ASCO Value Framework Should Allow For Customization, Drug Firms Urge

In comments, the Pharmaceutical Research and Manufacturers of America and Biotechnology Industry Organization outline long lists of recommended changes in the American Society for Clinical Oncology’s proposed framework for valuing cancer drugs.

The American Society for Clinical Oncology’s framework for valuing oncology drugs should ensure that patient preferences regarding drug benefits versus toxicity can be used to adjust any value score that is produced, biopharmaceutical trade groups asserted in comments submitted to ASCO Aug. 21.

The Pharmaceutical Research and Manufacturers of America and Biotechnology Industry Organization submitted comments advising a number of changes to the way the framework would work. They also urged additional safeguards to ensure that value scores would not be taken out of context and used to limit access to treatments.

With regard to recognizing patient preferences, PhRMA recommended that ASCO “develop a mechanism to enable and provide guidance for patients and their providers to vary the clinical benefit weights and toxicity points to better reflect a patient-specific preference of balancing the survival benefits and side effects of the drugs.”

PhRMA noted in its comments that in the manuscript outlining its framework, ASCO acknowledges the importance of creating a personalized score that takes into account existing comorbidities, personal preferences and values. The association added: “PhRMA strongly agrees with this statement, and encourages ASCO to ensure customization is incorporated into its tool.”

Separate comments from BIO make a similar argument. “In the absence of discrete mechanisms to take patient preferences into account, BIO is concerned that the value framework will encourage one-size-fits-all oncology care, which directly contradicts ASCO’s stated goal of improving information at the point of decision-making to drive appropriate care for each individual patient,” the group maintained.

A draft version of the value framework, released June 22, offers an approach to developing a single numerical “net health benefit” (NHB) score for cancer drugs that would be presented along with the drug’s cost in a decision tool designed to help physicians and patients select the appropriate treatment (Also see "ASCO Value Framework Presents ‘Net Health Benefit’ Score For Drugs" - Pink Sheet, 22 Jun, 2015.).

The NHB score represents the added clinical benefit (minus toxicities) that patients can expect from a new drug compared with the current standard of care, based on randomized clinical trials. The score is meant to offer a rapid, standardized way of summarizing trial results. PhRMA and BIO applauded ASCO’s efforts to improve decision-making at the point of care. But the groups also cited a number of problems with the framework as it currently exists.

In fact, both groups advise that ASCO more explicitly acknowledge the limitations in the net health benefit score by changing its name. BIO suggested a narrower term, such as “relative summary of measured benefits,” which “would help avoid confusion among providers and patients.”

Expanding The Evidence Base

PhRMA urged that ASCO expand the types of evidence used in creating a benefit score beyond the randomized clinical trial used in a drug’s first approval.

“Defining value based on the initial trial and initial indication may not reflect the true value of the drug over the entire life cycle because the patients treated can vary substantially as new evidence emerges, and as new indications are approved,” the group said.

ASCO should develop a method for updating the tool, at least quarterly, to capture and integrate new research, PhRMA added.

“This will be essential not only for capturing the full body of available scientific evidence, but ensuring the framework remains up-to-date as new research becomes available. Without a method for synthesizing new research, ASCO risks creating a framework that is not flexible enough to keep pace with the quickly evolving evidence base in oncology.”

PhRMA additionally called for inclusion of trial subgroup data, including those “illuminated” through molecular diagnostics, and real-world data into the value assessment tool.

Undervaluing Breakthrough Drugs

Both groups took issue with ASCO’s reliance on median overall survival (OS) as a key benefit metric in measuring value.

“We found the framework’s reliance on median OS unsound for several reasons,” BIO stated. Median OS in advanced disease “may not be as appropriate a measure of the benefit of newer therapies (e.g., immune-oncology therapies) as it is for older chemotherapeutic agents,” in part because new drugs may have a more significant impact on long-term survival and result in delayed clinical effects.

“Thus, relying on median OS can result in ‘undervaluing’ a new therapy regimen or ‘overvaluing’ a control regimen and, in turn, provide inaccurate and/or incomplete information to patients and providers,” BIO pointed out. PhRMA suggested that other measures of survival, such as mean OS, time to tumor progression and time to treatment failure might be helpful to include.

ASCO should also modify the way it mathematically calculates benefit scores to ensure it does not undervalue new drugs, PhRMA recommended.

The framework’s current approach is to apply a significantly lower multiplier for response rates relative to survival. When weighting is factored in, the maximum score a drug could be assigned for overall survival would be 80, the maximum for progression-free survival would be 55 and the maximum for response rates would be 40.

However, study results for breakthrough drugs focus more heavily on response rates. As a result, the NHB score of breakthrough drugs “will nearly always be lower than older drugs that demonstrate an improvement in overall survival or progression-free survival, even when it is generally recognized that the new medicine is superior,” PhRMA stated.

As a remedy, the group recommended ASCO “place greater weight” on orphan drugs, breakthrough therapies, fast track products and priority review products. Furthermore, “ASCO should consider a mechanism to allow the physicians to adjust the NHB score based on his or her knowledge of the anticipated benefit” for breakthrough and targeted therapies, PhRMA said.

Drug Acquisition Costs

PhRMA and BIO generally supported the proposal to include a consideration of patient out-of-pocket costs in weighing the relative value of drugs. But both took issue with ASCO’s approach to identifying a “drug acquisition cost” for consideration.

“It is unclear how this measure is meant to be calculated based on the draft value framework (in the examples provided, both average sales price data at an arbitrary date and payer-specific acquisition costs are used),” BIO noted.

PhRMA advised, “Should ASCO decide to move forward with inclusion of [drug acquisition costs] in the framework, it should ensure that any cost data is updated regularly and appropriately account for discounts and rebates provided by manufacturers, in order to reflect actual drug costs.”

The groups also argued that drug costs represent a minor part of overall treatment expenses and do not capture the potential cost savings related to a course of treatment, including fewer hospitalizations, fewer office visits and less time away from work.

“An incomplete estimate of a patient’s total potential costs and savings will yield incomplete information that can serve to misrepresent patients’ total costs of care, confusing rather than clarifying this input into a patient’s decision-making process,” PhRMA said.

Using The Score Out Of Context

ASCO needs stronger safeguards against the possible use of the benefit score out of context, according to the organizations. BIO “remains concerned that there is a significant potential for other stakeholders to use the proposed NHB and cost metrics out of context, and to the direct detriment of appropriate patient care.”

BIO explained its concerns stem from “a lack of guidance” on how to interpret scores from different trials comparing the same treatment regimens and from “the potential for payers to misuse these metrics to limit patient access to certain therapies.”

PhRMA recommended that ASCO “include clearer, stronger language on the limitations of using the framework in population-level decision-making.” The “importance of such language” is illustrated by recent suggestions that the framework could be used to support or validate clinical pathway or similar utilization management tools developed by payers, the group pointed out (Also see "ASCO Value Framework Could Inform Clinical Pathways, Payers Say" - Pink Sheet, 13 Jul, 2015.).

ASCO should continue to test drive the framework by a “transparent” evaluation of additional drugs, PhRMA advised. In the original proposal, ASCO attempted to illustrate the framework by evaluating a number of drugs. However, PhRMA disputed the approach taken to valuing Eli Lilly & Co.’s lung cancer drug, Alimta (pemetrexed), and ASCO subsequently agreed to revise the score (Also see "Alimta Value Revisited: ASCO Raises Score In Framework Update" - Pink Sheet, 14 Jul, 2015.).