Causal Inference from Human Studies

About the course

The course content is structured in six sections, each consisting of preparation through self-study of selected literature (3.5 hours preparation per session) and 3-hour in-person sessions that include a theoretical component (90 minutes per session) and a bioinformatics lab (90 minutes per session). The final exam consists of a 2-page structured essay (mini-review) about a pre-specified causal inference topic (workload 20 hours).

The specific contents of each course section is listed below.

Session 1: Introduction to causal thinking

Theory

Ø  Objective: Introducing basic concepts of causality.

Ø  Topics:

·       History and philosophy of causality

·       Introduction to causal reasoning and its importance in research

    Preparation: Reding excerpts from Modern Epidemiology (Rothmann, et al.)

    Lecture (45 minutes): Clemens Wittenbecher

    Group work (45 minutes): Moderated discussion on the causal mechanism behind published associations making explicit use of different causal concepts and causal language.

Lab

Ø  Objective: Describing univariable and multi-variable distributions.

Ø  Topics:  Introducing statistical measures and basic concepts of frequentist hypothesis testing.

·       Measures of Location and Distribution

·       Measures of Correlation and Association

·       Interpretation and misconceptions concerning P-values

    Preparation: Install R and software packages

    Lecture (30 minutes): Jakub Morze

    Group work (60 minutes): Generate histograms, violine plots, heat maps, and association tables.

Session 2: Causal concepts and statistical models

Theory

Ø  Objective: Linking causal concepts to data analysis.

Ø  Topics: Introduce counterfactual thinking and methodologies to formalize causal assumptions.

·       Counterfactuals and Potential Outcomes

·       Directed Acyclic Graphs (DAG)

    Preparation: Reding excerpts from The Book of Why (Judea Pearl), Observation & Experiment” (Paul Rosenbaum)

    Lecture (45 minutes): Clemens Wittenbecher

    Group work (45 minutes): Using DAGs to formalize and explain specific causal mechanisms.

Lab

Ø  Objective: Understanding that a statistical model can encode causal assumptions.

Ø  Topics:

·       Multi-variable linear regression

·       Derive sufficient adjustment sets from DAGs estimates.

    Preparation: Download datasets and install R packages

    Lecture (30 minutes): Jakub Morze

    Group work (60 minutes): Analyze cross-sectional data and compare effect estimates across models with different adjustment sets.

Session 3: Study design I – ecological and cross-sectional studies

Theory

Ø  Objective: Understanding cross-sectional study designs and their strengths and limitations in etiological research.

Ø  Topics: Introduce basic cross-sectional study design and highlight important contributions.

·       Ecological studies

·       Cross-sectional studies

·       Reverse causation and other study design-specific sources of bias

    Preparation: Paper I (Cross-sectional studies)

    Lecture (45 minutes): Clemens Wittenbecher

    Group work (45 minutes): Extracting the causal assumptions from Paper I and evaluating the validity of causal conclusions

Lab

Ø  Objective: Learning to analyze cross-sectional data in linear and logistic regression models.

Ø  Topics:

·       Continuous outcomes and multi-variable linear regression models

·       Categorical outcomes and logistic regression models

    Preparation: Download datasets and install R packages

    Lecture (30 minutes): Jakub Morze

    Group work (60 minutes): Analyze cross-sectional data and visualize effect estimates and confidence intervals.

Session 4: Study design II – longitudinal and prospective studies

Theory

Ø  Objective: Understanding the design of prospective studies and the advantages of longitudinal data collection.

Ø  Topics: Introduce basic longitudinal and prospective studies and highlight important contributions.

·       Prospective cohort studies

·       Nested case-control and case-cohort studies

·       Examples of repeated exposure assessment

·       Remaining sources of bias and the role of measurement error in prospective data analysis

    Preparation: Paper II (Prospective studies) and Paper III (Repeated measurements)

    Lecture (45 minutes): Clemens Wittenbecher

    Group work (45 minutes): Extracting the causal assumptions and evaluating sources of bias from Paper II or Paper III and evaluating the validity of causal conclusions

Lab

Ø  Objective: Learning to analyze matched case control studies in conditional logistic regression models and time-to-event data in Cox PH regression models.

Ø  Topics:

·       Conditional logistic regression models

·       Cox PH regression models

    Preparation: Download datasets and install R packages

    Lecture (30 minutes): Jakub Morze

    Group work (60 minutes): Analyze prospective cohort data in conditional logistic regression (nested matched case-control studies) and time-to-event data (Cox PH regression) visualize effect estimates and confidence intervals.

Session 5: Causal mediation analysis

Theory

Ø  Objective: Understanding the design, assumptions, and interpretation of causal mediation analysis.

Ø  Topics:

·       Decomposition of total effects into direct and indirect effects

·       Counterfactuals and do calculus

    Preparation: Reding excerpts from Causality (Judea Pearl) and Paper III (applied mediation analysis)

    Lecture (45 minutes): Clemens Wittenbecher

    Group work (45 minutes): Evaluate the applied mediation analysis in Paper III against the assumptions for causal interpretation of the mediation analysis results

Lab

Ø  Objective: Conducting causal mediation analysis.

Ø  Topics:

·       Statistical approaches and R-packages for causal mediation analysis

·       Communicating results from causal mediation analysis

    Preparation: Download datasets and install R packages

    Lecture (30 minutes): Jakub Morze

    Group work (60 minutes): Implement and report a pre-specified causal mediation analysis.

Session 6: Effect modification analysis

Theory

Ø  Objective: Understanding the assumptions underlying causal inferences based on population averages and recognizing potential sources of effect heterogeneity.

Ø  Topics:

·       The concept of effect modification.

·       Interaction in biomedical research: synergies and antagonistic effects.

    Preparation: Paper IV and paper V (additive interaction analysis theory and example)

    Lecture (45 minutes): Clemens Wittenbecher

    Group work (45 minutes): Using DAG(s) to illustrate the causal mechanism(s) underlying known interactions and effect modifications in biomedical research 

Lab

Ø  Objective: Learning basic statistical approaches to detect and quantify effect heterogeneity.

Ø  Topics:

·       Stratification

·       Additive vs. multiplicative interaction tests

·       Reporting of model estimates in the presence of effect modifiers

    Preparation: Download datasets and install R packages

    Lecture (30 minutes): Jakub Morze

    Group work (60 minutes): Conduct interaction tests and communicate study results when interactions were detected.

More information

Clemens Wittenbecher

Literature

Textbook excerpts: Modern Epidemiology (Rothman et al.), The Book of Why (Judea Pearl), Causality (Judea Pearl), Observation & Experiment (Paul Rosenbaum)

Session-specific selection of original research articles

Lecturer

Clemens Wittenbecher, Jakub Morze