Clinical Pathways Congress

The second annual Clinical Pathways Congress (CPC) was held over the weekend of September 8th in Washington, DC. A diverse group of stakeholders representing patients, providers, payers, and the pharmaceutical industry gathered to hear and share perspectives on the development and implementation of clinical pathways across various disease states. CPC, which was moderated by Alan Balch, PhD, chief executive officer of the Patient Advocate Foundation, featured more than a dozen presentations and lectures on various topics within value-based care. Highlights included a mock clinical pathways development session facilitated by Bruce A Feinberg, DO, Journal of Clinical Pathways (JCP) Editorial Advisory Board member and chief executive officer and vice president of clinical affairs at Cardinal Health Specialty Solutions.

JCP staff were on hand to cover the meeting and engage with stakeholders throughout the weekend. We encourage all who are able to attend next year’s CPC, which will be held October 26-28, 2018, in Boston, MA!

Can Clinical Pathways Support Person-Centered Care and Improve Outcomes?

Clinical pathway development needs to better take into account the patient perspective of cancer care, according to Dr Balch.

Representing the Patient Advocate Foundation, Dr Balch gave a presentation to clinical pathway developers and stakeholders regarding the inclusion of patient preferences into the pathway decision-making process. The objectives of his lecture were to relay the importance of designing decision support tools that can identify appropriate variations in care, as well as explaining how clinical pathways can support shared decision-making and clinical judgment.

Dr Balch began with sharing his belief that personalized care is the future of oncology care. A personalized approach, he shared, is more consistent with multiple factors emerging in oncology care, such as precision medicine, cost shifting to the patient, payment models shifting from volume to value, and IT interfaces and mobile technology. Disease and illness are very personal and vulnerable experiences for the patients, Dr Balch explained, and personalization helps identify appropriate variation in care based on the unique characteristics of the individual patient. A personalized approach should result in better outcomes at a lower cost, because “it allows the right treatment to be applied to the right patient at the right time.”

In a survey deployed to a sample that was representative of the total served population (n = 1349), Dr Balch found that most patients consider personalized care to be extremely important (83%) and that 96% of patients would choose personalized care over standard care.

Continuing his discussion of patient-centered care, Dr Balch explained that cost is simply one component of how individual patients determine quality of care. What matters most will vary from patient to patient and will change over time. Understanding the patient’s concept of quality as it relates to cost, benefits, and risks of care requires both hearing the individual patient voice in patient/provider interactions and the collective voice through data collection and analysis.

Dr Balch stressed that all patients are capable of making shared decisions about their care—regardless of their health, social status, or health literacy—and they all expect and deserve respect.

The discussion then shifted to decision support tools. Dr Balch explained that decision aids are useful for when there is more than one suitable option for care, when no option has a clear advantage, and when each option has benefits, harms, and costs that patients may value differently.  The care team must identify and apply patient goals, needs, and preferences to align with choices about treatment options personalized to benefits, risk, and costs. Adjustments must be made for certain variable that may impact appropriate treatment selection as well (ie, race/ethnicity, transportation, genetics, financial toxicity).

Once decision support tools have been considered, the development of a goal-concordant care plan is needed that includes identification of social support and care navigation needs.

A truly person-centered decision support tool involves the individual patient’s health and quality of life; a focus on what matters to the patients; engaging the patient to help arrive at a care regimen that reflects the balance that is right for them between benefit, risk, and cost; and measuring outcomes that matter to the patient, as well as involving the patient in selecting and reporting those outcomes.

Dr Balch concluded this part of the discussion with how person-centered care and decision support tools can be implemented in clinical pathways. In his words, properly designed and implemented pathways should support clinical evidence-based judgment, help customize treatment and care protocols to the unique characteristics of the patient, reduce costs and variability in care, and navigate patients through various health care decisions (ie clinical trials). It is essential for patients to be reassured that pathways are not simply a “hidden tool” to steer them to a limited range of treatment options preselected by an external stakeholder based on cost savings, he said.

Additionally, Dr Balch recommended that pathways should be assessed for their ability to improve quality of care, be based on efficacy and safety while also incorporating relevant personalized drivers, allow for variance in the clinical and biological characteristics of individual disease processes, use total cost of care only as the final factor in defining initial on-pathway selection, and enable patients—with their providers—to consider additional cost information as a secondary step in the process.

Biosimilars: The Next Big Thing in Oncology Clinical Pathways?

