™) reached out to Daryl Pritchard, PhD, vice president for Science Policy at the Personalized Medicine Coalition (PMC), an organization created “to promote the understanding and adoption of personalized medicine concepts, services, and products.”

 PMC’s membership boasts a broad spectrum of academic, industrial, patient, and healthcare provider constituencies, and they are very active with educational and advocacy efforts that will draw attention to the advantages of personalized medicine in healthcare. 

 What are your thoughts on the existing FDA drug approval process? Are there ways in which the process can be improved? 

Scientific progress in personalized medicine is driving an increase in the number of personalized medicine products that are subject to regulatory review. In fact, nearly 1 out of every 4 drugs that were FDA approved between 2014 and 2016 was a personalized medicine. This is a sharp increase in personalized medicine drug approvals. In 2005, personalized medicines accounted for just 5% of new drug approvals. The FDA has responded to the growing demand for regulatory clarity by issuing guidance documents, most notably on principles of co-development of therapeutics with companion diagnostics. 

The Center for Drug Evaluation and Research (CDER) within the FDA has indicated strong support for a personalized medicine approach to drug development. In her FDA Voice blog, Janet Woodcock, MD, wrote, “CDER uses a lot of flexibility when reviewing applications for targeted drugs. For example, among the targeted therapies approved in recent years, 90% used 1 or more of FDA’s expedited programs such as Breakthrough, Fast Track, Priority Review and Accelerated Approval.”

Although regulatory oversight of targeted therapeutics has done a great job keeping up with the science, regulatory oversight for diagnostic tests remains problematic. There are currently 2 separate regulatory pathways for different kinds of diagnostic tests. In vitro diagnostic testing kits are regulated by FDA, while laboratory developed tests are subject to oversight through CMS’ Clinical Laboratory Improvement Amendments, commonly called CLIA. This has caused different stakeholders to raise issues about consistency, transparency, and the creation of an uneven playing field in the development of advanced diagnostics. 

 A companion diagnostic for every drug product on the market would be an ideal situation. But is that feasible, at least in oncology? 

As the science regarding individual variability in drug response continues to unfold, more and more drugs will be associated with companion diagnostics. It would be ideal if one day doctors and pharmacists had the complete genetic profile for all patients that could be easily used to guide treatment decisions by allowing them to consider all known genetic variants that help predict which drug would be most effective or which drugs would likely cause adverse side effects. However, the scientific process for understanding the complete range of the impact of genetic variability in drug response is not feasible for a very long time. At first, scientists will likely work on understanding genetic variability that has the greatest impact on drug response for diseases with clear molecular mechanisms, and we are seeing a great deal of that research in oncology. The key is to add novel diagnostics, as they are developed, to the expanding toolbox for personalized medicine as quickly as is appropriate. 

 Can you describe PMC’s policy efforts to improve clinical acceptance of genetic testing? 

PMC is engaged in various policy efforts to accelerate clinical acceptance of genetic testing, including: 

		Understanding the landscape for personalized medicine development 

		Advocating for appropriate incentives for the development of novel diagnostics and targeted therapeutics

		Assuring appropriate regulatory oversight mechanisms for new diagnostic and targeted therapies, including next generation sequencing—based diagnostic tests

		Building the evidence of clinical and economic value of diagnostic tests and targeted treatment strategies, and assuring that personalized medicine is appropriately considered in value assessments

		Promoting value-based reimbursement of diagnostic tests

		Understanding the challenges to integrating personalized medicine into clinical practice and developing strategies to overcome those challenges 

How can reimbursement for diagnostic tests be improved? What are your thoughts on existing policies by CMS and private health plans? 

Reimbursement can be improved by establishing payment rates for diagnostic tests that appropriately reflect the value they bring to care. 

Many coding and payment policy policies used by both CMS and private payers have led to significant challenges regarding reimbursement for molecular diagnostic tests. CMS’ decision, for example, to use the gap-fill methodology, which allows regional contractors to set prices for laboratory and molecular diagnostic tests, coupled with other payment decisions, has resulted in decreased payment rates for many personalized medicine tests. This, in turn, has placed a consistent downward pressure on physicians and laboratories interested in using novel, high-value molecular diagnostics to inform treatment decisions. 

Coverage and payment rate determinations by private payers lack consistency and transparency. Lack of coverage and under-reimbursement threatens access and further exacerbates the downward pressure on utilization of these technologies. Decision-making processes lack mechanisms that capture the value of targeted treatment, and may therefore threaten progress. 

