The Value of Regulatory and Healthcare Policy Changes in Oncology Care

Evidence-Based OncologyPeer Exchange: Spring 2017 Oncology Stakeholders Summit

At the The American Journal of Managed Care®'s Spring 2017 Oncology Stakeholders Summit, the discussion touched off-label communication, the evolving clinical trial design, and healthcare reform, all while ensuring care is patient-centered.

With a new administration in Washington, DC, change is expected over the next year, including a new direction in healthcare policy. Although the American Health Care Act (AHCA) failed to garner support from the House of Representatives in March, Republican efforts to replace the Affordable Care Act (ACA) are expected to continue. Concurrent changes within the drug regulatory body are expected—policies that will provide wheels to the FDA’s slow-moving drug approval process.

At its Spring 2017 Oncology Stakeholders Summit, The American Journal of Managed Care® hosted Robert W. Carlson, MD, CEO of the National Comprehensive Cancer Network (NCCN); Elizabeth Carpenter, senior vice president, Avalere Health; John L. Fox, MD, associate chief medical officer, Priority Health; and Bhuvana Sagar, MD, national medical director, Cigna Healthcare, to discuss how these changes will affect how a patient receives care in the clinic. The discussion was moderated by Joseph Alvarnas, MD, director of value-based analytics and associate clinical professor in the Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, in Duarte, California, and editor-in-chief of Evidence-Based Oncology™.

Off-Label Communication

The conversation began with a discussion around the level of evidence and the scope of off-label communications, which the FDA has been openly pursuing. The FDA even conducted a public hearing in November 2016 to gather input as it continues to review its policy prohibiting the promotion of FDA-approved drugs for off-label uses.1

Carlson explained that the FDA buckets off-label communication into health economic information—which, he said, might be of most interest to payers and pharmacy and therapeutic (P&T) committees—and off-labelled indications, meaning “uses of the drug for which there is a label, but using them in circumstances or situations where the drug is active, presumably, but not actually, on the label.”

The FDA has made available an updated draft guidance,2 which Carlson said provides specific criteria on appropriate off-label communication between the pharmaceutical industry and the provider, payer, and patients. With both scientific and legal issues surrounding off-label communications, Carlson said that with patient safety as its top priority, the FDA wants to ensure appropriate communication that is not false or misleading.

As for vetting this information for accuracy, Carlson told Alvarnas that the pharmaceutical industry, fearing legal backlash, has not provided much healthcare economic information to P&T committees, and drug companies are extra cautious with the off-label information. The FDA’s guidance in this regard, Carlson said, says that such information:

  • Should not be derived from a primary request by a company, such as an article written and funded by industry
  • Should be readily available in the public domain

Healthcare Costs

Fox, citing concerns with the health economics data provided by the pharmaceutical industry, brought up the conflict that is introduced for a company’s health economics and outcomes research (HEOR) department, which often claims that the product will reduce healthcare costs. “If everybody reduces the cost to the degree that they said, healthcare would be free, I think,” Fox said. To ensure that the health economics data reviewed by a health plan is valid, Fox would like to see HEOR data generated by an independent, unbiased source. He added that the FDA opening a door for increased communication may not “make life any better or the information any more credible.”

Fox drew attention to the NCCN Guidelines, which he said is information vetted by experts and is readily accessible to everyone, including health plans, especially information on the safety and issues related to drug administration. Using this comment as a segue, Alvarnas was curious about the level of evidence that a manufacturer should share with physicians.

Carlson noted that for a new drug, there will be a significant amount of evidence available for the on-label indications. “Unapproved does not mean unproven,” he added, explaining that off-label evidence for a drug might be equally good. As data emerge on older off-patent agents that support off-label indications, “someone who had a vested interest in getting a labeled indication could do so,” Carlson said. The motivation is stunted by the fact that it would require generating high-level data for drugs that are now less expensive and may not yield much profit.

Does this assist or obstruct patient access? “It varies by state,” Fox replied, adding that in Michigan, where Priority Health operates, all FDA-approved drugs are covered. Off-label indications are covered if a physician can provide documentation in the form of 2 peer-reviewed articles for the indication or if the indications are included in a compendium, such as the NCCN Compendium.3 “Most health plans today will cover that as long as it’s in the Compendium, as will Medicare,” Fox added.

