Department of Animals in Science and Society, Faculty of Veterinary Sciences, Utrecht University, Utrecht, The Netherlands.
Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
J Transl Med. 2019 Jul 15;17(1):223. doi: 10.1186/s12967-019-1976-2.
Drug development is currently hampered by high attrition rates; many developed treatments fail during clinical testing. Part of the attrition may be due to low animal-to-human translational success rates; so-called "translational failure". As far as we know, no systematic overview of published translational success rates exists.
The following research question was examined: "What is the observed range of the animal-to-human translational success (and failure) rates within the currently available empirical evidence?". We searched PubMed and Embase on 16 October 2017. We included reviews and all other types of "umbrella"-studies of meta-data quantitatively comparing the translational results of studies including at least two species with one being human. We supplemented our database searches with additional strategies. All abstracts and full-text papers were screened by two independent reviewers. Our scoping review comprises 121 references, with various units of measurement: compound or intervention (k = 104), study/experiment (k = 10), and symptom or event (k = 7). Diagnostic statistics corresponded with binary and continuous definitions of successful translation. Binary definitions comprise percentages below twofold error, percentages accurately predicted, and predictive values. Quantitative definitions comprise correlation/regression (r) and meta-analyses (percentage overlap of 95% confidence intervals). Translational success rates ranged from 0 to 100%.
The wide range of translational success rates observed in our study might indicate that translational success is unpredictable; i.e. it might be unclear upfront if the results of primary animal studies will contribute to translational knowledge. However, the risk of bias of the included studies was high, and much of the included evidence is old, while newer models have become available. Therefore, the reliability of the cumulative evidence from current papers on this topic is insufficient. Further in-depth "umbrella"-studies of translational success rates are still warranted. These are needed to evaluate the probabilistic evidence for predictivity of animal studies for the human situation more reliably, and to determine which factors affect this process.
药物开发目前受到高淘汰率的阻碍；许多开发的治疗方法在临床试验中失败。部分淘汰可能是由于动物到人类的转化成功率低；所谓的“转化失败”。据我们所知，目前还没有对已发表的转化成功率的系统综述。
研究了以下研究问题：“在现有经验证据中，观察到的动物到人类转化成功率（和失败率）范围是多少？”。我们于 2017 年 10 月 16 日在 PubMed 和 Embase 上进行了搜索。我们纳入了综述和所有其他类型的元数据分析“伞”研究，这些研究定量比较了至少包括两种物种的研究的转化结果，其中一种是人类。我们通过其他策略补充了我们的数据库搜索。两位独立评审员筛选了所有摘要和全文论文。我们的范围综述包括 121 篇参考文献，有各种测量单位：化合物或干预（k=104）、研究/实验（k=10）和症状或事件（k=7）。诊断统计数据与成功转化的二进制和连续定义相对应。二进制定义包括误差低于两倍的百分比、准确预测的百分比和预测值。定量定义包括相关/回归（r）和荟萃分析（95%置信区间重叠的百分比）。转化成功率范围从 0 到 100%。
我们研究中观察到的转化成功率范围很广，这可能表明转化成功率是不可预测的；即，初步动物研究的结果是否有助于转化知识，可能一开始并不清楚。然而，纳入研究的偏倚风险很高，而且大部分纳入的证据都很陈旧，而新的模型已经出现。因此，目前关于这一主题的论文的累积证据的可靠性不足。进一步深入研究转化成功率的“伞”研究仍然是必要的。这些研究需要更可靠地评估动物研究对人类情况的预测概率的概率证据，并确定哪些因素影响这一过程。
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