Walking the Tightrope Between Treatment Efficacy and Price

Although consumers and governments regularly make decisions on the basis of both informal and rigorous cost-effectiveness analyses, it is well recognized that we do not let cost-effectiveness get in the way of how medicine is practiced in the United States. In fact, the key comparative-effectiveness research entity in the United States, the Patient-Centered Outcomes Research Institute, states on its Web site that it does not consider cost-effectiveness to be an outcome of direct importance to patients. So why bother reading the article from Durkee et al that accompanies this editorial? I can think of a few reasons. For one, if you are curious about the discipline of analyzing how much something helps patients comparedwith howmuch it costs, this report is one of the clearest. The authors elegantly explain how they arrived at their answers and which assumptions they made that might matter. They also do a particularly admirable job of walking readers through one of the murkiest features of such analyses: the multiple simulations, calledMarkov models, that allow analysts to determine the possible effect of chance on their numbers. In addition, the authors provide a thoughtful set of guideposts for readers so that their results can be interpreted within the confines of potential policy. They note commonly bandied-about thresholds of $50,000 per quality-adjusted life year (QALY) for cost-effectiveness and an alternative threshold of three times the gross domestic product per capita, which is currently approximately $160,000 per QALY. But, they note that these thresholds have little bearing on much of anything. They also note that adding pertuzumab to docetaxel and trastuzumab in the metastatic setting is strongly recommended by the National Comprehensive Cancer Network, a recommendation that appears to have beenmade despite the incremental cost of the agents. However, the real reason to peruse the study by Durkee et al is because it not only raises questions that beg to be answered but also comes perhaps at a moment in oncology when the discussion of costs is no longer one conducted in settings far from the point of care. Instead, cost issues have found their way into the examination room, into professional guidelines, and into the dialogue regarding how to ensure that patients have access to the best cancer care science has uncovered. How did we get ourselves into a situationwhere a highly effective, new treatment like pertuzumab in the metastatic setting can cost so much money that the cost per QALYapproaches $1 million? We have seen numbers like this before occasionally, but it is usually for treatments that offer miniscule incremental benefits at enormous cost. Those benefits are often in domains that are gauged to be less important than improved survival. Durkee et al mention proton beam therapy as one such domain that at best reduces complication rates modestly. A recent review from the American Society of Clinical Oncology (ASCO) notes the extreme cost of growth factors in primary prevention of neutropenia as another. But, in pertuzumab, we have an agent that confers a large improvement in survival, and still the numbers do not make sense. This is a hard problem. Then there is the paradox that highly expensive pertuzumab costs the same in adjuvant and metastatic settings although its efficacy is so different in each. This scenario mathematically guarantees lower costeffectiveness in the less-effective setting, which is metastatic disease in this case. Pertuzumab is not unique in this regard. Many cancer agents are indicated for use in multiple conditions for which they have varying efficacies. This is why I recently proposed that we reconfigure oncology drug pricing in amanner that anchors the price to the use of the drug and not the drug itself. In this model, which I called indication-specific pricing, payers could reimburse differently, and patients could pay different levels of coinsurance if they received pertuzumab for adjuvant ormetastatic treatment. One possiblemerit of the approach, beyond its intrinsic rationality, is that it would cut both ways. A relatively ineffective indication would not weigh down a value-based price if the drug were highly effective in another setting. Likewise, a follow-on indication for which the drug worked less well would not drag down a value-based price set when the first indication was highly effective. Express Scripts recently announced they will pursue indication-specific pricing in 2016 for some cancer drugs, building on this model. The article by Durkee et al also arrives at a time when the discussion about not only prices but also value, a cousin of costeffectiveness, is entering the domain of clinical relevance. This is partly because high costs are carrying through our insurance benefit system in a manner that harms patients. Dusetzina et al demonstrated that when out-of-pocket costs are higher, patients discontinue taking even highly beneficial drugs such as imatinib. ASCO recently released a framework for contemplating the value of treatments. The organization created a common scale for benefits and adverse effects across therapies and disease areas as a first step toward thinking about the construct. Building on this effort, the organization’smost recent guidelines onwhite-cell growth factors have a section contemplating costs. The European Society of Medical Oncology also published a value framework this summer, and the National