Pivotal Considerations for Optimal Deployment of Healthy Volunteers in Oncology Drug Development
Mariam A Ahmed1, Chirag Patel2, Nicole Drezner1
1Center of Drug Evaluation and Research, US Food and Drug Administration.
Abstract:
Oncology drug development is among the most challenging of any therapeutic area, with first-in-human trials expected to deliver information on both safety and activity. Until recently, therapeutic approaches in oncology focused on cytotoxic chemotherapy agents, ruling out even the possibility of enrolling normal healthy volunteers (NHVs) in clinical trials due to safety considerations. The emergence of noncytotoxic modalities, including molecularly targeted agents with more favorable safety profiles, however, has led to increasing numbers of clinical pharmacology studies of these agents being conducted in NHVs. Beyond rapid enrollment and cost savings, there are other advantages of conducting specific types of studies in NHVs with the goal of more appropriate dosing decisions in certain subsets of the intended patient populations, allowing for enrollment of such patients in therapeutic trials from which they might otherwise have been excluded. Nevertheless, the decision must be carefully weighed against potential disadvantages, and although the considerations surrounding conduct of clinical trials using NHVs are generally well-defined in most other therapeutic areas, they are less well-defined in oncology.
Insights
Clinical trials for oncology drugs are evolving. Non-cytotoxic cancer therapies allow the use of normal healthy volunteers (NHVs) in early-phase studies, aiding drug development and dosing decisions.
Area of Science:
- Oncology
- Clinical Pharmacology
- Drug Development
Background:
- Oncology drug development presents significant challenges, particularly in early-phase trials requiring safety and activity data.
- Historically, cytotoxic chemotherapy agents limited the use of normal healthy volunteers (NHVs) due to safety concerns.
Purpose of the Study:
- To explore the increasing use of NHVs in clinical pharmacology studies for non-cytotoxic oncology agents.
- To evaluate the advantages and disadvantages of conducting trials in NHVs for oncology drug development.
Main Methods:
- Review of the evolving landscape of oncology drug development, focusing on non-cytotoxic modalities.
- Analysis of the rationale and considerations for employing NHVs in early-phase oncology clinical trials.
Main Results:
- The advent of molecularly targeted agents with improved safety profiles facilitates NHV enrollment.
- NHV studies offer benefits such as faster enrollment, cost savings, and informed dosing decisions for specific patient populations.
Conclusions:
- Conducting clinical trials in NHVs for oncology drug development is becoming more feasible with non-cytotoxic agents.
- Careful consideration of potential risks and benefits is crucial when deciding to include NHVs in oncology trials, as guidelines are less defined than in other therapeutic areas.
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