Twenty years ago, the National Comprehensive Cancer Network (NCCN) began as a cooperative effort of 12 prestigious cancer centers, working to define and promote national guidelines for the care of patients with cancer. A major goal was to encourage uniformity in the management of malignant diseases, such that U.S. cancer patients could be assured of receiving up-to-date, science-based, standard-of-care management, regardless of their point of entry into the care system.
In large measure, NCCN has been a stunning success, having now grown to 26 member institutions. Its published guidelines, compendium, and educational offerings have indeed become a national treasure. Further, its international reach is apparent from the large number of guideline inquiries that come from beyond U.S. borders.
Just as physicians have looked to NCCN for authoritative guidance in patient care, agencies such as the Center for Medicare & Medicaid Services (CMS) and numerous commercial payers couple insurance coverage with NCCN Guidelines, which are designated as one of the three approved compendia for reimbursement. At one point several years ago, Medicare even offered additional payment for office visits where documented care was in compliance with NCCN Guidelines. Veterans Affairs clinician notes today generally include a statement indicating that patients were informed of NCCN Guidelines for their particular diagnosis.
In effect, NCCN’s profound influence on oncology care has come to define a national standard for reimbursement in many instances and for determination of quality of care in other settings. Reimbursement and quality have always been important, but more so now that the term “unsustainable” is frequently and legitimately used to describe new (and sometimes old) oncology drug costs, which often exceed $10,000 per month.
The Way Forward
Going forward, there are shortcomings in medical oncology practice that NCCN can help address. To begin, physician compliance with clinical guidelines is far from universal. Physician requests for oncology drugs are often “custom-crafted” and not supported by consensus-based scientific guidelines such as those developed by NCCN or other evidence-based guidelines such as those developed by ASCO, Cancer Care Ontario, or other guideline organizations. Sometimes this is because the physician is unfamiliar with treatment algorithms for a given disease or is requesting a “promising but unproven” therapy, in advance of U.S. Food and Drug Administration (FDA) approval or support from an NCCN Guideline that is directly linked to reimbursement.
In many cases involving Medicare, Medicaid, or private health insurers, it is the responsibility of preauthorization utilization review to weed out oncology drug requests that are not compliant with a guideline from an organization such as NCCN or other compendia for which reimbursement is linked—much to the dismay of physicians who regard such interventions as high-handed, intrusive, wasteful of precious clinic time, and counter to the best interests of their patients. Insurers legitimately oppose payment in most of those situations, though it is not uncommon for compassionate exceptions to be made in situations where other standard options have been exhausted.
Cost Issues
Until now, most clinical guidelines offered no guidance in terms of value. Equally effective drug choices may be listed side by side in guidelines, one very costly and the other less so, offering the physician no information about “choosing wisely” between the two options.
In the United States, the FDA and the CMS do not weigh in on drug costs. A physician is left to figure it out alone—a difficult assignment amid a busy office day—sometimes resulting in the “dreaded” phone call from a utilization management physician who is making the case for equally effective care utilizing a less costly or less toxic regimen. As more novel prospective payment models appear online, oncologists will be more in need of a quick and efficient reference for factoring drug costs into regimen prescriptions. We are pleased that NCCN and ASCO have reported that help is on the way.
Evidence Limitations
Although the vast majority of consensus-based NCCN recommendations are based on solid level 1 scientific evidence, there are examples where recommendations from a consensus of an NCCN committee do not reflect evidence-based information. For instance, the combination of two costly long-acting antiemetics is supported by NCCN for use in chemotherapy regimens with moderate risk of nausea and vomiting, although no level 1 scientific evidence supports this regimen, and a combination of a short-acting and a long-acting agent is much more cost-effective.
Formerly, the febrile neutropenia risk of carboplatin/paclitaxel regimens was listed as high by the NCCN Guidelines, until physicians advised NCCN that only patients of Asian ancestry were at that level of risk. NCCN subsequently amended its recommendations. For reasons that are unclear, FDA-approved doxorubicin fell off the NCCN list of active agents for treatment of ovarian cancer, in favor of liposomal doxorubicin; the former was reinstated in response to a petition to NCCN from clinical oncologists.
Most recently, NCCN has supported the use of biologic agents in some cases of non–small cell lung cancer (NSCLC) that share molecular/genetic markers with other neoplasms such as breast cancer and melanoma, with no level 1 data to support that extrapolation. Two of these agents have subsequently been removed from the NCCN list of recommended drugs.
NCCN shoulders the obligation that all of its guidelines, which are relied on for quality and/or reimbursement considerations, must stay with the data, not venture prematurely into promising therapies that have not yet met full scientific scrutiny, and avoid supporting regimens that are commonly used but unsupported by solid scientific evidence. A particularly worrisome downstream effect of such variations is that participation in clinical trials can be discouraged unwittingly.
In the case of NSCLC biologics, for example, an NCCN classification of 2A (even if premature) may become wedded to insurance coverage for some of those drugs. Knowing that, a physician and patient may decide to treat off-protocol with a covered drug rather than enroll in important data-generating phase II or III clinical trials. With clinical trial participation at such an abysmal low point in the United States, the last thing needed is yet another incentive to avoid gathering important clinical data.
Outside Petitions: A Unique Aspect of NCCN Guidelines
NCCN has always strived to maintain transparency in its work. For example, it has been open to considering and publishing on its website most (but not all) outside petitions sent to various Guidelines committees. Interestingly, only 7 of 194 petitions since 2010 have requested more rigid scientific scrutiny (and reconsideration) of NCCN recommendations, 3 of which resulted in palpable guidelines changes; the rest (96%) have come from pharmaceutical and diagnostic companies lobbying for inclusion of their products into NCCN Guidelines and occasionally from patient advocacy groups. This disproportionate pressure from industry is notable but not surprising.
By comparison, providers petition NCCN very infrequently, usually requesting additional scrutiny of the science behind NCCN recommendations. These petitions are not always published on the NCCN Web page.
NCCN needs to maintain its commitment to rigid scientific evidence as the foundation of its guidelines and compendium, thereby retaining the confidence of clinicians and insurers. In addition, and of increasing importance, NCCN must continue its groundbreaking work of incorporating financial considerations into its guidelines, thus facilitating the practice of value-based oncology care. Its recent work on resource stratification of NCCN Cervical Cancer Guidelines is an important step in the right direction. Even more welcome is NCCN’s plan to issue financial and efficacy information on the drug regimens it recommends, starting with chronic myeloid leukemia and multiple myeloma.
By moving value considerations further into the limelight of public awareness, as it plans to do in upcoming conferences, NCCN will be taking unprecedented action to address the “financial toxicity” determinants of the individual’s and society’s ability to afford the ever-increasing cost of care. As NCCN has always led the way as a trusted source of clinical information, it is now positioned to define the practice of value-based oncology medicine—an expanded and hugely important mission going forward into NCCN’s third decade. ■
Disclosure: Drs. Bennett and Shimp are consultants for Oncology Analytics, Inc, an oncology utilization management organization based in Plantation, Florida.
Dr. Bennett is the SmartStarte Center Chair and Frank P. and Josie M. Fletcher Professor of Medication Safety and Efficacy at the South Carolina College of Pharmacy and the Hollings Cancer Center, Charleston, South Carolina, and Dr. Shimp is a medical oncologist and former Chief Medical Officer of Park Nicollet Health Services in Minneapolis, Minnesota.
Disclaimer: This commentary represents the views of the authors and may not necessarily reflect the views of ASCO.
