A cohort study follows a group over time to see who develops a disease based on their exposures (for example, comparing smokers and non-smokers for lung cancer incidence), while a case-control study works backward, starting with people who already have a disease and comparing their past exposures to those without it -- making case-control studies faster and cheaper for rare diseases. A randomized controlled trial (RCT) randomly assigns participants to an intervention or control group, which is considered the gold standard for establishing cause and effect because randomization balances out both known and unknown confounding factors between groups, something observational designs like cohort and case-control studies cannot fully achieve. This is reflected in the evidence hierarchy used in evidence-based medicine, which typically ranks systematic reviews and meta-analyses of multiple RCTs at the top, followed by individual RCTs, then cohort studies, case-control studies, and expert opinion at the bottom. No study design is ethical without informed consent -- ensuring participants understand the study's purpose, risks, and their right to withdraw -- and independent ethics review (an Institutional Review Board or research ethics committee), standards that trace back to the Nuremberg Code and were later formalized in the Declaration of Helsinki after historical abuses in medical research.