How to put figures on the benefits of WGS pathogen surveillance

Can WGS be cost-effective when the cost of a test is still considered expensive?

Just like exercise gives the best results when it becomes a habit, so does WGS for infection control. Working proactively with WGS surveillance gives results, and the way it is implemented matters. One of the biggest questions is how to actually adopt a WGS surveillance strategy, for what pathogens and how it would then support interventions. Can WGS be cost-effective when the cost of a test is still considered expensive?

We have read four different health economic evaluations of WGS, all published in 2020 and 2021, which using different methods still come to the same conclusion. Transmissions can be minimized and lives can be saved, while also lowering costs.

The Dymond et al. study from Cambridge University Hospital, in which a cohort of 65 000 patients passing through the hospital were investigated to see if either a standard protocol or standard protocol + WGS would result in a relative reduction of MRSA acquisitions. The results with the authors’ input demonstrated a cost reduction of 728 297 GBP, primarily based on savings from MRSA related care.

General surveillance with WGS - estimated a 46% reduction in transmissions

In the Kumar et al. paper from Pittsburgh, they aimed to improve general pathogen surveillance by, instead of waiting for two related cases, sequencing upon incidence of an identified relevant pathogen. The pathogens were selected based on the following criteria:

  1. Negative clinical impact
  2. Antibiotic resistance
  3. Hospital transmission and outbreak risk

The method was retrospective and investigated previous outbreaks based on the transmission and efficacy of interventions; with the focus being on how many transmissions could have been avoided with timely knowledge from WGS. The cost of those transmissions were calculated based on the condition prevented and the estimated cost of treatment for such cases.

As a result, they estimated the prevention of 46% of all transmissions and the cost-effectiveness of the program to be 80%, if an investment to support the methods exceeded 2 400 USD per transmission averted.

Regional WGS Surveillance of six multi-drug resistant bacteria - saving 650 lives

A similar setup with focus on modelling the potential prevention of transmissions and infections with early whole-genome sequencing of six multi-drug resistant bacteria was performed in Queensland, by LG Gordon et al. The article was published in BMJ Open 2021 and used retrospective data to simulate a five year scenario at 27 hospitals in Queensland. Results showed an estimated reduction of 36 726 transmission and avoided 650 deaths, all in all showing an annual cost reduction of 30.8 million AUD.

Computational hybrid models can assist in cost-effective WGS adoption

The third paper, from Elliott et al., chose the perspective of modelling based on a single outbreak of a carbapanamase producing E.coli, an OXA-181, intending to understand how the knowledge from WGS influences outbreak intervention. Without moving too far into the intricacies of this fairly detailed and complex model, the conclusion is the same. Initiating investigation with WGS at the first sign of an E.coli OXA-181 saves both health care-related costs and prevents further colonization and transmissions.

Prospective studies needed

In all studies, the cost for microbiology tests was the greatest investment, which increased due to the expansion of their WGS programs; while savings were mainly in pathogen related care and to some extent in QALYs. Prospective studies are needed, but will be difficult due to the stochastic appearance of outbreaks. Additionally, other benefits, like continuous operations due to outbreak limitations or using WGS alongside antibiotic stewardship, remain to be studied, as they may have an overall positive impact on both lives saved and lowered costs.

References

  1. Dymond A, Davies H, Mealing S, et al. Genomic Surveillance of Methicillin-resistant Staphylococcus aureus: A Mathematical Early Modeling Study of Cost-effectiveness. Clin Infect Dis. 2020;70(8):1613-1619. doi:10.1093/cid/ciz480
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145999/
  2. Kumar P, Sundermann AJ, Martin EM, Snyder GM, Marsh JW, Harrison LH, Roberts MS. Method for economic evaluation of bacterial whole genome sequencing surveillance compared to standard of care in detecting hospital outbreaks. Clin Infect Dis. 2020 May 5:ciaa512. doi: 10.1093/cid/ciaa512
    https://pubmed.ncbi.nlm.nih.gov/32367125/
  3. Gordon LG, Elliott TM, Forde B, et alBudget impact analysis of routinely using whole-genomic sequencing of six multidrug-resistant bacterial pathogens in Queensland, AustraliaBMJ Open 2021;11:e041968. doi: 10.1136/bmjopen-2020-041968
    https://bmjopen.bmj.com/content/11/2/e041968
  4. Elliott TM, Lee XJ, Foeglein A, Harris PN, Gordon LG. A hybrid simulation model approach to examine bacterial genome sequencing during a hospital outbreak. BMC Infect Dis. 2020;20(1):72. Published 2020 Jan 23. doi:10.1186/s12879-019-4743-3
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979342/