The disclosure of individual genetic research results to study participants continues to be the subject of vigorous debate, centered primarily on the nature of the results. We suggest that research ...context, which is foreseeable when a study is designed, is a vital consideration that has not been sufficiently incorporated into the discussion. Adapting an ancillary care framework to explore what different contexts might call for with regard to offering individual genetic research results, our analysis suggests that, beyond exceptionally rare circumstances that give rise to a duty to rescue, a one-size-fits-all threshold cannot be developed for decisions about returning individual results. Instead, researchers and institutional review boards must consider the scope of entrustment involved in the research, as well as the intensity and duration of interactions with participants and the vulnerability and dependence of the study population.
Despite early predictions and rapid progress in research, the introduction of personal genomics into clinical practice has been slow. Several factors contribute to this translational gap between ...knowledge and clinical application. The evidence available to support genetic test use is often limited, and implementation of new testing programs can be challenging. In addition, the heterogeneity of genomic risk information points to the need for strategies to select and deliver the information most appropriate for particular clinical needs. Accomplishing these tasks also requires recognition that some expectations for personal genomics are unrealistic, notably expectations concerning the clinical utility of genomic risk assessment for common complex diseases. Efforts are needed to improve the body of evidence addressing clinical outcomes for genomics, apply implementation science to personal genomics, and develop realistic goals for genomic risk assessment. In addition, translational research should emphasize the broader benefits of genomic knowledge, including applications of genomic research that provide clinical benefit outside the context of personal genomic risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The American College of Medical Genetics and Genomics (ACMG) recommended that clinical laboratories performing next-generation sequencing analyze and return pathogenic variants for 56 specific genes ...it considered medically actionable. Our objective was to evaluate the clinical and economic impact of returning these results.
We developed a decision-analytic policy model to project the quality-adjusted life-years and lifetime costs associated with returning ACMG-recommended incidental findings in three hypothetical cohorts of 10,000 patients.
Returning incidental findings to cardiomyopathy patients, colorectal cancer patients, or healthy individuals would increase costs by $896,000, $2.9 million, and $3.9 million, respectively, and would increase quality-adjusted life-years by 20, 25.4, and 67 years, respectively, for incremental cost-effectiveness ratios of $44,800, $115,020, and $58,600, respectively. In probabilistic analyses, returning incidental findings cost less than $100,000/quality-adjusted life-year gained in 85, 28, and 91%, respectively, of simulations. Assuming next-generation sequencing costs $500, the incremental cost-effectiveness ratio for primary screening of healthy individuals was $133,400 (<$100,000/quality-adjusted life-year gained in 10% of simulations). Results were sensitive to the cohort age and assumptions about gene penetrance.
Returning incidental findings is likely cost-effective for certain patient populations. Screening of generally healthy individuals is likely not cost-effective based on current data, unless next-generation sequencing costs less than $500.
To evaluate the cost effectiveness of next-generation sequencing (NGS) panels for the diagnosis of colorectal cancer and polyposis (CRCP) syndromes in patients referred to cancer genetics clinics.
We ...developed a decision model to evaluate NGS panel testing compared with current standard of care in patients referred to a cancer genetics clinic. We obtained data on the prevalence of genetic variants from a large academic laboratory and calculated the costs and health benefits of identifying relatives with a pathogenic variant, in life-years and quality-adjusted life-years (QALYs). We classified the CRCP syndromes according to their type of inheritance and penetrance of colorectal cancer. One-way and probabilistic sensitivity analyses were conducted to assess uncertainty.
Evaluation with an NGS panel that included Lynch syndrome genes and other genes associated with highly penetrant CRCP syndromes led to an average increase of 0.151 year of life, 0.128 QALY, and $4,650 per patient, resulting in an incremental cost-effectiveness ratio of $36,500 per QALY compared with standard care and a 99% probability that this panel was cost effective at a threshold of $100,000 per QALY. When compared with this panel, the addition of genes with low colorectal cancer penetrance resulted in an incremental cost-effectiveness ratio of $77,300 per QALY.
The use of an NGS panel that includes genes associated with highly penetrant CRCP syndromes in addition to Lynch syndrome genes as a first-line test is likely to provide meaningful clinical benefits in a cost-effective manner at a $100,000 per QALY threshold.
This article is based on the address given by the author at the 2021 virtual meeting of the American Society of Human Genetics (ASHG). The video of the original address can be found at the ASHG ...website.
Alzheimer disease is the most common cause of dementia. It occurs worldwide and affects all ethnic groups. The incidence of Alzheimer disease is increasing due, in part, to increased life expectancy ...and the aging baby boomer generation. The average lifetime risk of developing Alzheimer disease is 10–12%. This risk at least doubles with the presence of a first-degree relative with the disorder. Despite its limited utility, patients express concern over their risk and, in some instances, request testing. Furthermore, research has demonstrated that testing individuals for apolipoprotein E can be valuable and safe in certain contexts. However, because of the complicated genetic nature of the disorder, few clinicians are prepared to address the genetic risks of Alzheimer disease with their patients. Given the increased awareness in family history thanks to family history campaigns, the increasing incidence of Alzheimer disease, and the availability of direct to consumer testing, patient requests for information is increasing. This practice guideline provides clinicians with a framework for assessing their patients' genetic risk for Alzheimer disease, identifying which individuals may benefit from genetic testing, and providing the key elements of genetic counseling for AD.
Whole-Genome Sequencing in Healthy People Lindor, Noralane M.; Thibodeau, Stephen N.; Burke, Wylie
Mayo Clinic proceedings,
01/2017, Letnik:
92, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Recent technological advances have radically changed genetic testing from an expensive and burdensome undertaking to a rapid and less costly option for many purposes. The utility of “next-generation” ...sequencing has been found to establish the diagnosis for hundreds of genetic disorders, to assess pharmacogenomic variants, and to identify treatable targets within malignant neoplasms. The ready availability of genomic information has led to the question of whether there would be clinical benefit of sequencing the genome of individuals who are not seeking a diagnosis, that is, genomic screening in generally healthy people, to provide anticipatory insights for their health care. Little research has been conducted in this area. We examine the considerable unresolved scientific and ethical issues encountered when considering whole-genome sequencing of healthy people.
Genomic information is poised to play an increasing role in clinical care, extending beyond highly penetrant genetic conditions to less penetrant genotypes and common disorders. But with this shift, ...the question of clinical utility becomes a major challenge. A collaborative effort is necessary to determine the information needed to evaluate different uses of genomic information and then acquire that information. Another challenge must also be addressed if that process is to provide equitable benefits: the lack of diversity of genomic data. Current genomic knowledge comes primarily from populations of European descent, which poses the risk that most of the human population will be shortchanged when health benefits of genomics emerge. These two challenges have defined my career as a geneticist and have taught me that solutions must start with dialogue across disciplinary and social divides.
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