Use of Real-World Data for the Research, Development, and Evaluation of Oncology Precision Medicines

Abstract

Although randomized controlled trials remain the scientific ideal for determining the efficacy and safety of new treatments, they are sometimes insufficient to address the evidentiary requirements of regulators and payers. This is particularly the case when it comes to precision medicines because trials are often small, deliver incomplete insights into outcomes of most interest to policymakers (eg, overall survival), and may fail to address other complex diagnostic and treatment-related questions. Additional methods, both experimental and observational, are increasingly being used to fill critical evidentiary gaps. A number of modified early- and late-phase trial designs have been proposed to better support earlier biomarker validation, patient identification, and selection for regulatory studies, but there is still a need for confirmatory evidence from real-world data sources. These data are usually provided through observational, postapproval, phase IIIB and IV studies, which rely heavily on registries and other electronic data sets—most notably data from electronic health records. It is, therefore, crucial to understand what ethical, practical, and scientific challenges are raised by the use of electronic health records to generate evidence about precision medicines.

First-line therapy in chronic lymphocytic leukemia: a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013

“…Randomized controlled trials (RCTs) remain the scientific ideal for evaluation of novel treatments. However, in studies on malignancies, RCTs are sometimes not sufficient to address the evidentiary requirements of regulating authorities 30 and payers as patients are selected on strict inclusion/exclusion criteria and sufficient data on overall survival and long-term follow up is often not provided. 31 In addition, the comparative arm in clinical trials may be chosen to favor the treatment of investigation.…”

“…Hence, long-term results, including OS estimates, in real-life treated patients are important to determine the optimal therapy for patients with CLL. 22…”

Value of Precision Medicine in Advanced Non-Small Cell Lung Cancer: Real-World Outcomes Associated with the Use of Companion Diagnostics

“…This study has several advantages over other precision medicine trials. Whereas previous trials were usually small [36], making it difficult to generalize findings to other patients, this study comprised a large cohort of patients with non‐Sq aNSCLC ( n = 17,555) who were treated primarily in a community‐based setting for an evaluation period of up to 7 years (January 1, 2011–May 31, 2018). Using EHRs from the Flatiron Health database enabled longer‐term follow‐up of well‐defined cohorts in a real‐world setting.…”

“…Another advantage is that our study incorporated any type of CDx testing, increasing the likelihood of including biomarkers that are likely screened for by clinicians in real‐world clinical practice settings. By contrast, patients in other precision medicine trials were usually selected based on a single biomarker or a biomarker that is not routinely evaluated in community‐based practice settings [36].…”

Weighing false hope in population anticancer drug decision making

“…There is also the question of societal cost-the right to try, some would argue, adds to the evidence base around these medications and their potential for use to extend life or for use in other earlier disease contexts (as adjuvant/neoadjuvant treatment) and therefore they may justify their cost to society and the individual. On the other hand, the costs to society may be too high in absolute financial terms, when considering the opportunity cost of money diverted from evidence-based therapies, as well as generating concern the promised evidence may not materialize due to real-world bias, rather than real-world data [13,14].…”