# Preface

The Hitchhiker’s Guide to the tlverse, or a Targeted Learning Practitioner’s Handbook is an open-source and fully-reproducible electronic handbook for applying the targeted learning methodology in practice using the tlverse software ecosystem. This work is currently in an early draft phase and is available to facilitate input from the community. To view or contribute to the available content, consider visiting the GitHub repository for this site.

## 0.1 Outline

The contents of this handbook are meant to serve as a reference guide for applied research as well as materials that can be taught in a series of short courses focused on the applications of Targeted Learning. Each section introduces a set of distinct causal questions, motivated by a case study, alongside statistical methodology and software for assessing the causal claim of interest. The (evolving) set of materials includes

## What this book is not

The focus of this work is not on providing in-depth technical descriptions of current statistical methodology or recent advancements. Instead, the goal is to convey key details of state-of-the-art techniques in an manner that is both clear and complete, without burdening the reader with extraneous information. We hope that the presentations herein will serve as references for researchers – methodologists and domain specialists alike – that empower them to deploy the central tools of Targeted Learning in an efficient manner. For technical details and in-depth descriptions of both classical theory and recent advances in the field of Targeted Learning, the interested reader is invited to consult van der Laan and Rose (2011) and/or van der Laan and Rose (2018) as appropriate. The primary literature in statistical causal inference, machine learning, and non/semiparametric theory include many of the most recent advances in Targeted Learning and related areas.

### Jeremy Coyle

Jeremy R. Coyle, Ph.D., is a consulting data scientist and statistical programmer, currently leading the software development effort that has produced the tlverse ecosystem of R packages and related software tools. Jeremy earned his Ph.D. in Biostatistics from UC Berkeley in 2016, primarily under the supervision of Alan Hubbard.

### Nima Hejazi

Nima S. Hejazi is a Ph.D. candidate in biostatistics with a designated emphasis in computational and genomic biology, working jointly with Mark van der Laan and Alan Hubbard. Nima is affiliated with UC Berkeley’s Center for Computational Biology and NIH Biomedical Big Data training program. His research interests span causal inference, nonparametric inference and machine learning, targeted loss-based estimation, survival analysis, statistical computing, reproducible research, and high-dimensional biology. He is also passionate about software development for applied statistics, including software design, automated testing, and reproducible coding practices. For more information, see https://nimahejazi.org.

### Ivana Malenica

Ivana Malenica is a Ph.D. student in biostatistics advised by Mark van der Laan. Ivana is currently a fellow at the Berkeley Institute for Data Science, after serving as a NIH Biomedical Big Data and Freeport-McMoRan Genomic Engine fellow. She earned her Master’s in Biostatistics and Bachelor’s in Mathematics, and spent some time at the Translational Genomics Research Institute. Very broadly, her research interests span non/semi-parametric theory, probability theory, machine learning, causal inference and high-dimensional statistics. Most of her current work involves complex dependent settings (dependence through time and network) and adaptive sequential designs.

### Rachael Phillips

Rachael is a Ph.D. student in biostatistics, advised by Alan Hubbard and Mark van der Laan. She has an M.A. in Biostatistics, B.S. in Biology with a Chemistry minor and a B.A. in Mathematics with a Spanish minor. Rachael’s research focuses on narrowing the gap between the theory and application of modern statistics for real-world data science. Specifically, Rachael is motivated by issues arising in healthcare, and she leverages strategies rooted in causal inference and nonparametric estimation to build clinician-tailored, machine-driven solutions. Rachael is also passionate about free, online-mediated education and its corresponding pedagogy.

### Alan Hubbard

Alan E. Hubbard is Professor of Biostatistics, former head of the Division of Biostatistics at UC Berkeley, and head of data analytics core at UC Berkeley’s SuperFund research program. His current research interests include causal inference, variable importance analysis, statistical machine learning, estimation of and inference for data-adaptive statistical target parameters, and targeted minimum loss-based estimation. Research in his group is generally motivated by applications to problems in computational biology, epidemiology, and precision medicine.

