Cancer Clinical Trials — A Chronic but Curable Crisis

Published at www.nejm.org June 16, 2010 (10.1056/NEJMp1005843)
Cancer Clinical Trials — A Chronic but Curable Crisis
Robert C. Young, M.D.

In April, the Institute of Medicine (IOM) released a comprehensive review of the clinical trials program of the National Cancer Institute (NCI), in which it concluded that "the system for conducting clinical trials in the United States is approaching a state of crisis."1 The report, which was commissioned by the National Cancer Institute, drew the attention of the New York Times, which published an editorial on April 25 highlighting cumbersome procedures, excessive bureaucracy, poor coordination, and failure to complete 40% of the trials.2 On May 5, during hearings of the Senate Appropriations Committee, which holds jurisdiction over funding for the NIH, committee member Tom Harkin (D-IA) cited the report and the editorial in expressing concern about the funding of the NCI's clinical trials network and the impending crisis.

Created 55 years ago and modified intermittently since then, the NCI's clinical trials program is by far the largest trials network in the country. The program includes 10 cooperative groups, more than 3100 institutions, and 14,000 investigators and enrolls more than 25,000 patients in trials each year. Cancer-related clinical trials are also performed by industry, individual institutions and cancer centers, international cooperative groups, and the Department of Veterans Affairs.

The program has been central to many important clinical advances in cancer in the past 50 years. Its trials have defined effective treatments for childhood cancers, improving survival rates from less than 10% to more than 80%. Its landmark trials in early breast cancer defined standard surgery for localized breast cancer. Other group-led trials have established the standard of care for many advanced cancers, demonstrated that adjuvant therapy improves survival in many cancers, and shown that certain drugs have preventive effects in patients at high risk for colon adenomas, breast cancer, and prostate cancer. With such a stream of accomplishments, the clinical trials program is crucial to continued progress in cancer treatment.

Unfortunately, the program is bloated, cumbersome, inefficient, slow-paced, overmanaged, and expensive. Layers of bureaucracy at participating institutions, the NCI, and other government agencies slow the review process, so it takes about 3 years, on average, from concept to protocol approval. Trials remain uncompleted because of poor enrollment, lack of interest, excessive administrative burdens, and inadequate funding. These abandoned trials are at best a terrible waste of resources and at worst unethical, since they subject patients to risks without producing definitive results. The program currently costs $145 million per year, but the budget has been flat in recent years and since 1999 has actually declined 20% when adjusted for inflation. Clinical investigators see this level of funding as insufficient to sustain a clinical trials infrastructure, support enrollment, and ensure proper follow-up.

These problems are not new. The last three NCI directors have struggled to identify strategies to address them. Each has commissioned an external review to provide recommendations, the latest being the IOM assessment.

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