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By Brenda Noggy
Engaging patients and removing barriers to patient participation in clinical trials is critically important to the development of new therapies to improve human health. If you’re reading this article, you know that, on average, only five percent of adult cancer patients participate in clinical trials. You might not know that trial enrollment numbers are much lower outside of academic settings. In fact, most community cancer centers enroll only one percent of their patients in trials.
Addressing this gap is one of the keys to conquering cancer given that more than 80 percent of newly diagnosed cancer patients receive treatment in community settings. If you consider that more than 1.8 million new cancer cases were expected in the U.S. by the end of 2021, the enormity of the problem, and the opportunity, is clear.
Patients are interested in exploring participation in clinical trials. When given the option of enrolling in a trial, as many as 55 percent of cancer patients are willing to participate, according to researchers from the Fred Hutchinson Cancer Research Center in a study published in the Journal of the National Cancer Institute in October 2020.
However, patients face multiple barriers to participation. They include institutional, clinical trial design, provider and patient factors.
It is important to understand how critical cancer providers are to introducing potential trials to their patients. Cancer patients are faced with myriad fears, anxieties and uncertainty about their diagnosis, survival, and treatment options. Providers want to provide the best treatment options to their patients.
Unfortunately, many patients are never offered the option of enrolling in a clinical trial. Or, if given the option, it’s presented as a last resort. By the time many patients start considering clinical trials, they are often heavily pretreated or quite sick. Both decrease their likelihood of qualifying for a clinical trial.
To introduce trials to patients at initial contact, along with standard of care treatment options, we need to change outdated perceptions of the role of clinical trials in care. We also need to overcome administrative barriers that hold treating physicians back from offering clinical trials. We need to do this without adding additional burdens to physicians’ workload, and leverage technology to maximize efficiency. If we get this right, we can achieve multiple aims, including increasing patient diversity in trials.
No longer a ‘last resort’ and the evolution of trial design
It is important that everyone who has a role in clinical research work to dispel the popular misconception that clinical trial participants are “guinea pigs,” or that trials are a “last resort” and the option should be for patients who have failed all other treatment options.
The advent of precision or personalized medicine, immunotherapy and targeted therapies are starting to dispel these ideas.
Clinical trial designs have evolved along with advances in cancer medicine. Many trials in the neoadjuvant and adjuvant categories can be given to patients at the time of diagnosis or early in their cancer treatment journey, with better quality of life and even curative results.
In the breast cancer space alone, the FDA has approved more than five drugs as first line treatment in newly diagnosed and advanced metastatic settings. That means patients who participated in the trials had better outcomes compared to patients with the same diagnosis who received standard treatments. In lung cancer, at least 10 therapeutics were approved recently, five in immunotherapy and five in targeted therapy, all as first line treatment.
Trial design is evolving as well. Many trials are now designed to keep patients’ and investigators’ needs in consideration, allowing for more screening time and flexibility in visits to minimize deviations. Later phase oncology trial designs can provide two treatment arms, as described earlier, where 50 percent of patients receive standard of care with the other 50 percent receiving an investigational therapy.
There are also “basket” trials. These are multi-arm trials based on genomics instead of the cancer’s origin site. Patients may be diagnosed with various types of cancer, and grouped based on biomarkers, accelerating the trial process.
This evolution in trial design will continue as genomic characterization continues to become standard of care for many types of tumors. Yet only a small minority of cancer patients are enrolled in basket trials, and these trials remain largely concentrated in academic research institutions.
It’s no longer science that’s holding us back. The next great leap for cancer research will depend on our ability to address what the Fred Hutchinson researchers identified as structural and clinical hurdles, and to bring trial options to patients earlier, and in fact at the beginning of their journey.
Overcoming provider challenges
Let’s be pragmatic. It takes a village to run complex oncology clinical trials. Many of our providers, particularly our community-based physicians, are already struggling with clinical staffing support in their busy practices. It is simply not feasible to insert the additional rigors of clinical trials into their normal course of care. These frontline physicians are entitled to support, to make it as easy as possible for them to conduct, implement or refer patients to clinical trials.
Here are some of the key challenges:
Clinical Trial Training
Community oncology centers provide care to a wide range of cancer patients, and this broad mission may not allow for a defined specialty.
If a physician does not feel they’ve mastered trial treatment regimens for specific types of cancer, they may want to take care in what they introduce to patients. They may conclude the patient is best served by a known standard of care treatment regimen, one with which they are well versed.
It requires time to train and familiarize a physician to best serve patients through the different components of a clinical trial protocol. Good Clinical Practice training has become the industry standard to ensure we have qualified investigators. However, this is not enough to guarantee compliance, there is a need for investigator mentorship and training opportunities. Opening training for our providers on the benefits and challenges of clinical trials is crucial.
The screening process takes time. Providers do not want to discuss clinical trial treatment options without making sure the patient is at least eligible on the major criteria and is a good fit for the trial. Time is of the essence when providers have a full clinic, and they may not have the time to look for a trial match.
We must allow for dialog on treatment options. Trial explanation takes time. Comparing the trial versus standard of care options, the pros, and the cons, and citing previous trial data requires time and effort and can delay the clinical workflow. The consenting process takes an average of two hours for oncology treatment trials. If you multiply that across the number of newly diagnosed or relapsed patients seen on any given day, the number of patients that can be seen drops dramatically.
Competent clinic and research staff are needed to ensure all the checks and balances are in place for quality protocol management and patient care. It is of utmost importance that the clinic is running smoothly. Otherwise, it is difficult to insert the research process in a chaotic clinic workflow.
But additional staff requires investment and represents a budgetary risk if clinical research does not become a sustained part of the practice and its economics.
Referring doctors in the community setting may be hesitant to refer patients to a trial institution for fear they might lose their ability to support their patients if they are referred to clinical trials at another location.
Referring providers will need to understand that in most trials, the trial sponsor will cover for the research visits. And patients can still make regular standard of care visits and consult with their referring doctors. That will most likely be covered by the patient’s insurance.
The patient will also have the benefit of multiple oncology experts. When patients are off the study for any reason, they will have the option to stay in the trial center to continue their care. But they will typically opt to return to their primary oncologist.
Leveraging Technology in Research
With the rise and integration of new technologies into clinical trials, the right technology impacts the quality and efficiency of patient screening for clinical trials.
Artificial intelligence has the power to address many of the operational and clinical hurdles that continue to slow the process of patient identification. Perhaps most important is the power of technology to save time. The work of patient matching, which typically requires human experts spending hours reviewing patient data against trial options, can now be done almost instantly. If patient data is uploaded to platforms which can match their eligibility, the process becomes easier for physicians and researchers.
It is unfortunate that big data technologies life sciences companies have available to accelerate research are out of reach for most cancer centers, who continue with manual processes. Site research process automation is often only available to sites with the funding, staffing resources and experience to use it.
In the end, we cannot lose focus on the fact that if tomorrow’s clinical trial treatment options are to fulfill their promise, patients must all have access to all treatments today, including trials regardless of race, gender, or socio-economic status.
Providers swear an oath to always do what’s best for their patients. But they are working in the real world, within a variety of constraints. If we are going to close the gap between the five percent of adult cancer patients enrolling in trials and the 55 percent who are open to it, it’s going to start with helping our oncology practices.
The sooner that we can provide our patients with clinical trials as an option at the beginning of their cancer treatment journey, the sooner we can empower them to choose the right treatment that will offer them the best disease outcomes and, in the process, help advance the science and innovation in cancer research.
Brenda Noggy is Executive Director of Cancer Center Development and Deployment at Inteliquet.