Carlson emphasized the importance of considering the “totality of evidence,” because peer-reviewed literature may not always be credible. “Having a therapy in the peer-reviewed literature does not necessarily mean it’s an appropriate therapy, even if that study shows advantage, because it may be poorly conducted, poorly analyzed, [or] may not include a meaningful endpoint,” he added.

Drug Price Policy

Looking at the bigger picture, would off-label information assist with formulary management and healthcare costs? Carlson said that off-label communication would mainly be available for patent-protected drugs because generic manufacturers do not gain much to communicate such information to payers or providers. For Fox, the bigger challenge is dealing with decisions made when information is taken out of context. “While off-label indications may not impact the practice of medicine, if physicians take this out of context, it could have a deleterious effect on patients when we have better evidence to support alternative therapies,” he said.

Alvarnas asked Carpenter to share her thoughts on how the new administration might address drug costs, since prices have been on President Donald Trump’s radar since the early days of his campaign. Carpenter agreed that although Trump has been outspoken about the role of drug prices, “perhaps more fascinating and challenging for the pharmaceutical industry is what’s going on at the state level.” She cited New York as an example of a state that passed legislation to create a drug price control program within Medicaid.4 During his 2017 State of the State address in January, New York Governor Andrew Cuomo announced a 3-pronged approach: protecting the Medicaid program from prescription price overcharge, a surcharge on manufacturers that charge exorbitant prices, and protection from intermediaries who cause a spike in drug prices.

Lack of competition creates an uneven playing field, Fox said. “What we see typically is that with each new incremental improvement, the 6 weeks of overall survival (OS) or progression-free survival (PFS), that there is a nonincremental price increase,” he added, voicing his support for Medicare to negotiate drug prices, which, he added, would be a game changer since most payers follow in Medicare’s footsteps.

According to Carpenter, there’s a broad spectrum to government negotiation of drug prices: on one end is the President who is very active on social media and on the other end is the government negotiating drug prices for all drugs and plans in the Medicare market, which she thinks is not likely to happen. In place of such blanket policy changes, Carpenter thinks the government might consider negotiating prices for medications that do not have market competition and demand a major share of federal spending. She said the Center for Medicare & Medicaid Innovation, created by the ACA, could provide a good vehicle for this process, independent of Congressional approval.

Whereas Alvarnas does not see this movement gaining much traction, Carpenter said more action at the state level seems likely. She also brought up the impact of third-party negotiators, such as pharmacy benefit managers (PBMs). “One of the big debates that we’ll see transpire is, should the government be the one negotiating drug prices or should the private sector, whether it’s a PBM or some other kind of third-party entity working that way?” Carpenter explained.

The discussion then moved on to biosimilars and how they would impact prescription drug prices. Fox argued that a 15% price reduction5 is not a deal because “it’s going to take you back to 2015 prices” rather than to the cost of the reference product when it was first marketed. “I think that’s the real challenge for us. We can negotiate around the edges, but it doesn’t change the basic economic structure that’s breaking the bank,” Fox reasoned.

Both Carpenter and Fox agreed that drug importation could have a significant impact on drug prices and access, although Fox believes that the impact might be greater in the nononcology space.

FDA’s Oncology Center of Excellence

To accelerate the drug approval process, the FDA, under the leadership of Richard Pazdur, MD, has established the Oncology Center of Excellence (OCE).6 Carlson vouched his trust in Pazdur and added that OCE will achieve its objective of a faster drug review process. “I do think the approval process is likely to accelerate, and that will allow the FDA to focus more attention on defining what is required to get a drug approved so that it’s more clear what endpoints they’re willing to accept and what the trade-offs [are] between toxicity and efficacy,” Carlson said.

Fox said a faster approval process raises safety concerns, such as approvals based on a single phase 2 nonrandomized trial. Citing a study published in JAMA Internal Medicine last year7—which found that 18 of 36 cancer drugs that were approved based on surrogate endpoints showed no OS benefit in postmarketing studies—Fox said that 17 of the 18 drugs in the study either had no improvement or worsened quality of life, yet they still were approved. He voiced his concern about approvals that are based on insufficient information, which is “a cost to all of us, not only as a payer and the employers that we serve, but to society as a whole.”

