Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News

Tools for Assessing Treatments Offer Separate, yet Promising, Potential Answers

Fifty years ago, the average monthly cost of a cancer therapy stood at $100 a month ($754.94 in today’s dollars). By 2013, that monthly figure zoomed to a monthly average of $10,000, with some newly approved drugs costing more than $30,000 a month, according to the American Society of Clinical Oncology (ASCO).

With patients seeing ever-rising treatment prices—as 118 oncologists recently noted in demanding action from Washington—and payers and governments increasingly clamoring to contain costs, two key oncologist groups and a team of doctors at Memorial Sloan Kettering Cancer Center (MSK) offer separate, yet promising, potential answers to the longstanding question: How best to assign value to cancer drugs?

ASCO last month published its initial version of a conceptual Value Framework. The six-step framework assigns up to 80 points for clinical benefit based on overall survival (OS), progression-free survival (PFS), or response rate. Toxicity is graded from -20 to +20 points. Up to 30 more points are assigned for data showing palliation of symptoms and/or treatment-free interval. The points—up to a maximum 130—are calculated into a “net health benefit” (NHB) representing the added benefit that patients can expect from the therapy, versus current standard of care.

“If fully realized, this would represent an individualized approach to cancer care that is consistent with provision of the best available therapy at the lowest achievable cost,” ASCO declared in a statement published June 22 in Journal of Clinical Oncology. “The ultimate purpose of this process is for patients to have transparent information about their treatment options so that they make more fully informed decisions.”

ASCO has set an August 21 deadline for submitting comments about its value framework.  “ASCO envisions publishing additional iterations of the framework, practical applications, recommendations regarding the additional evidence needed to develop the most useful value tools, and more detailed examinations of value in these and other disease states,” ASCO’s statement said.

No timeframe has been set for such publication, Lowell E. Schnipper, M.D., chair of ASCO’s Value in Cancer Care Task Force, told GEN. “Within maybe four to six months after that, we will, I think, find a way, either on the website or in publication form, to share a refined version,” added Dr. Schnipper, clinical director of the Cancer Center at Beth Israel Deaconess Medical Center, where he is also chief of hematology/oncology. ASCO’s next immediate challenge, he said, will be finding an IT vendor to develop versions of the value framework for desktop, laptop, tablet, and smartphone use.


Cost-Benefit Analyses

While the ASCO framework quantifies cost and clinical benefit, both are measured separately, rather than combined into a single rating. The task force opted to display NHB separately from cost “so that the physician and patient could view the clinical information independent of cost considerations as part of the decision-making process,” ASCO stated. According to Dr. Schnipper, “the decision was made to keep them separate, in large part, because the responsible way to adjudicate cost is to try to include as many of the costs within a treatment context as possible.”

Many of these costs, he said, are hard to get hold of—such as unintended hospitalizations as a result of toxicity of therapy, emergency room visits, and time lost from work. “Because we didn’t have access to that breadth of information, we decided to provide what we could document, and that’s why we included those costs that we did.”

ASCO’s framework emerged about a month after the European Society for Medical Oncology (ESMO) unveiled its own value measurement tool.  The ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) is actually two measures: An A-B-C scale for curative drugs in which A and B represent high levels of clinical benefit; and a 1-to-5 scale for noncurative agents or cancer management approaches, where grades 5 and 4 represent high levels of proven clinical benefit. The scale derives clinical benefit from comparative outcome studies, most commonly Phase III trials.

Noncurative treatments are assessed based on how their primary outcomes were measured in studies—by OS, by PFS or TTP, or by quality of life (QoL), toxicity or response rate, plus noninferiority studies. Noncurative drugs can only attain a “5” if their OS data shows reduced toxicity or improved QoL.

ESMO says the ESMO-MCBS score for a specific drug or approach can vary depending on indication, and may vary between studies. The scale’s initial version has been developed for solid cancers, and was field-tested on 77 treatments across 10 types of cancer.

“ESMO aims to highlight those treatments which bring substantial improvements to the duration of survival and/or the QoL of cancer patients, which need to be distinguished from those whose benefits are more modest, limited or even marginal,” ESMO stated in a paper published May 30 in Annals of Oncology. “The ESMO-MCBS is an important first step to the major ongoing task of evaluating value in cancer care which is essential for appropriate uses of limited public and personal resources for affordable cancer care.”


Making an “Abacus”

The oncology groups are not the only ones wrestling with what cancer medicines should be worth. Peter B. Bach, M.D., MAPP, director of MSK’s Center for Health Policy and Outcomes, led the MSK team in developing an interactive tool for calculating the value of cancer drugs. The tool, “DrugAbacus,” lets users compare the U.S. Medicare monthly price at launch (in 2014 dollars) of a cancer drug to an “Abacus price” based on value for 54 cancer treatments approved since 2001, the year Gleevec (imatinib) won U.S. approval. DrugAbacus lets users adjust its six criteria. The first is efficacy, which is based on a dollars-per-life-year measure, on a scale of $12,000 to $300,000. Efficacy is measured as improvement in OS or a surrogate endpoint as shown in the highest level of evidence clinical trial leading to FDA approval for the first indication.

