The FDA is working to modernize the clinical trial process and answer the right questions about today’s innovative cancer drugs, but regulators need help from payers—or, more precisely, from their data, according to FDA Commissioner Scott Gottlieb, MD.
Gottlieb called for more data sharing during remarks at the National Comprehensive Cancer Network Oncology Policy Summit held June 25 in Washington, DC. The commissioner covered 4 policy areas he said were linked by “the need to modernize drug development to harness the full medical potential of this rapidly advancing science, while ensuring that innovation remains affordable for patients.”
He added that patients will not benefit from outdated regulatory frameworks that keep lifesaving drugs off the market, stretch out the process, and make drugs more expensive. Although the FDA does not have direct authority over drug costs, Gottlieb said, a different approach can take time and costs out of the approval process, as well as promote competition and encourage generics and biosimilar development. “If FDA-approved drugs are priced out of reach of patients, then the full benefits of innovation won’t be realized,” he said.
Over the past 20 years, as both cancer therapies and survival rates have improved, more patients have been matched to drugs in trials based on “tumor biology,” Gottlieb said. This has allowed the FDA to approve drugs based on smaller trials with fewer patients and leapfrog from phase 1 studies directly to later phases. Oncology accounts for more breakthrough therapy designations than any other therapeutic area, including 50% of all designations granted since 2013.
“We had to ask ourselves some hard questions,” he said. “What should we do, for example, guided both by ethics and science, when a new drug in a heavily pretreated group of terminal cancer patients is in a phase 1 study, where it shows a dramatic response in more than half of these patients?” And, he asked, how are patients randomized in phase 2 based on that result?
Although some criticize the FDA’s approach to approvals based on smaller groups of patients, “this criticism lacks historical and scientific context,” he said.
When cancer drugs were more toxic and less effective, the fact that they worked at all was the most relevant outcome, so overall survival was the most appropriate end point. “They were standards designed for an era that no longer exists,” he said.
The FDA has consulted extensively with stakeholders, including patient groups, and is now more interested in progression-free survival, tumor shrinkage, and the severity of adverse effects. It’s not that these measures weren’t relevant in the past, Gottlieb said: “It’s just that the drugs were so toxic that these benefits generally were not seen as sufficient to justify the risks.” Today’s drugs are far less toxic, and looking at how patients fare over longer periods is highly relevant. The FDA’s changing approach “didn’t evolve overnight,” Gottlieb said. “We didn’t do it on a whim.”
The approach is working: Of 51 oncology accelerated approvals with postmarketing requirements and verified benefits, the average time from approval to verification is 3.4 years. Just 5 drugs have been pulled from the market for failing to confirm benefits.
In response to critics who say surrogate end points bring uncertainty about the eventual efficacy, Gottlieb said, “That’s, in fact, the whole point.”
In some cases, trials would take far too long; without crossover trials, some patients would miss the opportunity for lifesaving treatment. “We would literally be asking patients to die so that we could achieve a lower P value,” he said.
To promote cost-saving solutions such as value-based contracting, Gottlieb called on payers to aid the process by sharing data that will guide FDA on how drugs work in different populations and over the long haul: “It’s not enough to point fingers. We all need to work together.”
Payers who want to help the FDA ultimately drive down prices or show how therapies affect hospitalization rates must “put your data where your arguments are,” instead of charging huge sums for this information, Gottlieb said.
Real-world data do not replace the gold standard of randomized clinical trials but can fill in knowledge gaps. As a result, Gottlieb said, for the 2019 budget, the FDA seeks $23 million to invest in advanced analytics and data analysis, which he said will give the agency the ability to do “near real-time” analysis of evidence from electronic health records for 10 million individuals.
During a question-and-answer period, Gottlieb said the FDA is working to help overcome impediments to using real-world data for value-based contracting by issuing a recent guidance on this topic. When asked if he’s confident that the FDA will get the real-world evidence it needs to shift its approach, Gottlieb said that’s the role of enforcement.
At the time of Gottlieb’s speech, the FDA had just sent a letter to a manufacturer that has not fulfilled its postmarketing requirements. “The agency feels far more confident it will get the data,” he said. “The system is dependent on that.”
As Ron Kline, MD, put it: If figuring out how to pay for innovation in cancer care was easy, someone would have already done it.
