PhD thesis assessing the role of non-randomized studies with randomized in evidence syntheses of health interventions. / Randomized studies (RS) are considered the best source of evidence for knowledge syntheses (e.g., systematic reviews, health technology assessments, health guidelines, among others) about healthcare interventions. Historically, non-randomized studies (NRS) have been usually discarded from knowledge syntheses of interventions due to their intrinsic risk of bias and confounding, and they are used only when RS are considered unfeasible or unethical to conduct. With better research methods in observational studies and new tools for the evaluation of risk of bias, NRS are more likely to be a helpful source of information when used as replacement, sequential, or complementary evidence. This, together with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, provide an opportunity for guiding decisions about using RS and NRS in knowledge synthesis and increasing our certainty in a body of evidence. This work aims to improve research synthesis methods by assessing the role and use of RS and NRS in knowledge syntheses using GRADE. This can help health professionals, researchers, guideline developers, and policy-makers build better and more complete healthcare recommendations. / Thesis / Doctor of Philosophy (PhD) / All recommendations about healthcare interventions (from common medicines to strategies to prevent diseases) should ideally come from an adequate synthesis (e.g., systematic reviews) of the least biased studies. Many researchers and authors of health syntheses consider randomized studies (RS), the ‘gold standard’ to demonstrate if an intervention is truly effective. Unfortunately, they are not always available, feasible, or ethical to conduct. Non-randomized studies (NRS), also called observational studies, can potentially provide complementary evidence for a research question. Unfortunately, they are usually considered of poorer quality because of their intrinsic nature of being prone to bias and confounding. In most circumstances, authors of syntheses discard these types of studies from the outset, without considering their potential for providing evidence that could complement or even replace that from randomized studies. This work aims to improve this situation by offering methods for evaluating the appropriateness of integrating both RS and NRS, guiding authors and researchers in cases where this is possible, hence increasing the certainty in a body of evidence and help all stakeholders reach decisions.