Evolving Cancer Clinical Trial Design

What would then be an “ideal” clinical trial design? Is a phase 3 randomized blinded trial ideal in today’s world of personalized medicine or will the Targeted Agent and Profiling Utilization Registry (TAPUR)8 and National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH)9 studies be the norm?

Alvarnas said that TAPUR and NCI-MATCH both have adaptive trial designs and a personalized approach; TAPUR includes approved targeted agents in patients whose tumor genomic profiles are already on file. He asked the panelists if the prerequisite of genomic information might be a barrier to trial enrollment.

Fox responded that while the ACA mandated covering trial participation, Michigan has had a law in place for several decades to cover the therapeutic agents, not the diagnostic testing required for participation. “We’ve made a decision, as a health plan, that we’re going to cover the diagnostic test to determine if patients are eligible. It’s kind of an end around the requirement if you say we’ll cover the trial, but you have to pay the $5000 to enter into the trial,” he explained.

Fox said that for a patient who has failed first- and second-line therapy, but would like to continue treatment, enrollment in any clinical trial—not just TAPUR and NCI-MATCH—to identify optimal therapy is important. Carlson said that TAPUR and NCI-MATCH are designed to provide options for patients who have exhausted all else for their solid tumors. Being FDA-approved, all TAPUR agents have a known toxicity profile, but the small sample size for each arm will only assist with hypothesis generation for future trial design, Carlson added.

Carlson, who’s an investigator on the NCI-MATCH trial, said a challenge he has faced with the design is the 30 treatment arms. “I cannot legitimately maintain that sort of expertise and know-ledge on 30 different arms, realizing that the arms in that trial come and go,” he said. Fox said he strongly believes in empowering those other than the principal investigator at each participating institution to provide expertise and keep patients informed about their eligibility to participate in these trials.

Besides the administrative burden and the need for a different style of analyzing the data that emerges from the small sample size, Carlson said that “we need to figure out ways to correct for that if we make the wrong inference from the data that we have.” This point raised the discussion to a new level of the quality of tumor biopsies, the timing and the actual site to collect the tumor sample, and selecting the laboratory to evaluate the tissue. Although Fox was concerned with substituting a tumor tissue biopsy with circulating tumor DNA, Carlson pointed out the discrepancy

over the number of sites to collect the biopsy samples from for a patient with multiple metastases. “Do you depend upon the biopsy at diagnosis? Do you depend upon the biopsy at recurrence? With each subsequent therapy, are you forced to re-biopsy?” he queried.

Sequencing these tissue samples for mutations is getting complicated, Fox said, especially with many hospitals choosing to conduct multigene sequencing or whole DNA sequencing, “which raises another quality issue. How do I know the results are comparable?”

Keeping Care Patient Centered

While standards are established and changes made to ensure the standard of care is maintained to keep patients safe and to improve outcomes, patient centricity is much more than that. “I think that patient-centered care becomes important right at the time of diagnosis, possibly even at the time of suspicion of cancer,” said Sagar. She emphasized the need for physicians to have a clear conversation with the patients on their diagnosis, stage, and treatment options, as well as palliative care early in treatment.

Carlson agreed that patient centricity should be a constant throughout healthcare, but warned that patient-centric need not always translate into keeping the patient happy. Rather, it should ensure that the patient’s well-being is at the center of what we do.

But Fox asked who defines the outcomes that should be measured, since the norm in clinical journals is only to report on endpoints such as PFS or OS, adding, “At what point do patients define what an important outcome is? And are we good as a delivery system about considering patient perspectives on what’s important?” With the diversity in perspectives from multiple stakeholders, the optimal outcomes to be measured probably reside among all the different perspectives, said Carlson.

Fox raised a very important point: have a conversation with patients on what their goals are from the care they receive. “We make the assumption, an erroneous assumption sometimes, that patients want to continue going,” Fox said. Making treatment decisions based on patients’ goals is critical, he added. Sagar believes that if patients with advanced-stage cancer understand what they are up against, that we don’t yet have a cure for their disease despite all the great advances, they may not want to go through a lot of these treatments.

