Approaches to informed consent for hypothesis-testing and hypothesis-generating clinical genomics research

Flavia M Facio,Amy Linn,Leslie G Biesecker,Julie C Sapp

doi:10.1186/1755-8794-5-45

Abstract

BackgroundMassively-parallel sequencing (MPS) technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results.DiscussionWe propose that the consent process in these studies be based on whether they use MPS to test a hypothesis or to generate hypotheses. To demonstrate the differences in these approaches to informed consent, we describe the consent processes for two MPS studies. The purpose of our hypothesis-testing study is to elucidate the etiology of rare phenotypes using MPS. The purpose of our hypothesis-generating study is to test the feasibility of using MPS to generate clinical hypotheses, and to approach the return of results as an experimental manipulation. Issues to consider in both designs include: volume and nature of the potential results, primary versus secondary results, return of individual results, duty to warn, length of interaction, target population, and privacy and confidentiality.SummaryThe categorization of MPS studies as hypothesis-testing versus hypothesis-generating can help to clarify the issue of so-called incidental or secondary results for the consent process, and aid the communication of the research goals to study participants.

Highlights

Massively-parallel sequencing (MPS) technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results
Advances in DNA sequencing technologies and concomitant cost reductions have made the use of massively-parallel sequencing (MPS) in clinical research practicable for many researchers
We describe an approach to the informed consent process as a mutual opportunity for researchers and participants to assess one another’s goals in MPS protocols that employ both hypothesis-generating and hypothesis-testing methodologies

Summary

Introduction

Massively-parallel sequencing (MPS) technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results. Is the range of the disorders broad, but the variants have a wide range of relative risks from very high to nearly zero This is a key distinction of MPS when compared to common SNP variant detection (using so-called gene chips). Because some variants discovered by MPS can be highly penetrant, the detection of such variants can have enormous medical and counseling impact While many of these informed consent issues have been addressed previously [1,3], the use of MPS in clinical research combines these issues and is on a scale that is orders of magnitude greater than previous study designs

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