“We know it’s hard. We know it’s going to take a while,” said Kline, medical officer in the Patient Care Models Group for the Center for Medicare and Medicaid Innovation (CMMI) at CMS.
Kline was on hand to discuss the Oncology Care Model (OCM), the 5-year effort to rethink cancer care delivery and cut costs in Medicare, during a discussion by the National Comprehensive Cancer Network (NCCN) on how to balance the revolution in cancer therapy with the need to pay for it.
During the session “Paying for Innovation,” part of NCCN’s June 25, 2018, Policy Summit in Washington, DC, Kline explained that the OCM shouldn’t be easy from the get-go—if it was, then CMMI would know it hadn’t truly pushed the envelope. But CMMI wants practices to succeed, and early results show that 25% of practices cut costs 7%. “Sixty percent of practices decreased costs, compared with the baseline,” he said.
Guided by questions from Moderator Cliff Goodman, PhD, of The Lewin Group, panelists discussed today’s challenges in cancer care: the need to simultaneously overhaul delivery systems and learn to use—and bill for—some of most complex therapies and technologies ever conceived. Heading that list: chimeric antigen receptor (CAR) T-cell treatments, gene therapies that can take 2 to 4 weeks to manufacture for a specific patient, at a cost of up to $475,000 just for the drugs.
But paying for innovation is more complicated than figuring out how to pay for CAR T-cell treatments or targeted therapies. It’s also about helping patients who will live with cancer as a chronic condition, such as those with certain blood disorders.
“The advance of novel, innovative therapies has transformed treatment,” said Meghan Gutierrez, chief executive officer of the Lymphoma Research Foundation. The combination of new treatments, diagnostic tests, and sequencing has produced more information about the disease. Patients have more opportunities than ever for better care, but for many, treatment will not be a one-time event. “Patients recognize they are likely to be in and out of care for the rest of their lives,” she said.
Innovation isn’t just about approving new therapies, said Pavan Reddy, MD, FACP, of the Cancer Center of Kansas. Precision medicine means identifying treatments that are “tumor agnostic,” based on biomarkers, as well as research that tells clinicians when they can de-escalate or stop treatment, he said.
Reimbursement drives decisions
Patients are citing treatment costs as a factor in their medical decisions, according to Gutierrez. “Increasingly, patients are speaking to the economic burden across their lifetime,” she said. Therapies can extend life well beyond what was once imaginable, but with these advances come rising out-of-pocket costs.
Stephanie Farnia, MPH, director of health policy and strategic relations for the American Society for Blood and Marrow Transplantation, is a veteran of dealing with reimbursement challenges. Things such as delays in getting treatment codes, which allow physicians to bill properly, can be a barrier to lifesaving advances.
Panelist Stefanie Joho, a cancer survivor, lives with fatigue from the immunotherapy that saved her life, but, as Goodman noted, “some long-term impacts are unknown.” In Joho’s case, that’s better than what she was facing when her sister, refusing to accept the grim prognosis that nothing could be done for Joho’s colon cancer, scoured the internet until she found an appropriate clinical trial. Other panelists conceded that some oncologists, especially in rural areas, don’t always refer patients for clinical trials. At this point, CAR T-cell therapies are unlikely to be delivered outside of a major academic medical center with expertise in transplants, said Caron A. Jacobson, MD, of the Dana Farber Cancer Institute/Brigham and Women’s Hospital in Boston, Massachusetts.
Kline, however, called this a copout. As a pediatric oncologist, he said, he finds that clinical trials for young patients “are the standard of care.”
Joho and others said they’d like to see more patients enroll in clinical trials, although they recognize barriers such as travel. Michael Ybarra, MD, representing the Pharmaceutical Research and Manufacturers of America, said that drugmakers are concerned about the ability of rural patients to gain access to trials, but factors such as hospital consolidations and benefit design also create access barriers. A major driver of consolidation in the health care industry has been the 340B program, which groups such as the Community Oncology Alliance say has been exploited beyond its original mission, to the detriment of community providers.
