 For many years, the oncology industry has progressed toward standardized care using evidence-based pathways as a method of improving outcomes and reducing the cost of cancer care. Now, one of the most widely talked about trends in healthcare is precision medicine, which uses detailed genetic information about a patient’s cancer to more precisely treat the disease, effectively targeting the tumor. This heightened awareness raises an important question: are precision medicine and pathways compatible?

On the surface, precision medicine and pathways seem to conflict with each other. After all, it seems counterintuitive for physicians to “personalize” care based on a patient’s genetic make-up, yet also follow standardized treatment guidelines set forth by evidence-based pathways. A closer look at the goals and methods of both, however, reveals that not only are precision medicine and pathways compatible, but they are also similar and most certainly complementary, in some ways.

	As a result of ongoing research and drug development, the number of drugs available for treating cancer has significantly increased. Variation in treatment patterns can vary widely, and accumulated evidence suggests that some treatment options are more effective and/or less toxic than others. Both precision medicine and pathways help identify appropriate diagnostic testing, procedures, and effective treatment options. Pathways, developed and adopted by oncologists, use broad-based guidelines as a foundation to narrow treatment recommendations. They originated as a means of standardizing care, with the primary goal of improving the quality of care patients receive, and are designed to limit variation without compromising clinical efficacy. The goal of pathways is to match the right patient with the right treatment. Sounds familiar, right? When you look at precision medicine, the goal is very similar. By understanding more specifically a tumor’s biology, drug developers can focus on treatment that specifically targets the mutation causing the tumor or the tumor’s growth. Precision medicine is not a new concept. It has been around for quite some time and has already proven that increasing understanding and knowledge of human genomes and their effect on cancer and other diseases has a profound effect on how we assess risk and make treatment decisions. Perhaps the most well known example is the identification of HER2/neu protein expression. This important discovery in the mid-1980s dramatically changed the way we identify women with elevated risk due to HER2 protein overexpression, as well as how we treat women with HER2-positive breast cancer.

 mutation, which may be present in a subset of patients with non-small cell lung cancer (NSCLC). In 2011, ASCO issued a provisional clinical opinion on using 

 testing to help predict the benefit of treating patients with advanced NSCLC with an EGFR-targeted tyrosine kinase inhibitor (TKI). This recommendation occurred because data were reported that indicated that lung cancer patients with an 

 mutation are more likely to respond to targeted therapy compared with patients without the mutation. Pinpointing this mutation in patients who have NSCLC helps direct oncologists to the most effective treatment option. The recommended first-line treatment for patients with NSCLC with the mutation is an EGFR TKI instead of the conventional approach of combination chemotherapy for patients without the 

	These examples highlight an important link between precision medicine and pathways. In both cases, identification of genetic mutations is key to offering treatments most likely to have a beneficial effect on a patient’s disease. In addition, pathways, developed by reviewing research, best practices, and expected outcomes, point physicians to the lines of treatment proven to impact the quality of patient care and lead to improved outcomes.

	Since President Obama’s announcement of the Precision Medicine Initiative earlier this year, precision medicine has received a great deal of attention. There has been much discussion about the role it will play in how physicians diagnose and treat patients in the future. Most experts agree that it will have a major impact on the future of healthcare as physicians are able to more specifically target treatment to a patient’s disease.

	The hope is that the investment in precision medicine by the National Institutes of Health will deliver on its promise to speed the rate of advancing knowledge about many diseases. As it does, it will also create the need for doctors to discern which patients should be tested for which mutations and when. As with most new diagnostics testing, technologies, and treatments, genetic testing costs can be significant and are not necessary or recommended for every patient. Not only will pathways continue to be relevant as a means to reduce variance in care and thereby improve outcomes, but they will also be important tools for providing guidelines to physicians on how and when to employ testing.

Jody Sheehan Garey, PharmD, is senior manager of clinical content & pharmacy services for McKesson Specialty Health and The US Oncology Network.

Articles

One of the most widely talked about trends in healthcare is precision
medicine, which uses detailed genetic information about a patientâ€™s cancer to
more precisely treat the disease, effectively targeting the tumor. This heightened
awareness raises an important question: are precision medicine and
pathways compatible?