### Mark van der Laan

Mark J. van der Laan, PhD, is Professor of Biostatistics and Statistics at UC Berkeley. His research interests include statistical methods in computational biology, survival analysis, censored data, adaptive designs, targeted maximum likelihood estimation, causal inference, data-adaptive loss-based learning, and multiple testing. His research group developed loss-based super learning in semiparametric models, based on cross-validation, as a generic optimal tool for the estimation of infinite-dimensional parameters, such as nonparametric density estimation and prediction with both censored and uncensored data. Building on this work, his research group developed targeted maximum likelihood estimation for a target parameter of the data-generating distribution in arbitrary semiparametric and nonparametric models, as a generic optimal methodology for statistical and causal inference. Most recently, Mark’s group has focused in part on the development of a centralized, principled set of software tools for targeted learning, the tlverse. For more information, see https://vanderlaan-lab.org.

## 0.2 Learning resources

To effectively utilize this handbook, the reader need not be a fully trained statistician to begin understanding and applying these methods. However, it is highly recommended for the reader to have an understanding of basic statistical concepts such as confounding, probability distributions, confidence intervals, hypothesis tests, and regression. Advanced knowledge of mathematical statistics may be useful but is not necessary. Familiarity with the R programming language will be essential. We also recommend an understanding of introductory causal inference.

For learning the R programming language we recommend the following (free) introductory resources:

For a general introduction to causal inference, we recommend

## 0.3 Setup instructions

### 0.3.1 R and RStudio

R and RStudio are separate downloads and installations. R is the underlying statistical computing environment. RStudio is a graphical integrated development environment (IDE) that makes using R much easier and more interactive. You need to install R before you install RStudio.

#### 0.3.1.1 Windows

##### 0.3.1.1.1 If you already have R and RStudio installed
• To check which version of R you are using, start RStudio and the first thing that appears in the console indicates the version of R you are running. Alternatively, you can type sessionInfo(), which will also display which version of R you are running. Go on the CRAN website and check whether a more recent version is available. If so, please download and install it. You can check here for more information on how to remove old versions from your system if you wish to do so.
##### 0.3.1.1.2 If you don’t have R and RStudio installed
• Run the .exe file that was just downloaded
• Under Installers select RStudio x.yy.zzz - Windows XP/Vista/7/8 (where x, y, and z represent version numbers)
• Double click the file to install it
• Once it’s installed, open RStudio to make sure it works and you don’t get any error messages.

#### 0.3.1.2 macOS

##### 0.3.1.2.1 If you already have R and RStudio installed
• To check the version of R you are using, start RStudio and the first thing that appears on the terminal indicates the version of R you are running. Alternatively, you can type sessionInfo(), which will also display which version of R you are running. Go on the CRAN website and check whether a more recent version is available. If so, please download and install it.
##### 0.3.1.2.2 If you don’t have R and RStudio installed
• Select the .pkg file for the latest R version
• It is also a good idea to install XQuartz (needed by some packages)
• Under Installers select RStudio x.yy.zzz - Mac OS X 10.6+ (64-bit) (where x, y, and z represent version numbers)
• Double click the file to install RStudio
• Once it’s installed, open RStudio to make sure it works and you don’t get any error messages.

#### 0.3.1.3 Linux

• Follow the instructions for your distribution from CRAN, they provide information to get the most recent version of R for common distributions. For most distributions, you could use your package manager (e.g., for Debian/Ubuntu run sudo apt-get install r-base, and for Fedora sudo yum install R), but we don’t recommend this approach as the versions provided by this are usually out of date. In any case, make sure you have at least R 3.3.1.
• Under Installers select the version that matches your distribution, and install it with your preferred method (e.g., with Debian/Ubuntu sudo dpkg -i rstudio-x.yy.zzz-amd64.deb at the terminal).