Douglas S. Rabin M.D. Medical Director, Women’s Health Quest Diagnostics

Making the Case for Responsible Innovation in Genetic Testing

In the dozen years since the sequencing of the human genome, the pace of innovation in genetic testing has exploded. We are now able to screen, diagnose, and monitor numerous medical conditions based on insights gleaned from lab tests based on genetic markers identifiable in a blood specimen. For many patients, these diagnostic advances have helped to deliver significantly better care and outcomes than would have been possible a few short years ago.

With this fast rate of advance in gene-based knowledge and innovation, scientists and the medical community must make decisions within a more dynamic—yet ambiguous—environment than ever before. Peering into the human genome is akin to seeking to unravel the depths of the universe. With every new discovery come new questions—and uncertainties. How do we interpret a new piece of genetic information for clinicians? Can we ensure insights into a genetic mutation are actionable for our patients? Genetic advances are fascinating, but they may not always be helpful to delivering better care or outcomes. 

Case in point: noninvasive prenatal screening (NIPS), a field that has experienced rapid growth in the recent years. New screening technologies can help identify a pregnancy affected by an aneuploidy through assessment of cell-free fetal DNA (cfDNA) circulating in the maternal blood stream. Utilization of NIPS is growing, with the market estimated to be $750 million for high-risk pregnancies and up to $3.25 billion when use of NIPS is recommended in medical guidelines for average-risk pregnancies. (As of the summer of 2015, several health plans had adopted NIPS into their policies for average-risk as well as high-risk pregnancies.)

NIPS has enormous potential clinical value, as it may help more women avoid amniocentisis or chorionic villus sampling (CVS), which are invasive procedures that involve a small risk of miscarriage. Yet, the speed at which NIPS has been adopted into mainstream medical care has greatly outpaced the knowledge that women and even some physicians have about the limitations of these tests and how to interpret results.

For instance, NIPS tests in the United States generally have outstanding sensitivity and specificity rates that approach 100%. Yet, it will be some time before researchers can amass large datasets on positive predictive and negative predictive values in real-world populations. These performance characteristics are important for conditions like fetal aneuploidies, which tend to have low prevalence rates. In August 2014, Genetics in Medicine published a peer-reviewed study by several of my colleagues that determined that the chance that a positive NIPS test result was actually a false positive could be 50% or higher for some aneuploidies. (Source: Wang JC, Sahoo T, Schonberg S, et al. Discordant noninvasive prenatal testing and cytogenetic results: a study of 109 consecutive cases. Genetics in Medicine. 2015;17(3):234-236.)

NIPS also presents a risk that some people may make family planning decisions based on a screening result. NIPS are not diagnostic; medical guidelines from the American College of Obstetricians and Gynecologists emphasize that NIPS is a screening tool and diagnostics such as CVS or amniocentesis should confirm a positive NIPS test result. Despite these guidelines, recent research suggests that some fetal maternal specialists rely on the results of NIPS in clinical decisions without confirmation by established diagnostic procedures. (Source: Non-invasive prenatal testing: a review of international implementation and challenges, Int J Womens Health. 2015; 7: 113–126)

To tackle these challenges, the Perinatal Quality Foundation (PQF) has launched a campaign that aims to replace confusion and misconceptions with clarity about the advantages and limitations of NIPS. With support from Quest Diagnostics, the PQF will provide women and health care providers with access to educational information about the types of prenatal screening and diagnostic tests, their strengths and limitations, test results interpretation, and actions to consider based on results. 

Another important part of the campaign is the development of an online patient registry to track outcomes and help determine the true predictive ability of NIPS tests being provided. Outcomes research and patient/clinician education are both vital to minimizing the potential for false positives and negatives.

Efforts, such as those of the PQF, to ensure that patients and providers use medical advances responsibly may have application in several other areas. These include providing education about large gene mutation screening panels, where large amounts of genetic information about disease risk may promote anxiety and confusion, and education about the appropriate use of cancer screening to choose proper therapy. The use of genetic screening should be linked to improvements in quality of care.

Uncovering the secrets of the human genome is a critical step on the path to realize the potential of precision medicine. Ensuring that newly discovered genetic screening information is clinically actionable and can be understood by clinicians and patients is a great challenge for scientists and the medical community. Transforming discoveries into diagnostic tests that will help improve outcomes may be an even greater challenge, and one we consider essential to our work at Quest.  

Douglas S. Rabin, M.D. ([email protected]), serves as the medical director, women’s health, for Quest Diagnostics.

This article was originally published in the November 2015 issue of Clinical OMICs. For more content like this and details on how to get a free subscription to this digital publication, go to



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