RESUMO
Statistical regression models are used for predicting outcomes based on the values of some predictor variables or for describing the association of an outcome with predictors. With a data set at hand, a regression model can be easily fit with standard software packages. This bears the risk that data analysts may rush to perform sophisticated analyses without sufficient knowledge of basic properties, associations in and errors of their data, leading to wrong interpretation and presentation of the modeling results that lacks clarity. Ignorance about special features of the data such as redundancies or particular distributions may even invalidate the chosen analysis strategy. Initial data analysis (IDA) is prerequisite to regression analyses as it provides knowledge about the data needed to confirm the appropriateness of or to refine a chosen model building strategy, to interpret the modeling results correctly, and to guide the presentation of modeling results. In order to facilitate reproducibility, IDA needs to be preplanned, an IDA plan should be included in the general statistical analysis plan of a research project, and results should be well documented. Biased statistical inference of the final regression model can be minimized if IDA abstains from evaluating associations of outcome and predictors, a key principle of IDA. We give advice on which aspects to consider in an IDA plan for data screening in the context of regression modeling to supplement the statistical analysis plan. We illustrate this IDA plan for data screening in an example of a typical diagnostic modeling project and give recommendations for data visualizations.
Assuntos
Modelos Estatísticos , Humanos , Análise de Regressão , Interpretação Estatística de Dados , Análise Multivariada , Reprodutibilidade dos Testes , Software , Análise de DadosRESUMO
Initial data analysis (IDA) is the part of the data pipeline that takes place between the end of data retrieval and the beginning of data analysis that addresses the research question. Systematic IDA and clear reporting of the IDA findings is an important step towards reproducible research. A general framework of IDA for observational studies includes data cleaning, data screening, and possible updates of pre-planned statistical analyses. Longitudinal studies, where participants are observed repeatedly over time, pose additional challenges, as they have special features that should be taken into account in the IDA steps before addressing the research question. We propose a systematic approach in longitudinal studies to examine data properties prior to conducting planned statistical analyses. In this paper we focus on the data screening element of IDA, assuming that the research aims are accompanied by an analysis plan, meta-data are well documented, and data cleaning has already been performed. IDA data screening comprises five types of explorations, covering the analysis of participation profiles over time, evaluation of missing data, presentation of univariate and multivariate descriptions, and the depiction of longitudinal aspects. Executing the IDA plan will result in an IDA report to inform data analysts about data properties and possible implications for the analysis plan-another element of the IDA framework. Our framework is illustrated focusing on hand grip strength outcome data from a data collection across several waves in a complex survey. We provide reproducible R code on a public repository, presenting a detailed data screening plan for the investigation of the average rate of age-associated decline of grip strength. With our checklist and reproducible R code we provide data analysts a framework to work with longitudinal data in an informed way, enhancing the reproducibility and validity of their work.
Assuntos
Análise de Dados , Estudos Longitudinais , Humanos , Reprodutibilidade dos Testes , Masculino , Feminino , Projetos de PesquisaRESUMO
Clinical trials are primarily conducted to estimate causal effects, but the data collected can also be invaluable for additional research, such as identifying prognostic measures of disease or biomarkers that predict treatment efficacy. However, these exploratory settings are prone to false discoveries (type-I errors) due to the multiple comparisons they entail. Unfortunately, many methods fail to address this issue, in part because the algorithms used are generally designed to optimize predictions and often only provide the measures used for variable selection, such as machine learning model importance scores, as a byproduct. To address the resulting unclear uncertainty in the selection sets, the knockoff framework offers a model-agnostic, robust approach to variable selection with guaranteed type-I error control. Here, we review the knockoff framework in the setting of clinical data, highlighting main considerations using simulation studies. We also extend the framework by introducing a novel knockoff generation method that addresses two main limitations of previously suggested methods relevant for clinical development settings. With this new method, we empirically obtain tighter bounds on type-I error control and gain an order of magnitude in computational efficiency in mixed data settings. We demonstrate comparable selections to those of the competing method for identifying prognostic biomarkers for C-reactive protein levels in patients with psoriatic arthritis in four clinical trials. Our work increases access to the knockoff framework for variable selection from clinical trial data. Hereby, this paper helps to address the current replicability crisis which can result in unnecessary research efforts, increased patient burden, and avoidable costs.
Assuntos
Algoritmos , Aprendizado de Máquina , Humanos , Simulação por Computador , Biomarcadores , IncertezaRESUMO
We present the motivation, experience, and learnings from a data challenge conducted at a large pharmaceutical corporation on the topic of subgroup identification. The data challenge aimed at exploring approaches to subgroup identification for future clinical trials. To mimic a realistic setting, participants had access to 4 Phase III clinical trials to derive a subgroup and predict its treatment effect on a future study not accessible to challenge participants. A total of 30 teams registered for the challenge with around 100 participants, primarily from Biostatistics organization. We outline the motivation for running the challenge, the challenge rules, and logistics. Finally, we present the results of the challenge, the participant feedback as well as the learnings. We also present our view on the implications of the results on exploratory analyses related to treatment effect heterogeneity.