Title:First-in-human Phase 1 CRISPR Gene Editing Cancer Trials: Are We Ready?
VOLUME: 17 ISSUE: 4
Author(s):Francoise Baylis* and Marcus McLeod
Affiliation:Novel Tech Ethics, Faculty of Medicine, Dalhousie University, P.O. Box 15000, 1379 Seymour Street Halifax, NS, Novel Tech Ethics, Faculty of Medicine, Dalhousie University, P.O. Box 15000, 1379 Seymour Street Halifax, NS
Keywords:CRISPR, Phase 1, Cancer, Gene editing, Research ethics, Scientific validity.
Abstract: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.
