We presented an overview of the average healthcare costs of patients admitted to the NICU. We estimated the economic impact of the inclusion of WES as part of the diagnostic trajectory on the resources spent on genetic testing and on the overall healthcare costs. We modelled multiple scenarios to find a balance between making maximal benefits of the use of WES in this patient population, while limiting the socio-economic impact on the healthcare system. Our results showed that care for patients who received genetic diagnostic tests (€43,804 per patient) was more expensive compared to care for patients who did not receive genetic diagnostic testing (€18,404 per patient). This has been calculated for the first two years after the patients were admitted to the NICU. Of these costs, €2,523 (5.8% of all costs) and €99 (0.5% of all costs) was spent on genetic testing, respectively. Apart from spending more budget on genetic testing for the patients with (multiple) CAs, the main difference was attributed to costs for hospitalization and consultations. This was in line with results obtained by others, showing that more complex patients often have higher healthcare costs [22]. We observed a similar trend between patients with isolated and multiple CAs: care for patients with multiple CAs was more expensive than for patients with isolated CAs (€53,686 vs. €27,350 per patient). Care for patients without CAs were the least expensive (€15,210 per patient).
Of the 57 patients that received a conclusive genetic diagnosis and were included in the scenario analyses, 52 presented CAs, highlighting that such anomalies can have a genetic origin [11]. In the total cohort, 461 patients presented with (multiple) CAs, but not all patients received genetic testing. An argument of not testing in these patients is often related to the long turnaround times. Since these have been drastically reduced by the introduction of WES, we modelled three scenarios to determine the anticipated impact on diagnostic yield and healthcare costs for wider spread implementation in a NICU setting.
In case of scenario A, all 1,428 patients would receive genetic diagnostic testing by WES. Compared to the current costs, genetic costs increased with 949.8% and overall healthcare costs with 22.2%. Although costs will increase significantly, testing all patients will allow to identify all 57 diagnoses in the cohort in one test, at the start of the diagnostic trajectory. Moreover, testing allows to identify an extrapolated number of diagnoses that currently remain undetected because patients are not subjected to diagnostic testing. Since only 5 diagnoses were made in patients without CAs, one might wonder whether clinical preselection on who should receive WES based on having CAs is not a more economically sustainable option.
We therefore modelled scenario C, where WES was only performed for patients with multiple CAs, as this clinical sub-cohort of NICU patients had relative highest diagnostic yield. Testing all 136 patients with multiple CAs by trio-WES, but refraining genetic testing in all other patients (n = 1,428), resulted in no change in healthcare costs. Whereas there may be an economic benefit when introducing trio-WES for patients with multiple CAs, this scenario seems unethical as the diagnostic yield in patients with isolated CAs in this cohort is 5.8% (18 out of 310 patients). Hence, at cohort level, this scenario would leave 40.4% of patients (23 out of 57) undiagnosed.
Scenario B, allowing to perform WES for those patients with either isolated or multiple CAs, seemed as such most beneficial. The costs related to genetic testing increased with 227.4% for trio-WES, but the average total healthcare costs increased with 5.3% (€1,411). Although the costs are higher compared to the current diagnostic trajectory, this would allow the detection of >99% of all genetic diagnoses in the cohort. This scenario includes both the diagnoses established in the current situation, but also the diagnoses of those patients who currently remain untested despite a clinical presentation suspicious to be of genetic origin. This approach would miss the genetic diagnosis in the 5 of 982 patients without CAs. They now received a conclusive genetic diagnosis after performing genetic testing well after the neonatal period because of (neuro)developmental delay. It might, however, be expected that these patients would still receive genetic testing later in life, similar to the current situation, because of developmental delay [11].
A possible limitation of this study was that the diagnostic trajectory was not completed for all patients included in the scenario analysis. Although we did not include any restrictions regarding follow-up length, total healthcare costs used in this scenario analyses are probably higher due to an increase in the amount of healthcare costs in case a longer follow-up period is included. This can also has impact on the increase in costs when healthcare costs are compared to the WES-scenarios. The same holds for the calculated costs related to surgery and medication, which might also be underestimated. Unfortunately, it was not possible to collect all unit costs taking into account the amount of medication prescribed and unit costs related to surgery. Therefore, which is also a strength of this study, the results of this study showed the maximum increase in costs when WES is performed. If this study is repeated after a certain amount of time, results of the scenario analyses will probably be more positive (i.e. less increase in costs due to increase in current healthcare costs and decrease in costs related to WES). According to earlier research, it is very valuable that patients were followed over time for several years [23]. The genetic diagnostic trajectory can be very long and costly, so including a longer follow-up period in an economic evaluation provides a more accurate overview of the actual costs.
Another assumption made in this study was that performing WES provides the same results as the standard diagnostic trajectory. Furthermore, in this study, costs related to prenatal diagnostic testing were not taken into account. Prospective follow-up studies are needed in order to create more evidence to support these assumptions and to increase insight in the exact effects of implementing WES into diagnostic care. Ideally, a prospective follow-up study is performed, in which patients receive current diagnostics and trio-WES to see what the exact clinical and economic impact is of implementing WES.
In conclusion, genetic diagnostic testing in a NICU patient cohort accounts for a small fraction of total costs. Only half of patients whose clinical presentation is suspective of a genetic disorder, are currently being tested. We showed that with limited increase in overall healthcare budget on this cohort, all patients presenting with CAs can be tested by trio-WES. This will not only increase the overall diagnostic yield of this cohort, but may also allow for improved personalized treatments options guided by the diagnoses made.