Defining Cancer Treatment Cost-Effectiveness
Patients with cancer, the reasoning goes, ought to receive the best value of care, accounting for efficacy, toxicity, comorbidities, price, and so forth.
Value-based care, an increasingly important concept in oncology, is grounded on the relationship between the efficacy and cost of an anticancer drug. Patients with cancer, the reasoning goes, ought to receive the best value of care, accounting for efficacy, toxicity, comorbidities, price, and so forth.
The authors of an article recently published in The New Bioethics note, however, that the notion of value requires that an arbitrary price be put on life.1 This refers to the often-small improvements in overall survival seen with some newly approved cancer treatments. Some of these benefits improve the average patient's life expectancy by as little as 10 days.
Yet these survival benefits, no matter how marginal, are often the basis for drug approvals and consequent marketing campaigns. Richard Sullivan, MD, PhD, founding director of the Institute of Cancer Policy in London, England, and co-author of this essay, noted that “the bar for marketing authorisation is set low, and is getting lower. This means greater and greater uncertainty as to the efficacy, toxicity, tolerability, and overall value.
“All the evidence from current studies shows that more cancer medicines are being approved which do not deliver clinically meaningful benefit and this is in the context of clinical trials. We know in the real world most cancer medicines' efficacy drops some 20 to 40% because we start treating real patients with a variety of comorbidities.”
Patients in the “real world” do not, according to recent research, resemble patients who participate in clinical trials. This sometimes negates whatever improvements justify drug approvals in the United States and Europe.2,3
Doubts about the true efficacy of recently approved drugs combined with effective marketing campaigns make “value” a difficult term to quantify. If the efficacy for the average patient outside of a clinical trial cannot be guaranteed by the results seen in a clinical trial, the notion of reproducibility — or rather the purpose of reproducibility — is undermined, and a drug's value determined by a clinical trial is not the value seen in the clinic.
Bishal Gyawali, MD, a medical oncologist working in Japan who is affiliated with the Institute of Cancer Policy and the Anticancer Fund, Belgium, and co-author of the recent essay, noted to me that this issue is particular to cancer treatments, because “cancer medicines usually target metastatic disease where pushing away death is the main focus…paradoxically [these drugs] receive special treatment by the oncology community compared with surgery or radiotherapy services that aim at ‘curing' early stages of cancer.”
Dr Gyawali noted a recent article published in the Annals of Oncology that questioned the value added by England's National Health Service (NHS) Cancer Drug Fund, which was established to “improve access” to cancer medications not necessarily approved by the National Institute for Health and Care Excellence (NICE).4
Of 47 indications approved by the Cancer Drug Fund, only 18 “reported a statistically significant OS [overall survival] benefit, with an overall median survival of 3.1 months.” The authors concluded that the Fund did not meaningfully benefit patients or society.
This problem of marginal benefits is not, Dr Gyawali noted, a consequence only of cancer medicines having a special status in society, but “that the industry can easily hijack the tools of evidence-based medicine to prove small marginal gains as statistically significant while they have no clinical meaning to patients.
“A few such strategies are: overpowered trials that can show even a week of OS gain as significant, using non-inferiority trial design to show that the new drug is not inferior rather than superior to a previous drug, using inferior controls to show the intervention arm as doing better, and using excellent patients in trials to show gains that get lost when used in real world patients.”
The foundational qualities upon which a cancer drug is priced and marketed — efficacy and value — are therefore not only difficult to qualify, but difficult to accurately define. Small survival benefits may not be benefits at all, and value may be indeterminate even if the benefit is accurately described: much as NICE and the FDA may have policies about the maximum potential value of a new drug that confers a 10-day survival benefit, no one can tell a patient what his or her last 10 days are worth.
This points to a fundamental disconnect between health care policy and demand from the public for new cancer drugs. Demand from patients with cancer and their families increases the value of drugs, though the consequent high drug prices drive down cost-effectiveness. This puts creating demand among patients — which can be achieved through effective marketing campaigns and promotion — in the interest of those setting the drug prices to begin with.
Dr Sullivan added that “we have to get the message across to patients, patient organisations, and policy-makers that demanding good value is a fundamental matter of fairness. It is not about denying people life-saving treatment. This means fair price for the outcome the medicine gives as judged by a competent health technology assessment program.
“When a company over-prices we need to focus on this and not on the 'failure' of governments to fund the drug for access.”
This system of problems may be a consequence of the financial interests industry has in showing one drug is even marginally more efficacious than another. To the extent that each approval allows a company to show it offers something new that can extend a patient's life, pressure from patients, industry, and the public will be put on governments and health care systems to provide these drugs. And while cost-effectiveness is driven down by high prices, demand will be high, creating the illusion of great value where only little is offered.
The disconnect between the subjective value a patient and his or her family place on a survival benefit and the “objective” value of a survival benefit debated by policy makers is, however, exploitable. Pfizer recently announced its intention to offer palbociclib, a CDK4/6 inhibitor used to treat breast cancer, for free on the NHS — for a maximum of about 5 months.5 With letrozole, palbociclib extends progression-free survival by about 10 months over letrozole alone.6
After 5 months of successful treatment — half as long as it takes acquired resistance to develop — NICE will face pressure from industry, patient and families, and the press to negotiate for the drug. Despite any policies in place, NICE may be left in an indefensible position, as patients clamor for the continuation of their successful therapy.
A full palbociclib treatment course costs about £79,650.7
In February 2017, NICE recommended against paying for the drug, which they determined to be too expensive for the benefits it provides.
- Gyawali B, Sullivan R. Economics of cancer medicines: for whose benefit? New Bioeth. 2017;23(1):95-104. doi: 10.1080/20502877.2017.1314885
- Mailankody S, Prasad V. Overall survival in cancer drug trials as a new surrogate end point for overall survival in the real world. JAMA Oncol. 2016 Nov 17. doi: 10.1001/jamaoncol.2016.5296 [Epub ahead of print]
- Sanoff HK, Chang Y, Lund JL, O'Neil BH, Dusetzina SB. Sorafenib effectiveness in advanced hepatocellular carcinoma. Oncologist. 2016;21(9):1113-20. doi: 10.1634/theoncologist.2015-0478
- Aggarwal A, Fojo T, Chamberlain C, Davis C, Sullivan R. Do patient access schemes for high-cost cancer drugs deliver value to society?-lessons from the NHS Cancer Drugs Fund. Ann Oncol. 2017 Apr 27. doi: 10.1093/annonc/mdx110 [Epub ahead of print]
- Burki TK. Pfizer to make palbociclib temporarily free on NHS. Lancet Oncol. 2017 May 11. doi: 10.1016/S1470-2045(17)30343-1 [Epub ahead of print]
- Finn RS, Martin M, Rugo HS, et al. PALOMA-2: primary results from a phase III trial of palbociclib plus letrozole compared with placebo plus letrozole in postmenopausal women with ER+/HER2- advanced breast cancer. J Clin Oncol. 2016;34(suppl; abstr 507).
- Breast cancer drug costs too high in relation to benefits for routine NHS funding [news release]. National Institute for Health and Care Excellence; February 3, 2017. https://www.nice.org.uk/news/article/breast-cancer-drug-costs-too-high-in-relation-to-benefits-for-routine-nhs-funding. Accessed May 26, 2017.