Considering stakeholders in policy around secondary findings in genomics

By Michael Mackley

It took nearly thirteen years and an army of scientists to generate the first sequence of the human genome. Now, patients around the world are having their genomes sequenced every day. Since the first sequence was unveiled in 2003, the cost of whole-genome sequencing (WGS) has dropped from almost $1 billion to less than $1,000—allowing WGS to enter routine clinical care, potentially transforming the way we diagnose and treat disease. Large national initiatives to read individuals’ genomes are helping to drive this transition; the UK’s NHS England is currently sequencing 100,000 genomes, and the USA has plans to sequence 1 million genomes in the near future. A 2015 study predicts that up to 2 billion people worldwide could have their genomes sequenced within the next decade—comparable to the current reach of the Internet. With so many genomes to be sequenced, it is imperative that laws and policy ensure that individuals, and society, are protected from harm. While larger pieces of legislation—such as those protecting against discrimination—are needed internationally, guidance and policies around routine management are also required.

One area of particular concern is that of ‘secondary’ (or ‘incidental’) findings. While WGS provides a valuable opportunity to learn about genetic contributions to disease (‘primary’ findings), it can also reveal genetic information that may not be relevant to the health condition affecting the patient or their family. This includes genetic changes associated with other health conditions—ranging from medically actionable findings, such as genetic predispositions to breast cancer where treatment is available, to non-actionable findings, such as genetic changes associated with an increased risk of Alzheimer’s. The American College of Medical Genetics and Genomics published recommendations suggesting a moral obligation to seek and return actionable secondary findings, fueling significant debate (1,2). Medical Genetics organizations from other countries (including Canada and Europe) have published more conservative guidelines restricting generation of secondary findings, at least until more evidence is available to support (or refute) clinical utility and assess wider impacts.

It is critical that policy around secondary findings is informed by the views of the stakeholders it will affect. In an effort to inform policy development, and future areas for research, we conducted a systematic review of studies that explored views toward secondary findings in genomics. Stakeholders included medical genetics specialists, researchers, patients affected with rare disease or cancer, parents and members of the public.

We found that individuals were broadly supportive of returning ‘actionable’ findings, but definitions of actionability varied. Unlike survey studies showing wide support for returning ‘all’ genomic findings, we found many examples of more conservative views; experience of genetic illness and testing resulted in greater caution about secondary findings. This suggests that truly informed decisions require an understanding of the implications and limitations of genomic sequencing and possible findings, and that wishes can change with experience. The views of potential WGS recipients were largely influenced by a perceived sense of rights: both autonomy and ownership. Conversely, the views of genomics professionals were largely informed by a sense of responsibility, including duty of care, often demonstrating greater circumspection around secondary findings. Concerned about logistics, including analysis and interpretation, providers expressed concerns about causing psychological harm by returning secondary findings to participants.

For such innovative technology, we need equally innovative policy. One proposition is to use dynamic forms of consent, which allow decisions around the receipt of secondary findings (and other results) to be changed over time. Using a digital interface, dynamic consent facilitates ongoing communication and would allow participants to change their consent choices at any time—accounting for decisions that are often time- and context-dependent. This could be a powerful way to respect patient autonomy and maximize benefit, protecting both participants’ rights and the responsibilities of healthcare professionals. As secondary findings are returned, policy will need to prioritize research into the actual impact of returning these results. Where current findings are largely hypothetical, empirical data on the clinical utility and psychosocial impact of returned findings is vital to shaping future management. While increasingly limited resources will be a deciding factor, imagination need not be limited—an innovative solution to protect professionals, individuals, and wider interests, is imperative if we are all to benefit from this ‘genomic revolution’.

Read the full article in Genetics in Medicine

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