Biosimilars occupy a huge place in the oncology treatment conversation these days. But what are they exactly, and how will they impact clinical pathways?

Gary H Lyman, MD, MPH, professor of medicine, public health, and pharmacy at University of Washington School of Medicine (Seattle, WA), and Robert M Rifkin, MD, clinical associate professor of medicine at University of Colorado Denver (Denver, CO), addressed these questions.

Biosimilars are drugs shown to be highly similar to a reference product. They differ from generics, which are exact copies of their reference product, because they are produced by living cells and are constructed of large molecules. A mainstay of medical management in Europe for more than a decade, the Food and Drug Administration (FDA) approved the first biologic product in the United States in 2015.

There are currently six biosimilar products currently approved by the FDA or in the approval pipeline, according to Dr Rifkin.

Data from Dr Lyman’s presentation show a marked increase in medication costs between 1965 and the present day, with the sharpest increases occurring within the last 15 years. Biosimilars, which provide a nearly identical product to reference drugs, are seen by many as a potential cost control measure as drug prices continue to rise. “Expensive treatments make appropriate cancer care a hardship of unaffordable,” Dr Lyman said.

But the interest in biosimilars has not come without some questions and knowledge gaps, according to Dr Rifkin. These include variability and drift, since no batch of biosimilars can be said to be exactly the same; immunogenicity concerns, which can have clinical consequences; and the potential for rare but serious adverse events. Pharmacovigilance will play an important role in the integration of biosimilars into standard clinical pathways.

“Postapproval pharmacovigilance for efficacy and safety of biologic agents is of particular importance when considering biosimilars,” Dr Rifkin said. “Biosimilar manufacturers should work early with the FDA to develop an approach.”

Drs Lyman and Rifkin believe that biosimilars will quickly earn a place in oncology clinical pathways as they continue to be approved by the FDA. However, they identified potential barriers to this adoption, including physician resistance, lack of patient incentive, and pushback from professional societies. Still, they found numerous benefits for adding biosimilars to the pathway conversation, including the addition of more low-cost treatment options to the oncology armamentarium; global savings for the health care system; the fostering of further research in the area of biologics; and equivalent or better overall health care outcomes.

“Do pathways add value?” Dr Rifkin asked. “I think they do. And pathways and biosimilars are a perfect fit.”

Emerging Treatments and Evolving Pathways for Chronic Lymphocytic Leukemia

Jennifer R Brown, MD, PhD, director of the Chronic Lymphocytic Leukemia Center, Dana-Farber Cancer Institute (Boston, MA), presented the emerging treatments and management options for frontline and relapsed or refractory chronic lymphocytic leukemia (CLL).

The goals of the presentation were to explain the significance of CLL biomarkers and staging in prognostic assessment and subsequent treatment decisions, as well as to evaluate efficacy and safety data of novel CLL agents with respect to age, comorbidities, and overall health.

Dr Brown began her discussion by explaining that while high-risk CLL is conventionally defined solely by clinical features—such as stage, lymphocyte doubling time, and therapy resistance—biologic prognostic factors are becoming increasingly important. In particular, Dr Brown referenced fluorescence in situ hybridization (FISH), TP53 mutation, and IGHV mutation. She cited 17p deletion as one of the worst prognostic indicators and indicating high-risk CLL.

Among high-risk CLL determinants are patient factors (ie, age and comorbidities) and biologic factors (17P, UM, 11q, B2M).

Dr Brown then moved the discussion into the evolution of conventional treatment pathways for previously untreated CLL. While the early 2000s featured chemo-immunotherapy agents (ie, alemtuzumab monotherapy and bendamustine), recent years have witnessed a rise in novel agents (BCR/BCL-2 inhibitors).

In reference to the best available treatment for previously untreated disease, Dr Brown highlighted various studies that have demonstrated the benefits of ibrutinib. These studies further strengthened the prognostic value of 17p deletion, TP53 mutation, and IGHV mutation status. Additionally, the combination chemotherapy regimen of fludarabine, cyclophosphamide, and rituximab has shown the ability to prolong survival in physically fit patients.

