Behind the Scenes: How Research Ideas become COG Clinical Trials
This is the first in a series of articles about how COG clinical trials come to be.
Future newsletters will delve into how the concept of a clinical trial becomes a protocol, different types of clinical trials, and more.
Future newsletters will delve into how the concept of a clinical trial becomes a protocol, different types of clinical trials, and more.
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Children’s Oncology Group (COG) researchers are constantly coming up with new ideas to study cancer in children. But how exactly do those ideas evolve into clinical trials that break new ground in treating kids with cancer? The answer: a rigorous process of considering research ideas from every possible angle, so that only the very best ideas move forward.
Pediatric cancer treatments have come a long way in recent decades. But doctors who treat pediatric cancer are keenly aware of the limits and drawbacks of today's treatments. So they're constantly looking for ways to make current treatments better and develop new, more effective treatments with fewer side effects, so that more kids can live long, healthy lives.
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It’s one thing to have an idea. It's another thing to decide whether that idea is promising enough to justify an extensive research process that could take years to run, cost hundreds of thousands of dollars — often millions — and require testing in children.
“The process of vetting a research idea involves intense review and collaboration by many experts, inside and outside of COG, to make sure there's a critical mass of scientific evidence that a clinical trial might work, that it answers an important question to improve therapy, and addresses a compelling, unmet need,” said Jeffrey Dome, MD, PhD, Senior Vice President of the Cancer and Blood Disorders Center at Children’s National Hospital in Washington, D.C.
Dr. Dome led the COG Renal Tumor Committee and now serves as a member of the COG Scientific Council, made up of senior COG leaders who have extensive research experience and review every idea that becomes a COG clinical trial.
Dr. Dome led the COG Renal Tumor Committee and now serves as a member of the COG Scientific Council, made up of senior COG leaders who have extensive research experience and review every idea that becomes a COG clinical trial.
STEP 1: Committees come up with an idea
It can take months to years of painstaking vetting before a research idea is ready to be formally presented to the Scientific Council for review and approval. Three types of COG committees generate ideas and gather data to bolster research concepts during this first phase of the process:
- Disease committees are multidisciplinary teams that focus on a specific type of cancer, with representation from multiple disciplines (i.e., surgeons, medical oncologists, radiologists, nurses, statisticians, and others).
- Domain committees have thematic areas of focus that encompass different disease types. Examples include epidemiology, stem cell transplant, and developmental therapeutics (i.e., studying new drugs to treat cancer).
- Discipline committees represent a single type of medical professional (i.e., pathologists, radiologists, epidemiologists, patient advocates, and others).
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“We all think of things from a different perspective,” Dr. Dome said. “The ideas we develop into clinical trials have some aims that surgeons recommend, some questions that pathologists want answered, some chemotherapy questions, some radiation therapy questions … so a trial is a compilation of the input from all these different disciplines.”
These committees typically meet once a month and review research ideas at each meeting. In some cases, they’re reviewing an idea for the first time. Other times, they’re revisiting an idea after multiple rounds of feedback. The chair of a committee appoints a task force with leaders to develop and assess the pitfalls of an idea giving it a better chance of being funded and succeeding once it becomes a clinical trial. Task force leaders often assume the roles of study chair or vice-chair as an idea evolves into a clinical trial.
“You want to make sure every stakeholder who should be represented is represented,” said Jennifer Foster, MD, MPH, a neuroblastoma researcher at Texas Children’s Cancer Center, and member of COG’s Neuroblastoma, Cancer Control and Supportive Care, and Developmental Therapeutics Committees. |
What's In a Name?
This simplified graphic gives an overall understanding of COG clinical trial names. There are exceptions: the last 'number' is sometimes a letter, as in 'P' for pilot. Additionally, Pediatric Early Phase Clinical Trials Network (PEP-CTN) studies start with PEPN.
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STEP 2: Researchers draw up a clinical trial concept summary
Once a committee reaches consensus that an idea is strong enough to move forward, it’s time to draw up a concise, high-level overview called a clinical trial concept summary to gauge initial interest in their idea and how feasible it might be.
This step pulls together all the key considerations committee members have discussed in their meetings — the research question, target population, the treatment or procedure that will be tested, and expected outcomes.
Once a concept summary gets a thumbs-up at the committee level, it goes to the COG Scientific Council.
Once a committee reaches consensus that an idea is strong enough to move forward, it’s time to draw up a concise, high-level overview called a clinical trial concept summary to gauge initial interest in their idea and how feasible it might be.