Oncology trials such as TAPUR and NCI-MATCH have a very different approach to trial design. They have even seen collaboration among pharmaceutical companies. Do you see this as the new standard? 

In oncology, basket trials, which enroll patients with cancers that originated in all different types of tissue so that researchers can study treatment effects based on molecular pathways, are rapidly becoming more routine. This trial design allows for more rapid examination of a targeted drug’s efficacy across tumor types and could lead to more effective targeted therapies being approved at one time for use in multiple cancer types. It’s a more sensible way to examine drugs that target molecular pathways, and we believe this will become the standard trial approach for these types of drugs. 

is vice president for Science Policy at the Personalized Medicine Coalition (PMC). 

PMC is very active with educational and advocacy efforts to promote the understanding and adoption of personalized medicine concepts, services, and products. 

1. Mission. Personalized Medicine Coalition website. http://www.personalizedmedicinecoalition.org/About_Us/About_PMC. Accessed March 31, 2017. 

2. Woodcock J. FDA continues to lead in precision medicine. FDA website. https://blogs.fda. gov/fdavoice/index.php/2015/03/fda-continues-to-lead-in-precision-medicine/. Published March 23, 2015. Accessed March 30, 2017. 

Articles

Evidence-Based Oncology

An interview with Daryl Pritchard, PhD, vice president for Science Policy at the Personalized Medicine Coalition, on the FDA's drug approval process, developments in the personalized medicine field, and reimbursement models that integrate diagnostics.

Q&A With Daryl Pritchard, PhD, of the Personalized Medicine Coalition

In January 2017, the FDA officially established the Oncology Center of Excellence (OCE) to expedite the development of oncology and malignant hematology-related medical products and support an integrated approach to the clinical evaluation of drugs, biologics, and devices for the treatment of cancer. The FDA began work on forming the OCE more than a year ago, after President Barack Obama announced the National Cancer Moonshot Initiative in his final State of the Union address. This new center leverages the combined skills of regulatory scientists and reviewers with oncology clinical expertise across the FDA, emulating the multidisciplinary organizational model of academia and cancer care centers and building on the integrative approach to medical product development that the agency’s broader oncology community has embraced over the past decade.

The OCE already has begun coordinating clinical reviews of oncology products. Sponsors with product applications that have proposed medical oncology or malignant hematology indications should submit their applications to the medical product center they always have: the Center for Drug Evaluation and Research, the Center for Biologics and Evaluation Research, or the Center for Devices and Radiological Health. After the submission is received and if deemed appropriate, the OCE will form a clinical review team comprising experts from the 3 medical product centers, as necessary, based on the specific application. The review team will make its recommendations on the clinical portion of the application only. As OCE director, I review and sign off on their recommendation, after which the application is returned to the corresponding center to make a final product approval determination. Other aspects of product review, such as quality review, toxicological review, statistical review, and facilities inspection, as well as final action on the application, remain the responsibility and authority of the center that normally has jurisdiction over the oncology-related medical product. 

By bridging the various medical product centers of the FDA, the OCE is ideally suited to support innovation and address the recognition that multiple treatment and diagnostic options are in the best interests of patients. An important aim of the OCE is to facilitate incorporation of the patient view into regulatory decision making. The OCE’s Patient-Focused Drug Development program will foster collaboration between the FDA, patients, and advocacy groups; nurture research into measurement of the patient experience; and generate science-based recommendations for regulatory policy.

 An ongoing initiative at the OCE is an effort to modernize and broaden the eligibility criteria for patients enrolling in cancer clinical trials. The OCE will continue to encourage clinical trial designs that allow enrollment of patients who reflect the real-world population likely to receive a therapy, including older adults.

Improved patient selection made possible by early biomarker discovery has enabled drug development to shift away from the conventional phase 1, phase 2, and phase 3 paradigm to a more seamless approach, using expansion cohorts to assess efficacy in additional patient populations or to evaluate alternative dosing regimens. The OCE recently published its perspective on seamless development, which could provide earlier access to highly effective therapies and complement the FDA’s expedited regulatory programs, such as Breakthrough Therapy Designation and Accelerated Approval, to get products to patients more efficiently.

