Abstract
A recent review of newborn screening for Krabbe disease in the Journal of Public Health Ethics examined some of the controversies of population-based screening (Dees and Kwon, 2012). Krabbe disease is a type of leukodystrophy that results in neurodegeneration, with a prevalence rate of 1 in 100,000 and no specific treatment options (Wenger, 2011). Hematopoietic stem cell transplant has been successful in preserving some functionality in some cases when done before symptoms arise, but this protocol is still experimental and carries a risk for death and morbidity (Duffner et al., 2009). There are two forms of Krabbe disease—infantile and late-onset—but the latter has greater variation of onset and etiology. Since the inception of screening for Krabbe disease in New York in 2006, ethicists, clinicians, families, and researchers have discussed whether it is appropriate for the disease to be included in mandated screening given its low prevalence, an unclear natural history for its late-onset variation, and its limited, possibly life-threatening treatment options. In 2012, Missouri became the second state to screen for Krabbe disease as part of mandated newborn screening. This is despite the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children decision against Krabbe disease screening as part of the Recommended Uniform Screening Panel. This trend of state-based screening will continue as more states pass legislation to include lysosomal storage disorders to their screening panels in 2013.
Advocates have rallied for expanded screening both in public health and in the clinical setting. For some, the benefit of early detection and the potential to learn more about these conditions outweigh the economic and ethical burdens. Proponents of screening argue that without broad screening for these conditions there will still be gaps in information on the condition and in development of appropriate treatment protocols. The low prevalence of a condition may make it less desirable to screen because little may be known about its etiology, but it is this very screening and detection that can lead to more data points that expand the knowledge base for the condition. Although a very specific example of genetic screening, these issues reflect the growing challenges in the field.
An underlying question in discussing any type of genetic testing is who defines the benefit. In 1968, James Wilson and Gunner Jungner drafted a report for the World Health Organization laying out criteria for screening the public for disease. These criteria focused on the impact of the health problem, availability of treatment, and economic balance between finding a case and treating a person. Although these criteria are a mainstay of public health, in recent years researchers and policymakers alike have pondered whether it is time to reevaluate them within the contexts of both genomic advances and changing resources (Andermann et al., 2008). In 2011, four former and active members of the U.S. Preventive Services Task Force presented a new model to review the appropriateness of screening programs that emphasized health outcomes and predictors of poor health, not just disease (Harris et al., 2011). This article indicates a drive to reframe the decision-making process regarding population-based screening that includes not only outcomes and resources but also the changing landscape of what is medically feasible.
Researchers, clinicians, academics, and the public need open dialogue about social expectations for screening and disease detection. Guidelines and principles should not be established without the input of the people whose lives will be most affected. The gap between the ability to detect disease and the capability to fully address the consequences (e.g., treatment, clinical follow-up, net benefit) increases each time a new condition is deemed a target for a specific population. By blurring the line between research and clinical use, entities responsible for population-based screening are put in an ever more precarious situation of learning information about a person or family that may not be immediately actionable within the context of traditional public health. On the other hand, as we move toward a healthcare learning system, the distinctions disappear.
The completion of the sequencing of the human genome spurred great anticipation of the development of genomic-based solutions for health problems. However, people still grapple with the notion of increased data without a corresponding increase in immediately actionable steps for health management. As more people encounter the option to incorporate genetic testing into their healthcare — as early as 10 weeks' gestation with new noninvasive prenatal testing — there is opportunity for further confusion and unmet expectations. Krabbe disease is a clear example of what can happen when population-based screening leads to more questions, for clinicians and researchers as well as families. The perceptions of harm and benefit are as varied as the stakeholders involved in and affected by screening programs. This is not merely a newborn screening issue; it can help set the stage for concrete dialogue of the anticipated outcomes, benefits, and harms of screening throughout the life course using genetic technologies.