Prediction of infectious disease epidemics via weighted density ensembles

Accurate and reliable predictions of infectious disease dynamics can be valuable to public health organizations that plan interventions to decrease or prevent disease transmission. A great variety of models have been developed for this task, using different model structures, covariates, and targets for prediction. Experience has shown that the performance of these models varies; some tend to do better or worse in different seasons or at different points within a season. Ensemble methods combine multiple models to obtain a single prediction that leverages the strengths of each model. We considered a range of ensemble methods that each form a predictive density for a target of interest as a weighted sum of the predictive densities from component models. In the simplest case, equal weight is assigned to each component model; in the most complex case, the weights vary with the region, prediction target, week of the season when the predictions are made, a measure of component model uncertainty, and recent observations of disease incidence. We applied these methods to predict measures of influenza season timing and severity in the United States, both at the national and regional levels, using three component models. We trained the models on retrospective predictions from 14 seasons (1997/1998 - 2010/2011) and evaluated each model's prospective, out-of-sample performance in the five subsequent influenza seasons. In this test phase, the ensemble methods showed overall performance that was similar to the best of the component models, but offered more consistent performance across seasons than the component models. Ensemble methods offer the potential to deliver more reliable predictions to public health decision makers.Comment: 20 pages, 6 figure

Evaluating epidemic forecasts in an interval format

For practical reasons, many forecasts of case, hospitalization and death counts in the context of the current COVID-19 pandemic are issued in the form of central predictive intervals at various levels. This is also the case for the forecasts collected in the COVID-19 Forecast Hub (https://covid19forecasthub.org/). Forecast evaluation metrics like the logarithmic score, which has been applied in several infectious disease forecasting challenges, are then not available as they require full predictive distributions. This article provides an overview of how established methods for the evaluation of quantile and interval forecasts can be applied to epidemic forecasts in this format. Specifically, we discuss the computation and interpretation of the weighted interval score, which is a proper score that approximates the continuous ranked probability score. It can be interpreted as a generalization of the absolute error to probabilistic forecasts and allows for a decomposition into a measure of sharpness and penalties for over- and underprediction

The Effect of Cluster Size Variability on Statistical Power in Cluster-Randomized Trials

The frequency of cluster-randomized trials (CRTs) in peer-reviewed literature has increased exponentially over the past two decades. CRTs are a valuable tool for studying interventions that cannot be effectively implemented or randomized at the individual level. However, some aspects of the design and analysis of data from CRTs are more complex than those for individually randomized controlled trials. One of the key components to designing a successful CRT is calculating the proper sample size (i.e. number of clusters) needed to attain an acceptable level of statistical power. In order to do this, a researcher must make assumptions about the value of several variables, including a fixed mean cluster size. In practice, cluster size can often vary dramatically. Few studies account for the effect of cluster size variation when assessing the statistical power for a given trial. We conducted a simulation study to investigate how the statistical power of CRTs changes with variable cluster sizes. In general, we observed that increases in cluster size variability lead to a decrease in power

Comparison of combination methods to create calibrated ensemble forecasts for seasonal influenza in the U.S.

The characteristics of influenza seasons vary substantially from year to year, posing challenges for public health preparation and response. Influenza forecasting is used to inform seasonal outbreak response, which can in turn potentially reduce the impact of an epidemic. The United States Centers for Disease Control and Prevention, in collaboration with external researchers, has run an annual prospective influenza forecasting exercise, known as the FluSight challenge. Uniting theoretical results from the forecasting literature with domain-specific forecasts from influenza outbreaks, we applied parametric forecast combination methods that simultaneously optimize model weights and calibrate the ensemble via a beta transformation and made adjustments to the methods to reduce their complexity. We used the beta-transformed linear pool, the finite beta mixture model, and their equal weight adaptations to produce ensemble forecasts retrospectively for the 2016/2017, 2017/2018, and 2018/2019 influenza seasons in the U.S. We compared their performance to methods that were used in the FluSight challenge to produce the FluSight Network ensemble, namely the equally weighted linear pool and the linear pool. Ensemble forecasts produced from methods with a beta transformation were shown to outperform those from the equally weighted linear pool and the linear pool for all week-ahead targets across in the test seasons based on average log scores. We observed improvements in overall accuracy despite the beta-transformed linear pool or beta mixture methods\u27 modest under-prediction across all targets and seasons. Combination techniques that explicitly adjust for known calibration issues in linear pooling should be considered to improve probabilistic scores in outbreak settings

The Zoltar forecast archive, a tool to standardize and store interdisciplinary prediction research

Forecasting has emerged as an important component of informed, data-driven decision-making in a wide array of felds. We introduce a new data model for probabilistic predictions that encompasses a wide range of forecasting settings. This framework clearly defnes the constituent parts of a probabilistic forecast and proposes one approach for representing these data elements. The data model is implemented in Zoltar, a new software application that stores forecasts using the data model and provides standardized API access to the data. In one real-time case study, an instance of the Zoltar web application was used to store, provide access to, and evaluate real-time forecast data on the order of 108 rows, provided by over 40 international research teams from academia and industry making forecasts of the COVID-19 outbreak in the US. Tools and data infrastructure for probabilistic forecasts, such as those introduced here, will play an increasingly important role in ensuring that future forecasting research adheres to a strict set of rigorous and reproducible standards

Visualizing Clinical Evidence: Citation Networks for the Incubation Periods of Respiratory Viral Infections

Simply by repetition, medical facts can become enshrined as truth even when there is little empirical evidence supporting them. We present an intuitive and clear visual design for tracking the citation history of a particular scientific fact over time. We apply this method to data from a previously published literature review on the incubation period of nine respiratory viral infections. The resulting citation networks reveal that the conventional wisdom about the incubation period for these diseases was based on a small fraction of available data and in one case, on no retrievable empirical evidence. Overall, 50% of all incubation period statements did not provide a source for their estimate and 65% of original sources for incubation period data were not incorporated into subsequent publications. More standardized and widely available methods for visualizing these histories of medical evidence are needed to ensure that conventional wisdom cannot stray too far from empirically supported knowledge