In addition, the OCE encourages novel trial designs, such as:

		Large, simple trials that use easily measurable endpoints to reduce the amount of data needed to determine benefit

		Common control trials that share a control arm, but may involve multiple drugs for the same indication, thus decreasing the number of patients that need to be enrolled and potentially decreasing development time.

Other OCE programs include Precision Oncology, Immuno-Oncology, Pediatric Oncology, the Information Exchange and Data Transformation Program (INFORMED), Oncology Devices and Diagnostics, Oncology Cell and Gene Therapy, and Oncology Regulatory Affairs.

Another important goal of the OCE is to focus on the “of Excellence” aspect and strive for excellence in drug and device regulation and emerging oncology science. Achieving that goal will require collaboration with academia, industry, patient groups, and professional societies. This work has been initiated by scheduling public meetings and small collaborative workshops to discuss key oncology-related issues across the FDA and bring in perspectives from our external stakeholders. Specific areas of emphasis include:

		Harmonizing cancer-specific regulatory approaches across the FDA’s medical product centers

		Coordinating oncology-specific regulatory science initiatives and outreach

		Implementing cross-center, oncology-focused meetings

		Engaging with external stakeholders, including government agencies, industry, academia, professional societies, and patient advocacy groups

		Communicating with international regulatory agencies regarding oncology issues

These initiatives will allow us to expedite drug development and approval of truly novel agents that will have a major impact on our patients while allowing us to make thoughtful decisions regarding the risk-benefit ratio of oncology drugs. 

is director of the Oncology Center of Excellence, FDA, and acting director of the FDA’s Office of Hematology and Oncology Products. 

US Food and Drug Administration, WO22 Room 2212, 10903 New Hampshire Avenue, Silver Spring, MD 20993 

The author reports no financial interests or relationships with the commercial sponsors of any products discussed in this report.

Note: This is a U.S. government work. There are no restrictions on its use. 

1. Pazdur R. Leveraging the power of collaboration—FDA’s New Oncology Center of Excellence. FDA website. https://blogs.fda.gov/fdavoice/index.php/2016/06/leveraging-the-power-of-collaboration-fdas-new-oncology-center-of-excellence/. Published June 29, 2016. Accessed April 6, 2017. 

2. Patient-focused drug development. FDA website. https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/OCE/ucm544143.htm. Updated March 9, 2017. Accessed April 6, 2017. 

3. Singh H, Beaver JA, Kim, G, Pazdur R. Enrollment of older adults on oncology trials: an FDA perspective [published online December 22, 2016]. 

4. Prowell TM, Theoret MR, Pazdur R. Seamless oncology drug development. 

. 2016;374(21):2001-2003. doi: 10.1056/NEJMp1603747.

5. Pazdur R. Evaluating FDA’s approach to cancer clinical trials. FDA website. https://blogs.fda.gov/fdavoice/index.php/2016/09/evaluating-fdas-approach-to-cancer-clinical-trials/. Published September 16, 2016. Accessed April 6, 2017.

6. Oncology Center of Excellence. FDA website. https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/ucm509057.htm#OCE_Programs. Updated March 9, 2017. Accessed April 6, 2017.

An overview of the FDA's Oncology Center of Excellence-a collaborative approach to the clinical approval process.

FDA Oncology Center of Excellence Moves Forward on Coordinated Clinical Reviews, Integrated Approach to the Clinical Evaluation of Oncology Products

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, 

 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 

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.

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&mdash;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,

 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 

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.

 “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. 

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.

 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 reduction

 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. 

To accelerate the drug approval process, the FDA, under the leadership of Richard Pazdur, MD, has established the Oncology Center of Excellence (OCE).

 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 

—which found that 18 of 36 cancer drugs that were approved based on surrogate endpoints showed no OS benefit in postmarketing studies&mdash;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.” 

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)

 and National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH)

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&mdash;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?”

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. 

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. 

At the The American Journal of Managed CareÂ®'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.

The Value of Regulatory and Healthcare Policy Changes in Oncology Care

Assessing the value of new drugs, diagnostics, or other health system interventions, often called health technology assessment (HTA), can become an academic exercise that loses sight of the fact that these technologies ultimately have a single purpose: to help patients. The patient perspective should therefore be central to HTA. The Institute for Clinical and Economic Review (ICER), a leading HTA research group in the United States, has established a robust strategy for engaging patients so that the entire process is informed by the patient experience and what “value” means to them.

