Cancer clinical trials yield crucial information about cancer treatment and care, and they have led to nearly immeasurable improvements when it comes to care and outcomes for people with cancer. But there's room for improvement. Enrollment on average across clinical trials is often lower than planned or needed and doesn't represent the diversity of patients with the cancers being studied. And even when clinical trials are successful, patients often receive better care (leading to better treatment outcomes) in trials compared to when treatment approaches are used in post-trial, real-world settings. The difference may be attributed to strict adherence to treatment protocols on trials or other infrastructural benefits of the clinical trial processes and support. This suggests there's an implementation gap in benefits between trials and real-world settings. That's why there's a need for implementation science to be applied to cancer trials, a group of cancer researchers argue in a recent article in the journal Cancer (2022; doi.org/10.1002/cncr.34357).
"By applying implementation science approaches, we propose that specific barriers to trial implementation could be identified, and targeted improvement strategies designed and adapted to work for different trials, sites, and populations," noted the article's lead author Kristian Stensland, MD, Clinical Instructor in the Department of Urology at Michigan Medicine at the University of Michigan. "Another advantage is the ability to robustly test how these improvement strategies work so that we can apply them in other settings in targeted ways," he noted. "All of this has the benefit of being built on top of a solid scientific foundation of implementation science that has been developed and tested in other settings, so we can rely on transferring those theories and proven methods over instead of constructing brand new approaches." Stensland shared how this approach would work and the upcoming work he and his team have planned.
1 Why did you write on the implementation science being applied to cancer clinical trial design?
"First, the importance of clinical trials has been brought into the public spotlight in the past few years with vaccines and treatments for COVID-19 during the pandemic, including challenges with designing and running trials. While in the oncology space [where] we're generally more familiar with clinical trials, our trials have also struggled in various ways. Our prior work has shown, for example, that about one in five cancer clinical trials will end early for noninformative reasons (J Natl Cancer Inst 2014; doi: 10.1093/jnci/dju229). There are a number of root causes for this, but a big one is low and slow enrollment to trials.
"Identifying these issues and figuring out how to address them is tough-and this is where the other timing factor comes in. We recently received funding from the National Cancer Institute to develop frameworks to help improve trials for participants, trialists, and other stakeholders. This commentary is an overview of our work and a direct result of that NCI funding."
2 What does "implementation science" mean and why is it important?
"Implementation science is an emerging field focused on improving the use of evidence-based practices. In other words (with respect to Geoffrey Curran's previous definition in the journal Implementation Science Communications), implementation science takes things we want people to do and figures out how to get people to do those things (2020; doi.org/10.1186/s43058-020-00001-z). "For example, we know that stopping smoking is good for you. Implementation science takes this evidence-based thing (smoking cessation) and figures out how best to get people to actually do it (that is, stop smoking). There are a number of implementation science frameworks that help identify barriers to doing evidence-based things, measure how well those things are done, and apply strategies to implement them better within different contexts. Ultimately, implementation science is looking at how best to find acceptable ways to get people to do beneficial things.
"Cancer clinical trials are similar to other evidence-based practices, like smoking cessation, in that they have proven beneficial effects to society and individual participants. In addition to advancing science and improving care for future people with cancer, participation in a clinical trial can be considered the best management for a person with cancer.
"However, despite these benefits, cancer trials often fail to meet their enrollment goals and primary endpoints, including some of our work showing how many cancer clinical trials end for noninformative reasons (one in five), and a third of completed urologic oncology trials do not meet enrollment goals (JCO Clin Cancer Inform 2020; doi: 10.1200/CCI.20.00031). Taken together, cancer trials are beneficial interventions suffering from poor implementation. Taking an implementation science approach could allow us to improve how trials are implemented, address problems when they arise, and better address the contextual needs of people with cancer, trialists, and other stakeholders."
3 What's important to know about integration of more implementation science into cancer research?
"[Our commentary] article is an overview of our proposed approach to using implementation science for clinical trials. We have some other work coming soon with more specific adaptations of frameworks and applications to clinical trials. Using this implementation language can be helpful to have a shared vocabulary for trial improvement so we can all be specific about what we're describing in our improvement efforts. Taking on other aspects of implementation for trials and rigorously studying them is also helpful for everyone involved in trials. And even if not formally applying frameworks and methods, being mindful of how clinical trials will be implemented and what that means for participants and trial staff could go a long way in improving trial conduct. One of the key aspects of this work and approach is to make it easier to get the best care possible for people who need it. For cancer care providers, our work will hopefully help lay a foundation to make participating in a trial easier and more acceptable for participants and providers."