San Diego, CA—Patient-centered clinical pathways may hold the promise of truly personalized medicine, improving value-based care and clinical outcomes. However, according to Cary P. Gross, MD, Director, Cancer Outcomes, Public Policy and Effectiveness Research Center, Yale School of Medicine, New Haven, CT, substantial challenges still stand in the way of including the patient’s voice in these pathways.
At the 2019 ASCO Quality Care Symposium, Dr Gross discussed the crucial importance of incorporating the patient perspective in pathways, while highlighting the limitations of clinical evidence and pathways design.
“As the treatment landscape continues to grow in the era of precision medicine and targeted therapy, the clinical motivation for cancer pathways is greater than ever,” said Dr Gross. He cited a recent study of more than 6700 patients with advanced non–small-cell lung cancer that identified 44 different regimens that people were receiving in clinical practice.
“It’s still the Wild West out there in terms of treatment. Patients aren’t really impressed that there are 44 different treatment options they can receive. They want to know what’s best for them, which is why we need these pathways.”
Strength of Evidence Lack
Significant limitations are hindering providers’ ability to design and implement patient-centered clinical pathways, Dr Gross said. One of these limitations is the strength of evidence to support newly approved cancer treatments.
Between 2005 and 2012, the FDA approved 37 new cancer therapies for 39 indications, according to Dr Gross. After the initial approval of these drugs, 21 subsequent indications were added by the FDA, along with 16 off-label indications used by providers. However, even for the initial indications approved by the FDA, less than 50% were approved based on a randomized clinical trial, he said. Rather, the vast majority (82%) of FDA-approved indications were based on a surrogate outcome.1
A review of the National Comprehensive Cancer Network (NCCN) guidelines, which are often incorporated in clinical pathways and often use off-label recommendations, showed similarly low levels of evidence.2 Of the more than 1000 recommendations (comprising 10 different NCCN guidelines across multiple cancer types) reviewed in that article, less than 6% were supported by Category I evidence. Additional analysis of off-label recommendations by the NCCN showed that 36% of those had no evidence cited, and only 23% were based on a randomized clinical trial.3
“The evidence supporting guidelines, and therefore the evidence supporting clinical pathways in current practice, is quite shaky, which hampers our ability to tell patients with confidence which treatments are most likely to help them to achieve their outcome,” said Dr Gross.
“As a group, we need to strengthen our evidence base and make sure we’re answering questions that are relevant to patients. Although we’re never going to be able to run enough trials for every pair of treatments to see which one is better, we at least need to do so for the most commonly used ones,” he added.
Challenges of Pathway Implementation
ASCO’s vision for high-quality pathways, Dr Gross explained, is that they be developed by clinical oncologists, incorporating their understanding of the doctor–patient relationship. Although the foundation of pathways is drug efficacy, if 2 different treatment regimens offer similar efficacy, then the drugs’ toxicity profiles are brought to bear. Finally, cost is considered, although this poses an array of challenges.
“Cost is really challenging to incorporate, because it varies tremendously across patients, based upon their insurance status, their copay, even the time of year within their copay framework, as well as their own personal financial status,” Dr Gross said.
In addition, qualitative research has shown that patients vary dramatically in the themes that are important to them and the factors that will affect their decisions.
“Whether it’s physical concerns, psychosocial factors, family and treatment issues, concerns about prognosis or the healthcare system itself, clinicians must strive to incorporate individual patient goals into complex treatment decisions as we move ahead with pathways,” Dr Gross observed. “We need greater flexibility in terms of patient preferences and priorities, and pathway tools should incorporate patient-identified factors that can impact decision-making.”
Real-World Evidence Meets Randomized Trials
Despite the challenges that stand in the way of their implementation, clinical pathways offer unprecedented research opportunities, including the potential to capture head-to-head comparisons with patient-centered outcomes. According to Dr Gross, this does not necessarily mean sending patients to clinical trials of new medications, but rather ensuring that information about all patients is being gathered.
“We need to incorporate more point-of-care trials into clinical care,” said Dr Gross. “It would be great if we had pathways reconfigured so that instead of popping up with one or two suggestions, for drugs in which there is no clear separation, patients could be randomized at the point of care, and outcomes associated with specific treatments and being on or off pathway could be captured.”
“Real-world evidence does not necessarily mean that it’s not a randomized trial,” Dr Gross concluded. “We can bring those two worlds together.”
- Su KW, Gross CP, Downing NS, Adelson KB. Cancer therapeutic clinical trials supporting FDA approval and compendia inclusion. Am J Pharm Benefits. 2017;9:122-130.
- Poonacha TK, Go RS. Level of scientific evidence underlying recommendations arising from the National Comprehensive Cancer Network Clinical Practice Guidelines. J Clin Oncol. 2011;29:186-191.
- Wagner J, Marquart J, Ruby J, et al. Frequency and level of evidence used in recommendations by the National Comprehensive Cancer Network guidelines beyond approvals of the US Food and Drug Administration: retrospective observational study. BMJ. 2018;360:k668.