ICER’s reports evaluate the evidence on the comparative clinical effectiveness and cost-effectiveness of new therapies. An ICER report process has distinct phases, starting with announcing the topic for a report, collecting open input, and clarifying the scope of the report. As the report is developed, a draft version is made available for public comment, and the report process culminates with a public hearing at which an independent committee discusses the report, public comment is heard, and a roundtable of patients, clinical experts, and other stakeholders discusses how to apply the evidence to practice and medical policies. Input from patients and patient groups plays an important role in all phases.

The first phase of the process is called “scoping.” During this phase, ICER identifies relevant patient groups and solicits open input

 from them and all other relevant stakeholders. ICER has developed a Patient Participation Guide

 to help patient groups understand the overall HTA process and how they can contribute. Patient input during the scoping phase allows patients to help set the stage for the entire report by sharing information on what living with a certain medical condition is like for different patients, and by identifying the outcomes and other aspects of treatment that are most important to them. While much of the data considered in the report come from rigorous clinical trials, ICER recognizes that these trials may not capture important information about the patient experience with disease and treatments.

Where feasible, ICER encourages patient groups to gather primary data on the patient experience that can be used to complement clinical trial data. Patient input can provide a guiding influence during scoping:

		In a review of therapies for non—small cell lung cancer (NSCLC),

 patient groups noted that levels of distress and anxiety are particularly high for patients with lung cancer. As a result, ICER looked for evidence that the therapies being assessed affected these outcomes. When ICER did not find such evidence, a discussion in the report of other potential benefits and disadvantages of the therapies noted this absence. The report also raised issues about generalizability from randomized trials, as patients in clinical trials may have greater resources, potentially leading to lower levels of distress than experienced by the general population of lung cancer patients.

The perspectives and evidence from patients and patient groups thus help inform ICER’s analysis of comparative clinical effectiveness and guide a description of “other benefits or disadvantages” included in every ICER report. Other benefits or disadvantages include important elements of overall value that may not be captured in the available clinical evidence or in a cost-effectiveness model. These elements include the potential for some treatments to ease family and caregiver burden, offer new modes of administration that can simplify treatment regimens, or allow patients to return to work or other activities earlier in treatment: 

		The ICER report on treatments for multiple myeloma discussed input received from patients on the benefit of having oral treatment options available.

These may also include contextual considerations, such as issues of equity:

		Based on patient input, ICER’s NSCLC report noted that lung cancer disproportionately affects patients in lower socio-economic groups who are least able to deal with the financial toxicities of treatment.

 The report also noted input from patient groups, pointing out that patients with NSCLC often have high rates of vascular and pulmonary comorbidities, which would have excluded many of them from clinical trials of newer therapies. Some newer therapies, however, are better tole-rated by patients with poor performance status than are older treatments, and so only comparing newer agents to existing treatments in randomized trials with restricted entry criteria misses a potential “other benefit”: the use of these agents in patients who would never have been candidates for treatment previously.

With the patient perspective firmly embedded in the analysis of comparative clinical effectiveness and other benefits or dis-advantages, an initial draft version of an ICER report is posted for a 4-week period to gather public comment. At this point, all stakeholders, including patients and patient groups, see how ICER has described the clinical and cost-effectiveness evidence and put them into context. This public comment period allows patient groups to express concerns if they feel that their perspectives have been inadequately or incorrectly addressed.

A revised draft report based on this further input becomes the subject of a public meeting of one of ICER’s independent appraisal committees. Each of these committees includes practicing clinicians, methodology experts, and public representatives with a background in patient advocacy. At the public meeting, there are numerous opportunities for additional patient input. First, with invited patient community representatives at the table, the information in the report on comparative clinical effectiveness and other benefits and disadvantages is debated by the appraisal committee and formally weighed as part of a vote on the long-term value for money of the treatment under consideration. Before votes are taken, there is another opportunity for public comment during which other patients and/or representatives of patient groups have the opportunity to speak. The cumulative impact of hearing from the invited patients and additional public commenters contending with issues of illness, disability, treatment, adverse effects, and insurance coverage is substantial in informing the way that the evidence is interpreted by the committee in its votes.

Following the voting, each meeting concludes with a moderated roundtable discussion that includes invited patients, expert clinicians, and representatives from the payer and manufacturer communities. The goal of this discussion is to frame recommendations for how best to apply the evidence to guide practice as well as medical policies, such as coverage and pricing determinations. Here, again, patient input is central: 

		At the ICER meeting on multiple myeloma, patients pointed out that as they live longer and are on treatment longer, manufacturers are receiving more money over time for their treatment. This led to a recommendation that manufacturers consider this effect when setting prices.