Compatibility Check: Can Precision Medicine and Pathways Co-Exist?

Site neutrality sounds like something from the Cold War—a zone on a bridge between two ideologically different countries, for instance. In oncology, it’s something completely different. It’s actually the idea that large institutions like hospitals should not be compensated more for delivering the same services that private practices do. It has received a lot of emphasis as a goal in President Obama’s 2016 budget, but it’s not getting consistent support within the medical community.

Much of the payment structure associated with oncology has a built-in aspect. If you want to change something, you are liable to cause a great deal of disruption to an awful lot of people whose livelihoods and investments depend upon the status quo.

There’s another quality to the resistance to site neutral payments in oncology. There is the argument that if you throw in all of the ancillary services that large hospitals provide in addition to plain-vanilla oncology, you are technically able to claim that there is, in business parlance, a lot of “value added.” In other words, for all of the extra money patients are spending for oncological care at a city center hospital, they are getting their money’s worth.

This is the argument that ASCO has put forth in a recent attempt to influence the public discussion of the merits of switching to a site-neutral payment structure for Medicare. ASCO contends that such a move would be arbitrary and far less successful than what it recommends be done: create a patient-centered approach that diverts more resources toward implementing value care that heads off expensive treatment through proper intervention.

Associations of community physicians, for their part, contend that the payment differential for hospital versus private practice care is simply too wide to be justified by any ancillary services delivered. They cite the huge markups that can be 100% or more for standard procedures. Community practices not only deliver these services for significantly less payment, some might argue that it is better to specialize by allowing community practices to do what they can more economically and leave the rest to the bigger facilities.

There seems to be merit to both sides of the argument, but undoubtedly, there is room enough within the bigger picture for some acknowledgement that perhaps the lopsided payment structure is a little unfair to community practices, and also that there may be some unfunded services within the larger institutions that are subsidized, in part, by the higher Medicare payments afforded them for oncological care.

It is certainly hard for an entrenched lobby organization to offer concessions in a debate that could leave its membership with a disastrous readjustment in the aftermath. But one only has to look at the example created by the 340B program to see the long term results of such a willful game of myopia.

We do need our community oncology practices. To continue insisting that they do the same quality job as the bigger cancer centers while working with such a huge payment disadvantage is not only unreasonable, it could be construed as reckless. On the flip side, let’s do what we can to promote interventional care so that expense liability can be contained down the line.

Site neutrality sounds like something from the Cold Warâ€”a zone on a bridge between two
ideologically different countries, for instance. In oncology, itâ€™s something completely different.

Work Out the True Value of Services Rendered

In the end, it was much ado about almost nothing. Certainly, there have been worse complications brought on by lesser events, said Kathy Oubre, chief operating officer for Pontchartrain Hematology Oncology in Covington, Louisiana, a practice of two clinics, two MDs, a nurse practitioner, and 17 support staff.

The advent of ICD-10—the compendious new set of medical codes that threatened to submerge practices underneath mountains of rejected claims and red tape&mdash; turned out to be a lot like the Y2K scare of 15 years ago when a structural programming characteristic dating from the dawn of the computer age seemed likely to cause the digital world to grind to a halt.

ICD-10, more formally known as the 10th version of the International Statistical Classification of Diseases and Related Health Problems, was imposed by the Centers for Medicare & Medicaid Services (CMS). Starting October 1, CMS began requiring medical workers to use codes from among the 150,000 available for diagnosis coding, procedure coding for inpatient services, and other health services. Oubre said staff in her clinic were well prepared for the changeover from the older, smaller set of medical codes known as ICD-9 and that the numbers on payer rejections or denials were no worse in October than they were in September before the switch.

“That was my big concern, what the payers were going to do, but we didn’t have a large rise in denials or claim rejections,” Oubre said. “We’ve seen a slight reduction in our reimbursement from Medicare, but not a significant one.”

