European Journal of Clinical Pharmacology ( IF 2.4 ) Pub Date : 2023-06-06 , DOI: 10.1007/s00228-023-03517-0 Alexandra Wendler 1 , Martin Wehling 1
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Background
The ongoing pandemic of severe acute respiratory syndrome coronavirus 2 has led to an enormous surge of clinical research. So far, the speed and success rate of related drug development projects, especially of vaccines, is unprecedented. For the first time, this situation allowed for the opportunistic evaluation of a translatability score, originally proposed in 2009, in a prospective manner.
Methods
Several vaccines and treatments under development in clinical phase III trials were selected for translational scoring with the translatability score. Six prospective and six retrospective case studies were performed. The scores had to be determined for a fictive date before any results of the phase III trial were reported in any media. Spearman correlation analysis and a Kruskal Wallis test were performed for statistical evaluation.
Results
A significant correlation between the translatability scores and the clinical outcomes in translation was found, as judged on the basis of positive/intermediate/negative endpoint studies or market approval. The Spearman correlation analysis of all cases (r = 0.91, p < 0.001), the prospective cases alone (r = 0.93, p = 0.008), and the retrospective cases alone (r = 0.93, p = 0.008) showed a strong correlation between the score and outcome; R2 demonstrated a score-derived determination of outcomes by 86%.
Conclusions
The score detects strengths and weaknesses of a given project, resulting in the opportunity of selective amelioration of a project, as well as prospective portfolio risk balancing. Its substantial predictive value that has been demonstrated here for the first time could be of particular interest for biomedical industry (pharmaceutical and device manufacturers), funding agencies, venture capitalists, and researchers in the area. Future evaluations will have to address the generalizability of results obtained in an exceptional pandemic situation, and the potential adaptations of weighing factors/items to particular therapeutic areas.
中文翻译：
前瞻性和回顾性新冠病毒药物开发案例中的可翻译性评分
背景
严重急性呼吸综合征冠状病毒 2 的持续流行导致了临床研究的激增。迄今为止，相关药物尤其是疫苗的开发速度和成功率是前所未有的。这种情况第一次允许以前瞻性的方式对最初于 2009 年提出的可译性评分进行机会主义评估。
方法
选择了几种正在临床 III 期试验中开发的疫苗和治疗方法，通过可翻译性评分进行翻译评分。进行了六项前瞻性案例研究和六项回顾性案例研究。在任何媒体报道第三阶段试验的任何结果之前，必须确定虚构日期的分数。进行 Spearman 相关分析和 Kruskal Wallis 检验进行统计评估。
结果
根据阳性/中间/阴性终点研究或市场认可来判断，可译性评分与翻译临床结果之间存在显着相关性。所有病例 ( r = 0.91, p < 0.001)、单独前瞻性病例 ( r = 0.93, p = 0.008) 和单独回顾性病例 ( r = 0.93, p = 0.008) 的 Spearman 相关分析显示出很强的相关性分数和结果之间； R 2证明了 86% 的结果是通过评分得出的。
结论
该分数可检测给定项目的优势和劣势，从而提供选择性改进项目的机会以及预期投资组合风险平衡。在此首次展示的其巨大的预测价值可能会引起生物医学行业（制药和设备制造商）、资助机构、风险投资家和该领域研究人员的特别兴趣。未来的评估必须解决在特殊大流行情况下获得的结果的普遍性，以及权衡因素/项目对特定治疗领域的潜在调整。
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