Comparative Effectiveness Research, Genomics-Enabled Personalized Medicine, and Rapid Learning Health Care: A Common Bond

Abstract

Despite stunning advances in our understanding of the genetics and the molecular basis for cancer, many patients with cancer are not yet receiving therapy tailored specifically to their tumor biology. The translation of these advances into clinical practice has been hindered, in part, by the lack of evidence for biomarkers supporting the personalized medicine approach. Most stakeholders agree that the translation of biomarkers into clinical care requires evidence of clinical utility. The highest level of evidence comes from randomized controlled clinical trials (RCTs). However, in many instances, there may be no RCTs that are feasible for assessing the clinical utility of potentially valuable genomic biomarkers. In the absence of RCTs, evidence generation will require well-designed cohort studies for comparative effectiveness research (CER) that link detailed clinical information to tumor biology and genomic data. CER also uses systematic reviews, evidence-quality appraisal, and health outcomes research to provide a methodologic framework for assessing biologic patient subgroups. Rapid learning health care (RLHC) is a model in which diverse data are made available, ideally in a robust and real-time fashion, potentially facilitating CER and personalized medicine. Nonetheless, to realize the full potential of personalized care using RLHC requires advances in CER and biostatistics methodology and the development of interoperable informatics systems, which has been recognized by the National Cancer Institute's program for CER and personalized medicine. The integration of CER methodology and genomics linked to RLHC should enhance, expedite, and expand the evidence generation required for fully realizing personalized cancer care.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

“…Objective Process to Develop and Evaluate Guidelines for Tumor Biomarker Tests Many reviews and commentaries have discussed the nature of evidence required to support conclusions that the use of biomarker test results to guide treatment decisions improves health outcomes for patients with a malignancy. [5][6][7][8][9][10][11][12] The present guideline and the companion guideline on systemic therapy for women with metastatic breast cancer have endorsed the semantic descriptions first proposed by the Evaluation of Genomic Applications in Practice and Prevention Working Group 13,14 and subsequently adapted by the Institute of Medicine Committee on Evolution of Translational Omics. 15 As described in this guideline and in Data Supplement 1, Table S1, the working group defined three criteria for evidence: analytic validity, clinical validity, and clinical utility.…”

Comparative Effectiveness Research in Oncology

“…One of the greatest challenges as well as opportunities for CER pertains to efforts to provide more personalized care to patients based on clinical, molecular, and genomic markers associated with treatment response, resistance, or safety (Table 3) [39,40]. Targeted interventions have the potential to increase effectiveness while reducing complications by identifying patients most likely to benefit.…”

Elements of Effective Practice in Patient-Centred Laboratory Medicine

“…Molecular diagnosis development is the future trend in medicine and has become the frontline in disease identification [16]. Genomics and biomarkers based personalised medicine in some human diseases like cancer therapy and cardiovascular diseases have been under clinical testing in recent years [17][18][19]. There is a systematic programme in computing based diagnostic analysis available for clinical science technologies which may facilitate the development of molecular diagnosis and new technology transfer [20].…”