# Negative Control Diagnostics in causaldef

#### Deniz Akdemir

#### 2026-08-10

## Introduction

This vignette demonstrates how to use negative control outcomes to screen for residual confounding and compute a corresponding sensitivity bound using the `causaldef` package. Negative controls provide an empirical diagnostic for whether your adjustment strategy may have failed to remove confounding.

## Theoretical Background

### What is a Negative Control Outcome?

A negative control outcome (\(Y'\)) is a variable that:

1. Shares confounders with the true outcome \(Y\) — it is affected by the same unmeasured variables \(U\) that confound the treatment-outcome relationship
2. Is NOT causally affected by treatment \(A\) — the true causal effect of \(A\) on \(Y'\) is zero

### The Diagnostic Logic

The key insight is:

> If your adjustment strategy correctly removes confounding, then the residual association between \(A\) and \(Y'\) should be zero.

If you observe a non-zero association between \(A\) and \(Y'\) after adjustment, this indicates that confounding remains and your causal estimates may be biased. Conversely, a small or non-significant residual association is not a proof of identification; it is a one-sided screen that should be reported together with `delta_nc` or `delta_bound`.

### Negative Control Sensitivity Bound (manuscript `thm:nc_bound`)

The `causaldef` package combines two ingredients:

1. a screening test for residual association between treatment and the negative control after adjustment, and
2. the manuscript’s negative control sensitivity bound (`thm:nc_bound`):

\[\delta(\hat{K}) \leq \kappa \cdot \delta_{NC}(\hat{K})\]

where: - \(\delta(\hat{K})\) is the true deficiency (what we want to know) - \(\delta_{NC}(\hat{K})\) is a negative-control association proxy (what we can measure) - \(\kappa\) is an alignment constant reflecting how well \(Y'\) proxies for \(Y\)’s confounding

## Practical Example

### Simulating Data with a Negative Control

Let’s create a dataset where we have: - An unmeasured confounder \(U\) - An observed covariate \(W\) (correlated with \(U\)) - Binary treatment \(A\) - Outcome \(Y\) affected by \(A\) and \(U\) - Negative control \(Y'\) affected only by \(U\) (not \(A\))

    library(causaldef)
    set.seed(42)

    n <- 500

    # Unmeasured confounder
    U <- rnorm(n)

    # Observed covariate (partially captures U)
    W <- 0.7 * U + rnorm(n, sd = 0.5)

    # Treatment assignment (confounded by U via W)
    ps_true <- plogis(0.3 + 0.8 * U)
    A <- rbinom(n, 1, ps_true)

    # True causal effect
    beta_true <- 2.0

    # Outcome (affected by A and U)
    Y <- 1 + beta_true * A + 1.5 * U + rnorm(n)

    # Negative control outcome (affected by U only, NOT by A)
    Y_nc <- 0.5 + 1.2 * U + rnorm(n, sd = 0.8)

    # Create data frame
    df <- data.frame(W = W, A = A, Y = Y, Y_nc = Y_nc)

### Creating the Causal Specification

We specify the causal problem including the negative control:

    spec <- causal_spec(
      data = df,
      treatment = "A",
      outcome = "Y",
      covariates = "W",
      negative_control = "Y_nc"
    )
    #> ✔ Created causal specification: n=500, 1 covariate(s)

    print(spec)
    #>
    #> -- Causal Specification --------------------------------------------------
    #>
    #> * Treatment: A ( binary )
    #> * Outcome: Y ( continuous )
    #> * Covariates: W
    #> * Sample size: 500
    #> * Estimand: ATE
    #> * Negative control: Y_nc

### Running the Negative Control Diagnostic

Now we test whether our IPTW adjustment materially reduces confounding:

    set.seed(123)
    nc_result <- nc_diagnostic(
      spec,
      method = "iptw",
      alpha = 0.05,
      n_boot = 200
    )

    print(nc_result)

### Interpreting the Results

The diagnostic returns:

- `screening$statistic`: Weighted residual association between \(A\) and \(Y'\) after adjustment
- `p_value`: Permutation p-value for that residual association
- `delta_nc`: The observed negative-control association proxy
- `delta_bound`: Upper bound on true deficiency (\(\kappa \times \delta_{NC}\))
- `falsified`: Whether the residual-association screening test rejects

