Nordic Cochrane Centre, Rigshospitalet 7811, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Syst Rev. 2020 Feb 28;9(1):42. doi: 10.1186/s13643-020-01300-1.
No study has looked at differences of pooled estimates-such as meta-analyses-of corresponding study documents of the same intervention. In this study, we compared meta-analyses of human papillomavirus (HPV) vaccine trial data from clinical study reports with trial data from corresponding trial register entries and journal publications.
We obtained clinical study reports from the European Medicines Agency and GlaxoSmithKline, corresponding trial register entries from ClinicalTrials.gov and corresponding journal publications via the Cochrane Collaboration's Central Register of Controlled Trials, Google Scholar and PubMed. Two researchers extracted data. We compared reporting of trial design aspects and 20 prespecified benefit and harm outcomes extracted from each study document type. Risk ratios were calculated with the random effects inverse variance method.
We included study documents from 22 randomized clinical trials and 2 follow-up studies with 95,670 healthy participants and non-HPV vaccine comparators (placebo, HPV vaccine adjuvants and hepatitis vaccines). We obtained 24 clinical study reports, 24 corresponding trial register entries and 23 corresponding journal publications; the median number of pages was 1351 (range 357 to 11,456), 32 (range 11 to 167) and 11 (range 7 to 83), respectively. All 24 (100%) clinical study reports, no (0%) trial register entries and 9 (39%) journal publications reported on all six major design-related biases defined by the Cochrane Handbook version 2011. The clinical study reports reported more inclusion criteria (mean 7.0 vs. 5.8 [trial register entries] and 4.0 [journal publications]) and exclusion criteria (mean 17.8 vs. 11.7 and 5.0) but fewer primary outcomes (mean 1.6 vs. 3.5 and 1.2) and secondary outcomes (mean 8.8 vs. 13.0 and 3.2) than the trial register entries. Results were posted for 19 trial register entries (79%). Compared to the clinical study reports, the trial register entries and journal publications contained 3% and 44% of the seven assessed benefit data points (6879 vs. 230 and 3015) and 38% and 31% of the 13 assessed harm data points (167,550 vs. 64,143 and 51,899). No meta-analysis estimate differed significantly when we compared pooled risk ratio estimates of corresponding study document data as ratios of relative risk.
There were no significant differences in the meta-analysis estimates of the assessed outcomes from corresponding study documents. The clinical study reports were the superior study documents in terms of the quantity and the quality of the data they contained and should be used as primary data sources in systematic reviews.
The protocol for our comparison is registered on PROSPERO as an addendum to our systematic review of the benefits and harms of the HPV vaccines: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20180320.pdf: CRD42017056093. Our systematic review protocol was registered on PROSPERO on January 2017: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20170030.pdf. Two protocol amendments were registered on PROSPERO on November 2017: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20171116.pdf. Our index of the HPV vaccine studies was published in Systematic Reviews on January 2018: https://doi.org/10.1186/s13643-018-0675-z. A description of the challenges obtaining the data was published on September 2018: https://doi.org/10.1136/bmj.k3694.
尚无研究关注对应干预措施的研究文件（如荟萃分析）的汇总估计值的差异。在这项研究中，我们比较了来自临床研究报告的人乳头瘤病毒（HPV）疫苗试验数据的荟萃分析与对应试验注册入口和期刊出版物中的试验数据。
我们从欧洲药品管理局和葛兰素史克公司获得临床研究报告，从 ClinicalTrials.gov 和 Cochrane 协作中心的对照试验注册处、Google Scholar 和 PubMed 获得对应试验注册入口和对应期刊出版物。两名研究人员提取数据。我们比较了每个研究文件类型的试验设计方面和 20 个预先指定的获益和危害结局的报告情况。使用随机效应倒数方差法计算风险比。
我们纳入了来自 22 项随机临床试验和 2 项随访研究的 95670 名健康参与者和非 HPV 疫苗对照（安慰剂、HPV 疫苗佐剂和肝炎疫苗）。我们获得了 24 份临床研究报告、24 份对应试验注册入口和 23 份对应期刊出版物；中位数页数分别为 1351 页（范围为 357 至 11456 页）、32 页（范围为 11 至 167 页）和 11 页（范围为 7 至 83 页）。所有 24 份（100%）临床研究报告、没有（0%）试验注册入口和 9 份（39%）期刊出版物均报告了 Cochrane 手册第 2.11 版定义的 6 项主要设计相关偏倚中的所有内容。临床研究报告报告了更多的纳入标准（平均 7.0 比 5.8[试验注册入口]和 4.0[期刊出版物]）和排除标准（平均 17.8 比 11.7 和 5.0），但更少的主要结局（平均 1.6 比 3.5 和 1.2）和次要结局（平均 8.8 比 13.0 和 3.2）比试验注册入口。19 份试验注册入口（79%）发布了结果。与临床研究报告相比，试验注册入口和期刊出版物包含了 7 个评估获益数据点的 3%和 44%（6879 比 230 和 3015），以及 13 个评估危害数据点的 38%和 31%（167，550 比 64，143 和 51，899）。当我们比较对应研究文件数据的汇总风险比估计值作为相对风险的比值时，没有一个荟萃分析估计值有显著差异。
对应研究文件中评估结果的荟萃分析估计值没有显著差异。临床研究报告在包含的数据数量和质量方面是更优的研究文件，应作为系统评价的主要数据来源。
我们比较的方案作为 HPV 疫苗获益和危害系统评价的补充，在 PROSPERO 上注册：https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20180320.pdf：CRD42017056093。我们的系统评价方案于 2017 年 1 月在 PROSPERO 上注册：https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20170030.pdf。2017 年 11 月，PROSPERO 上注册了两项方案修正案：https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20171116.pdf。我们的 HPV 疫苗研究索引于 2018 年 1 月在系统评价中发布：https://doi.org/10.1186/s13643-018-0675-z。关于获取数据的挑战的描述于 2018 年 9 月发布：https://doi.org/10.1136/bmj.k3694.
