A Multidisciplinary Evaluation of Barriers to Enrolling Cancer Patients into Early Phase Clinical Trials: Challenges and Patient-centric Recommendations

ABSTRACT

Introduction: Early phase clinical trials are the first clinical research step to bringing new cancer therapeutics to patients. At this stage, a new drug’s safety, dosing, and scheduling profiles are established as the main endpoints. However, excellent responses due to biomarker-guided and immune checkpoint trials in early phase have resulted in direct approvals of new anti-cancer drugs. Despite doubling of the success rate of new drug approvals, many barriers exist to expeditiously bring active new drugs to the clinic.

Areas covered: This review covers roles of members of the early phase program and the challenges they face in enrolling advanced cancer patients to trials. Practical solutions are provided from the perspective of the investigators, regulatory, investigational pharmacy, research nurses, clinical research coordinators, budgets, contracts, and data management.

Expert opinion: We are witnessing a burgeoning era in drug development with rapid approval of efficacious drugs. This is achieved by a strong collaboration between investigators, academic institutions, pharmaceutical sponsors, scientists, Food and Drug Administration (FDA), and community practices. Herein, we discuss some of the challenges faced by early phase clinical trials programs and discuss methods of improvement.

KEYWORDS:

• Phase I
• early
• challenges
• research
• cancer
• cancer patients

Article Highlights

• Currently, 800 cancer drugs are being developed and 10,000 cancer clinical trials are ongoing in the USA. This is a burgeoning era in drug development and it is quintessential to educate and incentivize early career investigators to participate in phase I trials.

• Chief suggestions: (1) streamlined review process, (2) increased education on facilitating and coordinating early phase clinical trials for providers, institutions, sponsors, and CROs, and (3) greater focus on the needs and comfort of our cancer patients and their caregivers.

• Gathering large amounts of PK, multiple biopsies, and toxicity data presents huge concerns for patient comfort and workload of investigators and study staff. Re-evaluation of the minimum effective data necessary to ensure patient safety could greatly aid in reducing workload and patient burden.

• Participating in clinical trials should not be financially cumbersome for patients. A Cancer Care Equity Program can help address financial disincentives. It is also imperative to educate intra-institutional finance staff on finance logistics of phase I trials. It is imperative for insurance companies not to deny patients participation in clinical trials specifically when no other treatment options exist.

• Strict eligibility criteria restrict and exclude relevant patients from enrolling on early phase trials. More inclusive trials will provide treatment options for more patients.

• Adequate staffing and retention of properly educated and trained personnel at all levels is important and recognition of the value of early clinical trials in the current era of expedited drug development is essential.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has received honoraria or speakers’ fees from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche and research grants from I.A.S.L.C. (International Association for the Study of Lung Cancer), L.I.L.T. (Lega Italiana per la Lotta contro i Tumori), Fondazione Cariverona, Astra-Zeneca, Roche, and Open Innovation. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

The work of the authors is funded by 2P30 CA023074 supplement of the Cancer Center Support Grant from the NCI/NIH to the University of Arizona Cancer Center.