The arrival of CAR T-cell therapy
The fact that administering CAR T-cell therapy demands special expertise and permission means that certain centers are likely to have several patients receiving the therapy, increasing that institution’s risk. This creates lots of discussion among leading oncologists and hospital executives, according to the panelists. Jacobson said she’s been “pleasantly surprised” at the speed with which CAR T-cell therapies have moved from FDA approval into general use, but it hasn’t been without its challenges. Patients outside of clinical trials may have less economic means and family support, and thus far, reimbursement with commercial payers is done through individual patient contracts, so there’s a heavy administrative burden.
Even so, Jacobson said, for tisagenlecleucel (Kymriah)—the first CAR T-cell therapy approved for forms of pediatric leukemia—“you’re only charged if you respond in the first 30 days.” In pediatric patients, responses rates are 96%, she said, and although adult responses to CAR T-cell treatments are not quite that high, they are “still very impressive.”
CAR T-cell therapy is such a game changer that so far, CMMI is not including it in cost-of-care for OCM purposes, Kline said, because that would “overwhelm everything.”
Variables in the OCM
That said, Kline explained 2 factors in the OCM model—the novel therapy adjustment and the trend adjustment, which is based on regional cost factors—that allow practices to deal with externalities. But Goodman asked, “Are you confident that the novel therapy adjustment will accommodate all this new stuff?”
The adjustments are receiving attention within CMMI to make them work, Kline said. He acknowledged Goodman’s observation that so far, there’s virtually no update of 2-sided risk in OCM, but he said that practices are just now getting back early rounds of data to see how they are faring.
When asked for a 1-sentence summary of what’s next, Jacobson said, “It’s ultimately about solving the problem of reimbursement.” As CAR T-cell therapies are shown to work for more types of cancers, single-patient contracts won’t be sustainable, she said. The next step must be to pair innovation in technology with payment systems that can work out approvals “in real time,” she said.
Reddy sees the growing ranks of underinsured as a challenge, and Ybarra agreed that matching benefits designs to patient needs—to do something about huge out-of-pocket costs—is essential.
Said Kline, “It’s about putting the responsibility for the cost in the physician—patient relationship.”
Narrow networks, which limit where patients can receive care, are holding down costs, but the price to patients with cancer and providers in lack of convenience can be high, according to panelists who discussed changes in care delivery at a policy summit of the National Comprehensive Cancer Network (NCCN), held June 25 in Washington, DC.
“The Evolving Healthcare Landscape: Implications for Access to Quality Cancer Care,” brought together leading oncologists, policy experts, and patient advocates to address the conundrum for today’s cancer patient: Therapeutic advances bring more options than ever, but for many, barriers to the best treatments will be too high.
Joseph Alvarnas, MD, a hematologist/oncologist who serves as vice president of government affairs and senior medical director of employer strategy at City of Hope in Duarte, California, said that unlike many other parts of the country, his state has lots of health plans—but that doesn’t mean a patient will find adequate networks.
“The challenge here is [that] if the motivation is to deliver low-cost care, [health plans] can find a low-cost provider in every market,” said Alvarnas, who is also the editor-in-chief of Evidence-Based Oncology™. Narrow networks can work if there is a commitment to quality, but when price is the only priority, that can pose a problem: “Their decisions are not based on ‘Where do I get the best care?’ but ‘Where do I get the lowest price?’”
Narrow networks have proliferated under the Affordable Care Act (ACA) because of lower-cost plans sold on the marketplace. In some cases, that has left leading academic medical centers and NCCN member health systems on the sidelines, because their costs are considered too high. Alyssa Schatz, MSW, policy director for NCCN, presented research to the group showing that most cancer centers are in some exchange networks but not all in their region. A few have not been placed in any exchange network, she said.
It’s reached a point that the National Association of Insurance Commissioners, which creates policies and model legislation to help bring uniformity across state lines, needs to revisit the narrow network issue, said Jenny Carlson, associate vice president of government affairs at The Ohio State University’s Wexner Medical Center.
John Cox, DO, a medical oncologist at University of Texas Southwestern and Parkland Health and Hospital System, agreed that although the ACA brings coverage to many uninsured, it has its drawbacks. “On the 1 side, I love that our patients have a secure insurance contract. They have access to care,” he said. But he’s seen examples of patients who must travel long distances, often carrying their medical records, to use the lone specialist approved by their plan. “It just puts up tons of barriers,” he said.
