In sbalci/ClinicoPathJamoviModule: Analysis for Clinicopathological Research

knitr::opts_chunk$set(
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Overview

The meddecide package provides comprehensive tools for medical decision-making, including:

• ROC Analysis: Receiver Operating Characteristic curve analysis with optimal cutpoint determination
• Diagnostic Test Evaluation: Sensitivity, specificity, predictive values, and likelihood ratios
• Interrater Reliability: Cohen's kappa and Fleiss' kappa for agreement analysis
• Power Analysis: Sample size calculations for kappa statistics

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Vignette 1: ROC Analysis with psychopdaroc

Introduction

ROC (Receiver Operating Characteristic) analysis is fundamental in evaluating diagnostic tests. The psychopdaroc function provides comprehensive ROC analysis with multiple methods for determining optimal cutpoints.

Basic Usage

library(meddecide)

# Load example data
data(cancer_biomarker)  # Hypothetical dataset

# Basic ROC analysis
roc_result <- psychopdaroc(
  data = cancer_biomarker,
  dependentVars = "PSA",           # Test variable
  classVar = "cancer_status",      # Binary outcome (0/1)
  positiveClass = "1"              # Which level is positive
)

Understanding ROC Curves

An ROC curve plots sensitivity (true positive rate) against 1-specificity (false positive rate) across all possible cutpoints. The area under the curve (AUC) summarizes overall diagnostic accuracy:

• AUC = 0.5: No discrimination (diagonal line)
• AUC = 0.7-0.8: Acceptable discrimination
• AUC = 0.8-0.9: Excellent discrimination
• AUC > 0.9: Outstanding discrimination

Optimal Cutpoint Methods

The package offers several methods to determine optimal cutpoints:

# Method 1: Maximize Youden's Index (default)
roc_youden <- psychopdaroc(
  data = cancer_biomarker,
  dependentVars = "PSA",
  classVar = "cancer_status",
  positiveClass = "1",
  method = "maximize_metric",
  metric = "youden"  # Sensitivity + Specificity - 1
)

# Method 2: Cost-benefit optimization
roc_cost <- psychopdaroc(
  data = cancer_biomarker,
  dependentVars = "PSA",
  classVar = "cancer_status",
  positiveClass = "1",
  method = "oc_cost_ratio",
  costratioFP = 2.5  # False positives cost 2.5x more than false negatives
)

# Method 3: Equal sensitivity and specificity
roc_equal <- psychopdaroc(
  data = cancer_biomarker,
  dependentVars = "PSA",
  classVar = "cancer_status",
  positiveClass = "1",
  method = "oc_equal_sens_spec"
)

Comparing Multiple Tests

# Compare multiple biomarkers
roc_comparison <- psychopdaroc(
  data = cancer_biomarker,
  dependentVars = c("PSA", "CA125", "CEA"),  # Multiple tests
  classVar = "cancer_status",
  positiveClass = "1",
  combinePlots = TRUE,        # Show all curves in one plot
  delongTest = TRUE           # Statistical comparison of AUCs
)

Advanced Features

# Bootstrap confidence intervals
roc_bootstrap <- psychopdaroc(
  data = cancer_biomarker,
  dependentVars = "PSA",
  classVar = "cancer_status",
  positiveClass = "1",
  bootstrapCI = TRUE,
  bootstrapReps = 2000
)

# Partial AUC (focus on high specificity region)
roc_partial <- psychopdaroc(
  data = cancer_biomarker,
  dependentVars = "PSA",
  classVar = "cancer_status",
  positiveClass = "1",
  partialAUC = TRUE,
  partialAUCfrom = 0.8,  # Specificity range 80-100%
  partialAUCto = 1.0
)

# Net Reclassification Index (NRI) and IDI
roc_nri <- psychopdaroc(
  data = cancer_biomarker,
  dependentVars = c("PSA", "NewBiomarker"),
  classVar = "cancer_status",
  positiveClass = "1",
  calculateIDI = TRUE,
  calculateNRI = TRUE,
  refVar = "PSA",  # Compare NewBiomarker against PSA
  nriThresholds = "0.2,0.5"  # Risk categories: <20%, 20-50%, >50%
)

Visualization Options

# Publication-ready plots
roc_publication <- psychopdaroc(
  data = cancer_biomarker,
  dependentVars = c("PSA", "CA125"),
  classVar = "cancer_status",
  positiveClass = "1",
  plotROC = TRUE,
  cleanPlot = TRUE,           # Clean plot for publications
  showOptimalPoint = TRUE,    # Mark optimal cutpoint
  legendPosition = "bottomright"
)