Oncology claims consultant Roberta Buell, a principal with onPoint Oncology of San Francisco, said that her data from 150 non-hospital practices, representing 2000 physicians around the country, bears out the statements made by individual physicians for this article in that ICD-10 so far has not caused a significant disruption in the payment cycle.

She cautions that it will take more than a month to get an accurate picture on whether coding issues have gummed up the system in the wake of the October 1 initiation. “I don’t know whether we’re seeing the tip of the iceberg or whether this will hold out. It’s very hard to say. We don’t have a tremendous amount of data.”

Buell said there have been some issues. For example, claims for erythropoiesis- stimulating agents such as Procrit, Epogen and Aranesp have been rejected more than others. Buell said that’s probably because physicians may have assumed that there was a grace period that applied to these drugs and that coding issues would be overlooked. That isn’t the case. In addition, there have been more claims rejected for not being “medically necessary,” and the cause of that may be incorrect coding, but it is not clear yet what is happening, she said.

Newer drugs, for which codes have not yet been established, may be a source of payment bottlenecks, she added.

Ultimately, however, things have gone far more smoothly than she expected, and she said that observation is supported by remarks she has heard from practitioners.

Oubre, a member of the administrative network of the Community Oncology Alliance, sat in on a roundtable in October that included other private practice representatives who also reported only minor problems connected with the changeover.

“Most are not seeing a significant bump in denial rates,” she said. Bigger problems resulted when the Centers for Medicare & Medicaid Services began rolling out National Provider Identifier numbers, which caused a “40% to 50% cut in our Medicare payments,” Oubre recalled.

Oubre is among the oncology professionals who envision strong benefits coming out of the transition, including a far greater store of useful data on cancer that can help to identify trends and population characteristics. For example, a broader array of codes has been established to identify where in a patient’s body certain neoplasms have occurred, such as the left or right breast or the left or right lung. For hematology, vitamin deficiencies can be identified with far greater specificity under ICD-10 than before. 

“I’m excited about seeing the data that comes out from this a year from now,” Oubre said. I’m interested in that, and I think that’s going to be really relevant for us. It’ll allow us to tighten our standard of care and understand even better what we can do for the patients moving forward. It might take some extra time right now, but I think it’s going to have significant benefit.”

		Figure 1. Hematology - ICD-10 Before and After

		Source: Blue Cross Blue Shield of Michigan, 2014.

The extra time involved to look up new codes and input them where appropriate has certainly added to the physician’s daily workload, said Philip Stella, MD, chair of the ASCO Government Relations Committee and medical director of the Oncology Program at St. Joseph Mercy Hospital Cancer Center in Ypsilanti, Michigan. He has not yet seen the numbers on payer denials or rejections and says the greater workload has had the biggest impact so far.

Such an administrative workload addition falls into the ranks of “unfunded mandates,” he said. However, like Oubre, Stella agrees that there will be long term advantages to ICD-10, among them the detailed documentation that will help physicians to make their case that they are improving their game when measured against the new reporting and performance standards that will be imposed under the Medicare Access and CHIP Reauthorization Act of 2015, otherwise known as MACRA.

“A smart practice will figure out ways of making sure that all those comorbidities are in there so that they can really appropriately compare and try to make sure that they’re accurately depicting the patient population,” he said. This will enable fair and realistic comparisons to be made when evaluating practice performance. “They can match it and see how you’re doing, above the mean or below the mean, or whatever cutoff they use, to give you either a penalty or a step up in reimbursement or a bonus,” he noted.

		Figure 2. Oncology: ICD-10 Before and After

It’s not as though this has been stated officially as a primary reason for switching to ICD-10, but it makes sense for practices that they see the value of these codes in helping to distinguish their efforts where misunderstandings might otherwise arise, Stella added. “What’s going to happen is the more accurately they code to get those co-morbidities, the better off we’re going to be.”

Both Stella and Oubre said that in the aftermath of the heavy training and preparation for the changeover, physicians and other health staff appear to be well adjusted to using the new set of codes. “We had all the docs go through an educational program because [ICD-10] raised huge questions— are people going to be ready?” Stella said. “For all the radiology tests that you have to do, you have to have ICD-10s in there. So, there was a lot of coordination; there was a lot of work to make that happen. By now, we’ve pretty much adjusted to it.”