This step pulls together all the key considerations committee members have discussed in their meetings — the research question, target population, the treatment or procedure that will be tested, and expected outcomes.
Once a concept summary gets a thumbs-up at the committee level, it goes to the COG Scientific Council.
STEP 3: COG Scientific Council reviews concept summary
Senior leaders on the COG Scientific Council bring decades of experience running clinical trials to their analysis of research ideas. They meet twice a month, asking critical questions about every aspect of each concept they consider:
Senior leaders on the COG Scientific Council bring decades of experience running clinical trials to their analysis of research ideas. They meet twice a month, asking critical questions about every aspect of each concept they consider:
- Is there sufficiently compelling background to support the primary objectives of the study?
- Are the primary objectives and theories about potential outcomes on point and clearly stated?
- Are the secondary aims (e.g., addressing potential side effects or differing effects in subgroups) justified?
- Are the criteria for including or excluding patients appropriate?
- Have researchers ruled out any significant feasibility issues, such as competing studies on the same population?
If the answer to those and other key questions is yes, the Scientific Council approves the concept summary, which research leaders then develop into a full concept proposal that undergoes further Scientific Council review.
There are often several iterations of a concept summary that go between the committees and Scientific Council on its way to becoming a full concept proposal outlining the concept in greater detail. The Scientific Council is the final set of eyes that reviews a trial concept before it gets pitched outside of COG’s walls.
There are often several iterations of a concept summary that go between the committees and Scientific Council on its way to becoming a full concept proposal outlining the concept in greater detail. The Scientific Council is the final set of eyes that reviews a trial concept before it gets pitched outside of COG’s walls.
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STEP 4: Full concept proposal goes to National Cancer Institute (NCI)
The National Cancer Institute (NCI), part of the National Institutes of Health (NIH), is the largest funder of cancer research in the world. Leading experts in their fields serve on NCI Scientific Steering Committees, which focus on specific types of cancer and domains of research — gauging the strength of research concepts just like the COG Scientific Council does. A clock starts ticking with this step, and researchers have up to a year and a half (400 to 540 days, to be precise) to clear the final approval hurdle and open a clinical trial. From this point on, there’s lots of back-and-forth communication between the NCI and COG. Once the NCI approves the full concept proposal, it’s time to develop the full protocol for a clinical trial. STEP 5: Researchers develop full protocol for clinical trial
Clinical trial protocols are the all-encompassing road maps that outline research goals, which patients are eligible, methodologies for tests and treatments, safety considerations, data management plans, a timeline — everything about how a trial will be conducted. Once the NCI OK’s a full protocol, it advances to the finish line of a research idea’s marathon concept to actual clinical trial. The NCI’s Central Institutional Review Board (CIRB) combs through every aspect of the protocol to make sure the trial will meet the highest ethical standards. |
Clinical Trial Phases
Phase 1 studies are the first step in testing a new medicine. They focus on finding the best dose to give patients. Sometimes, these new drugs are tested on their own, and other times they are tested together with other drugs.
Phase 2 studies look at how well the new medicine works for patients who have a specific type of cancer or a certain genetic change. These studies often involve patients whose cancer has come back, but that’s not always the case. Phase 3 studies are larger and aim to show clearly whether the new medicine or combination of medicines helps patients more than existing treatments. In these studies, patients are usually randomly assigned to receive either the new treatment or a standard treatment for comparison. Sometimes, they might compare the new treatment to past patients who had similar conditions. |
As the CIRB reviews a protocol, the COG Operations Office works with the study committee to develop case report forms that participating institutions fill out to provide data on the demographics of study participants, information about the tumor such as disease stage and size, treatment response, and toxicity.
After the CIRB approves a protocol and the case report forms are complete, the study is ready for activation. At each hospital or research center participating in the trial, institutional principal investigators then decide whether to activate the studies at their own sites.
About a dozen ideas for COG clinical trials go through this process each year. Most become clinical trials, Dr. Dome said, noting that in many cases, “we start anticipating the next study before the current study opens. We’re always thinking ahead.”
As the CIRB reviews a protocol, the COG Operations Office works with the study committee to develop case report forms that participating institutions fill out to provide data on the demographics of study participants, information about the tumor such as disease stage and size, treatment response, and toxicity.
After the CIRB approves a protocol and the case report forms are complete, the study is ready for activation. At each hospital or research center participating in the trial, institutional principal investigators then decide whether to activate the studies at their own sites.
About a dozen ideas for COG clinical trials go through this process each year. Most become clinical trials, Dr. Dome said, noting that in many cases, “we start anticipating the next study before the current study opens. We’re always thinking ahead.”