Alvarnas asked the panelists if there was a method to measuring whether patient care was actually delivered in a way that can achieve the “human-centered goals. Do we have a way of developing meaningful quality measures or metrics to let us know who does this well?”

Fox pointed out that one of the measures in the Oncology Care Model (OCM)’s care plan is documenting whether a treatment goal is curative or palliative. He said a discordance between the patient’s understanding of the treatment and the physician’s expectation at that point would be an appropriate and simple measure of poor quality of care. “The likelihood is that we’re paying for healthcare services that might not be necessary,” he added.

For Sagar, understanding the value of services being delivered is important, be it drug treatment or surgery. Fox, who believes in the phrase “Not everything that can be measured matters and not everything that matters can be measured,” said that measuring what’s important to patients is not being measured in the real world outside of a clinical trial, except for OCM-participating practices.

“I don’t think we’re really going to get to measures that matter,” Alvarnas said, adding that electronic health records (EHRs) don’t do a very good job of capturing patient-reported outcomes, such as asthenia, insomnia, pain, depression, hopelessness, and functionality. Citing the disconnect between survival information and billing information, Alvarnas said that it might need someone within the payer space to dictate the data collection requirements.

Carlson and Fox agreed that there is need to place more thought into identifying the measures that matter to patients, with Fox highlighting the importance of having the end-of-life conversation, possibly through a trained staff member, “to assess, for those patients who died, was the care that they received consistent with what their state of preferences were? Did we provide care concordant with those preferences?”

Noting that many of these issues stem from the lack of care coordination, both within and between sites of care, Alvarnas asked the panelists how care coordination can be improved and whether reimbursement models can be designed to avoid these gaps. Shared decision making is a priority in Cigna’s patient-centered medical home model, Sagar responded, and includes family and patient education on diagnosis, treatment, and expected side effects. She pointed out that the health plan encourages practices to use nurse navigators and has in-house case managers to assist with care coordination. The goal is to keep patients out of the hospital.

Drawing attention to the gaps in care coordination, Alvarnas noted that it’s important to at least have a system in place to capture these patients, either before or after their visit to the emergency department. Fox noted that whereas uninterrupted access to an EHR is one way to avoid confusion and be aware of the care that patients receive, communication is of utmost importance. “I think there are lots of opportunities, but all that requires time and energy and skill sets that most practices, at least community-based practices, don’t have.” He thinks the care management fee for OCM practices can help fund some services, such as social workers, pharmacists, and financial planning, that are currently not reimbursed, but are integral to transforming cancer care delivery.

Cancer Care in the Era of the ACA

Key provisions of the ACA that affect patients with cancer include expanding Medicaid, eliminating the preexisting diagnosis clause, and capping maximum out-of-pocket spending. Has access to care and care delivery changed in the last 6 years for patients with chronic conditions such as cancer? These changes under the ACA have benefited the patient community, Carpenter said, but access remains a challenge even though more people were insured.

“I think we’re really faced with the fundamental question of whether or not access to healthcare is a right or a privilege,” responded Fox. He agreed that the ACA provided the newly insured individuals a source for paying for their healthcare, which can prevent cases when patients with cancer seek healthcare only after their disease has advanced.

Alvarnas noted that in California, where he practices, Medicaid expansion took the form of Medi-Cal, a program that now covers nearly one-third of the state’s 40 million people. Alvarnas said Medi-Cal is hugely successful, with about 11 plans still in the market. However, there are other states, Texas for example, that have chosen not to expand their Medicaid program.

Carpenter agreed that Medicaid expansion has certainly reduced the number of uninsured in California and some other states, but there has also been increased Medicaid enrollment in states that chose not to expand the program to those earning up to 138% of the federal poverty line. “People were eligible for Medicaid prior to the ACA, but the outreach and enrollment associated with the law really literally had them come out and get insured,” which she described as the “woodwork effect.”

