Purpose: Health care interventions are often targeted using risk prediction models. However, there is a lack of work, that both develops and evaluates the cost-effectiveness of alternative risk prediction strategies, within a single study. This paper develops new risk prediction models, and evaluates whether using the risk models in prevention strategies is cost-effective. We illustrate this approach in the Fungal Infection Risk Evaluation (FIRE) study, which developed and validated risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive fungal disease (IFD).
Method: A decision-analytical model was developed to compare alternative strategies to prevent IFD. The alternative prevention strategies, comprised assessment according to predicted risk of IFD at up to three decision time points (critical care admission, after 24 hours, end of day 3), with antifungal prophylaxis for those judged ‘high’ risk according to three thresholds, versus no formal risk assessment or prophylaxis, which is UK current practice. Data on risk factors were available for 54,289 eligible admissions to 96 UK adult, general critical care units. Risk models were developed and validated to predict the risk of IFD before hospital discharge. The decision model was populated with estimates of positive predictive value (PPV) and negative predictive value (NPV) from the best fitting risk model at each time point. Estimates of the effectiveness of antifungal prophylaxis were taken from a systematic review of published RCTs. We projected lifetime cost-effectiveness and the value of further information for groups of parameters (VOPPI).
Result: The baseline risk of IFD was low (0.4%). The best fitting prognostic model, gave PPVs and NPVs that varied across strategies from 0.57%-1.94% and 99.65%-99.95% respectively. Incremental Quality-Adjusted Life Years (QALY) of the risk assessment strategies compared with current practice were positive but small, versus incremental costs. Current practice was the strategy with the highest probability of being cost-effectiveness (between 40%-80%). The VOPPIs were relatively high for PPV or NPV (£4m-£13m) and QALYs (£4m-£12m).
Conclusion: It is effective but not cost-effective to formally assess the risk of IFD for non-neutropenic, critically ill adult patients, but the value of further research is high. This integrated approach to developing, and evaluating risk models within the same study is useful for informing clinical practice and future research investment. Grant Acknowledgement: NIHR Health Technology Assessment Programme