		The ICER report on treatments for moderate-to-severe plaque psoriasis found that all the targeted immunomodulators provided reasonable long-term value for money.

As such, the report recommended that insurers consider abolishing step-therapy requirements—a major concern raised by patients. 

Without input from patients, ICER’s reports would lack critical perspective on how a condition affects day-to-day life, the financial and insurance challenges patients face in accessing their treatment, information about what outcomes or adverse effects hold most importance to patients, and much more.

The traditional system through which manufacturers develop and price new drugs, and through which insurers evaluate evidence and make coverage decisions, has lacked transparency and offered few opportunities for patient input. We believe that ICER’s efforts to incorporate the patient perspective—through engagement in the HTA process, and through fostering a public dialogue&mdash;is an important step towards a more evidence-based healthcare system that can achieve high value while being grounded in clinical experience and firmly centered on advancing the best quality of care for all patients. 

is chief medical officer, Institute for Clinical and Economic Review, Boston, MA.

is executive vice president and chief operating officer, Institute for Clinical and Economic Review, Boston, MA.

Chief Medical Officer, Institute for Clinical and Economic Review

2 Liberty Square, Ninth Floor, Boston, MA 02109

1. Guide to open input. Institute for Clinical and Economic Review website. http://icer-review.org/wp-content/uploads/2016/02/ICER-Guide-to-Open-Input-012417.pdf. Accessed March 30, 2017.

2. Perfetto EM, Oehrlein E, Boutin M, Reid S, Gascho E. Value to whom? the patient voice in the value discussion. 

2017;20(2):286-291. doi: 10.1016/j.jval.2016.11.014.

3. Patient participation guide. Institute for Clinical and Economic Review website. https://icer-review.org/patient-participation-guide/. Published January 2017. Accessed March 30, 2017.

4. Treatment options for advanced non-small cell lung cancer: effectiveness, value and value-based price benchmarks. Final evidence report and meeting summary. Institute for Clinical and Economic Review website. https://icer-review.org/wp-content/uploads/2016/10/MWCEPAC_NSCLC_Final_Evidence_Report_Meeting_Summary_110116.pdf. Published November 1, 2016. Accessed March 30, 2017.

5. Treatment options for relapsed or refractory multiple myeloma: final evidence report and meeting summary. Institute for Clinical and Economic Review website. https://icer-review.org/wp-content/uploads/2016/06/MWCEPAC_MM_Final_Evidence_Report_061016V3.pdf. Published June 9, 2016. Accessed March 30, 2017.

6. Targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: effectiveness and value. Final evidence report. Institute for Clinical and Economic Review website. https://icer-review.org/wp-content/uploads/2016/11/NE_CEPAC_Psoriasis_Evidence_Report_FINAL_012317.pdf. Published December 2, 2016. Accessed April 3, 2017. 

The Institute for Clinical and Economic Review (ICER), has established a robust health technology assessment strategy for engaging patients so that the entire process is informed by the patient experience and what “value” means to them.

ICER's Value Assessment Framework: Capturing the Patient Experience

Both Republicans and Democrats agree healthcare is too expensive in the United States. While a focus of the potential repeal of the Affordable Care Act (ACA) is how access to care will be affected, the cost of delivery and quality of care remain ascendant challenges. Patients and payers continue to demand high-quality care and sophisticated tools to demonstrate care quality. Therefore, it is a fundamental premise that providers and health systems who want to succeed in this uncertain environment must remain focused on delivering value—the highest-quality care at the most efficient price. 

While numerous questions remain about how healthcare “re-reform” might look, many important insights into President Donald Trump’s potential path forward have been identified. Six key trends indicate that high-value care will remain the important differentiator for successful health systems and providers: 

Greater consumer responsibility for health spending. 

The existing trend of shifting costs to consumers and patients is unlikely to be slowed by any of the proposals set forth by Trump or his Cabinet. In fact, greater use of tax credits and health savings accounts is likely to accelerate this shift. An increasing array of online tools makes it easier for consumers to identify lower-cost providers and to differentiate based on quality. As more of the cost of care comes directly out of consumers’ accounts, expect continued shifts away from high-cost providers. This shift is already evident in such areas as elective outpatient imaging. 

