Individualizing the informed consent process for whole genome sequencing: a patient directed approach

ABSTRACT Whole genome sequencing (WGS) and whole exome sequencing (WES) are two comprehensive genomic tests which use next-generation sequencing technology to sequence most of the 3.2 billion base pairs in a human genome (WGS) or many of the estimated 22,000 protein-coding genes in the genome (WES). The promises offered from WGS/WES are: to identify suspected yet unidentified genetic diseases, to characterize the genomic mutations in a tumor to identify targeted therapeutic agents and, to predict future diseases with the hope of promoting disease prevention strategies and/or offering early treatment. Promises notwithstanding, sequencing a human genome presents several interrelated challenges: how to adequately analyze, interpret, store, reanalyze and apply an unprecedented amount of genomic data (with uncertain clinical utility) to patient care? In addition, genomic data has the potential to become integral for improving the medical care of an individual and their family, years after a genome is sequenced. Current informed consent protocols do not adequately address the unique challenges and complexities inherent to the process of WGS/WES. This dissertation constructs a novel informed consent process for individuals considering WGS/WES, capable of fulfilling both legal and ethical requirements of medical consent while addressing the intricacies of WGS/WES, ultimately resulting in a more effective consenting experience. To better understand components of an effective consenting experience, the first part of this dissertation traces the historical origin of the informed consent process to identify the motivations, rationales and institutional commitments that sustain our current consenting protocols for genetic testing. After understanding the underlying commitments that shape our current informed consent protocols, I discuss the effectiveness of the informed consent process from an ethical and legal standpoint. I illustrate how WGS/WES introduces new complexities to the informed consent process and assess whether informed consent protocols proposed for WGS/WES address these complexities. The last section of this dissertation describes a novel informed consent process for WGS/WES, constructed from the original ethical intent of informed consent, analysis of existing informed consent protocols, and my own observations as a genetic counselor for what constitutes an effective consenting experience.