Maurie Markman, MD
Vice President of Patient Oncology Services
National Director for Medical Oncology
Cancer Treatment Centers Of America
The term “clinical benefit” is widely employed in the oncology arena.1 The question is, from whose perspective should “clinical benefit” be defined and documented: the investigator’s, the health care economist’s or the patient’s?
A clinical trial examining the therapeutic potential of a novel antineoplastic agent may define something labeled “clinical benefit” to have occurred when there is a documented objective response of a measurable tumor mass on an imaging study (e.g., RECIST criteria). Increasingly, trials may conclude that a benefit has occurred when cancers have not progressed for a prospectively declared period of time (e.g., two to six months) following the initiation of treatment. This is often called stable disease.1
These days, the proportion of individual patients achieving these clinical states may be used in the calculation of the cost-effectiveness of a particular treatment paradigm. This is frequently discussed as a method to demonstrate the value of a specific therapeutic approach. Again, in this scenario, “clinical benefit” may be defined by a somewhat arbitrary measure that includes the percentage of patients who exhibit tumor shrinkage, the failure to discover any new visible lesions or the absence of a certain amount of growth on imaging studies for a specified period of time. Alternatively, statistically significant differences in overall survival (e.g., median) between arms of a Phase III randomized trial, certainly a more definitive end point, may be used in this calculation of “benefit.”
Unfortunately, it is far from clear what role more patient-centric parameters, such as relief of cancer-related symptoms, development of treatment-related side effects or the impact of the disease or its therapy on activities of daily living and a patient’s emotional well-being, play in either the academic (clinical trials) or economic (cost-effectiveness analysis) assessment of “clinical benefit.”
Although it is understandable that clinical investigators and economists might use these measurable, even if questionably rather arbitrary, indicators to define therapeutic effectiveness, one must ask if these definitions accurately reflect what individual cancer patients consider to be of greatest value to them.
In fact, limited data exploring the goals of patients with advanced cancer and people with other serious medical conditions suggest that many individuals in these very difficult situations may be willing to undergo rather aggressive care and considerable potential risk to attain what reasonably could be considered quite modest measurable outcomes.2-4
In such circumstances, patients might believe that continuing life of acceptable quality for objectively rather short periods of time is of genuine value to them. These individuals may conclude that a particular treatment regimen that appears to permit a three-, two-, or even a one-month period of “stable disease,” with pain and other problematic symptoms being well controlled and with the continued ability to conduct personally gratifying activities of daily living (e.g., being actively engaged with family and friends, enjoying hobbies) to be of meaningful clinical benefit.
Of course, an individual’s conclusion that a period of apparent disease stability with an accompanying acceptable quality of life is of value does not mean that, scientifically, the specific treatment regimen in question is actually responsible for this favorable clinical state, which may in reality simply represent the “natural history of the cancer.” An individual’s conclusion also may be independent of whether the antineoplastic therapy in a specific setting falls within the health economist–defined parameter of being cost-effective. However, from the patient’s perspective, there may have been genuine clinical benefit.
There should be no confusion regarding the preceding statements specifically related to who should define “clinical benefit” and the truly stark economic reality of our dysfunctional payment system for the delivery of health-related services. It is absolutely understood that the escalating costs associated with cancer management mandate future changes in the manner in which medical care is both evaluated and financed in this country. And it is certainly quite reasonable in this national debate to carefully consider the value of the care being delivered as an essential component of the discussion.
However, as we move forward in what will surely be an extremely complex, emotional and potentially troublesome debate on how to define “value,” let us not forget that the primary focus of all our efforts is (and absolutely should be) the patient. As such, should it not be from the patient’s perspective, rather than—or at least as much as—that of the researcher or economist, that we view any definition of “clinical benefit” in future discussions of the value of cancer care being delivered?
Finally, perhaps those who disagree with this conclusion regarding the ultimate foundation for a definition of “clinical benefit” in oncology should be asked to justify their opinion.
1. Markman M. “Clinical benefit rate” in Phase II gynecologic cancer trials: implying more than the data support? Gynecol Oncol. 2010;117:348-349, PMID: 20167354.
2. Slevin ML, Stubbs L, Plant HJ, et al. Attitudes to chemotherapy: comparing views of patients with cancer with those of doctors, nurses and general public. BMJ. 1990;300:1458-1460, PMID: 2379006.
3. Murphy DJ, Burrows D, Santilli S, et al. The influence of the probability of survival on patient’s preferences regarding cardiopulmonary resuscitation. N Engl J Med. 1994;330:545-549, PMID: 8302322.
4. Everhart MA, Pearlman RA. Stability of patient preferences regarding life-sustaining treatments. Chest. 1990;97:159-164, PMID: 18955642.
This article first appeared in Clinical Oncology News, a sister publication to Pharmacy Practice News. If you'd like to read more opinion pieces by oncology physicians, please let us know at firstname.lastname@example.org