Addressing the challenge of cancer trial accrual

Edwin Watson highlights the challenge of cancer trial accrual in our oncology themed month, and questions how we can encourage physicians to refer more patients to oncology clinical trials.

The Current Landscape

Enrolling a sufficient number of patients to any clinical trial is a universal challenge; in oncology, however, calling trial accrual a challenge would be a gross understatement.

Even the world's leading academic centers and government- supported sites struggle with enrollment. With 8,000 cancer trials competing for subjects in the United States and the fact that the vast majority of physicians are not referring patients, it is no wonder that 40% of National Cancer Institute (NCI) sponsored phase III trials close without accruing enough patients to attain meaningful results (NCI, 2010).

NCI refers to the small number of physicians who do participate in clinical trials as an "all volunteer army" because the disincentives far outweigh the incentives. This helps to explain why only 13% of physicians are clinical investigators. While community-based oncologists are aware that clinical trials are essential to the development of new treatments, many are unaware of available clinical trials for their eligible patients.

With massive amounts of new data made available through biomarkers, advanced knowledge of disease pathways and the use of combination therapies to inhibit multiple pathways - the criteria for trials is increasingly specific. Effectively researchers are looking for smaller and smaller needles in ever larger haystacks. The number of eligible patients diagnosed in large metropolitan practices is often in low single digits for an entire year, begging more involvement from the non-research oncology community.

A robust clinical trials infrastructure depends on a critical mass of physicians and patients willing to participate, but that is not the norm today. Recent NCI data show that only 3–5% of newly diagnosed cancer patients participate in clinical trials despite the fact that the Institute of Medicine recommends that the therapies offered through clinical trials should be considered the preferred treatment choice for physicians and patients when they are available (IOM, 2010). NCI projects from its data that if the participation rate could be increased to 10%, the average study could be completed in one year, instead of the three to five currently required.

The Challenges

Our firm recently concluded a two-year program, evaluating solutions specifically designed to improve oncology trial accrual. We set out to define the issues inhibiting trial accrual, review the host of strategies that succeed in other therapeutic areas but fail in oncology in hope of understanding why they fail.

Cancer patients present some particular impediments:

Narrow windows of eligibility / opportunity for trials.

The vast majority of trials cannot accept patients who have initiated some form of therapy. Unlike many other diseases, cancer therapies will not be discontinued until they are deemed a failure, usually when the disease progresses, which in turn impacts the type of trial opportunities.

Patients are largely unable to navigate trial options on their own.

While the internet provides many comprehensive clinical trial resources, patients are rarely aware of the complex details of their diagnosis and thus unable to assess whether a particular therapy is suited to their case. Should a therapy be appropriate they then must navigate complex inclusion / exclusion criteria for the trial to determine if they may be eligible. And of course if they are "on therapy" they will not likely be eligible for the trial until that therapy has failed.

Patients need the active support of knowledgeable medical professionals who have access to the details of their diagnosis.

With literally thousands of trials ongoing medical staff cannot rely on memory alone to remain aware of the best options for treatment.

The time required to research and later discuss trial options is rarely adequately reimbursed, and often means sacrificing time available for other patients in the practice.

Our findings were clear: while physicians and patients are generally positive about the idea of furthering cancer research, the complexity of trials and the burden of information gathering and assessment make it difficult for them to participate. Patients need help and information that physicians may not have time to give.

What doesn't work

Traditional non-personal patient recruitment tactics that work for other disease states have had limited success with patients or physicians in increasing cancer trial enrollment. They are either not receiving or not motivated by messages from opt-in databases, optimized web search tools, oncology trial matching websites, and online cancer registries. Traditional media advertising casts too wide a net, stimulating the interest of far more unqualified than qualified patients whose queries must be reviewed by already overburdened investigators.

"Patients need help and information that physicians may not have time to give."

What DOES Work

Our research and analyses pointed to personal, trial specific peer level interaction with both research center and community oncologists as the key to success in improving accrual in oncology clinical trials.

For the cancer patient facing difficult treatment choices and the oncologist stretched to capacity, we concluded that what was needed was a return to the basics of collegial peer-to-peer interaction, information sharing and support in order to drive better rates of cancer trial participation.

We funded a one year effort effort, enlisting experienced oncology science and medical staff located in five "home" metropolitan areas, each focused on supporting 3–5 specific trials. Contacting both research sites and potential referrers (community oncologists) by telephone and face to face to discuss the details of the trials, answer questions and provide technical support, we concluded it was possible positively impact the accrual rates.

This approach can be economically viable, but as a small company we were unable to self fund the effort long enough to generate sufficient data to garner the support or funding from industry study sponsors. While profoundly disappointed, it is our hope that others will continue our line of inquiry, garner industry support and find the means to improve cancer research and the lives of those diagnosed.

About the author:

Ed Watson is Senior Director Corporate Development at Acurian Inc.— Acurian is a leading full-service provider of clinical trial patient enrollment and retention solutions for the life sciences industry.

Prior to joining Acurian Watson spent fourteen years at large pharmaceutical companies Glaxo SmithKline and Schering Plough and seven years in major industry consultancies. He holds graduate degrees from Wake Forest and Duke Universities.

How can we encourage physicians to refer patients to oncology clinical trials?