity, and the behavioural and psychological assessments—are part of standard or optimal medical care for children with short stature. It follows that they are consistent with competent medical care, that is, they meet component analysis’ requirements for therapeutic procedures.

Determining whether the main active interventions, the growth hormone

injections and the no treatment control meet the requirement of clinical equipoise requires careful scrutiny. To determine whether these interventions meet the requirement of clinical equipoise, a research ethics board should ask two questions: (1) is the evidence supporting the experimental intervention sufficient that, were it widely known, expert practitioners would disagree about the preferred treatment? (2) Is the control group being unfairly deprived of the experimental or proven, effective treatment? A research ethics board must answer yes to the first question and no to the second for the therapeutic procedures of the trial to be permissible.

To answer the first question, a research ethics board should examine whether there is disagreement within the community of expert practitioners about the efficacy of hGH for healthy children. A survey of the medical literature reveals that experts disagree about the safety and efficacy of hGH in healthy children. Several studies provide

evidence that children with idiopathic short stature may benefit from an increase in height as the result of hGH interventions (Genentech Collaborative Study Group, 1989; Gertner et al., 1984). For example, the Genentech Collaborative Study Group’s trial of 121 children with idiopathic short stature found that treating children with idiopathic short

stature with growth hormone for one year significantly increased their mean growth rate. They report that roughly 75% of children in the treatment group had an incremental increase in growth rate of more than 2 cm, whereas children in the control group showed no increase in predicted height (Genentech Collaborative Study Group, 1989).

However, others disagree; Allen argues that height gain attributed to hGH may be overestimated because untreated children with idiopathic short stature often show a spontaneous increase in height with age (Allen, 2006). Others agree that while hGH may help to increase height in children with idiopathic short stature in the short term, it has no effect on their overall adult height (Hintz et al., 1999; Allen & Fost, 1990). Some have also raised concerns about the role of hGH in the development and progression of certain cancers (Stoll, 1992). Finally, recent studies summarizing the current state of knowledge about the effects of hGH on short but healthy children conclude that the risks and benefits remain uncertain (Allen, 2011; Cohen & Cosgrove, 2010; Allen, 2006). The

disagreement among expert practitioners over hGH treatment for healthy but short children suggests that a state of clinical equipoise exists.

To meet the moral requirements of clinical equipoise, researchers and research ethics committee should also examine whether the control group is being unfairly deprived of the experimental treatment. Unfair deprivation of an experimental

intervention occurs when a subject’s participation in a trial prevents her from receiving a therapy that she would otherwise receive as part of standard care. Children in the control arm of this trial receive a no treatment control. Are they unduly deprived of hGH? Allen and Fost reason that evidence suggesting that healthy children may respond to hGH interventions combined with the fact that hGH therapy is the standard medical

intervention for children who are hGH deficient provides a compelling reason to provide healthy children with hGH treatment. Further, they think that depriving healthy but very short children of hGH treatment would be unfair discrimination on the basis of growth hormone deficiency (Allen & Fost, 1990). And if healthy but very short children are entitled to hGH treatment, then it follows that subjects in the placebo arm of the NIH trial would be unduly deprived of standard care.

However, a closer analysis reveals that offering no treatment to very short but medically normal children is consistent with standard care. A placebo control is morally

appropriate in several circumstances, including when there is no standard therapy for the condition of interest, and when treatment exists but “no treatment” is nonetheless

consistent with competent medical care (Freedman, 1990; Weijer & Miller, 2004). For example, treatments exist for some minor medical conditions, like mild hypertension, but a competent physician may nonetheless recommend no treatment. In these kinds of situations, the use of a placebo control for minor medical conditions is permissible (Weijer & Miller, 2004). For children who are very short but medically normal, there is no standard intervention. Some physicians offer hGH treatment but others—perhaps because of safety or efficacy concerns as well as concerns over the cost or availability of the drug—prescribe no treatment at all. As a result, it seems reasonable for a research ethics board to conclude that subjects in the control arm of the NIH study were not unduly deprived of standard care. Given that a research ethics board could reasonably find that all the study’s therapeutic procedures meet the requirements of clinical

equipoise, the NIH growth hormone trial meets component analysis’s moral requirements for therapeutic procedures.