match the actual demographics of the cancer burden under study (334). Underrepresentation in clinical trials compromises the applicability of such research findings to the entire U.S. patient population. Understanding and eliminating barriers to clinical trial participation for all segments of the population is vital if we are to accelerate the pace of progress against cancer for everyone. Numerous studies have investigated the existing barriers that limit participation of racial and ethnic minorities and other medically underserved populations in cancer clinical trials. These studies have identified a range of factors such as lack of awareness of clinical trials, financial challenges, limited health literacy, inadequate or complete lack of insurance, medical distrust, implicit biases among health care providers, lack of trial availability, and narrow eligibility criteria, among others (13). These barriers operate at individual, systemic, and societal levels (340). Increased knowledge of the barriers to clinical trial accrual is helping researchers, regulators, and policymakers design and implement evidence-based adaptations that can broaden participant access and promote accrual to clinical research. Such interventions focus on addressing social determinants of health (see Figure 2, p. 19), and include decentralizing many of the trial activities to ease patient participation, expanding eligibility criteria, improving the efficiency of data collection, including patient reported outcomes (PRO), and enhancing community outreach and patient navigation efforts to raise awareness of trials. One critical area of focus for all stakeholders in medical research is fostering greater diversity, equity, and inclusion within the clinical research workforce so the workforce will resemble the patient populations it serves. U.S. lawmakers and FDA are working on legislation and guidelines intended to increase the diversity of clinical trial participants (see Diversifying and Decentralizing Trials, p. Therapeutic Development TARGET VALIDATION Potential targets identified by discovery science are confirmed to play a causal role in disease development. DRUG SCREENING Large numbers of chemical or biological agents are screened to identify and validate molecules that hit the target. LEAD IDENTIFICATION Agents that hit the target are evaluated to determine which ones bind the target with the greatest specificity and have the most promising medicinal properties. LEAD OPTIMIZATION The characteristics of lead compounds are optimized to enhance potency and drug-like properties, and to reduce side effects by enhancing specificity. PRECLINICAL TESTING Optimized lead compound(s) are tested in cell-based and animal models for effectiveness, potential toxicity, optimal starting dose, and dosing schedule for clinical or “first-in-human” testing. The final compound(s) are considered to be clinical candidate(s). INVESTIGATIONAL NEW DRUG One or more clinical candidates are generated through good manufacturing practices and assessed in rigorous good laboratory practice studies before submission to the U.S. Food and Drug Administration for approval for use in clinical trials. Adapted from (4). SIDEBAR 26 5K-10K compounds 1-5 compounds 5-10 years AACR Cancer Progress Report 2023 Advancing the Frontiers of Cancer Science and Medicine 70
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