Before the relative value of a drug can be determined, one must first consider how value is defined by the patient.
Cancer care is expensive, and evaluating costs in cancer care is complex. Drug costs are only part of the cost equation for systemic therapy in cancer care. When comparing regimens, one must also look at the ancillary costs of administration, monitoring, treatment setting, toxicity management, and likelihood of hospitalization. Other financial stresses of cancer care, including imaging and other diagnostics, transportation, and absence from work, must be considered as well. Thus, the overall cost of an expensive but minimally toxic oral medication may be less than that of an infusional, highly toxic regimen composed of inexpensive agents that frequently results in hospitalization.
Another consideration is the duration of therapy. The considerations include providing opportunities for obtaining biologic profiles to enhance patient selection for treatment and to guide treatment decisions relevant to a continuum of care, which may prolong life. As more cancers become controllable with ongoing therapy, patients and payers must figure out how to pay for maintenance therapy that sometime can last a lifetime. Systemic therapies for hematologic malignancies have led the way; with the advent of tyrosine-kinase inhibitors, median survivals for people with chronic myelogenous leukemia have increased from 5–6 years in the pre-imatinib era to nearly normal lifespans today.1 But trends toward long-term therapy are also developing in solid tumors. Adjuvant hormonal therapy for breast cancer for 10 years rather than 5 years is becoming more common.2 With data indicating that sequential exposure to all active agents leads to longer survival in metastatic colorectal cancer,3 the concept of a continuum of care lasting up to several years is the norm.
Payers will find ways to recover their share of the costs through higher premiums, deductibles, copays, coinsurance, and narrower formularies. With 20% copays and higher coinsurance payments becoming common, regimens costing upward of $100,000 per year can be unaffordable for all but the most affluent, fully insured patients. Patients are increasingly responsible for multiple copays, and, as they live longer and receive multiple regimens over time, the price for longer survival rises. Medical bills are now the most common reason for personal bankruptcy in the United States. A recent Kaiser Foundation study found that 50% of Americans take prescription medicines. Among them, 25% said they or a family member had not filled a prescription because of its cost, and 18% had skipped a dose of medicine or cut pills in half.4 Either of these practices can significantly reduce the efficacy of cancer treatment where the therapeutic index of an agent can be narrow or a side effect not managed well enough to continue therapy.
One’s opinion with respect to value of oncology drugs depends largely upon one’s perspective. In the business and economics of medicine, there are societal and individual perspectives on cost. As a society, we want to provide excellent care to patients but at a cost that does not bankrupt the health care system. Given the prevalence of cancer in the population of adults over the age of 65 years, the cost of cancer treatment affects the sustainability of the Medicare program and ultimately the federal budget.
At the individual level, patients generally want to know what their care will cost them. However, unlike most purchased services, most patients receiving health care are paying a fraction of the full cost of their care and thus are somewhat “protected” from the full impact of cost, whether on a personal or societal level. Nevertheless, even a fraction of that cost can result in significant financial hardship for the patient and family.
Although the problems related to the high costs of cancer care in general must be addressed in the long term, in the meantime, patients and clinicians must make treatment decisions within the current cost environment. The patient’s perspective must be honored in the decision-making process. Different patients value different characteristics of cancer treatments. A 30-year-old with young children and a high-risk cancer might value efficacy over every other consideration. An 85-year-old with the same high-risk cancer might desire quality of life over longevity. Another might need a more affordable option. Given the range of values and issues, perhaps the most important contribution is to provide information upon which to make therapeutic decisions.
As the issue of cost has become more central to oncology care, several groups have undertaken initiatives to clarify cost and value. As previously mentioned, these include Memorial Sloan Kettering’s Drug Abacus5 and the Value Framework from the American Society of Clinical Oncology (ASCO)6. The former estimates the value-based cost of 51 oncology agents approved since 2001, related to the anticipated outcomes of the treatment, development costs, and size of patient population. This allows patients and clinicians to compare the sales price of the agent to its value-based cost. The latter looks at drug acquisition cost alongside clinical benefit and toxicity, but it compares only results from clinical trials testing a regimen against the existing standard of care—a strategy that can be problematic when there are a wide range of effective choices that have not been compared directly. Furthermore, because the result is a single estimate of the value of a regimen, it lacks transparency for evaluation of components individually to customize the value equation based on the patient’s circumstances.