The marketplace exchanges, however, have fallen short of expectations, Carpenter said. Together, the federal and state-run exchanges have enrolled only 50% of what was projected when the ACA passed in 2010. She anticipates that insurance commissioners and lawmakers in several states will be faced with the decision on what to do in exchange markets without carriers, where individuals qualify for ACA subsidies.

From a health plan perspective, Fox said that although their plan advertised to help attract patients, the results were mixed. He said the ACA needs fixes to help retain plans in the exchange marketplace and a more solid plan to ensure we improve clinical access in addition to payment access. Alvarnas said he would also like to see an increase in the number of nurse practitioners.

The discussion then moved on to the political motivation behind the repeal-and-replace movement against the ACA, and the subsequent grievances that led to the initial rejection of the House Republicans’ AHCA.10 Carpenter noted that the lack of alignment on what the replacement plan should be has hurt the Republican party, especially the pull-back on reforms like patient protections and coverage of some of the essential health benefits, which were demanded by conservative members in the Freedom Caucus. “So, unfortunately, for House Speaker Ryan and the Republican leadership, the party is pulling the policy in the bill in the opposite direction, and the question is whether they can come together and find a policy that reflects both sides’ ideology.”

Ensuring access to healthcare overall and for patients with preexisting conditions is an important part of the ACA, said Carlson, as is eliminating lifetime limits and high-risk pools, “so that patients can actually afford the healthcare. Healthcare that they can’t afford doesn’t help,” he added.

“Patients die if they don’t have health insurance, and that’s really what this boils down to. Are we, as a society, are we as a medical system and culture, going to configure healthcare so that we recognize that we just are writing off some lives? Or are we going to recognize that healthcare is a right and that we, as a society, have a responsibility to figure out how to responsively deliver affordable healthcare to individuals in our society?” Carlson asked.

The debate, Fox said, is whether we control costs of services or reduce access to those services, which, Carpenter said, is not the discussion that members of Congress are having. “They’re talking about the fact that they promised to repeal and replace the ACA and it’s been a campaign issue for 6 years, and now they’re in charge, it’s time to deliver, and it’s proving a challenge.” She added that the ACA has placed a limit on the out-of-pocket maximum in cancer care, not just in the individual marketplaces, but also in the commercial market.

For things to move forward with healthcare reform, market reform is essential, Carpenter added, because those gained popularity and that’s what the Freedom Caucus would like the states to have control of. In addition, provisions in the AHCA that would cut funding for the states are controversial, as this would leave the states a choice between raising taxes or reducing benefits.

Carlson foresees that the ACA will continue, maybe under a different name and slightly modified to make it more acceptable to different constituencies. Carpenter added that certain healthcare reforms that stand the chance of gaining bipartisan support should focus on stabilizing the ACA. Support for reinsurance programs and state-based risk programs could raise the interest of health plans, she said. “Those are things that could really shore up the existing ACA, and if members on both sides of the aisle decided that was their goal, there is certainly a path forward there; just a question if Congress gets to that place or not.”

“Diseases already ruin families. We don’t need finances to do the same, and so I think you’ve outlined several key things that can be done to stabilize it. I hope that’s the calmer set of heads that prevail on all this,” said Fox.

For his final thoughts, Carlson brought up the value of care, saying that the patient’s values are always his focus and that these values vary among patients, be it survival or finances or the ability to be able to do daily activities. “Let the patient tell me what value means and I’ll accept that definition and work to achieve value for them,” he said.

Avalere Health is working in partnership with FasterCures to build such a value framework, Carpenter said.

Agreeing that value frameworks are a good thing, Fox said that they help bring not just financial issues, but also the risk-to-benefit conversation to the table. “A clear discussion of all the available treatment options, what they cost, and what the side effects are is really where we need to go. And I think the patients will drive that, but they need physicians’ help. They can’t do that in a vacuum.”


Joseph Alvarnas, MD, is director of value-based analytics and associate clinical professor, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, and editor-in-chief of Evidence-Based Oncology™.

Robert W. Carlson, MD, is chief executive officer, National Comprehensive Cancer Network.

Elizabeth Carpenter is senior vice president, Avalere Health.

John L. Fox, MD, is associate chief medical officer, Priority Health.

Bhuvana Sagar, MD, is national medical director, Cigna Healthcare.


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