Moderator Cliff Goodman, PhD, asked: If oncologists and patients with cancer must live with narrow networks, are there any consumer protections?
Most people still get coverage through their employer, Antos said, and a patient who receives a cancer diagnosis is “locked in” to whatever that plan provides and may not know how to avoid large out-of-pocket costs. “Patients don’t know what to do,” he said, “and doctors aren’t very good at telling them.”
Many health plans don’t pay for social workers who could help a patient navigate the system, Franklin added.
Goodman asked whether CMS’ push for more of cancer care in Medicare to be provided through alternative payment models, or APMs, would make a difference. In theory, when setting reimbursement, APMs take a patient’s experience into account, not just cost.
A problem is that too many providers are simply trying to “game the system” for maximum reimbursement under the Merit-based Incentive Payment System, or MIPS, instead of aiming for excellence, Alvarnas said: “We should have transparency about what represents excellence, especially in cancer care.”
Patel noted that although the ACA contemplated APMs, they did not exist right after the law passed. MIPS is a tool to get doctors to experiment with taking on risk, because the transition to 2-sided risk in APMs cannot happen all at once. And in cancer care, this transition is happening just as the cost of immunotherapy is skyrocketing, giving doctors pause. She reminded the audience that the 2015 Medicare Access and CHIP Reauthorization Act, which set up MIPS and the ability of Medicare to pay doctors through APMs, is “budget neutral,” which suggests there will be winners and losers. That raises this question, Patel said: “What constitutes a loser?”
Carlson discussed experiments with Medicaid waivers, including the push by some states to add work or volunteerism requirements. She said this will be closely scrutinized in the courts. (Days after the summit, a federal judge blocked Kentucky’s plan to add work requirements to Medicaid.1) Schatz said the bureaucracy associated with Medicaid work rules is quite challenging.
An overlooked aspect of the ACA is that “it shifted resources, so there were winners and losers,” Antos said. Some previously uninsured people gained access for the first time, but when too few healthy people signed up for coverage, some lower-middle-class families that were not eligible for subsidies “could no longer afford the coverage they used to have,” he said.
The threat today is that the Trump administration’s decision to eliminate the individual mandate through the recently passed tax plan will drive healthy people out of the risk pool. Patel, who worked on the ACA as a member of the Obama administration, said calls for harsher penalties for not enrolling went unheeded. The loss of the individual mandate is a much bigger threat to the healthcare system than association health plans (AHPs), she said.
In addition, buying cheap coverage will end up as barrier to accessing the lifesaving treatments that are reaching the market, such as chimeric antigen receptor (CAR) T-cell therapies. Anna Griffin of Kite Pharma, developer of the CAR T-cell treatment Yescarta, said, “We’re not allowed to say ‘cure,’ because the data are still young,” but researchers are starting to get results for people 2 years after treatment, “and it still looks really good.”
“It’s such a great time to be in cancer medicine,” Cox said. But the downside is that for some patients, there’s no access to bone marrow transplants—very few cancer centers can take on a charity transplant patient, he said.
Franklin is not encouraged by the prospect of telling patients, “This potentially is a cure, but not for you, because you’re poor—or because you’re not near a major cancer center.”
Goodman asked each panelist to predict what’s ahead.
Alvarnas said he looks forward to “getting rid of the middlemen,” referring to pharmacy benefit managers (PBMs); reining in pharmaceutical costs; and getting rid of wasteful procedures. He expressed excitement about the upcoming venture among Berkshire Hathaway, Amazon, and JPMorgan Chase, which could bring analytics to the cause in a more powerful way.2
In discussing the Trump administration’s plan to hold down pharmaceutical costs, several panelists said the proposed merger of Medicare parts B and D will be much harder to achieve than most realize. Antos pointed out that Part D is very much driven by rebates, which have been a target of scorn among those who believe PBMs are largely responsible for pushing up prices. Antos said the extremely high costs of treatment will upset current financing models.
“I’m also concerned about patient safety,” Franklin said. She would like to see patient experience data on drug labels. Carlson foresees a broader use of telemedicine and, she hopes, more streamlined coverage decisions.
Schatz said there’s a great need for transparency of information so that consumers can make more informed choices.
Patel expects that by 2023, “50% of cancer care will be in some at-risk payment model.”
