Endocrinology trial design: adverse event reporting in randomised controlled trials of recombinant human GH in GH-deficient adults

Abstract

We have evaluated the reporting of withdrawals due to adverse effects and specific adverse effects in randomised controlled trials of recombinant human GH in adults. A systematic review was carried out of randomised controlled trials of the clinical effectiveness of recombinant human GH in adults with GH deficiency in relation to impact on quality of life. Trials were identified from searching electronic databases, bibliographies of related articles and consulting experts. There was reporting of withdrawals due to adverse effects and specific adverse effects. Rates of oedema and arthralgia were reported in included trials. Seventeen randomised controlled trials, published between 1990 and 1999, met the inclusion criteria for the review. Nine trials reported data on the effectiveness of GH on quality of life in adults. Only five trials (29%) reported both withdrawals from the study because of adverse events and specific adverse events with numbers per study arm and per type. Six further trials (35%) reported either withdrawal details or specific adverse event details or partial data on specific adverse events. Six trials (35%), however, did not report information on either withdrawals or specific adverse events. Ten of the 17 studies (59%) reported the number of patients who withdrew from the study due to adverse events per study arm and type of adverse event per study arm. Seven of the 17 trials (41%) reported the number of specific adverse events per study arm and six (35%) reported the type per study arm. The reporting of adverse events in randomised controlled trials of GH is variable and not consistent across trials. It is not possible to assess the impact that adverse events may have had on unblinding patients, and therefore the extent to which the effects of GH may have been overestimated. Therefore those conducting endocrinology trials in the future need to pay attention to the reporting of withdrawals due to adverse events and specific adverse events.

Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline

“…Consequently, dosages were reduced, resulting in fewer adverse effects and a much improved safety profile (137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147)(148).…”

Growth hormone replacement in adults and bone mineral density: a systematic review and meta‐analysis

“…The characteristics of the patients and treatment received are shown in Table 1. Blinding of patient or physician may have been undermined in those trials using higher doses of GH (Table 1), which caused side-effects (Bryant et al ., 2002). The reporting quality of most of the trials was poor, with serious omissions when describing study design.…”

“…Although described as 'double blind', most studies did not describe the status of treating physicians or observers. Blinding of patient or physician may have been undermined in those trials using higher doses of GH (Table 1), which caused side-effects (Bryant et al ., 2002). Follow-up was complete, or near complete, with any drop-outs accounted for.…”

Atypical depression in growth hormone deficient adults, and the beneficial effects of growth hormone treatment on depression and quality of life

“…The lengths of treatment and of washout periods have also varied, and some studies have been placebo controlled, whilst others have been open label and liable to a 'placebo effect'. Even with placebo-controlled trials, the side-effects of GH treatment potentially negate the effects of blinding, by revealing whether the subject is receiving GH or placebo (10). This may result in bias on the part of the observer and of the subjects, who are likely to be aware of the hypothesis being tested.…”