Study guide
16.4 Clinical Epidemiology, Biostatistics & Study Design
ABIM Internal Medicine Exam
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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy
0.1 Exam Format, Question Types & the 2026 Blueprint 0.2 Eligibility, Registration, Fees & Exam-Day Logistics 0.3 Scoring, the Passing Standard & Score Reports 0.4 Building a Blueprint-Weighted Study Plan
2 Chapter 1: Cardiovascular Disease (14% of Exam)
1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection
3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)
2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia
4 Chapter 3: Gastroenterology & Hepatology (9% of Exam)
3.1 Esophageal Disease 3.2 Stomach & Duodenal Disease and Gastrointestinal Hemorrhage 3.3 Inflammatory Bowel Disease 3.4 Celiac Disease & Irritable Bowel Syndrome 3.5 Diverticular Disease & Colorectal Cancer Screening 3.6 Viral Hepatitis, Steatotic & Alcohol-Associated Liver Disease 3.7 Cirrhosis & the Complications of Portal Hypertension 3.8 Acute Pancreatitis 3.9 Chronic Pancreatitis & Biliary Tract Disease 3.10 Inherited, Autoimmune & Drug-Induced Liver Disease 3.11 Small Intestinal Disease, Ischemia & Gastrointestinal Complications of HIV
5 Chapter 4: Infectious Disease (9% of Exam)
4.1 Lower Respiratory Tract Infections & Sepsis Syndromes 4.2 Viral Respiratory Pathogens & Tuberculosis 4.3 Central Nervous System Infections 4.4 Skin, Soft Tissue, Bone & Joint Infections 4.5 Infective Endocarditis & Cardiovascular Infection 4.6 Clostridioides difficile & Catheter-Related Bloodstream Infection 4.7 HIV Diagnosis, Antiretroviral Therapy & Prevention 4.8 Opportunistic Infections & Sexually Transmitted Infections 4.9 Fever of Unknown Origin, Neutropenic Fever & Toxic Shock 4.10 Travel-Related Illness, Vector-Borne Disease & Outbreaks 4.11 Infection Prevention, Nosocomial Infection & Postexposure Prophylaxis 4.12 Rheumatic Fever, Poststreptococcal Disease, Enteric & Hepatic Infections
6 Chapter 5: Pulmonary Disease (9% of Exam)
5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule
7 Chapter 6: Rheumatology & Orthopedics (9% of Exam)
6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease
8 Chapter 7: Hematology (6% of Exam)
7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation
9 Chapter 8: Medical Oncology (6% of Exam)
8.1 Breast, Lung, Colorectal & Prostate Cancer 8.2 Oncologic Emergencies 8.3 Genitourinary & Gynecologic Malignancies 8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary 8.5 Complications of Cancer & Its Treatment 8.6 Cancer Prevention, Survivorship & Psychosocial Care
10 Chapter 9: Nephrology & Urology (6% of Exam)
9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria
11 Chapter 10: Neurology (4% of Exam)
10.1 Acute Ischemic Stroke: Syndromes & Reperfusion 10.2 Transient Ischemic Attack, Secondary Prevention & Hemorrhagic Stroke 10.3 Headache & Facial Pain 10.4 Seizures, Epilepsy & Movement Disorders 10.5 Multiple Sclerosis & Neuromuscular Junction Disorders 10.6 Motor Neuron Disease & Acute Peripheral Neuropathy 10.7 Cranial Neuropathies & Neuro-Ophthalmology 10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders
12 Chapter 11: Psychiatry & Behavioral Health (4% of Exam)
11.1 Major Depressive Disorder & Medical Mimics 11.2 Antidepressant Pharmacotherapy & Treatment-Resistant Depression 11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity 11.4 Anxiety, Stress-Related & Obsessive-Compulsive Disorders 11.5 Alcohol Use Disorder & Withdrawal 11.6 Pharmacotherapy for Alcohol & Opioid Use Disorder 11.7 Toxidromes, Psychiatric Emergencies & Suicide Risk Assessment 11.8 Psychotic, Somatic Symptom, Factitious & Personality Disorders 11.9 Eating Disorders, Sleep Disorders & Sexual Health
13 Chapter 12: Dermatology (3% of Exam)
12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease
14 Chapter 13: Obstetrics & Gynecology / Women's Health (3% of Exam)
13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications
15 Chapter 14: Geriatric Syndromes (3% of Exam)
14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings
16 Chapter 15: Allergy & Immunology (2% of Exam)
15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders
17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology
16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design
18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)
17.1 Principles of Bioethics & Decisional Capacity 17.2 Informed Consent, Treatment Refusal & Special Scenarios 17.3 Surrogate Decision-Making, Advance Directives & Confidentiality 17.4 Patient Safety Science, Medical Error & Diagnostic Reasoning 17.5 Quality Improvement Methods, Health Disparities & Health Equity
19 Chapter 18: Perioperative Medicine & Medical Consultation
18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications
20 Chapter 19: Ophthalmology (1% of Exam)
19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease
21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)
20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders
16.4 Clinical Epidemiology, Biostatistics & Study Design
Key Takeaways Explain This Topic AI
Primarily epidemiology is one of three enumerated subsections within the 2% Miscellaneous blueprint category.
