The value of a drug should not be based solely on how long it extends survival, but on the quality of that survival as well.— Lowell E. Schnipper, MD
Last June, ASCO published its initial concept for a value framework in the Journal of Clinical Oncology (JCO).1 The framework, developed by ASCO’s Value in Cancer Care Task Force, is designed to provide a standardized approach to assist physicians and patients in assessing the “value” of a new antineoplastic agent or drug regimen. The value assessment is based on the magnitude of improvement in clinical benefit, toxicity, and cost when compared with the standard of care in a clinical trial. The clinical benefit, toxicity, and bonus points are added to calculate a net health benefit (NHB) score. A high net health benefit score correlates with substantial improvement of the test regimen in comparison with the agent or agents with which it has been compared.
The acquisition and out-of-pocket costs to the patient (based on the specifics of the patient’s health insurance policy) are shown in the framework to enable both the physician and patient to discern how costly a treatment will be in relation to how effective it is predicted to be in meeting the patient’s clinical needs.
After reviewing over 400 comments ASCO received from patients, patient advocates, physicians, and representatives of the pharmaceutical industry, among others, in response to the value concept, ASCO’s Value in Cancer Care Task Force revised the framework. The updated version, published in the June 1 issue of JCO,2 contains the areas in the framework that have been refined, most notably modification to the NHB score to more accurately reflect true differences among treatment options. For example, rather than assign a numerical score of 1 to 5 for an incremental percentage change in overall survival or progression-free survival when comparing the test and standard treatment approaches, the revision derives the clinical benefit score from the hazard ratio (1-HR ×100) or the percent improvement in overall survival or progression-free survival (×100).
The revised framework also now takes into account all side effects when calculating a treatment’s NHB score, not just the most severe, high-grade toxicities. The change reflects a concern expressed by patients who said that even mild side effects from therapy can have a major impact on their quality of life.
“The framework now adds or subtracts points from the clinical benefit depending on both the frequency and severity of treatment toxicity, rather than just for high-grade toxicity, because we didn’t feel we should be the judge of what was an important toxicity to patients. We wanted the patients to be the judge,” said Lowell E. Schnipper, MD, Chair of ASCO’s Value in Cancer Care Task Force; Theodore W. and Evelyn G. Berenson Professor in the Department of Medicine at Harvard Medical School; Clinical Director of the Cancer Center; and Chief of Hematology/Oncology, Emeritus, at Beth Israel Deaconess Medical Center in Boston.
“We also allotted bonus points to a drug’s NHB score when a clinical trial documents a statistically significant improvement in quality of life,” he continued. “We did the same for the improvement of a symptom, such as pain. We felt that if a patient has severe pain and the pain is relieved by a specific intervention, the drug regimen should be scored higher because that is the goal of treatment. The value of a drug should not be based solely on how long it extends survival, but on the quality of that survival as well.”
As with the original framework, the updated version evaluates treatments that were investigated in head-to-head prospective randomized clinical trials. Single-arm trials can be assessed as well using response rate and toxicity as domains to be measured.
Although Dr. Schnipper acknowledged the importance of considering other costs involved in cancer care, such as physician fees, hospital costs, and time lost from work, when evaluating the expenditure associated with caring for a patient with cancer, he said the value framework focuses on the costs of prescription drugs because they represent the most rapidly rising aspect of cancer care and are increasingly shared with patients through insurance deductibles and copayments.
The ASCO Post talked with Dr. Schnipper about the next steps for the value framework and when it is projected for clinical use.
A Vehicle for Shared Decision-Making
Can you explain a bit about the value framework that will be incorporated into a software application?
That is the next step in this process. I’m sure we will get additional feedback from the various stakeholders in the cancer community now that the updated version of the framework is published. But we think the revisions we have already made justify requesting proposals from software developers on building a value framework application. We are hoping that the detailed components in the framework can be translated into a software program that can easily be loaded into a desktop computer or mobile device and used by physicians and their patients to compare different drug regimens for specific clinical indications.
We are also planning for the software application to allow each of the domains of clinical benefit and toxicity to be adjusted based on the personal wishes of the patient. For example, if a patient were to say to her physician, “I love to play the flute and don’t want my fingers to be numb from treatment,” the NHB score could be based more on freedom from treatment toxicity than clinical benefit.
