Reply to L.W. Cuttino et al

Abstract

Angeles, wrote an editorial accompanying the Yale study entitled, "When Hope Hinders Science and Patient-Centered Care." 11 The progression of BB during the last 20 years from institutional phase I/II studies, to multiinstitution phase II trials, to the creation of patient selection guidelines from several major organizations, and finally to the implementation of prospective randomized trials that have enrolled more than 10,000 women to date is the very definition of rigorous scientific evaluation. Malin recognizes "the important role CER can have in providing data on therapies for which outcomes from randomized clinical trials are lacking," 11(p4283) but fails entirely to acknowledge the existence of randomized data on BB.Prospective data should not be ignored in favor of retrospective analyses that are based on billing claims data. Just as with the publication of the MD Anderson BB analysis, the media is reporting on the Yale study with fervor. On October 22, 2012, Reuters published a story entitled, "New breast cancer therapy tied to more complications," 12 which has been picked up by most of the lay press. In this article, the senior author of the Yale study, Gross, is cited as saying that "there is no solid research showing brachytherapy is a safe and effective alternative to whole-breast radiation." This statement ignores the results of multiple large, prospective studies. Unfortunately, this media sensationalism is creating a false equivalence between patient-derived prospective data and retrospective analyses that are based on billing claims.The efficacy of APBI and BB in comparison with WBI is best answered by randomized phase III clinical trials. Ioannidis of Stanford University recently observed, "…observational evidence about commonly and easily measured exposures and outcomes resembles an opinion poll or self-fulfilling prophecy: researchers can selectively mold… data into studies that produce the desired result." 13(p576) This type of analysis should simply never trump the results of carefully conducted randomized trials. Moreover, these data may serve as distractions and fruitless scientific detours that steal precious time and resources from the next generation of rigorously designed and conducted clinical trials. Thus far, there is absolutely no evidence to suggest increased toxicity or local failure after APBI in the thousands of women who have been treated prospectively in modern phase III trials.

Considerations for Observational Research Using Large Data Sets in Radiation Oncology

“…Furthermore, randomized trials can sometimes prioritize internal validity (the measurement of cause and effect with minimized bias within the study sample) over external validity (the application of study results to patients in the source population who are not included in the study sample). The external validity of randomized studies may be limited if the treatment arms, outcomes, or follow up periods tested are different or unrelated to current clinical practice 33 or if the participants are not representative of the patient population, a concern frequently voiced for elderly cancer patients. 34 Large observational studies are advantaged by their ability to draw information from a diverse array of patients, providers, and treating facilities in real world practice.…”

Uptake and Survival Outcomes Following Immune Checkpoint Inhibitor Therapy Among Trial-Ineligible Patients With Advanced Solid Cancers

“…26,27 Data from unstructured EHR-derived digital documents were manually reviewed by centrally managed and trained medical record abstractors using specifically defined abstraction protocols. [28][29][30][31]…”