# Additional diagnostic plots
roc_diagnostic <- psychopdaroc(
  data = cancer_biomarker,
  dependentVars = "PSA",
  classVar = "cancer_status",
  positiveClass = "1",
  showCriterionPlot = TRUE,   # Sensitivity/Specificity vs threshold
  showPrevalencePlot = TRUE,  # PPV/NPV vs prevalence
  showDotPlot = TRUE          # Distribution by class
)

---

Vignette 2: Diagnostic Test Evaluation with decision

Introduction

The decision function evaluates diagnostic test performance against a gold standard, calculating sensitivity, specificity, predictive values, and likelihood ratios.

Basic Analysis

# Evaluate a new rapid test against gold standard
decision_result <- decision(
  data = diagnostic_data,
  gold = "pcr_result",        # Gold standard test
  goldPositive = "positive",   # Positive level of gold standard
  newtest = "rapid_test",      # New test to evaluate
  testPositive = "positive"    # Positive level of new test
)

Understanding the Output

The function provides:

1. Confusion Matrix: True positives, false positives, true negatives, false negatives
2. Performance Metrics:
3. Sensitivity: Proportion of true positives correctly identified
4. Specificity: Proportion of true negatives correctly identified
5. PPV: Probability of disease given positive test
6. NPV: Probability of no disease given negative test
7. Likelihood ratios: How much a test result changes disease probability

Using Prior Probability

When the study population differs from the target population:

# Adjust for population prevalence
decision_adjusted <- decision(
  data = diagnostic_data,
  gold = "pcr_result",
  goldPositive = "positive",
  newtest = "rapid_test",
  testPositive = "positive",
  pp = TRUE,                  # Use prior probability
  pprob = 0.05                # 5% prevalence in general population
)

Confidence Intervals

# Add 95% confidence intervals
decision_ci <- decision(
  data = diagnostic_data,
  gold = "pcr_result",
  goldPositive = "positive",
  newtest = "rapid_test",
  testPositive = "positive",
  ci = TRUE                   # Calculate confidence intervals
)

Fagan Nomogram

Visualize how test results change disease probability:

# Create Fagan nomogram
decision_fagan <- decision(
  data = diagnostic_data,
  gold = "pcr_result",
  goldPositive = "positive",
  newtest = "rapid_test",
  testPositive = "positive",
  fagan = TRUE                # Generate Fagan nomogram
)

---

Vignette 3: Decision Calculator with decisioncalculator

Introduction

When you have summary statistics instead of raw data, use decisioncalculator.

Basic Usage

# From a published 2x2 table
calc_result <- decisioncalculator(
  TP = 85,    # True positives
  FP = 15,    # False positives  
  FN = 10,    # False negatives
  TN = 90     # True negatives
)

Adjusting for Prevalence

# Adjust for different population prevalence
calc_adjusted <- decisioncalculator(
  TP = 85,
  FP = 15,
  FN = 10,
  TN = 90,
  pp = TRUE,
  pprob = 0.02  # 2% prevalence in screening population
)

Interpreting Results

The calculator provides: - Accuracy: Overall correct classification rate - Prevalence: Disease frequency in the study - Post-test probabilities: Updated disease probability after testing - Likelihood ratios: Diagnostic test strength

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Vignette 4: Interrater Reliability with agreement

Introduction

The agreement function assesses how well multiple raters agree when classifying the same subjects.

Two Raters (Cohen's Kappa)

# Two pathologists rating tumor grades
kappa_result <- agreement(
  data = pathology_data,
  vars = c("pathologist1", "pathologist2")
)

Interpretation:

• κ < 0.00: Poor agreement
• κ = 0.00-0.20: Slight agreement
• κ = 0.21-0.40: Fair agreement
• κ = 0.41-0.60: Moderate agreement
• κ = 0.61-0.80: Substantial agreement
• κ = 0.81-1.00: Almost perfect agreement

Weighted Kappa for Ordinal Data

# For ordinal categories (e.g., grades 1-5)
weighted_kappa <- agreement(
  data = pathology_data,
  vars = c("pathologist1", "pathologist2"),
  wght = "squared"  # Squared weights for ordinal data
)

Multiple Raters (Fleiss' Kappa)

# Three or more raters
fleiss_kappa <- agreement(
  data = radiology_data,
  vars = c("radiologist1", "radiologist2", "radiologist3", "radiologist4")
)

Exact Kappa

# For small samples with 3+ raters
exact_kappa <- agreement(
  data = small_study,
  vars = c("rater1", "rater2", "rater3"),
  exct = TRUE  # Use exact method
)

---

Vignette 5: Power Analysis for Kappa with kappaSizePower

Introduction

Plan sample sizes for interrater reliability studies.

