Despite the recent progress in the field of causal inference, to date there is no agreed upon methodology to glean treatment effect estimation from observational data. The consequence on clinical practice is that, when lacking results from a randomized trial, medical personnel is left without guidance on what seems to be effective in a real-world scenario. This article showcases a pragmatic methodology to obtain preliminary estimation of treatment effect from observational studies. Our approach was tested on the estimation of treatment effect of the proning maneuver on oxygenation levels, on a cohort of COVID-19 Intensive Care patients. We modeled our study design on a recent RCT for proning (the PROSEVA trial). Linear regression, propensity score models such as blocking and DR-IPW, BART and two versions of Counterfactual Regression were employed to provide estimates on observational data comprising first wave COVID-19 ICU patient data from 25 Dutch hospitals. 6371 data points, from 745 mechanically ventilated patients, were included in the study. Estimates for the early effect of proning -- P/F ratio from 2 to 8 hours after proning -- ranged between 14.54 and 20.11 mm Hg depending on the model. Estimates for the late effect of proning -- oxygenation from 12 to 24 hours after proning -- ranged between 13.53 and 15.26 mm Hg. All confidence interval being strictly above zero indicated that the effect of proning on oxygenation for COVID-19 patient was positive and comparable in magnitude to the effect on non COVID-19 patients. These results provide further evidence on the effectiveness of proning on the treatment of COVID-19 patients. This study, along with the accompanying open-source code, provides a blueprint for treatment effect estimation in scenarios where RCT data is lacking. Funding: SIDN fund, CovidPredict consortium, Pacmed.
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Point cloud video has been widely used by augmented reality (AR) and virtual reality (VR) applications as it allows users to have an immersive experience of six degrees of freedom (6DoFs). Yet there is still a lack of research on quality of experience (QoE) model of point cloud video streaming, which cannot provide optimization metric for streaming systems. Besides, position and color information contained in each pixel of point cloud video, and viewport distance effect caused by 6DoFs viewing procedure make the traditional objective quality evaluation metric cannot be directly used in point cloud video streaming system. In this paper we first analyze the subjective and objective factors related to QoE model. Then an experimental system to simulate point cloud video streaming is setup and detailed subjective quality evaluation experiments are carried out. Based on collected mean opinion score (MOS) data, we propose a QoE model for point cloud video streaming. We also verify the model by actual subjective scoring, and the results show that the proposed QoE model can accurately reflect users' visual perception. We also make the experimental database public to promote the QoE research of point cloud video streaming.
We propose a doubly robust approach to characterizing treatment effect heterogeneity in observational studies. We utilize posterior distributions for both the propensity score and outcome regression models to provide valid inference on the conditional average treatment effect even when high-dimensional or nonparametric models are used. We show that our approach leads to conservative inference in finite samples or under model misspecification, and provides a consistent variance estimator when both models are correctly specified. In simulations, we illustrate the utility of these results in difficult settings such as high-dimensional covariate spaces or highly flexible models for the propensity score and outcome regression. Lastly, we analyze environmental exposure data from NHANES to identify how the effects of these exposures vary by subject-level characteristics.
Machine learning has successfully framed many sequential decision making problems as either supervised prediction, or optimal decision-making policy identification via reinforcement learning. In data-constrained offline settings, both approaches may fail as they assume fully optimal behavior or rely on exploring alternatives that may not exist. We introduce an inherently different approach that identifies possible ``dead-ends'' of a state space. We focus on the condition of patients in the intensive care unit, where a ``medical dead-end'' indicates that a patient will expire, regardless of all potential future treatment sequences. We postulate ``treatment security'' as avoiding treatments with probability proportional to their chance of leading to dead-ends, present a formal proof, and frame discovery as an RL problem. We then train three independent deep neural models for automated state construction, dead-end discovery and confirmation. Our empirical results discover that dead-ends exist in real clinical data among septic patients, and further reveal gaps between secure treatments and those that were administered.
The question of how individual patient data from cohort studies or historical clinical trials can be leveraged for designing more powerful, or smaller yet equally powerful, clinical trials becomes increasingly important in the era of digitalisation. Today, the traditional statistical analyses approaches may seem questionable to practitioners in light of ubiquitous historical covariate information. Several methodological developments aim at incorporating historical information in the design and analysis of future clinical trials, most importantly Bayesian information borrowing, propensity score methods, stratification, and covariate adjustment. Recently, adjusting the analysis with respect to a prognostic score, which was obtained from some machine learning procedure applied to historical data, has been suggested and we study the potential of this approach for randomised clinical trials. In an idealised situation of a normal outcome in a two-arm trial with 1:1 allocation, we derive a simple sample size reduction formula as a function of two criteria characterising the prognostic score: (1) The coefficient of determination $R^2$ on historical data and (2) the correlation $\rho$ between the estimated and the true unknown prognostic scores. While maintaining the same power, the original total sample size $n$ planned for the unadjusted analysis reduces to $(1 - R^2 \rho^2) \times n$ in an adjusted analysis. Robustness in less ideal situations was assessed empirically. We conclude that there is potential for substantially more powerful or smaller trials, but only when prognostic scores can be accurately estimated.
