1. Investigators determined that recent studies in the medical literature have provided conflicting results about the efficacy of Drug X on chronic kidney disease. They conduct a systematic review of observational studies comparing Drug X to conventional therapy to determine the best evidence. Several small studies show conflicting results. The studies are too heterogeneous to combine in a meta-analysis. Which of the following study designs is the best approach to resolve these conflicting study results about the efficacy of Drug X on chronic kidney disease?

1. A large, multicenter randomized controlled clinical trial
2. A large perspective, observational cohort study
3. A meta-analysis including a greater number of studies
4. Multiple case control studies