Basic Sample Size Calculation

# Sample size for binary outcome
sample_size <- kappaSizePower(
  outcome = "2",           # Binary outcome
  kappa0 = 0.4,           # Null hypothesis: fair agreement
  kappa1 = 0.6,           # Alternative: moderate agreement
  props = "0.3, 0.7",     # 30% positive, 70% negative
  raters = "2",           # Two raters
  alpha = 0.05,           # Type I error rate
  power = 0.80            # Statistical power
)

Multiple Categories

# Sample size for 3-category outcome
sample_size_3cat <- kappaSizePower(
  outcome = "3",
  kappa0 = 0.4,
  kappa1 = 0.6,
  props = "0.2, 0.5, 0.3",  # Category proportions
  raters = "2",
  alpha = 0.05,
  power = 0.80
)

Multiple Raters

# Sample size for 3 raters
sample_size_3raters <- kappaSizePower(
  outcome = "2",
  kappa0 = 0.4,
  kappa1 = 0.6,
  props = "0.4, 0.6",
  raters = "3",             # Three raters
  alpha = 0.05,
  power = 0.80
)

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Vignette 6: Confidence Interval Approach with kappaSizeCI

Introduction

Calculate sample size based on desired confidence interval width.

Basic Usage

# Sample size for precise kappa estimation
ci_sample_size <- kappaSizeCI(
  outcome = "2",
  kappa0 = 0.6,      # Expected kappa
  kappaL = 0.4,      # Lower CI bound
  kappaU = 0.8,      # Upper CI bound
  props = "0.2, 0.8",
  raters = "2",
  alpha = 0.05
)

Planning for Publication

# Narrow CI for publication standards
publication_size <- kappaSizeCI(
  outcome = "2",
  kappa0 = 0.7,      # Expected substantial agreement
  kappaL = 0.6,      # Lower bound still substantial
  kappaU = 0.8,      # Upper bound
  props = "0.3, 0.7",
  raters = "2",
  alpha = 0.05
)

---

Vignette 7: Fixed Sample Size Analysis with kappaSizeFixedN

Introduction

When sample size is predetermined, calculate expected kappa precision.

Usage

# What kappa precision with 100 subjects?
fixed_n_result <- kappaSizeFixedN(
  outcome = "2",
  kappa0 = 0.5,       # Expected kappa
  props = "0.4, 0.6",
  raters = "2",
  alpha = 0.05,
  n = 100             # Fixed sample size
)

Feasibility Assessment

# Check if available sample provides adequate precision
feasibility <- kappaSizeFixedN(
  outcome = "3",
  kappa0 = 0.6,
  props = "0.3, 0.4, 0.3",
  raters = "2",
  alpha = 0.05,
  n = 50              # Available subjects
)

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Best Practices

1. ROC Analysis

• Always verify positive class specification
• Consider clinical costs when choosing cutpoints
• Use bootstrap CIs for small samples
• Report both sensitivity and specificity at chosen cutpoint

2. Diagnostic Test Evaluation

• Account for spectrum bias in study design
• Adjust for target population prevalence
• Report confidence intervals
• Consider clinical context for interpretation

3. Interrater Reliability

• Use appropriate kappa variant (weighted for ordinal data)
• Ensure raters are properly trained
• Consider prevalence effects on kappa
• Report percentage agreement alongside kappa

4. Power Analysis

• Be realistic about expected agreement levels
• Consider dropout rates
• Account for category imbalance
• Plan for pilot studies when parameters uncertain

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References

1. DeLong ER, DeLong DM, Clarke-Pearson DL (1988). Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837-845.

2. Cohen J (1960). A coefficient of agreement for nominal scales. Educational and Psychological Measurement 20:37-46.

3. Fleiss JL (1971). Measuring nominal scale agreement among many raters. Psychological Bulletin 76:378-382.

4. Pencina MJ, D'Agostino RB Sr, D'Agostino RB Jr, Vasan RS (2008). Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Statistics in Medicine 27:157-172.

5. Fagan TJ (1975). Nomogram for Bayes theorem. New England Journal of Medicine 293:257.

sbalci/ClinicoPathJamoviModule documentation built on June 13, 2025, 9:34 a.m.