Sustained pressure on Medicare spending. 

Medicare makes up 15% of the federal budget today

 and is unlikely to see support for large spending increases from HHS Secretary Tom Price, MD, or CMS Administrator Seema Verma. Even as specific programs change and evolve within CMS, controlling costs will continue to be a priority for the new administration, especially with Speaker Paul Ryan, R-Wisconsin, leading the House. 

Continued demand for high-value, low-cost healthcare from employers. 

According to data collected by PwC’s Health Research Institute, health insurance premiums are expected to increase by 6.5% in 2017.

In addition, more than half of all Americans get health insurance through their employers and these employers are feeling crushed by rising costs. Employer focus on controlling costs, such as through the use of high-deductible health plans, will remain a key component in healthcare selection. It is likely we’ll see a rising number of employers enabling access to care via on-site primary care clinics available to employees. Partnerships with major insurers to provide coverage outside of these clinics will remain, but the majority of care will be administered and managed from primary care sites managed by the employer. 

Changes such as allowing interstate sales of health insurance products are likely to drive competition among payers for increasingly price-sensitive consumers and cost-conscious employers. This competitive environment will drive continued growth of emerging plan structures, such as tiered benefits and narrow networks that seek to reward high-value providers and to punish high-cost, highly variable ones. It’s also likely that more payers will launch bundle programs through these narrow networks with providers who focus on high-value care in specialist areas. This will drive further consolidation through the integration of multiple care settings, such as ambulatory surgery centers and integrated delivery networks. 

Increased experimentation at the state level. 

Those advocating for ACA repeal want increased control at the state level, especially for Medicaid. Paying attention to local state environments is likely to be even more important in the coming months and years. We’ll likely see strong success stories, and some failures, that will provide lessons for the whole nation.

Lessening the role of Center for Medicare and Medicaid Innovation (CMMI). 

Republicans have pushed back on the mandatory reporting requirements and participation in programs that have come out of CMMI. In September 2016, a group of 178 House Republicans and 1 Democrat signed a letter asking CMS to “cease all current and future planned mandates” under CMMI. The letter denounced new initiatives as potentially compromising patient care, as “patients are blindly being forced into high-risk, government-dictated reforms with unknown impacts.”

Other broad criticism from lawmakers includes the opinion that there are too many federal programs to manage.

 While Democrats argue that important innovations are more likely to be discovered by exploring different approaches, Republicans are skeptical that federal agencies can generate innovation; the latter party defers the role to states or other stakeholders like private payers. With a new Republican Congress, we could see a refocusing on certain programs that have already produced results, like bundled payments.

Continued pressure to control costs will escalate this year, both inside and outside Washington, DC. Health systems and providers need to recognize that variability of both quality and cost are becoming large influencers of payment decisions and patient choice alike. Legislation and existing regulation, like the Medicare Access and Children’s Health Insurance Program Reauthorization Act, already create the impetus for moving away from a fee-for-service world. One of the most important components of any plan that would aim to improve quality and reduce costs is to engage physicians in the process of standardizing care. 

is a professor in the School of Medicine, University of California at San Francisco and in the Fielding School of Medicine, University of California at Los Angeles. He is also the founder and president of QURE Healthcare. 

1. Cubanski J, Neuman T. The facts on Medicare spending and financing. Kaiser Family Foundation website. http://kff.org/medicare/issue-brief/the-facts-on-medicare-spending-and-financing/. Published July 20, 2016. Accessed February 23, 2017.

2. Sullivan P. Lawmakers call for end to Medicare ‘experiments.’ 

website. http://thehill.com/policy/healthcare/298769-lawmakers-call-for-end-to-medicare-experiments. Published September 30, 2016. Accessed February 23, 2017.

3. Medical cost trend: behind the numbers. PwC website. https://www.pwc.com/us/en/health-industries/health-research-institute/behind-the-numbers.html. Published June 2016. Accessed February 23, 2017. 

4. Casalino LP, Bishop TF. Symbol of health system transformation? assessing the CMS innovation center. 

. 2015;372(21)1984-1985. doi: 10.1056/NEJMp1500457. 

It is a fundamental premise that providers and health systems who want to succeed in the existing uncertain healthcare environment must remain focused on delivering value-the highest-quality care at the most efficient price. 

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ICER's Value Assessment Framework: Capturing the Patient Experience

Healthcare Re-Reform: Value-Based Care Remains a Constant Theme