Right now, we are thinking that the software program would be used as a vehicle for shared decision-making between physician and patient. We are envisioning that the massive amount of data from the highest-quality clinical trials used in the framework would be curated by specific cancer indication, and then the data would be organized in accordance with a computer program that would enable the physician and the patient to look at the two or three different treatment possibilities and compare them based on clinical benefit, level of toxicity, net health benefit, and cost.
Do you expect the software application to be ready for the clinic by the end of this year?
Realistically, the application probably won’t be ready for testing until 8 to 12 months from now.
Time Is Key
Will the value framework continue to be revised even after the updated version is published and developed into a software application?
Yes. One of the areas of concern we are keenly aware of is how much time the value framework will take up during an office visit. We have heard from physicians who said they thought the framework is a great idea, but not if it’s going to be time consuming to use.
We now need a software developer to make it into a sleek, efficient program that fits into the workflow in a busy office so it adds value to a clinician’s practice. If the program takes up too much time and is a drag on office efficiency, it won’t be used.
Melanoma and Leukemia Added
The original framework included four clinical scenarios: first-line treatment of metastatic non–small cell lung cancer; advanced-stage multiple myeloma; metastatic prostate cancer; and HER2-positive breast cancer. Does the revised framework have additional cancers and clinical scenarios?
Yes. The four original cancer types were selected to demonstrate the potential utility of the approach in diverse clinical scenarios and to inform refinements of the framework. The revised version includes two new clinical scenarios based on the most recent clinical trial data. One is a clinical trial of adjuvant ipilimumab (Yervoy) vs placebo after complete resection of stage III melanoma. The data show a rather modest NHB of 17.4 at a huge cost.
We also show a comparison of ibrutinib (Imbruvica) and chlorambucil (Leukeran) as initial therapy for chronic lymphocytic leukemia (CLL). And here the new drug is very effective when compared with the control of chlorambucil, and it gets a high NHB score of 77.2. The comparison of the two clinical scenarios show that the amount of NHB points you get with adjuvant ipilimumab was modest vs the huge cost investment; and for a considerably lower cost per month, ibrutinib presented a large advancement in the treatment of CLL.
A critically important point to emphasize is that these examples have been selected to see how the framework works in different clinical scenarios, not to evaluate agents or regimens cited in the JCO manuscript.
More Education Needed
There was a lot of controversy surrounding the value framework concept when ASCO released it a year ago. Since then, several other organizations have developed a similar concept, including the National Comprehensive Cancer Network’s Evidence Blocks (www.nccn.org/evidenceblocks) and Memorial Sloan Kettering Cancer Center’s Drug Abacus (www.drugabacus.org). Is the idea of providing a method to assess greater value in oncology care gaining acceptance among the public, especially patients?
I think patients are still very uncomfortable with the concept of value-based oncology care. They are uncertain about whether their range of freedom in the choice of how they get treated will be negatively impacted. So, there is more education we need to do to assure patients, and the general public, that the value framework provides a tool for physicians and patients to assess the value of a particular cancer treatment depending on the patient’s individual preferences and circumstances, including financial, and does not dictate treatment based on cost.
A Major Uncertainty
More cancers are now being converted into chronic diseases that require patients to be on continuous treatment. Will the value framework eventually include a module to fit that type of clinical scenario?
Ultimately, the value of a treatment is going to be determined by the good it does for a specific patient and what the cost is to the individual or society. One of the aspects of turning cancer into a chronic disease is that some of these treatments have to be given on a regular basis, such as a daily oral pill, and that gets to be pretty costly over time.
How society handles that type of cost/benefit ratio is a major uncertainty. We don’t have the answer to that scenario because it really is up to society as a whole to determine how to deal with this type of health-care cost. ■
Disclosure: Dr. Schnipper is a member and on the advisory board of Eviti, Inc; and is Co-Editor-in-Chief of UpToDate Oncology.
1. Schnipper LE, Davidson NE, Wollins DS, et al: American Society of Clinical Oncology statement: A conceptual framework to assess the value of cancer treatment options. J Clin Oncol 33:2563-2577, 2015.
2. Schnipper LE, Davidson NE, Wollins DS, et al: Updating the American Society of Clinical Oncology value framework: Revisions and reflections in response to comments received. J Clin Oncol. May 31, 2016 (early release online).