Consider drug efficacy before first-in-human trials

How well are Phase 2 cancer trial publications supported by preclinical efficacy evidence?

“…However, many trials in our sample would likely have been exempt from investigational new drug application (IND) requirements and have thus not required FDA approval . Moreover, FDA does not always scrutinize preclinical efficacy evidence when approving trials . Referees and journal editors should encourage a more comprehensive description of supporting preclinical evidence within reports of Phase 2 trials.…”

“…Various commentators have questioned the quality of design and reporting of preclinical studies in cancer . At the same time, preclinical evidence supporting early clinical hypotheses is often limited in quantity . In several instances, early phase trials launched based on equivocal preclinical evidence have resulted in unsuccessful drug development efforts, yet drug regulators often grant sponsors and academic investigators wide discretion on the preclinical rationale for launching early phase trials .…”

Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross‐sectional study

“…Such failures are costly and expose patients to ineffective therapeutic regimens. Many commentators have questioned design and reporting standards for preclinical efficacy studies (Prinz et al, 2011;Begley and Ellis, 2012;Kimmelman and Federico, 2017;Mattina et al, 2017). Better regulatory guidance on the design of preclinical efficacy studies might help reduce the burdens and costs associated with attrition during drug development.…”

“…Over the past 10 years, many commentators have raised concerns about the design and reporting of preclinical reports (Kilkenny et al, 2009;Prinz et al, 2011;Begley and Ellis, 2012;Howells et al, 2014), and some linked these concerns to the high attrition rates in clinical research (Prinz et al, 2011). Some have further argued that regulatory bodies do not routinely assess preclinical efficacy studies when authorizing early phase studies (Kimmelman and Federico, 2017). Recent analyses on how preclinical efficacy data are reported within investigator brochures for early phase studies intensified this concern (Wieschowski et al, 2018;Yasinski, 2018).…”

Tissue chips – innovative tools for drug development and disease modeling

“…Human volunteers may suffer unexpected and potentially catastrophic side effects if efficacy data is not adequately presented before drugs move to first-in-human trials 58 . Cook et al 41 investigated the reasons for failure of 142 small molecule drug development programs between 2005 and 2010 at AstraZeneca, and found that lack of efficacy caused failure rates of an astonishing 57–88% at phase II clinical trials.…”