The CBIC Certified Infection Control Exam Study Guide (6th edition) identifies the randomized clinical trial (RCT) as the study design that provides the strongest evidence of a causal relationship between a risk factor (or intervention) and an outcome. RCTs are considered the gold standard because they use random assignment to allocate participants to either an intervention group or a control group, which minimizes bias and balances both known and unknown confounding variables between groups.

By controlling exposure and randomly assigning participants, RCTs establish temporality, ensuring that the exposure precedes the outcome—an essential criterion for causality. This design also allows for direct comparison of outcomes under controlled conditions, making it possible to attribute observed differences in outcomes to the intervention or risk factor with a high degree of confidence.

In contrast, cohort studies and case-control studies are observational and can identify associations but are more susceptible to confounding and bias. While cohort studies can demonstrate temporal relationships and estimate risk, they cannot control exposures as precisely as RCTs. Case-control studies are particularly vulnerable to recall and selection bias. Cross-sectional studies assess exposure and outcome simultaneously and cannot establish causation.

For the CIC® exam, it is critical to recognize that randomized clinical trials offer the highest level of evidence for causality, particularly when evaluating interventions, preventive measures, or treatment effectiveness in infection prevention and healthcare epidemiology.