There’s still a great deal of system integration required to update former ICD-9 codes to ensure payment and tracking continuity, but Oubre said her practice in Louisiana is already back on its former schedule after reducing patient scheduling as a contingency measure during the first part of October. Members of staff are feeling more confident the further along they go with ICD-10, she said. “This was just one other event, and I think we’re stronger because of it. We’re ready to move forward.”

The advent of ICD-10 turned out to be a lot like the Y2K scare of 15 years ago
when a structural programming characteristic dating
from the dawn of the computer age seemed likely to cause the digital world
to grind to a halt.

ICD-10 Blows Over Like Y2K

The National Comprehensive Cancer Network (NCCN) announced a new series of cancer regimen guidelines that incorporate cost considerations to aid and facilitate broader discussion between physicians and patients about treatment.

The NCCN, a nonprofit alliance of 26 cancer centers, said its Evidence Blocks combine efficacy, safety, quality of evidence, consistency of evidence, and affordability, and represent those variables simply in a matrix block that awards each of the criteria a score from 1 to 5, with a score of 1 being the lowest.

The first two sets of evidence blocks were released for treatment options for chronic myelogenous leukemia (CML) and multiple myeloma (MM), with as many as four more sets to be added by the end of this year, 10 next year, and the remainder — for all 61 NCCN guidelines – to be finished by the end of 2017.

Affordability of the regimens in the guidelines is based on a spectrum of cost considerations that include the overall treatment cost, toxicity, and other elements of care, and not just the cost of a particular drug, Robert Carlson, MD, CEO of the NCCN, said.

“We did not provide a dollar amount, because as soon as you do, your methodology requires that, and dollar amounts are virtually impossible to come by,” Carlson said in a press conference.

Carlson said variability of costs between treating institutions and also individual differences in patient condition and choices in care complicate the search for exact cost totals for particular regimens; however, he said there was very strong consistency in consensus estimates of cost among panelists who contributed to the matrix rankings compiled so far.

Even so, simply having an affordability ranking assigned to a particular regimen can constitute a valuable aid to a patient who is facing a huge amount of information and struggling not only to comprehend the treatment choices available but also to overcome the shock and confusion associated with the emotional blow of having a cancer diagnosis, said cancer patients who spoke in support of the Evidence Blocks at the press conference.

“The evidence block demystifies the discussion of cost,” added George Somlo, MD, of City of Hope Comprehensive Cancer Center of Duarte, California, a member of the NCCN Guidelines Panels for Breast Cancer and Multiple Myeloma.  “Very few physicians are competent to talk about affordability,” he said.

A large proportion of personal bankruptcies have been shown to be the result of a medical expense pile-ups, and physicians are not sufficiently aware of the financial impact treatment decisions are having on their patients, Somlo said.

“My suspicion is that the physicians who were treating those patients had no clue what they were doing to those patients’ finances,” he said.

The Evidence Blocks are assigned to multiple possible regimens, and, further, regimens are divided into preferred and less-preferred columns. Somlo explained that comparative data and the amount and quality of evidence are key to which column a regimen appears in, with solid phase III evidence being a main determinant. This, he said, would explain why a hot new therapy with great potential would end up in the less-preferred column, as sufficient trial evidence had not been accumulated.

Ideally, patients and doctors would hold in-depth discussions about the multiple factors that go into individual treatment decisions, Carlson and Somlo said. Whereas cost might be a more important consideration for one patient than another, the risk of neuropathy might be a greater consideration to a professional pianist who relies on finger sensitivity, they said.

	Breast cancer survivor Marta Nicols, who has become a patient advocate since her diagnosis 10 years ago, said the Evidence Blocks provide critical simplification of the process for patients who are facing “an entirely different language” when they are first exposed to the breadth of treatment options and medical terminology.

	There’s much more pressure on the patient, given the wider variety of treatment options, to participate in selecting a course of therapy, she said.

