Objective

To summarize lessons learned while analyzing the costs of integrating whole genome sequencing into the care of cardiology and primary care patients in the MedSeq Project by conducting the first randomized controlled trial of whole genome sequencing in general and specialty medicine.

Methods

Case study that describes key methodological and data challenges that were encountered or are likely to emerge in future work, describes the pros and cons of approaches considered by the study team, and summarizes the solutions that were implemented.

Results

Major methodological challenges included defining whole genome sequencing, structuring an appropriate comparator, measuring downstream costs, and examining clinical outcomes. Discussions about solutions addressed conceptual and practical issues that arose because of definitions and analyses around the cost of genomic sequencing in trial-based studies.

Conclusions

The MedSeq Project provides an instructive example of how to conduct a cost analysis of whole genome sequencing that feasibly incorporates best practices while being sensitive to the varied applications and diversity of results it may produce. Findings provide guidance for researchers to consider when conducting or analyzing economic analyses of whole genome sequencing and other next-generation sequencing tests, particularly regarding costs.

Objective

We studied decision making regarding inhaled nitric oxide (iNO) in preterm infants with Pulmonary Hypertension (PH).

Study design

We asked members of the AAP-Society of Neonatal-Perinatal Medicine and Division-Chiefs to select from three management options- initiate iNO, engage parents in shared decision making or not consider iNO in an extremely preterm with PH followed by rating of factors influencing their decision.

Results

Three hundred and four respondents (9%) completed the survey; 36.5% chose to initiate iNO, 42% to engage parents, and 21.5% did not consider iNO. Provider's prior experience, safety, and patient-centered care were rated higher by those who initiated or offered iNO; lack of effectiveness and cost considerations by participants who did not chose iNO.

Conclusions

Most neonatologists offer or initiate iNO therapy based on their individual experience. The minority who chose not to consider iNO placed higher value on lack of effectiveness and cost. These results demonstrate a tension between evidence and pathophysiology-based-therapy/personal experience.

Purpose

Great uncertainty exists about the costs associated with whole-genome sequencing (WGS).

Methods

One hundred cardiology patients with cardiomyopathy diagnoses and 100 ostensibly healthy primary care patients were randomized to receive a family-history report alone or with a WGS report. Cardiology patients also reviewed prior genetic test results. WGS costs were estimated by tracking resource use and staff time. Downstream costs were estimated by identifying services in administrative data, medical records, and patient surveys for 6 months.

Results

The incremental cost per patient of WGS testing was $5,098 in cardiology settings and $5,073 in primary care settings compared with family history alone. Mean 6-month downstream costs did not differ statistically between the control and WGS arms in either setting (cardiology: difference = -$1,560, 95% confidence interval -$7,558 to $3,866, p = 0.36; primary care: difference = $681, 95% confidence interval -$884 to $2,171, p = 0.70). Scenario analyses showed the cost reduction of omitting or limiting the types of secondary findings was less than $69 and $182 per patient in cardiology and primary care, respectively.

Conclusion

Short-term costs of WGS were driven by the costs of sequencing and interpretation rather than downstream health care. Disclosing additional types of secondary findings has a limited cost impact following disclosure.

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening.

Objectives

The challenges of understanding how interventions influence follow-up medical care are magnified during genomic testing because few patients have received it to date and because the scope of information it provides is complex and often unexpected. We tested a novel strategy for quantifying downstream healthcare utilization after genomic testing to more comprehensively and efficiently identify related services. We also evaluated the effectiveness of different methods for collecting these data.

Methods

We developed a risk-based approach for a trial of newborn genomic sequencing in which we defined primary conditions based on existing diagnoses and family histories of disease and defined secondary conditions based on unexpected findings. We then created patient-specific lists of services associated with managing primary and secondary conditions. Services were quantified based on medical record reviews, surveys, and telephone check-ins with parents.

Results

By focusing on services that genomic testing would most likely influence in the short-term, we reduced the number of services in our analyses by more than 90% compared with analyses of all observed services. We also identified the same services that were ordered in response to unexpected findings as were identified during expert review and by confirming whether recommendations were completed. Data also showed that quantifying healthcare utilization with surveys and telephone check-ins alone would have missed the majority of attributable services.

Conclusions

Our risk-based strategy provides an improved approach for assessing the short-term impact of genomic testing and other interventions on healthcare utilization while conforming as much as possible to existing best-practice recommendations.