The scale assigns a discount of up to 30% depending on toxicity, and uses multipliers of 1 to 3 to assess rarity, and population burden of disease, novelty of mechanism, and cost of development. That cost is based on a continuous rating estimated from the number of patients enrolled in the clinical trials conducted for initial FDA approval, including completed confirmatory trials required by the FDA.

“DrugAbacus is essentially a policy tool, a thought experiment: Could we take attributes of the drug, and find the appropriate price?” Dr. Bach told GEN. “We tried to think about the different ways we talk about drug pricing, and the different ways we finance and put societal dollars, and societal contribution into the development of drugs.”

A handful of drugs are assigned prices well above their actuals. Treanda® (bendamustine hydrochloride), marketed by Teva Pharmaceuticals, has an Abacus price calculated at $21,517, nearly three times the DrugAbacus quoted price of $7,725. Roche’s Gazyva® (obinutuzumab) is valued at $4,468, almost 2-1/2 times its $5,878 price.

Most treatments are priced higher than their Abacus price. Provenge® (sipuleucel-T), acquired in February by Valeant Pharmaceuticals International, commands the highest price of $77,554 among drugs measured by DrugAbacus. However, the tool values Provenge at just $28,196. The $64,260 price cited for Amgen’s Blincyto® (blinatumomab) is more than five times the drug’s calculated value of $12,597.


Common Ground

The value measures unveiled in recent weeks raise enough similar concerns to warrant consideration of a common method for determining cancer drug value.

“What is possible is that there could be some degree of consensus among different large organizations such as ESMO and ASCO. If you look at their framework, and you look at ours, the concepts underlying them are quite similar,” Dr. Schnipper said. “We are actually enthused at the thought that there’s a transatlantic kind-of approach to this problem, that there are enough similarities that might justify a more detailed discussion with ASCO, for example, although that has not occurred.”

ESMO underscores the importance of at least addressing harmonization of its approach to value with ASCO’s, by calling the issue “a key challenge for the future.” One area where harmonization would prove very valuable is measuring median OS improvement. ESMO assesses time duration; ASCO, the percentage of improvement. Another area where common ground is measuring improvement of symptoms associated with treatments. ESMO assesses improved QoL, while ASCO assigns up to 10 bonus points for data on statistically significant improvement in cancer-related symptoms.

“Most dispassionate economists look at these things, and say, ‘Well, if you’re not gaining life-years, you’re not improving quality of life, you’re not doing anything,” Dr. Bach said. “Easing suffering, specifically, is something that drugs can do and should get value for.”


Industry Lauds ASCO Goals but Says more Work Is Needed

Biopharma’s two industry groups say they share the goals articulated by the American Society for Clinical Oncology (ASCO) in its recently released Value Framework (See above)—namely helping patients and doctors make better-informed treatment decisions and keeping those decisions in their hands rather than those of payers.

“We believe that patients must be presented with all treatment options available, regardless of cost, so that, along with their physicians, they can make informed decisions about their best course of medical treatment,” the Biotechnology Industry Organization (BIO) said in a statement to GEN. “The idea that a treatment option would be excluded solely because someone thinks a patient’s life may not be extended “enough” or the treatment is too expensive—is simply unacceptable.”

BIO, which is changing its name to the Biotechnology Innovation Organization next year, said it is still reviewing ASCO’s Value Framework and preparing more detailed comments on the tool. The organization is among stakeholders with which ASCO has established dialogue on its framework.

Pharmaceutical Research and Manufacturers of America (PhRMA) referred GEN to a statement that commended ASCO for its work in developing its framework, while expressing the hope that the society “continues to move the framework in a direction that is focused on patient values and physician-patient decision-making rather than shifting to focus on payer decision making and average value.”

PhRMA identified three key challenges it urged ASCO to address: integrating patient-centered information into assessments of value, conveying information that is relevant for patients, and accounting for individual patients’ preferences and goals.  “Such choices are not easily captured in a value framework like ASCO’s, which may present these regimens as equivalent to a patient. Failure to capture these nuances also increases the risk of the framework being misapplied by policy-makers,” PhRMA cautioned.

Joshua P. Cohen, Ph.D., research associate professor with the Tufts Center for the Study of Drug Development, told GEN that R&D spending should play no role in assessing drug value, as DrugAbacus posits and the biopharma industry has often argued.

Dr. Cohen added that patient-centered outcomes should be front and center in the calculation of value: “This implies there's lots of work to do, as determining patient-centered outcomes—what ultimately matters to individual cancer patients—is difficult and there are plenty of evidence gaps. We're only now building up a decent-sized evidence base.”