In this paper, we derive an optimal model for calculating the instantaneous reproduction number, which is an important metric to help in controlling the evolution of epidemics. Our approach, within a frequentist framework, gave us the opportunity to calculate a more realistic confidence interval, a fundamental tool for a safe interpretation of the instantaneous reproduction number value, so that health and governmental people pay more attention to it. Our reasoning begins by decoupling the incidence data in mean and Gaussian noise by using practical series analysis techniques; then, we continue with a likely relationship between the present and past incidence data. Monte Carlo simulations and numerical integrations were conducted to complement the analytical proofs, and illustrations are provided for each stage of analysis to validate the analytical results. Finally, a real case study is discussed with the incidence data of the Republic of Panama regarding the COVID-19 pandemic. We have shown that, for the calculation of the confidence interval of the instantaneous reproduction number, it is essential to include all sources of variability, not only the Poissonian processes of the incidences. This proposal is delivered with analysis tools developed with Microsoft Excel.