FDA’s Oncology Center of Excellence (OCE) was created in 2017 by the 21st Century Cures Act to provide dedicated staff to improve efficiency in oncology drug development and review. OCE facilitates collaborations between staff members with oncology expertise from other FDA centers, including the Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation (CBER), and Center for Devices and Radiological Health (CDRH). Diversifying and Decentralizing Trials Clinical trial participation yields advances in treatment and survival for the types of cancers and groups of patients represented (761). Additionally, clinical trial participants frequently experience improved outcomes compared to nonparticipants (762), as they receive a greater level of care during clinical visits (763). While more than half of adult patients with cancer choose to enroll in trials if asked by their providers (764), clinical trial participation rates remain very low in the United States. Only 8 percent of adult patients and 19.9 percent of pediatric and adolescent patients with cancer participate in clinical trials (765,766). Academic medical centers experience greater than average trial participation rates (765), but most patients with cancer are treated at community clinics or hospitals where trials have not been historically available. Unfortunately, more than 75 percent of patients with cancer are ineligible for trials because there are no trials available for their specific disease or they are excluded because of strict eligibility criteria related to other health conditions (765). Additional challenges to enrollment in clinical trials include absence of health care facilities in some communities, lack of trust in medical research and institutions, family responsibilities, and costs and time related to participating (767-769). These factors contribute to a clinical trial population which does not represent the real-world population of patients who may use the new therapies. This discrepancy leaves open questions on safety and efficacy for people from groups that are not adequately represented in clinical trials, and particularly groups that bear disproportionately higher cancer incidence and death. To improve representation in clinical trials, it will be critical that trial sponsors and researchers prospectively integrate diversity strategies with traditional drug development strategy. Historically, diversity has primarily been considered in hindsight, when it is too late to make meaningful changes to clinical trials underpinning regulatory submissions. Included in the federal appropriations omnibus for FY 2023 was a provision that allows FDA to require companies to develop a Diversity Action Plan for registrational trials as well as document their success at meeting diversity goals (770). The new law also allows FDA to require additional postmarketing clinical trials to follow-up on important signals for specific subgroups of patients identified during premarketing trials. In April 2022, OCE released draft guidance on creating prospective diversity action plans and is now working towards finalizing the guidance (771). In June 2023, AACR, FDA, and several industry partners collaborated on a special article that outlined steps clinical trial sponsors can take to improve diversity in clinical trials, thereby improving access to innovative cancer therapies for all patients (772). They called on the entire cancer research community to expand the number of clinical sites involved in research, broaden trial eligibility criteria, address barriers to participation, and continue ongoing conversations among broad stakeholders, including patients. Recommended changes to clinical trials to enhance diversity as well as other improvements are summarized in Table 4, p. 157. In the wake of the COVID-19 pandemic, every clinical trial now includes some form of decentralized element, such as consenting patients remotely, using local laboratory test and imaging facilities, and telehealth visits for monitoring side effects. These approaches have greatly reduced the burden of trial participation for patients and health clinics alike. Decentralization also provides value to industry by enabling cost savings, increasing patient enrollments, simplifying trial designs, and promoting faster completion of trials. When the pandemic’s public health emergency designation expired earlier this year, many in the cancer research community were concerned about a lapse in COVID-era guidance that enabled greater decentralization. In response, FDA issued guidance to continue supporting decentralized approaches (771). However, many of these decentralized elements were allowed prior to the COVID-19 pandemic and the limiting factors for widespread adoption revolve around implementation within industry and academic medical centers. As the use of decentralized elements grows, new data demonstrating the value of these changes will hopefully enhance further adoption. Rapidly Delivering Safe and Effective Therapies to Patients Waiting for definitive evidence of clinical benefit for new therapies before sponsors apply for FDA review can take many years. This delay can mean that patients with deadly diseases who could benefit may die before the drug becomes approved. In 1992, FDA created the Accelerated Approval pathway as a response to the devastating HIV pandemic (773). Accelerated Approvals leverage early outcome data that are suggestive of “clinical benefit,” but not necessarily a direct measure of clinical benefit for serious diseases that have unmet medical needs. Between 2011 and 2020, 45.6 percent of new cancer drugs were approved through the Accelerated Approval pathway, and cancer therapies accounted for 80 percent of all Accelerated Approvals (774). For cancer therapies, progression-free survival, response rate, and side effect rates are early endpoints frequently considered for Accelerated Approval. However, Accelerated Approval also carries a requirement for companies to continue studying the therapy to demonstrate clinical benefit, most often improved overall survival. In March 2023, FDA issued draft guidance on considerations for clinical trial designs to support enhanced Accelerated Approval AACR Cancer Progress Report 2023 156 Advancing the Future of Cancer Research and Patient Care Through the Adoption of Evidence-Based Policies
RkJQdWJsaXNoZXIy NTkzMzk=