Hero 2005.
| Methods | RCT (Finland) Allocation to treatment groups: randomised using computer‐generated blocks of 10 in the hospital pharmacy Randomisation ratio: 1 : 1 Superiority design Blinding: double‐blinded, randomisation codes not released until all data entered into computer at the end of the trial Comparability of treatment groups: no differences of significance at baseline Method of data analysis: not stated ITT. Mean (SD). Within‐group differences analysed by paired T tests, between‐group differences by unpaired T tests or repeated measures ANOVA. Friedman test used for within‐group and Mann‐Whitney U test used for between‐groups changes in Tanner staging Sample size/power calculation: planned sample size of 31 had 80% power to detect a difference in PAH between groups of 5 cm and allow for up to a 10% drop‐out rate Attrition/drop‐out: 1 withdrawal, developed type 1 diabetes after 6 months of treatment with placebo |
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| Participants | Total number: 31 boys Placebo: 15 Letrozole: 16 Characteristics of target population: boys aged 9‐14.5 years with ISS (height 2 SD below mean for age or 2 SD below mid‐parental height). GH deficiency excluded. 81% of letrozole‐ and 93% of placebo‐treated boys were prepubertal at enrolment. 4 boys in letrozole and 3 boys in placebo group were small for gestational age at birth Exclusion criteria: bone age > 14 years Setting: single tertiary paediatric endocrinology centre |
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| Interventions | Treatment arms:
Length of treatment: 2 years Other interventions used: none |
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| Outcomes | Change in PAH Effects on bone mineral density |
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| Study details | Study continued for pre‐specified duration of 2 years, no criteria used for early cessation | |
| Publication details | Published in English Work was supported by the Foundation for Pediatric Research (Helsinki, Finland) Publication status: full article in peer‐reviewed journal |
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| Stated aim for study | Quote from publication: "The primary end point of the study was the efficacy of Letrozole in improving PAH, as measured by a change in PAH after 24 months of treatment" | |
| Notes | Generalisability: inclusion and exclusion criteria well defined Outcomes: final adult height not reported. Difference in PAH disappeared 4 years from the end of the trial. Inter‐centre variability: single‐centre study Conflicts of interest: none reported |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote from publication: "Randomization was carried out in blocks of 10 at the hospital pharmacy by a computer generated randomization list" |
| Allocation concealment (selection bias) | Low risk | Comment: treatments were centrally allocated by the hospital pharmacy |
| Blinding of participants and personnel (performance bias) Objective outcomes | Low risk | Quote from publication: "Researchers and subjects were blind to treatment assignment until the end of follow‐up, when the randomization code was revealed to the researchers after the data had been entered into a computer" |
| Blinding of participants and personnel (performance bias) Subjective outcomes | Low risk | Quote from publication: "Researchers and subjects were blind to treatment assignment until the end of follow‐up, when the randomization code was revealed to the researchers after the data had been entered into a computer" |
| Blinding of outcome assessment (detection bias) Objective outcomes | Low risk | Quote from publication: "Researchers and subjects were blind to treatment assignment until the end of follow‐up, when the randomization code was revealed to the researchers after the data had been entered into a computer" |
| Blinding of outcome assessment (detection bias) Subjective outcomes | Low risk | Quote from publication: "Researchers and subjects were blind to treatment assignment until the end of follow‐up, when the randomization code was revealed to the researchers after the data had been entered into a computer" |
| Incomplete outcome data (attrition bias) Objective outcomes | Low risk | Comment: no stated withdrawals other than 1 boy excluded from placebo arm after 6 months having developed type 1 diabetes. All pre‐specified outcomes reported on |
| Incomplete outcome data (attrition bias) Subjective outcomes | Low risk | Comment: no stated withdrawals other than 1 boy excluded from placebo arm after 6 months having developed type 1 diabetes. All pre‐specified outcomes reported on |
| Selective reporting (reporting bias) | Low risk | Comment: no follow‐up data on final adult height; however, a subsequent paper (Hero 2010) reported no difference in near‐adult height. This was assessed in 23/31 participants initially randomised and attrition was even between groups |
| Other bias | Low risk | Comment: none detected |