### Scenarios

#### Scenario 1: Adjustment Succeeds

If \(W\) fully captures \(U\), the negative control test will typically NOT falsify:

    # When W = U (no unmeasured confounding)
    df_full <- df
    df_full$W <- U  # Perfect proxy

    spec_full <- causal_spec(
      df_full, "A", "Y", "W", negative_control = "Y_nc"
    )

    nc_full <- nc_diagnostic(spec_full, method = "iptw", n_boot = 100)
    print(nc_full)
    # Expect: falsified = FALSE

#### Scenario 2: Adjustment Fails

When \(W\) is a poor proxy for \(U\), falsification occurs:

    # When W is noise (no information about U)
    df_bad <- df
    df_bad$W <- rnorm(n)  # Useless proxy

    spec_bad <- causal_spec(
      df_bad, "A", "Y", "W", negative_control = "Y_nc"
    )

    nc_bad <- nc_diagnostic(spec_bad, method = "iptw", n_boot = 100)
    print(nc_bad)
    # Expect: falsified = TRUE

## Choosing Good Negative Control Outcomes

### Ideal Properties

The best negative control outcomes have:

1. Strong confounding alignment: \(Y'\) shares the same unmeasured confounders as \(Y\)
2. Zero treatment effect: No plausible mechanism by which \(A\) affects \(Y'\)
3. Measurable: Available in your dataset

### Examples by Domain

Domain | Treatment | Outcome | Possible Negative Control
--- | --- | --- | ---
Cardiovascular | Statin use | CVD events | Accidental injuries
Oncology | Chemotherapy | Tumor response | Hospital-acquired infections
Economics | Job training | Earnings in 1978 | Earnings in 1974 (pre-treatment)
Epidemiology | Vaccination | Flu incidence | Unrelated disease incidence

## Combining with Deficiency Estimation

The negative control diagnostic complements deficiency estimation:

    # Step 1: Estimate deficiency
    def_results <- estimate_deficiency(
      spec,
      methods = c("unadjusted", "iptw", "aipw"),
      n_boot = 100
    )

    print(def_results)

    # Step 2: Run negative control diagnostic on best method
    best_method <- names(which.min(def_results$estimates))
    nc_check <- nc_diagnostic(spec, method = best_method, n_boot = 100)

    # Step 3: Compute policy bounds if assumptions not falsified
    if (!nc_check$falsified) {
      bounds <- policy_regret_bound(
        def_results,
        utility_range = c(-5, 10),
        method = best_method
      )
      print(bounds)
    } else {
      warning("Causal assumptions falsified. Consider additional covariates.")
    }

## Advanced: Estimating Kappa

The alignment constant \(\kappa\) affects the bound’s tightness. The default \(\kappa = 1\) is conservative. You can estimate \(\kappa\) from domain knowledge:

    # If you believe Y' has 80% of Y's confounding structure:
    nc_tight <- nc_diagnostic(
      spec,
      method = "iptw",
      kappa = 0.8,
      n_boot = 100
    )

    print(nc_tight)

## Summary

Function | Purpose
--- | ---
`nc_diagnostic()` | Screen for residual association and compute a sensitivity bound
`delta_nc` | Observable negative-control association proxy
`delta_bound` | Upper bound on true deficiency
`falsified` | Screening rejection of residual association

Negative control diagnostics provide a data-driven way to assess causal assumptions. Use them alongside deficiency estimation as screening and sensitivity tools, not as stand-alone validation.

## References

1. Akdemir, D. (2026). Constraints on Causal Inference as Experiment Comparison. DOI: 10.5281/zenodo.21877511. See `thm:nc_bound` (Negative Control Sensitivity Bound).

2. Lipsitch, M., Tchetgen, E., & Cohen, T. (2010). Negative controls: A tool for detecting confounding and bias. Epidemiology, 21(3), 383-388.

3. Shi, X., Miao, W., & Tchetgen Tchetgen, E. (2020). A selective review of negative control methods. Current Epidemiology Reports, 7, 190-202.