According to Dr Brown, ibrutinib is clearly the standard of care for upfront therapy in 17p deleted CLL, given the currently available data. However, ibrutinib’s effectiveness as a single agent is “unsatisfying,” due to the continuous relapse data seen in any trial with long-term follow up. No combination data in an upfront setting exist, and “17p remains an unmet need not yet adequately addressed in clinical trials.” Another issue in regard to ibrutinib as an upfront therapy is that the existing data stems from a nonrepresentative population of healthy, older patients with low-risk disease.

“We’re not seeing in clinical practice the same rate of continuation and progression free survival as in the trials,” Dr Brown commented.

The discussion moved into the best option for heavily pretreated relapsed or refractory CLL. Dr Brown cited numerous studies that suggest single-agent venetoclax as the most data-supported therapy. Not only has venetoclax shown to achieve an objective response rate (ORR) of 76% in a study, but its activity is preserved in 17p deleted patients and those who have progressed on ibrutinib or idelalisib.

As for whether new biologic agents should replace traditional chemotherapy, there are many factors to consider. Biologic agents are well tolerated and highly effective even in high-risk disease, but at the expense of increased toxicity, increased cost, and the unknown ability to salvage after relapse. To address the negative aspects of biologic agents, Dr Brown suggests implementing risk-adapted frontline therapy and to study combinations that induce effective, well-tolerated, deep remissions. Achieving these would appeal to the patients’ preference, reduce long-term side effects, reduce costs significantly, and improve the likelihood that subsequent relapse will still be sensitive to prior agents.

While the treatment landscape for CLL has yet to lend itself to a clinical pathway due to a lack of long-term follow-up data, Dr Brown concluded her discussion by commenting that she would like to see clinical pathways designed for CLL take into consideration age stratification, risk stratification, and FISH testing.

ASCO’s Role in the Future of Pathways

Perhaps more than any other specialty, clinical pathways have taken the oncology world by storm. Approximately 170 million covered lives in oncology are potentially impacted by clinical pathways, representing 57% of the patient population. The American Society of Clinical Oncology (ASCO) has taken notice, and has actively participated in the conversation surrounding clinical pathways.

Robin T Zon, MD, FACP, FASCO, JCP Editorial Advisory Board member and hematologist/oncologist with Michiana Hematology Oncology (South Bend, IN), and Robert Daly, MD, medical oncologist at Memorial Sloan Kettering Cancer Center (New York, NY), highlighted ASCO’s ongoing commitment to clinical pathways. Dr Zon chairs ASCO’s Clinical Pathways Task Force, and Dr Daly was one of ASCO’s inaugural health policy fellows.

According to ASCO data, the percent of practices practicing in clinical pathways has precipitously risen in recent years, from 16% in 2014 to 58% in 2016. Dr Zon identified “the potential to protect patients” as a major reason for the increased uptake in pathway use. “Pathways can reduce variation in treatment and protect against over-, under-, or mistreatment,” she said.

ASCO’s interest in clinical pathways has largely centered around ensuring that oncologists can continue to provide the best possible care to their patients. Areas of concern within clinical pathways identified by ASCO include administrative burdens, a lack of transparency, and patient autonomy. “We want to be sure that doctors are caring for the patient, not the pathway,” said Dr Zon.

To this end, ASCO published nine recommendations to improve the development and use of clinical pathways in 2016. These criteria for high-quality pathways center on expert-driven pathway development, clear and achievable goals and outcomes, and outcomes-driven results.

However, questions remain about the ideal development of pathway programs, and many have identified potential issues that must be addressed. In his portion of the talk, Dr Daly focused on research into conflicts of interest among pathway developers at three major firms. He found that between 69% and 92% of voting members at United States pathway vendors received an industry general payment in 2015. These payments may negatively affect perceptions of clinical pathways, Dr Daly said.

The future of clinical pathways are necessary to ASCO’s mission of fostering the highest level of oncology care around the world, according to Dr Zon. “We are in a field that uses very expensive diagnostics and very expensive drugs,” she said. “We need to promote education, information, and transparency as we move forward.”

One future area of interest for ASCO is a California state legislation bill called The Oncology Clinical Pathways Act of 2017, which would “prohibit a plan or health insurer from, among other things, developing or implementing a clinical pathway that discourages clinical pathways or interferes with the independent clinical judgment of a provider.”

ASCO supports this legislation. In an official statement, Daniel F Hayes, MD, the organization’s then-president, called the bill “a critical first step towards ensuring that the process for developing oncology clinical pathways is consistent and transparent.” The bill is currently being held in the state appropriations committee, with no further legislative action expected in 2017.