Uncertainty in medicine : The Lancet

Uncertainty in Assessing Value of Oncology Treatments -- The Oncologist

abstract:
Patients, clinicians, payers, and policymakers face an environment of significant evidentiary uncertainty as they attempt to achieve maximum value, or the greatest level of benefit possible at a given level of cost in their respective health care decisions. This is particularly true in the area of oncology, for which published evidence from clinical trials is often incongruent with real-world patient care, and a substantial portion of clinical use is for off-label indications that have not been systematically evaluated.
It is this uncertainty in the knowledge of the clinical harms and benefits associated with oncology treatments that prevents postregulatory decision makers from making accurate assessments of the value of these treatments. Because of the incentives inherent in the clinical research enterprise, randomized control trials (RCTs) are designed for the specific purpose of regulatory approval and maximizing market penetration.
The pursuit of these goals results in RCT study designs that achieve maximal internal validity at the expense of generalizability to diverse real-world patient populations that may have significant comorbidities and other clinically mitigating factors.
As such, systematic reviews for the purposes of coverage and treatment decisions often find relevant and high-quality evidence to be limited or nonexistent. For a number of reasons, including frequent off-label use of medications and the expedited approval process for cancer drugs by the U.S. Food and Drug Administration, this situation is exacerbated in the area of oncology.....

"Until scientific advancements in treatment occur, significant gaps in real-world evidence will be pervasive in the area of oncology. This situation has negative consequences for a variety of players in health care, from patients and physicians to payers and policymakers. Addressing these gaps would result in better decisions that improve patient outcomes and reduce unnecessary costs."