OBJECTIVES: Increased drug costs have placed an emphasis at not only looking at a drug’s efficacy, but also its cost-effectiveness.  Cost-effectiveness of a drug depends on the study design elements of the cost-effectiveness analysis. These include elements that account for dynamic changes in market and clinical factors after a drug is approved. This literature review summarizes the frequency of specific study design elements that can affect a drugs cost-effectiveness METHODS:  Articles published between January 2000 and February 2015 were identified from PubMed, EMBASE, International Pharmaceutical Abstracts (IPA), and EconLit. Search terms were developed for three categories: Cost, Time Span, and Drug/Pharmaceutical. We included original cost-effectiveness analyses (CEA) from high-income OECD countries that were published in English and had at least 100 patients if they were based on clinical trials. Each article was evaluated by two reviewers using a stepwise approach. RESULTS: A total of 192 articles were included after full-text review from 710 screened articles. The most common type of analysis was cost-utility (n=124), followed by cost-effectiveness analysis (n=54) and cost minimization analysis/budget impact models (n= 12). The national health system (n=80), third-party payer (n=68), and societal perspectives (n=43) were taken in these analyses. Markov models (n=87) and decision tree (n=44) were the most frequently models used in the articles reviewed. Only a few of the cost-effectiveness articles (n=10) incorporated dynamic effects. The most common dynamic factor was drug price followed by market or clinical factors. These articles incorporated generic entry, adherence changes, new indications, and epidemiological changes into determining cost-effectiveness. CONCLUSIONS: This review documents a variety of approaches for design of CEAs with variations in study design approaches that effect cost and effectiveness. Few studies incorporated dynamic effects into the CEA.