Objective:

Caffeine is a first-line option for the neonatal intensive care management of apnea of prematurity (AOP) in preterm infants. This is the first study in the literature to evaluate the cost effectiveness of the off-label high dose (HD) of caffeine versus the approved standard lower dose (LD) of caffeine for the treatment of AOP in neonates.

Methods:

From the hospital perspective of the Hamad Medical Corporation (HMC) in Qatar, this was a cost-effectiveness analysis based on a conventional decision-analytic model that follows the use and potential consequences of HD maintenance caffeine of 20 mg/kg/dose versus a LD maintenance caffeine of 10 mg/kg/dose in a simulated cohort of AOP neonates, until discharge. The model clinical inputs were primarily published meta-analyses based, while the model cost inputs were locally extracted in HMC. The effectiveness endpoint (success of caffeine) was the neonatal survival with no apnea, with successful extubation removal within 72 hours. This can be with or without adverse events. In contrast, failure was the discontinuation of caffeine due to severe tachycardia adverse drug reaction, all-cause death, or extubation failure due to apnea persistence. At the base case of the model, the analysis was run based on a multivariate uncertainty analysis of the model probability inputs, using the Monte Carlo simulation.

Results:

With 0.236 (95% CI, 0.230-0.231) enhancement in success rate, at QAR 14,084 (95% CI, 13,916-14,251) added patient cost, the cost-effectiveness ratio of HD caffeine was QAR 61,500 (95% CI, 55,480-67,520) over LD caffeine per additional case of success. One-way and multivariate sensitivity analyses confirmed the robustness of the study outcome and increased the generalizability of the results.

Conclusion:

For AOP, based on the Qatar willingness-to-pay threshold, HD caffeine seems to be cost-effective over LD caffeine. This supports the recently increasing trend of HD caffeine use in HMC.