Clinical pharmacology studies (i.e., trials where the primary objectives are traditionally pharmacokinetic (PK)-related) focus on identifying and confirming appropriate dosing in various subsets of the intended patient populations. In most therapeutic areas, these trials are conducted in normal healthy volunteers (NHVs) and in special populations without the targeted disease (i.e., subjects who are renally or hepatically impaired but are otherwise healthy, and who, for the purposes of this paper, will be considered part of the NHV population). Results from these NHV PK studies are then used to expand the patient pool, including those with comorbidities or who are receiving concomitant medications, which might otherwise have resulted in them being excluded from enrollment in trials with therapeutic intent.

Until ~ 20 years ago, oncology drug development was almost exclusively focused on chemotherapeutics that were intentionally designed to be cytotoxic (and frequently genotoxic), limiting their development programs to patients with cancer. Given the terminal nature of most cancers and the generally short life expectancy following diagnosis, a higher level of toxicity than that observed in other marketed drugs has been considered acceptable for these agents. Poor tolerability is expected and mitigated, when possible, by supportive care measures as well as by frequent dose modifications and interruption. Given the poor long-term survival for patients wi th most types of cancer, the potential for development of long-term toxicities was considered less important in the overall risk-benefit assessment of the cytotoxic chemotherapeutic agent. Thus, safety considerations played a major role in exclusion of NHVs from oncology drug development.