	“Today, it’s intended to be a collaborative process, where the physician is expecting the patient to make the decision,” Nicols, vice president of investor relations for GoDaddy, said.

	The NCCN Evidence Blocks are but one of an increasing number of efforts lately to incorporate value into the treatment process. ASCO earlier this year came out with a rating system that it said was also in its prototype stages but that would be evolve into a means of assessing the value of new cancer therapies based on treatment benefits, toxicities, and costs.

	In response to the NCCN announcement, ASCO Chief Medical Officer Richard L. Schilsky, MD, FACP, FASCO, said, “We believe that increasing efforts by different stakeholders in the cancer community to define value in cancer care further underscores the need for more transparency and information for patients and their doctors in making sound treatment decisions.

The NCCN announced a new series of cancer regimen guidelines that incorporate cost considerations to aid and facilitate broader discussion between physicians and patients about treatment.

NCCN Evidence Blocks Inject Cost into Doctor-Patient Talk

The jury is still out on whether use of an algorithm to help classify risk levels in ovarian cancer can improve overall survival (OS), but a company is already marketing the system in Britain and plans to bring it to the United States before the end of the year, and women’s advocacy groups here are working out strategies for handling the interest in early testing that may result.

Results of the UKCTOCS trial of 200,000 postmenopausal women are expected out in mid-December on whether the ROCA (Risk of Ovarian Cancer Algorithm) reduces the number of women who die from the disease. ROCA is based on the idea that changes in CA-125 (glycoprotein) levels when measured on an individual basis can give better information about a woman’s health pattern than if assumptions are made on population characteristics in general.

Nevertheless, gynecologic oncologists say that the CA-125 test does not stand by itself as a fully reliable diagnostic tool and that careful study of UKCTOCS results will be needed to justify any assertions that the ROCA algorithm raises the test to the level of a routine screening tool.

“Previous trials have shown that screening results in excessive unnecessary surgery and associated harms, as well as patient anxiety, so any findings would have to include a careful assessment of this before changes in practice could be adopted,” says Elizabeth Suh-Burgmann, MD, chief of gynecologic oncology at Kaiser Permanente Walnut Creek Medical Center, California.

CA-125 levels are measured in monitoring of ovarian cancer treatment effectiveness, detection of recurrence, and screening for high-risk women. Tests have traditionally relied upon a cutoff point, above which levels of CA-125 may indicate disease progression. The UKCTOCS trial sought to examine whether the CA-125 test could improve survivability by detecting disease earlier in progression. Changes in women’s individual levels of CA-125 were measured and risk levels assigned using ROCA.

Initial UKCTOCS results issued in May of this year indicated that of 296,911 annual screens done over an average of 3 years follow-up, 640 women underwent surgery and 133 were found to have ovarian cancer, leading researchers to conclude that screening methodology had an 85.8% sensitivity for ovarian cancer. For each case of ovarian cancer, 4.8 operations were performed.

 Basing risk on a cutoff level would have identified only half the women with ovarian cancer, the researchers concluded.

Results of the trial due out in December will show whether there was an improvement in OS. However, marketing of ROCA by British company Abcodia is already under way with claims that the algorithm has been “validated” through trials and represents “a powerful aid to clinical decision making for the early detection of ovarian cancer.”

Abcodia is offering the test for postmenopausal women between 50 and 85 and those 35 to 85 who have ≥10% lifetime risk of ovarian cancer.

There is strong interest in a potential early screening tool that would enable physicians to catch the disease in early progression when the prospect of a cure is much greater, but oncologists are concerned about the potential for over-enthusiasm.

Previous trials have shown as many as 85% of women with ovarian cancer have elevated CA-125, and < 1% of woman without ovarian cancer have elevated values. High or low values may have no significance. For example, about 50% of stage I ovarian cancer patients have normal CA-125 values, as do the majority of patients with mucinous ovarian cancers.

“CA-125 has been a great marker with which to follow high grade, serious ovarian cancers, and it is the most common indication of recurrent disease after initial chemotherapy,” says Franco Muggia, professor of medicine (oncology) at New York University Perlmutter Cancer Center, and former chair of the Medical Oncology Committee of the Gynecologic Oncology Group. “However, as a screening tool even in high-risk populations, it has not been proven useful. In particular, a high value in premenopausal women has very low specificity.”

