By Jessica DeMartino, PhD, Manager, Health Policy Programs
In April 2010 the Institute of Medicine (IOM) released a report1 on the National Cancer Institute’s (NCI) Clinical Trials Program that concluded, “the system for conducting clinical trials in the United States is approaching a state of crisis.” The NCI’s Clinical Trials Program is the largest trials network in the country and in the past has greatly improved the care pediatric and adult oncology patients receive. The IOM report identified deficiencies in the current system and offered recommendations for four areas.
A recent New York Times article by Amy Harmon details the experience of two cousins with melanoma enrolled in the same clinical trial. The article highlights many aspects of the clinical trial system that frustrate patients and physicians alike. Many of the issues raised in this article mirrored challenges recognized in the IOM report.
At the NCCN Patient Advocacy Summit held on September 23, 2010, the topic of clinical trials was discussed in a session focused on biomarkers. Once again, many of the same issues highlighted in the IOM report and the New York Times article were raised by both clinicians and patient advocates.
All three of the above mentioned articles and events focused on the urgent need to re-evaluate the traditional trial design being used today. Validated biomarkers, high-quality annotated biorepositories, and maintenance of tissue banks will be necessary for the highly anticipated personalized medicine of the 21st century. Utilization of these technologies will require innovative trial designs and regulatory flexibility. The use of biomarkers in clinical trials should allow for the design of trials that require less patients, time, and resources. Trial designers, physicians, researchers, and regulators need to be able to prioritize trials and endpoints. They must be able to modify endpoints so that they are most applicable to the disease and the clinical setting of the trial. Current response criteria do not include the use of new technology and should be modified to include such advances.
Many physicians and researchers face an ethical conflict between their responsibility to patients and their commitment to gathering scientific information. They are torn between having their patients receive the new, possibly more effective care as soon as they feel it has been proven, and the need to scientifically prove the effectiveness of the agent and preserve the integrity of the data. Clinical trials are extremely expensive both in terms of time and financial resources. For many stakeholders, including physicians, administrators, and pharmaceutical companies, the trials must be completed in order to maintain data integrity and further utilize the results. Physicians are often asked to determine the balance of benefitting some patients now versus the health and treatment of all future patients. Some physicians may even be reluctant to enroll a patient in a trial with a new treatment option that has an early strong signal for efficacy if there is no crossover arm and the standard therapy is not very effective.
Patients often confront many issues when facing clinical trials. Many patients are unaware of clinical trials that may be available to them and the eligibility criteria for participating can be complex. Patients also face variable coverage of care expenses, though hopefully this will be rectified by health care reform that includes a provision taking effect January 1, 2014. It requires all health plans to cover the costs of routine care associated with clinical trials. Grandfathered health plans are exempt from this provision, but it is expected that a large majority of health plans will lose their grandfathered status over the next few years. Many patients are also afraid of clinical trials and of being placed in the control arm of a study. Patients do not understand that in cancer clinical trials the control arm is usually the current standard of care and is not sub-standard treatment. Patients may also be more likely to enroll in trials where crossover to the more effective treatment is an option. Patient advocates should be more involved in study design, increasing patient understanding, acceptance, and accrual to trials.
It is evident that some aspects of traditional trial design urgently need to be re-evaluated and redesigned in order to benefit patients in the most expeditious manner and with the lowest costs possible. Regulators, physicians, researchers, and patient advocates must all work together to develop clinical trial designs that meet the needs of patients but still satisfy the call for high-quality scientific results and data. Innovative trials designs and regulatory flexibility will be pivotal in advancing the science and care of patients and in continuing the past successes of the NCI Clinical Trials Program.