Helfer Bartosz, Leonardi-Bee Jo, Mundell Alexandra, Parr Callum, Ierodiakonou Despo, Garcia-Larsen Vanessa, Kroeger Cynthia M, Dai Zhaoli, Man Amy, Jobson Jessica, Dewji Fatemah, Kunc Michelle, Bero Lisa, Boyle Robert J
National Heart and Lung Institute, Imperial College London, London, UK.
Institute of Psychology, University of Wroclaw, Wroclaw, Poland.
BMJ. 2021 Oct 13;375:n2202. doi: 10.1136/bmj.n2202.
To systematically review the conduct and reporting of formula trials.
Systematic review.
Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from 1 January 2006 to 31 December 2020.
Intervention trials comparing at least two formula products in children less than three years of age were included, but not trials of human breast milk or fortifiers of breast milk. Data were extracted in duplicate and primary outcome data were synthesised for meta-analysis with a random effects model weighted by the inverse variance method. Risk of bias was evaluated with Cochrane risk of bias version 2.0, and risk of undermining breastfeeding was evaluated according to published consensus guidance. Primary outcomes of the trials included in the systematic review were identified from clinical trial registries, protocols, or trial publications.
22 201 titles were screened and 307 trials were identified that were published between 2006 and 2020, of which 73 (24%) trials in 13 197 children were prospectively registered. Another 111 unpublished but registered trials in 17 411 children were identified. Detailed analysis was undertaken for 125 trials (23 757 children) published since 2015. Seventeen (14%) of these recently published trials were conducted independently of formula companies, 26 (21%) were prospectively registered with a clear aim and primary outcome, and authors or sponsors shared prospective protocols for 11 (9%) trials. Risk of bias was low in five (4%) and high in 100 (80%) recently published trials, mainly because of inappropriate exclusions from analysis and selective reporting. For 68 recently published superiority trials, a pooled standardised mean difference of 0.51 (range -0.43 to 3.29) was calculated with an asymmetrical funnel plot (Egger's test P<0.001), which reduced to 0.19 after correction for asymmetry. Primary outcomes were reported by authors as favourable in 86 (69%) trials, and 115 (92%) abstract conclusions were favourable. One of 38 (3%) trials in partially breastfed infants reported adequate support for breastfeeding and 14 of 87 (16%) trials in non-breastfed infants confirmed the decision not to breastfeed was firmly established before enrolment in the trial.
The results show that formula trials lack independence or transparency, and published outcomes are biased by selective reporting.
PROSPERO 2018 CRD42018091928.
系统评价配方奶粉试验的开展情况及报告情况。
系统评价。
检索了2006年1月1日至2020年12月31日期间的Medline、Embase和Cochrane对照试验中央注册库（CENTRAL）。
纳入比较至少两种配方奶粉产品用于3岁以下儿童的干预试验，但不包括人乳或母乳强化剂试验。数据进行了双人提取，并对主要结局数据进行综合分析，采用随机效应模型，以逆方差法加权。采用Cochrane偏倚风险2.0版评估偏倚风险，并根据已发表的共识指南评估破坏母乳喂养的风险。从临床试验注册库、方案或试验出版物中确定纳入系统评价的试验的主要结局。
筛选了22201篇标题，确定了2006年至2020年期间发表的307项试验，其中13197名儿童的73项试验（24%）进行了前瞻性注册。还确定了另外111项未发表但已注册的试验，涉及17411名儿童。对2015年以来发表的125项试验（23757名儿童）进行了详细分析。这些最近发表的试验中，17项（14%）独立于配方奶粉公司开展，26项（21%）有明确目的和主要结局进行了前瞻性注册，11项（9%）试验的作者或资助者分享了前瞻性方案。最近发表的试验中，5项（4%）偏倚风险低，100项（80%）偏倚风险高主要是因为分析中的不适当排除和选择性报告。对于68项最近发表的优效性试验，计算出合并标准化均数差为0.51（范围-0.43至3.29），漏斗图不对称（Egger检验P<0.001），校正不对称后降至0.19。作者报告86项（69%）试验的主要结局为有利，115项（92%）摘要结论为有利。部分母乳喂养婴儿的38项试验中有1项（3%）报告对母乳喂养有充分支持，非母乳喂养婴儿的87项试验中有14项（16%）证实，在试验入组前就已确定不进行母乳喂养的决定。
结果表明，配方奶粉试验缺乏独立性或透明度，发表的结果因选择性报告而存在偏倚。
PROSPERO 2018 CRD42018091928