The Evidence Block initiative being launched by the National Comprehensive Cancer Network (NCCN) evaluates all regimens in the NCCN Guidelines on five characteristics: efficacy, safety, quality of evidence, consistency of evidence, and affordability. NCCN Panel members score each regimen on each characteristic using a standardized scale of 1 to 5, with 1 being the least favorable and 5 being the most favorable. For efficacy and safety, panel members use both their knowledge of the published data, often developed in highly selected patient populations, and their clinical experience with the treatments in the real-world patient population. Quality of the data and consistency of the data are rated using the NCCN Panel members’ knowledge of the data supporting the intervention. Affordability is rated using the NCCN Panel members’ knowledge of the overall cost of the regimen.
Resulting data are analyzed and final scores are calculated based on all panel members’ responses, rounding to the closest whole number. These scores are then used to build the 5x5 table that constitutes the Evidence Block for the intervention. Each column in the Evidence Block corresponds to an outcome characteristic. From left to right the outcome characteristics are efficacy (E), safety (S), quality of evidence (Q), consistency of evidence (C) and affordability (A). When the Evidence Blocks are placed on the Guideline algorithm, a user can quickly scan a group of potentially appropriate interventions and make treatment recommendations based on what is most important to the patient. Some patients will want an emerging therapy even with limited data; others will be most concerned about the expected side effects of the treatment indicated in the safety column. Still others may be very sensitive to cost. By considering the attributes of the range of possible therapies, the physician and the patient will be able to discuss the benefits and risks of each one and come to a decision most acceptable to the individual.
In the current environment, new advances that truly improve outcomes are intrinsically more valuable than those that provide little improvement in overall survival, control of disease, or symptom burden and could reasonably be priced to reflect these benefits. Even at a relatively higher price, these new treatments should be available to patients. This is not an argument for ever-higher drug prices, however. As cancer biology is better understood, combinations of newer agents likely will lead to even better outcomes. Drug developers need to price their products to recoup development costs and reasonable profit, but they should be mindful of fair pricing in an environment of limited healthcare dollars. To do otherwise poses a risk of limiting access to these agents for patients who need them.
However, many of the newer agents in the oncology sphere provide only small improvements in disease control compared to the existing standard of care, often with a different but still considerable toxicity profile. These may not justify significantly higher prices than existing standard of care agents, and payers may not be willing to cover these treatments at the same level as more effective choices. Evaluation by expert clinicians like NCCN Panel members can help to distinguish among the therapeutic options.
It is the responsibility of the medical profession to optimally present the evidence so that patients and insurers have a sense of overall impact on patient outcomes. The complexities of defining value is a work in progress, but it is important to place the patient and his or her values at the center of the discussion and in the context of the comprehensive, evolving care of the patient.
For another perspective on this issue, read the Viewpoint, "Overcoming the Political and Economic Roadblocks Stopping Effective Comparative Drug Evaluation," by Roger Longman, MA.
1. Experts in Chronic Myeloid Leukemia. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood. 2013; 121(22):4439–4442.
2. Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805–816.
3. Goldberg RM, Rothenberg ML, Van Cutsem E, et al. The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist. 2007;12(1):38–50.
4. DiJulio B, Firth J, Brodie M. Kaiser Health Tracking Poll: August 2015. The Henry J. Kaiser Family Foundation website. http://kff.org/health-costs/pollfinding/kaiser-health-tracking-poll-august-2015/. Published online August 20, 2015.
5. Memorial Sloan Kettering Cancer Center. Methods. Drug Abacus website. http://www.drugabacus.org/methods/. Accessed October 12, 2015.
6. Schnipper L, Davidson N, Wollins D, et al. American Society of Clinical Oncology Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options. J Clin Oncol. 2015;33(23):2563–2577.