**Core Concept**
Cohort studies are a type of observational study design that involves following a group of individuals over time to assess the relationship between an exposure and an outcome. In a cohort study, the exposure is typically determined before the outcome occurs, which allows researchers to examine the potential causal relationship between the two.

**Why the Correct Answer is Right**
The correct answer, **C. Exposure is usually determined prior to disease occurrence**, is the key characteristic that makes cohort studies less susceptible to bias. When the exposure is determined before the disease occurs, it is less likely that the outcome will influence the exposure, which reduces the risk of reverse causality bias. This is particularly important in cohort studies, where the outcome is often a disease or condition that may affect the individual's behavior or environment, potentially altering their exposure status. By determining the exposure before the disease occurs, researchers can minimize the impact of reverse causality bias and more accurately assess the relationship between the exposure and the outcome.

**Why Each Wrong Option is Incorrect**
**Option A:** Data collection is prospective is not a characteristic that makes cohort studies resistant to bias. While prospective data collection can be beneficial in many ways, it does not specifically address the issue of bias in cohort studies.
**Option B:** Large number of subjects is usually included can actually increase the risk of bias in cohort studies, particularly if the sample size is large and the study design is flawed.
**Option D:** Actual relative risk can be determined is a benefit of cohort studies, but it is not the reason why bias is unlikely to invalidate these studies.

**Clinical Pearl / High-Yield Fact**
When evaluating the validity of a cohort study, it is essential to consider the timing of the exposure in relation to the outcome. If the exposure is determined after the disease occurs, it may be subject to reverse causality bias, which can lead to inaccurate conclusions about the relationship between the exposure and the outcome.

**✓ Correct Answer: C. Exposure is usually determined prior to disease occurrence**