The Challenges of Validating in Precision Medicine: The Case of Excision Repair Cross-Complement Group 1 Diagnostic Testing

Abstract

Personalized medicine relies upon the successful identification and translation of predictive biomarkers. Unfortunately, biomarker development has often fallen short of expectations. To better understand the obstacles to successful biomarker development, we systematically mapped research activities for a biomarker that has been in development for at least 12 years: excision repair cross-complement group 1 protein (ERCC1) as a biomarker for predicting clinical benefit with platinum-based chemotherapy in non-small cell lung cancer. We found that although research activities explored a wide range of approaches to ERCC1 testing, there was little replication or validation of techniques, and design and reporting of results were generally poor. Our analysis points to problems with coordinating and standardizing research in biomarker development. Clinically meaningful progress in personalized medicine will require concerted efforts to address these problems. In the interim, health care providers should be aware of the complexity involved in biomarker development, cautious about their near-term clinical value, and conscious of applying only validated diagnostics in the clinic. The Oncologist 2017;22:89-96 Implications for Practice: Many hospitals, policy makers, and scientists have made ambitious claims about the promise of personalizing cancer care. When one uses a case example of excision repair cross-complement group 1 protein-a biomarker that has a strong biological rationale and that has been researched for 12 years-the current research environment seems poorly suited for efficient development of biomarker tests. The findings provide grounds for tempering expectations about personalized cancer care-at least in the near term-and shed light on the current gap between the promise and practice of personalized medicine.

Mapping ethical and social aspects of biomarker research and its application in atopic dermatitis and psoriasis: a systematic review of reason

“…The issue of complexity and/or uncertainty in biomarker development comes up repeatedly in translational biomarker research for AD/Pso 15,20,54,63 . The development of biomarkers for inflammatory skin diseases lags behind new therapies due to the complexity and heterogeneity of dermatological inflammatory diseases 63 .…”

“…Complexity and uncertainty in biomarker development, validation and qualification The issue of complexity and/or uncertainty in biomarker development comes up repeatedly in translational biomarker research for AD/Pso. 15,20,54,63 The development of biomarkers for inflammatory skin diseases lags behind new therapies due to the complexity and heterogeneity of dermatological inflammatory diseases. 63 The complexity of biomarker validation remains an issue which is addressed by several authors.…”

“…Various aspects of personalized medicine and research ethics such as questions of social justice and participation of patients have been mainly focused on oncology or genomics. [19][20][21][22][23] Besides, ethical and socially relevant arguments in current biomedical articles about biomarker research are frequently brief. Concepts such as autonomy, patient identity, personal responsibility, responsibilization and accountability are not discussed in detail for biomarker research in AD/Pso in the literature reviewed.…”

“…However, the academic controversy around biomarker research and application has hitherto mainly targeted ethical and social issues in the fields of genomics and oncology. [19][20][21][22][23] What is lacking is a coherent overview of social and ethical aspects concerning biomarkers for AD/Pso. This review systematically examines the available literature including medical and philosophical contributions on the ethical and social aspects of biomarker research on AD/Pso with the aim of mapping the ongoing debate and identifying research gaps for further investigation.…”

“…Despite the many promising possibilities, new biomarker projects on AD/Pso with integrative experimental models, advanced analytical technologies and larger data sets raise ethical questions on the individual and public health level, for example concerning risk stratification, incidental findings, informed consent and justice. However, the academic controversy around biomarker research and application has hitherto mainly targeted ethical and social issues in the fields of genomics and oncology 19–23 …”