“Patients are going to have some real options in cancer treatment—options that look different than they do today,” according to Franklin.
Rep Mark DeSaulnier, a California Democrat, has championed causes from reducing air pollution to fighting childhood obesity to improving gun safety.1 Rep Ted Poe, a Texas Republican, is still called “Judge” from his years handing down sentences, such as ordering thieves to carry signs outside stores where they stole merchandise.2
A political odd couple? For sure. But they also share a bond that guides their work in Congress: Both are leukemia survivors.
In 2017, DeSaulnier, who represents Contra Costa County in the San Francisco Bay Area, and Poe, whose district covers the Houston suburbs, formed the Congressional Cancer Survivors Caucus, a bipartisan group that is calling attention to the need for more research and removing the stigma that still lingers over cancer. Formed when the Trump administration was weighing a $5.8 billion budget cut to the National Institutes Health,3 the caucus advocates for issues that cross party lines. The group also hears from leading scientists so members can learn firsthand what’s happening in the world of research.
On June 25, 2018, DeSaulnier and Poe appeared at the National Comprehensive Cancer Network Policy Summit, where they discussed legislation they introduced in March: the Cancer Care Planning and Communications Act (HR 5160), which would allow doctors to bill Medicare for the time spent developing cancer care plans and coordinating services.4 Care planning and management are part of CMS’ Oncology Care Model (OCM), a 5-year initiative aimed at improving care and reducing costs, but not all practices are part of the OCM.5
Living well after cancer should not be a controversial topic, in their view. “It’s a nonpartisan issue that is really important,” Poe said. “You hear all the rhetoric. You hear all the fussing and fighting and feuding. This is not one of those issues.”
“It’s a quality-of-life issue, and Congress should be involved in quality-of-life issues,” DeSaulnier said. After 30 years as a public official, he sees fighting cancer as something that can allow Congress to get past its divisions and make a difference—by promoting better technology and ensuring that people with preexisting conditions can get care. “In the wealthiest country in the world, Americans should be assured that preexisting conditions are covered,” he said.
DeSaulnier and Poe agree on the need for more research, education about causes of cancer, and screening to identify people at risk. Prevention, Poe said, is much cheaper than being treated. “Take smoking,” he said. “[Back] when we had black-and-white TV, people smoked and thought nothing of it.…There was smoking in jails, in the Astrodome.”
As a judge, Poe convinced the Harris County commissioners to eliminate smoking from all county buildings, including the courthouse and the jail. “You would have thought the world had come to an end,” he said.
Today, no one questions the need to keep smoking out of public spaces, DeSaulnier said.
Poe had high praise for the treatment he received at The University of Texas MD Anderson Cancer Center in Houston, noting that access to care for all patients is key. “We have the best medical knowledge in the world. If people cannot have access to that knowledge, then we’re missing the whole point of having it,” he said. “We have to figure out a way so that people can have [access]. That is something we have to strive for.”
DeSaulnier, 66, and Poe, 69, received their diagnoses about a year apart. DeSaulnier found out he had chronic lymphocytic leukemia in 2015, during his first year in Congress. He went through treatment quietly and didn’t share the news until May 2016, when he announced he would seek a second term.6 For Poe, the diagnosis of leukemia came in 2016, more than 10 years after he was elected to Congress in 2004. Although his treatment has gone well and he said he’s in good health, he decided not to seek reelection this year.7
The focus on survivorship, DeSaulnier said, has emerged because living with cancer is now more like having a chronic disease. “We have these treatments that are capable of keeping you alive longer,” he said, but this can create new challenges, such as living with a weakened immune system.
Finding solutions means following the science, DeSaulnier said: “We are at the most elevated point in our existence. We both agree—must look at prevention, at intervention, and deployment of evidence-based research so that people will be better off.”
Franklin sees the AHPs as a real problem. “What happens when a 30-year-old gets cancer?” she asked. For many, the diagnosis will reveal how little their plan actually covers.
Both Joe Antos, PhD, of the American Enterprise Institute, and Elizabeth Franklin, LGSW, ACSW, executive director of the Cancer Policy Institute for the Cancer Support Community, said a key challenge for consumers is the complexity of insurance contracts. If healthcare experts have a hard time figuring out what’s covered and what’s not, they asked, how can patients navigate the system?