首先在人类第一阶段CRISPR基因编辑癌症试验：我们准备好了吗？

Title:First-in-human Phase 1 CRISPR Gene Editing Cancer Trials: Are We Ready?

Volume: 17 Issue: 4

关键词: CRISPR，第一阶段，癌症，基因编辑，研究伦理，科学有效性。

摘要: A prospective first-in-human Phase 1 CRISPR gene editing trial in the United States for patients with melanoma, synovial sarcoma, and multiple myeloma offers hope that gene editing tools may usefully treat human disease. An overarching ethical challenge with first-in-human Phase 1 clinical trials, however, is knowing when it is ethically acceptable to initiate such trials on the basis of safety and efficacy data obtained from pre-clinical studies. If the pre-clinical studies that inform trial design are themselves poorly designed – as a result of which the quality of pre-clinical evidence is deficient – then the ethical requirement of scientific validity for clinical research may not be satisfied. In turn, this could mean that the Phase 1 clinical trial will be unsafe and that trial participants will be exposed to risk for no potential benefit. To assist sponsors, researchers, clinical investigators and reviewers in deciding when it is ethically acceptable to initiate first-in-human Phase 1 CRISPR gene editing clinical trials, structured processes have been developed to assess and minimize translational distance between pre-clinical and clinical research. These processes draw attention to various features of internal validity, construct validity, and external validity. As well, the credibility of supporting evidence is to be critically assessed with particular attention to optimism bias, financial conflicts of interest and publication bias. We critically examine the pre-clinical evidence used to justify the first-inhuman Phase 1 CRISPR gene editing cancer trial in the United States using these tools.

We conclude that the proposed trial cannot satisfy the ethical requirement of scientific validity because the supporting pre-clinical evidence used to inform trial design is deficient.

Cite this article as:

First-in-human Phase 1 CRISPR Gene Editing Cancer Trials: Are We Ready?, Current Gene Therapy 2017; 17 (4) . https://dx.doi.org/10.2174/1566523217666171121165935