Burgmann agrees that UKCTOCS has shown improved sensitivity and specificity compared with use of a CA-125 benchmark. Strong data on OS could provide a compelling argument for the adoption of screening, Burgmann says, but she worries that objectivity may have been compromised, based on the early marketing of ROCA.

“It was developed in the UK and has been licensed to a private company in the UK who is advertising it already on their website as being clearly beneficial despite the lack of definitive data to this effect. This troubles me as it raises concerns about potential conflicts of interest. As with all trials, any conclusions will need to be reviewed carefully before making changes in patient care,” Burgmann says.

Testing that looks at variations in a woman’s CA-125 values has been endorsed by CA-125 discoverer Robert Bast, MD, of MD Anderson Cancer Center.

“Most encouraging is, if you use CA-125 in this manner only 1% of women will undergo ultrasound each year, and you ignore a lot of the benign disease that you would detect on imaging that would result in unnecessary surgery to be certain that the lesion is benign. Consequently, the specificity is much, much higher, so you do only 3 operations for each case of ovarian cancer detected instead of 30,” Bast told 

Researchers at MD Anderson indicate that the search for screening tools has gone far afield and has come back to CA-125 over the years, and that the elusive “Holy Grail” of early testing may eventually reveal itself as having some core constituency in CA-125.

In the UK, ROCA testing is offered on a self-pay basis for about $230; whereas here, Abcodia will roll out in a few states initially with a nationwide launch in 2016, according to a June report by Genomeweb.

 The company hopes to persuade payers to cover the test and hopes to gain FDA review, which, though not essential for marketing, could speed public acceptance.

In the United States, much of the action from ROCA screening would first go to primary care providers, if the test becomes part of a woman’s regular health checkup, says Teri Guidi, president and CEO of Oncology Management Consulting Group of Pipersville, Pennsylvania. Getting payer coverage might be a challenge, she adds.

To date, payers have been mostly willing to cover traditional CA-125 testing, as it is relatively inexpensive, says Calaneet Balas, CEO of the Ovarian Cancer National Alliance. Like other women’s health advocates, she is interested in what is reported from the UKCTOCS trial this December, but her enthusiasm is tempered by past results. “There might be too much faith out there in CA-125 as a point-in-time test for early detection of ovarian cancer,” she says. “I often hear women say every woman should get a CA-125, but that’s not necessarily the case.”

Strong OS findings from UKCTOCS won’t answer the question whether young women should go for regular screening, Balas notes.

“If the results are positive and we see an overall survival rate, that’s tremendous—that’s more than this community has seen in over 40 years. We’d like to see that. We also recognize that this is a study that has been looking at postmenopausal women, so this does not give us data about young women.”

As the debate over CA-125 remains vigorous and the UKCTOCS findings could foster a move toward regular testing, Balas and her fellow advocates have been thinking about their response. “We’ve talked about what the advocacy needs to be in order to get a regular test implemented, especially for women at higher risk.”

			Menon U, Ryan A, Kalsi J, et al. Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening [published online May 11, 2015]. 

			Bonislawski A. Abcodia to launch ROCA ovarian cancer test in UK and US this year. Genomeweb. 2015. https://www.genomeweb.com/proteomics-protein-research/abcodia-launch-roca-ovarian-cancer-test-uk-and-us-year. Published June 5, 2015. Accessed October 6, 2015.

The jury is still out on whether use of an algorithm to help classify risk levels in ovarian cancer can improve overall survival but a company is already marketing the system in Britain and plans to bring it to the United States before the end of the year.

November 2015 | Oncology Business News®

Compatibility Check: Can Precision Medicine and Pathways Co-Exist?

Work Out the True Value of Services Rendered

ICD-10 Blows Over Like Y2K

NCCN Evidence Blocks Inject Cost into Doctor-Patient Talk

Early Marketing of ROCA CA-125 Ovarian Test Sparks Concern