Sensitivity and specificity are properties of the test, whereas predictive values depend on disease prevalence.
Number needed to treat is the reciprocal of the absolute risk reduction and is more clinically informative than relative risk reduction.
Lead-time and length-time bias make screening appear to prolong survival without reducing mortality, so mortality is the appropriate endpoint.
Intention-to-treat analysis preserves randomization and protects against bias introduced by differential dropout.
Last updated: August 2026
- 1. Clinical Epidemiology & Biostatistics for Board Exams
- A. Diagnostic Test Performance & 2x2 Contingency Matrix
Diagnostic Test Matrix Disease Present (Gold Standard +) Disease Absent (Gold Standard -) Predictive Values
Test Result Positive (+) True Positive (TP) False Positive (FP) Positive Predictive Value (PPV) = T P T P + F P \frac{TP}{TP + FP} TP + FP TP
Test Result Negative (-) False Negative (FN) True Negative (TN) Negative Predictive Value (NPV) = T N T N + F N \frac{TN}{TN + FN} TN + FN TN
Diagnostic Metrics Sensitivity = T P T P + F N \frac{TP}{TP + FN} TP + FN TP Specificity = T N T N + F P \frac{TN}{TN + FP} TN + FP TN Accuracy = T P + T N T o t a l \frac{TP + TN}{Total} T o t a l TP + TN
Sensitivity (True Positive Rate): The probability that a test is positive among individuals who have the disease. SnNOut: A test with high S e n sitivity, when N egative, rules Out the disease (minimal false negatives). Ideal for screening tests (e.g., ELISA for HIV, D-dimer for PE, ANA for SLE).
Specificity (True Negative Rate): The probability that a test is negative among individuals who do NOT have the disease. SpPIn: A test with high Sp ecificity, when P ositive, rules In the disease (minimal false positives). Ideal for confirmatory tests (e.g., Western blot/differentiation immunoassay for HIV, biopsy for cancer).
Positive Predictive Value (PPV): The probability that a patient with a positive test actually has the disease. PPV depends heavily on disease prevalence : As disease prevalence increases, PPV increases and NPV decreases .
Negative Predictive Value (NPV): The probability that a patient with a negative test does not have the disease. As disease prevalence decreases, NPV increases and PPV decreases .
B. Likelihood Ratios (Prevalence-Independent Diagnostic Power)
Likelihood ratios quantify the odds of a given test result in diseased versus non-diseased individuals and are independent of disease prevalence . Positive Likelihood Ratio (LR+) = Sensitivity 1 − Specificity = True Positive Rate False Positive Rate \text{Positive Likelihood Ratio (LR+)} = \frac{\text{Sensitivity}}{1 - \text{Specificity}} = \frac{\text{True Positive Rate}}{\text{False Positive Rate}} Positive Likelihood Ratio (LR+) = 1 − Specificity Sensitivity = False Positive Rate True Positive Rate Negative Likelihood Ratio (LR-) = 1 − Sensitivity Specificity = False Negative Rate True Negative Rate \text{Negative Likelihood Ratio (LR-)} = \frac{1 - \text{Sensitivity}}{\text{Specificity}} = \frac{\text{False Negative Rate}}{\text{True Negative Rate}} Negative Likelihood Ratio (LR-) = Specificity 1 − Sensitivity = True Negative Rate False Negative Rate
Interpretation of Likelihood Ratios:
LR+ > 10: Generates a large, conclusive increase in post-test disease probability (rules in disease).
LR+ 5 to 10: Moderate increase in post-test probability.
LR 1.0: No diagnostic value (post-test probability equals pre-test probability).
LR- 0.1 to 0.2: Moderate decrease in post-test probability.
LR- < 0.1: Generates a large, conclusive decrease in post-test disease probability (rules out disease).
C. Measures of Association & Clinical Treatment Effects
Measure of Effect Mathematical Formula Study Design Application & Interpretation
Relative Risk (RR) RR = Incidence in Exposed Incidence in Unexposed = a / ( a + b ) c / ( c + d ) \text{RR} = \frac{\text{Incidence in Exposed}}{\text{Incidence in Unexposed}} = \frac{a / (a+b)}{c / (c+d)} RR = Incidence in Unexposed Incidence in Exposed = c / ( c + d ) a / ( a + b ) Used in Cohort Studies and Randomized Controlled Trials (RCTs) . RR < 1 \text{RR} < 1 RR < 1 indicates protective factor; RR > 1 \text{RR} > 1 RR > 1 indicates harmful factor.