In this study, we propose a time-dependent Susceptible-Exposed-Infected-Recovered (SEIR) model for the analysis of the SARS-CoV-2 epidemic outbreak in three different countries, the United States of America, Italy and Iceland using public data inherent the numbers of the epidemic wave. Since several types and grades of actions were adopted by the governments, including travel restrictions, social distancing, or limitation of movement, we want to investigate how these measures can affect the epidemic curve of the infectious population. The parameters of interest for the SEIR model were estimated employing a composite likelihood approach. Moreover, standard errors have been corrected for temporal dependence. The adoption of restrictive measures results in flatten epidemic curves, and the future evolution indicated a decrease in the number of cases.
A \emph{strong coreset} for the mean queries of a set $P$ in ${\mathbb{R}}^d$ is a small weighted subset $C\subseteq P$, which provably approximates its sum of squared distances to any center (point) $x\in {\mathbb{R}}^d$. A \emph{weak coreset} is (also) a small weighted subset $C$ of $P$, whose mean approximates the mean of $P$. While computing the mean of $P$ can be easily computed in linear time, its coreset can be used to solve harder constrained version, and is in the heart of generalizations such as coresets for $k$-means clustering. In this paper, we survey most of the mean coreset construction techniques, and suggest a unified analysis methodology for providing and explaining classical and modern results including step-by-step proofs. In particular, we collected folklore and scattered related results, some of which are not formally stated elsewhere. Throughout this survey, we present, explain, and prove a set of techniques, reductions, and algorithms very widespread and crucial in this field. However, when put to use in the (relatively simple) mean problem, such techniques are much simpler to grasp. The survey may help guide new researchers unfamiliar with the field, and introduce them to the very basic foundations of coresets, through a simple, yet fundamental, problem. Experts in this area might appreciate the unified analysis flow, and the comparison table for existing results. Finally, to encourage and help practitioners and software engineers, we provide full open source code for all presented algorithms.
Point cloud video has been widely used by augmented reality (AR) and virtual reality (VR) applications as it allows users to have an immersive experience of six degrees of freedom (6DoFs). Yet there is still a lack of research on quality of experience (QoE) model of point cloud video streaming, which cannot provide optimization metric for streaming systems. Besides, position and color information contained in each pixel of point cloud video, and viewport distance effect caused by 6DoFs viewing procedure make the traditional objective quality evaluation metric cannot be directly used in point cloud video streaming system. In this paper we first analyze the subjective and objective factors related to QoE model. Then an experimental system to simulate point cloud video streaming is setup and detailed subjective quality evaluation experiments are carried out. Based on collected mean opinion score (MOS) data, we propose a QoE model for point cloud video streaming. We also verify the model by actual subjective scoring, and the results show that the proposed QoE model can accurately reflect users' visual perception. We also make the experimental database public to promote the QoE research of point cloud video streaming.
Clinical studies often encounter with truncation-by-death problems, which may render the outcomes undefined. Statistical analysis based only on observed survivors may lead to biased results because the characters of survivors may differ greatly between treatment groups. Under the principal stratification framework, a meaningful causal parameter, the survivor average causal effect, in the always-survivor group can be defined. This causal parameter may not be identifiable in observational studies where the treatment assignment and the survival or outcome process are confounded by unmeasured features. In this paper, we propose a new method to deal with unmeasured confounding when the outcome is truncated by death. First, a new method is proposed to identify the heterogeneous conditional survivor average causal effect based on a substitutional variable under monotonicity. Second, under additional assumptions, the survivor average causal effect on the overall population is also identified. Furthermore, we consider estimation and inference for the conditional survivor average causal effect based on parametric and nonparametric methods with good asymptotic properties. Good finite-sample properties are demonstrated by simulation and sensitivity analysis. The proposed method is applied to investigate the effect of allogeneic stem cell transplantation types on leukemia relapse.
During the COVID-19 pandemic, governments and public health authorities have used seroprevalence studies to estimate the proportion of persons within a given population who have antibodies to SARS-CoV-2. Seroprevalence is crucial for estimating quantities such as the infection fatality ratio, proportion of asymptomatic cases, and differences in infection rates across population subgroups. However, serologic assays are prone to false positives and negatives, and non-probability sampling methods may induce selection bias. In this paper, we consider nonparametric and parametric seroprevalence estimators that address both challenges by leveraging validation data and assuming equal probabilities of sample inclusion within covariate-defined strata. Both estimators are shown to be consistent and asymptotically normal, and consistent variance estimators are derived. Simulation studies are presented comparing the finite sample performance of the estimators over a range of assay characteristics and sampling scenarios. The methods are used to estimate SARS-CoV-2 seroprevalence in asymptomatic individuals in Belgium and North Carolina.
In clinical research, the effect of a treatment or intervention is widely assessed through clinical importance, instead of statistical significance. In this paper, we propose a principled statistical inference framework to learning the minimal clinically important difference (MCID), a vital concept in assessing clinical importance. We formulate the scientific question into a novel statistical learning problem, develop an efficient algorithm for parameter estimation, and establish the asymptotic theory for the proposed estimator. We conduct comprehensive simulation studies to examine the finite sample performance of the proposed method. We also re-analyze the ChAMP (Chondral Lesions And Meniscus Procedures) trial, where the primary outcome is the patient-reported pain score and the ultimate goal is to determine whether there exists a significant difference in post-operative knee pain between patients undergoing debridement versus observation of chondral lesions during the surgery. Some previous analysis of this trial exhibited that the effect of debriding the chondral lesions does not reach a statistical significance. Our analysis reinforces this conclusion that the effect of debriding the chondral lesions is not only statistically non-significant, but also clinically un-important.
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