**Core Concept**
The question is asking about research methods that involve only individuals who are initially free of a specific disease, known as a "disease-free" or "healthy" cohort. This is a crucial concept in epidemiology and clinical research, where the goal is to study the natural history of a disease or the effectiveness of a treatment in people who are not yet affected.

**Why the Correct Answer is Right**
The correct answer is **C. Cohort Study**. A cohort study is a research design where a group of people who are initially free of the disease of interest (the cohort) is followed over time to observe the development of the disease. This type of study is useful for identifying risk factors and understanding the natural history of a disease. In a cohort study, the cohort is typically divided into exposed and unexposed groups, where the exposed group is the one that is at risk of developing the disease.

**Why Each Wrong Option is Incorrect**
**Option A:** **Case-Control Study** is incorrect because this type of study involves selecting people who already have the disease (cases) and comparing them to people who do not have the disease (controls). The goal is to identify potential risk factors for the disease, but it does not involve a disease-free cohort.

**Option B:** **Cross-Sectional Study** is incorrect because this type of study involves observing a sample of people at a single point in time to determine the prevalence of a disease. It does not involve following a disease-free cohort over time.

**Option D:** **Randomized Controlled Trial (RCT)** is incorrect because while an RCT may involve a disease-free cohort, its primary goal is to evaluate the effectiveness of a treatment or intervention, rather than to study the natural history of a disease.

**Clinical Pearl / High-Yield Fact**
Remember that cohort studies are particularly useful for identifying risk factors and understanding the natural history of a disease, but they can be time-consuming and costly to conduct.

**Correct Answer:** .