Maurie Markman, MD
There is much to be concerned about regarding the existing cost and payment structures of the American healthcare delivery system, particularly in the cancer arena. From the unrestrained increases in the prices of antineoplastic agents to the bewildering absence of a coherent policy regarding payment for off-label uses of drugs even when supported by high-quality peer-reviewed evidence, the system seems overtly dysfunctional.
Among the more disquieting features of the current cancer financing paradigm is the increasingly recognized and often stunningly irrational mismatch between existing approaches to payment for services and the rapidly developing favorable modifications in disease management. This stems from the acceleration in our understanding of the basic biology of malignancy and resulting improvements in care delivery.
For example, there is solid peer-reviewed evidence for the clinical utility of testing individual cancers to learn of the presence of mutations that might assist in the selection of a unique therapy not routinely considered for use in the patient’s particular tumor type. Although the collection of data generated from the treatment of individual patients with unique abnormalities (so-called N-of-1 experiences) would not fall into the classical domain of either a standard of care or a clinical investigation, the potential to gather clinically meaningful information about the utility, or lack thereof, associated with targeting that molecular finding with a specific antineoplastic simply cannot be overstated.
Yet, it is common for third-party payers to deny payment for such testing as “investigational/experimental” at the same time they continue to pay for multiple lines of chemotherapy that are approved in some recognized compendium for a particular clinical indication even though there is often little evidence that the particular patient’s cancer will respond or quality of life will be improved.
Discussions about the development of a more rational funding approach are not helped along when academics publish highly questionable research that inappropriately claims the lack of utility of this N-of-1 paradigm based solely on supposedly negative randomized trial results associated with a comparison of nonmolecularly selected antineoplastic drug therapy to a molecularly selected therapy that, stunningly, is of unknown relevance to the stated target of interest.1 Such study results inadvertently demonstrate the critical importance of an N-of-1 approach to attempt to elucidate the utility of specific agents for molecularly defined targets.
Third-party payers, as a group, could certainly elect to use these individual experiences among their insured population to learn if a particular drug or target combination is clinically meaningful. However, to date, they have unfortunately elected not to enter this potentially powerful knowledge-generating domain.
Lack of Support Detailed
Another example of a misalignment between third-party payment for medical services and the generation of highly clinically relevant molecular data is in the domain of genetic testing for the risk of hereditary cancers—specifically, the decision to provide payment for the rapidly evolving concept of hereditary cancer panels employing next-generation sequencing technology, a strategy that has the potential to examine multiple genes and hereditary syndromes within a single test platform.
Of course, genetic testing has been employed for years as the standard of care to examine for the presence or absence of a single gene abnormality for a specific well-defined cancer type, such as the BRCA mutation in breast or ovarian cancer. Notably, the process associated with achieving this standard-of-care status consisted of extensive research involving large numbers of human subjects, undertaken over many years, before the routine clinical use of any such predictive test gained acceptance or payment from third-party insurers or governmental agencies.
The carefully considered use of hereditary cancer panels among large patient populations undergoing genetic risk assessments has the potential to dramatically accelerate the ability to critically examine the clinical relevance, or lack thereof, of a putative association between the presence of a germline molecular finding (abnormality or normal polymorphism) and the subsequent risk of developing cancer. These data can be obtained by performing, just once, a far more extensive germline analysis than the examination of the presence or absence of a single genetic event. The potential impact of the combination of knowledge of the patient-level molecular findings and long-term clinical follow-up to determine if cancer ultimately developed cannot be overstated.