In 2001, Howard “Jack” West was in his final year as a medical oncology fellow at the Fred Hutchinson Cancer Research Center in Seattle, Washington, when he wanted to develop a clinical trial to test a molecularly targeted therapy for advanced bronchioloalveolar lung cancer. He knew that making the transition from clinician in training to lead investigator running a clinical trial would require expertise he lacked and an infrastructure he was unfamiliar with.
In an era of targeted cancer therapy, treatments that help some patients may not benefit others. Parsing data requires a sophisticated trial design that includes laboratory work. Such work, often called “translational medicine,” is considered the forefront of modern clinical trial design.
“It’s a lot for any single person to do and probably overwhelming for most fellows without that experience,” West says. So he applied for and was accepted to a then-new program run by the Southwest Oncology Group (SWOG), one of the handful of National Cancer Institute (NCI)–funded cooperative groups that design and run large clinical trials in cancer in the United States. During the training course, each early-career investigator completes a research protocol for a phase II or III clinical trial. “To be able to be walked through [the process] with a team of people who have walked that road before — that’s huge,” West says.
The SWOG course and a small handful of others are designed to teach young investigators the skills they need to design and carry out a clinical trial in cancer and to teach them where to find collaborators and mentors. There are other opportunities to learn these skills, too: Fellowships and university courses can also provide a strong foundation in clinical trial design. And there’s one key skill that applies whether you take a training course or not: finding mentors to help you through the process.
Participating in the SWOG workshop allowed West to put together a protocol design for a large multicenter phase II clinical trial, which became known as SWOG 0126. Writing the protocol, which would normally have taken many months, was completed in 3 weeks. Seven months later, the trial, which tested the effectiveness of a targeted epidermal growth factor receptor inhibitor in patients with advanced bronchioloalveolar carcinoma, was active and recruiting patients.
“In a large way, it helped define how I became identified and subsequently defined my area of expertise for the next decade,” says West, who is now a clinician at Swedish Medical Center in Seattle and remains an active participant in SWOG.
Participants spend the weeks leading up to the September workshop writing a rough draft of their proposal and completing an online component that introduces them to the intricacies of SWOG group membership and the procedures for reporting serious adverse events and quality-assurance audits. They then go to SWOG’s statistical center in Seattle for the intensive 3-day workshop. “At the meeting, a lot of the nuances of the study design are discussed, and all of the components of the protocol are brought together,” says Carolyn Hoban, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, who oversees the SWOG protocols in translational medicine.
Modern cancer clinical trials are costly and often take many years to complete. Their design usually has a primary goal or “endpoint” that, in the case of treatment trials, should provide the information required to make an informed decision about whether a treatment is safe and effective for patients. But in an era of targeted cancer therapy, treatments that help some patients may not benefit others. Parsing data requires a sophisticated trial design that includes laboratory work to characterize patient tumors using gene arrays, proteomics, and analysis of regulatory pathways, as well as complex statistical analysis of subsets of patient outcomes.
Such work, often called “translational medicine,” is considered the forefront of modern clinical trial design. Each year, Hoban teaches participants how to incorporate translational medicine approaches into their clinical trials. Participants learn how to ensure that a sufficient number of patients are recruited to ensure statistically significant results, how to choose the best endpoints to measure in the trial, how to build a list of resources, and how to meet all the regulatory requirements that accompany research in human subjects, among other topics. Because personalized therapy approaches often require collecting and maintaining tissue and blood samples for interrogation in the laboratory, participants also learn the logistics of biospecimen banking and how to ensure specimens retain their research value for years to come.
Learning how to incorporate molecular characterization of tumor samples into the study design was a particular help, West says. Coming from a clinical background, West didn’t have the experience necessary to design a lab-based protocol. But during the workshop, senior SWOG investigators helped make those connections for him. “You are actually plugging into this community of scientists,” Hoban says.
Beyond the SWOG course, the Methods in Clinical Cancer Research workshop, put on by the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR), is probably the best known short course designed to cover the essential elements of designing a cancer clinical trial. “I got to meet a lot of people who have continued to be mentors during my career,” says Heather Wakelee, who attended the ASCO/AACR workshop in 2002.
At the course, Wakelee, an oncologist at Stanford Cancer Center in California and an affiliate of the Eastern Cooperative Oncology Group (ECOG), was introduced to representatives from the pharmaceutical companies that made the compounds she wanted to test and provided the funding to support her first trial. “I found that [at ECOG] people were very supportive of me as an eager junior investigator,” she says.
At the time, her institution was developing its own immersive course in clinical trial development, which she participated in. Many institutions offer similar courses, including the Johns Hopkins Center for Clinical Trials and the University of Pennsylvania.
There are fellowships available through some professional organizations, such as one offered by the American Society of Hematology. Such fellowships give early-career researchers the opportunity to interact with leaders in their fields and to learn how to design and conduct clinical trials that incorporate a translational research component.
Through that mentoring process, “I learned to put together a question that could be asked in a clinical trial,” Wakelee says. In addition, through the mentorship process, she was given opportunities to lead data-analysis portions of larger clinical trials and get her feet wet without the responsibilities of running the trial. Through these mentored opportunities, she learned all the elements that have to come together to run a clinical trial, she says.
Getting her name out there in smaller studies also helped establish her professionally. And through ECOG mentor Joan Schiller, an oncologist at the University of Texas Southwestern Medical Center at Dallas, Wakelee was able to take the lead in developing a protocol to conduct a large phase III clinical trial examining adjuvant bevacizumab for the treatment of resected early-stage lung cancer.
“Good mentorship is the backbone of academics,” Wakelee says. “I’ve been very fortunate to find incredible mentors both at Stanford and in the larger lung cancer research community to guide me to this point in my career and am thrilled to now be able to act as a mentor for current oncology fellows. It is that continuum of learning and teaching which is part of what makes academic medicine such a wonderful career.”
The , put on by the American Society of Clinical Oncology and the American Association for Cancer Research, is held each summer in Vail, Colorado. The 1-week course accepts 75 clinical fellows and 25 clinical scientists each year. The American Society of Hematology and the European Hematology Association offerto help early-career scientists build careers in translational research. Selected fellows learn biostatistics, genetics and molecular biology, ethics, and phase I clinical study design. For medical fellows or new faculty at a member institution in the Southwest Oncology Group, theoffers a 3-day “boot camp” atmosphere to assist in quickly developing a clinical protocol. The National Cancer Institute maintains anto assist clinical trial design and development.