Odds Ratio (OR) OR = Odds of Exposure in Cases Odds of Exposure in Controls = a × d b × c \text{OR} = \frac{\text{Odds of Exposure in Cases}}{\text{Odds of Exposure in Controls}} = \frac{a \times d}{b \times c} OR = Odds of Exposure in Controls Odds of Exposure in Cases = b × c a × d Used in Case-Control Studies (and cross-sectional studies). Approximates RR when disease is rare ( Rare Disease Assumption ).
Absolute Risk Reduction (ARR) ARR = Control Event Rate (CER) − Experimental Event Rate (EER) \text{ARR} = \text{Control Event Rate (CER)} - \text{Experimental Event Rate (EER)} ARR = Control Event Rate (CER) − Experimental Event Rate (EER) The actual arithmetic difference in event rates between groups. Must be used to calculate NNT.
Relative Risk Reduction (RRR) RRR = CER − EER CER = 1 − RR \text{RRR} = \frac{\text{CER} - \text{EER}}{\text{CER}} = 1 - \text{RR} RRR = CER CER − EER = 1 − RR The proportion of baseline risk eliminated by the intervention (can exaggerate small absolute benefits).
Number Needed to Treat (NNT) NNT = 1 ARR = 1 CER − EER \text{NNT} = \frac{1}{\text{ARR}} = \frac{1}{\text{CER} - \text{EER}} NNT = ARR 1 = CER − EER 1 Number of patients who must receive the treatment to prevent 1 adverse event. Always round UP to the nearest whole integer.
Number Needed to Harm (NNH) NNH = 1 Absolute Risk Increase (ARI) = 1 EER − CER \text{NNH} = \frac{1}{\text{Absolute Risk Increase (ARI)}} = \frac{1}{\text{EER} - \text{CER}} NNH = Absolute Risk Increase (ARI) 1 = EER − CER 1 Number of patients exposed to a treatment for 1 patient to experience an adverse harm.
- 2. Epidemiological Study Designs & Methodological Biases
- A. Hierarchy of Study Designs
Randomized Controlled Trial (RCT): Gold standard for demonstrating causality . Participants are randomly allocated to experimental or control arms. Minimizes selection bias and baseline confounding.
Intention-to-Treat (ITT) Analysis: Analyzes all randomized patients in their assigned treatment groups, regardless of protocol non-adherence, crossover, or study dropout. Preserves randomization balance and avoids bias.
Per-Protocol (As-Treated) Analysis: Analyzes only subjects who strictly adhered to the assigned protocol. Introduces selection bias and confounding.
Cohort Study: Observational design where subjects are identified by exposure status and followed prospectively (or retrospectively) over time to measure disease incidence and Relative Risk (RR) . Prone to Loss to Follow-up / Attrition Bias .
Case-Control Study: Observational design where subjects are selected based on outcome status (Cases with disease vs. Controls without disease) and evaluated retrospectively for prior exposures. Measures Odds Ratio (OR) . Prone to Recall Bias .
Cross-Sectional Study: Observational snapshot measuring exposure and disease status simultaneously at a single point in time. Measures disease Prevalence . Cannot establish temporal sequence or causality.
B. High-Yield Methodological Biases
Selection Biases:
Berkson Bias: Selection bias occurring when hospitalized patients are used as control subjects (hospitalized patients have higher rates of comorbidities and risk exposures than the general population).
Healthy Worker Effect: Bias where working individuals exhibit lower mortality rates than the general population, because severely ill/disabled persons are excluded from the workforce.
Information & Measurement Biases:
Recall Bias: Patients with adverse clinical outcomes recall past exposures more vividly (or inaccurately) than healthy controls (classic in retrospective case-control studies).
Observer / Pygmalion Effect: Investigator knowledge of group assignment influences measurement of outcomes (prevented by double-blinding).
Hawthorne Effect: Study subjects alter their behavior simply because they know they are being observed.
Confounding: A distortion that occurs when an extraneous variable is associated with both the exposure and the outcome, without being an intermediate step in the causal pathway.
Methods to Control Confounding in Design Phase: Randomization , Restriction (limiting enrollment criteria), and Matching .
Methods to Control Confounding in Analysis Phase: Stratification and Multivariable Regression Analysis .
Screening Biases:
Lead-Time Bias: Early detection of disease creates the false statistical illusion of prolonged survival , even though the natural history and actual time of death are entirely unchanged.
Length-Time Bias: Screening preferentially identifies slow-growing, indolent, less aggressive cases with longer preclinical phases and inherently better prognoses, while missing rapidly fatal, aggressive cases that present symptomatically between screening intervals.