title: Inclusion of placebos and blinding for ascending dose first-in-human studies and other underpowered phase 1 studies has not been justified and on balance is not useful.
abstract: Today, the majority of phase 1 dose-escalation first-in-human studies are designed as blinded, placebo-controlled protocols. First-in-human phase 1 studies are a critical component of the drug development process, but in our opinion, the additions of blinding and placebo control to these study protocols are a matter of faith without scientific support to show that the increased complexity, time, burdensome nature and expense of such additions, plus the increase in human subjects studied, are justified and useful in the drug development process. Here, we document the prevalence of such studies, review and respond to the rationalizations for such protocols and propose that the addition of blinding and placebo control to first-in-human and many other underpowered phase 1 studies is unnecessary because these additions provide little documented benefit to the drug development process.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California, San Francisco, CA, USA.
authors.forename: Dolly A
authors.initials: DA
authors.lastname: Parasrampuria
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California, San Francisco, CA, USA.
authors.forename: Leslie Z
authors.initials: LZ
authors.lastname: Benet
mesh_terms: D015982:Bias; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000706:statistics & numerical data; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology; D023381:Endpoint Determination; D006801:Humans; D015990:Placebo Effect; D012107:Research Design / Q000706:statistics & numerical data; D018570:Risk Assessment; D016037:Single-Blind Method; D016896:Treatment Outcome