Introduction Clinical trial design impacts Level of Evidence Clinical trials may be either observational or experimental observational researchers observe patient groups without allocation of intervention may be either prospective or retrospective may be descriptive or analytic descriptive useful for obtaining background information for more advance studies examples case reports case series cross-sectional studies analytic explores the association between a given outcome and a potentially related variable examples case-control cohort meta-analysis experimental researchers allocate treatment allows the evaluation of efficacies of therapeutic interventions examples double-blinded, prospective, randomized clinical trial is the gold standard for evidence based medicine Conflict of interest statement submitted with each publication for each author discloses all financial interests of each author as it relates to the study and/or publication Randomized controlled trial Definition a study in which patients are randomly assigned to the treatment or control group and are followed prospectively provides the most compelling evidence that the study treatment causes the expected effect on human health randomization minimizes study selection bias by definition an experimental study because there is an intervention Study designs parallel-group each participant is randomly assigned to a group, and all the participants in the group receive (or do not receive) an intervention, crossover administration of two or more therapies, one after the other, in a random order susceptible to bias if washout period is inadequate factorial each participant is randomly assigned to a group that receives a particular combination of interventions or non-interventions. cluster pre-existing groups of participants (e.g., villages, schools) are randomly selected to receive (or not receive) an intervention. Blinding blinding of the outcome assessor likely to decrease the treatment effect reported in the study Analysis intent-to-treat analysis outcomes based on the group into which they were randomized, regardless of whether the patient actually received the planned intervention minimizes non-responder bias as-treated analysis outcomes based on actual intervention received, regardless of which group their were randomized to. by definition, when as-treated analysis is done, the results are no longer a RCT used when there is higher cross-over from randomization groups (e.g., a patient is randomized to nonoperative treatment, but elects to obtain surgical treatment). per protocol excludes patients who were not compliant with the protocol guidelines Example you want to determine whether your new toothpaste prevents cavities better than your old toothpaste. You randomly assign a large number of patients to either an intervention group, which uses the new toothpaste, or to a control group, which uses the old toothpaste. You would then measure the amount of cavities between the groups over time. Orthopaedic Literature Examples Cohort study Definition a study in which patient groups are separated non-randomly by exposure or treatment, with exposure occurring after (prospective), or before (retrospective), the initiation of the study Evidence 217480Level II or III evidence Analysis results usually reported as relative-risk Example you want to determine if smoking is a risk factor for the development of lung cancer. You identify a group of smokers and a group of non-smokers, and follow them over time measuring the desired outcome, in this case, lung cancer. Orthopaedic Literature Examples Case-control study Definition a study in which patient groups are separated by the current presence (cases) or absence (controls) of disease and examined for the prior exposure of interest Evidence Most are Level III evidence Analysis usually reported as odds-ratio Example you want to determine if smoking is a risk factor for the development of lung cancer. You compare the smoking history of individuals with lung cancer (cases) and those without (controls). Orthopaedic Literature Examples Meta-analysis Definition a systematic review that summarizes results of other studies Evidence may be used to increase the statistical power of several under-powered studies Example you want to determine if wearing sunscreen results in fewer cases of melanoma. You pool the results of 9 randomized controlled studies and statistically analyze the data to determine the effect of the relationship. Orthopaedic Literature Examples Cross-sectional Study Definition study group is analyzed at a given time ("snapshot") with no follow-up Example you want to determine the prevalence of baseball injuries during the 2003 little-league season Orthopaedic Literature Examples Case Series Definition a retrospective account of multiple patients with the same injury or treatment with no control or comparison group useful for generating hypotheses for additional studies Evidence level IV evidence Example you have found that several of your patients who have used a new lipid lowering medication have developed hemorrhagic cysts. You want to alert other members of the community of this possible association. Orthopaedic Literature Examples