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Levels of Evidence For Primary Research Question1Reprinted with permission. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.Study TypeQuestionLevel ILevel IILevel IIILevel IVLevel VDiagnostic –Investigating a diagnostic testIs this (early detection) test worthwhile?Is this diagnostic or monitoring test accurate?•Randomized controlled trial•Testing of previously developed diagnostic criteria (consecutive patients with consistently applied reference standard and blinding)•Prospective2 cohort3 study•Development of diagnostic criteria (consecutive patients with consistently applied reference standard and blinding)•Retrospective4 cohort3 study•Case-control5 study•Nonconsecutive patients•No consistently applied reference standards•Case series•Poor or non-independent reference standards•Mechanism-based reasoningPrognostic –Investigating the effect of a patient characteristic on the outcome of a diseaseWhat is the natural history of the condition?•Inception2 cohort study (all patients enrolled at an early uniform point in the course of their disease)•Prospective2 cohort3 study (patients enrolled at different points in their disease)•Control arm of randomized trial•Retrospective4 cohort3 study•Case-control5 study•Case series•Mechanism-based reasoningTherapeutic – Investigating the results of a treatmentDoes this treatment help? What are the harms6•Randomized controlled trial•Prospective2 cohort3 study•Observational study with dramatic effect•Retrospective4 cohort3 study•Case-control5 study•Case series•Historically controlled study•Mechanism-based reasoningEconomicDoes the intervention offer good value for dollars spent?Computer simulation model (Monte Carlo simulation, Markov model) with inputs derived from level I studies, lifetime time duration, outcomes expressed in dollars per quality-adjusted life year’s (QALYs) and uncertainty examined using probabilistic sensitivity analysesComputer simulation model (Monte Carlo simulation, Markov model) with inputs derived from level II studies, lifetime time duration, outcomes expressed in QALYs and uncertainty examined using probabilistic sensitivity analysisComputer simulation model (Monte Carlo simulation, Markov model) with inputs derived from level II studies, relevant time horizon, less than lifetime, outcomes expressed in QALYs and uncertainty examined using stochastic multilevel sensitivity analysisDecision tree over the short time horizon with inputs data for original level-II and III studies and uncertainty as examined by univariate sensitivity analysisDecision tree over the short time horizon with inputs data informed by prior economic evaluation and uncertainty as examined by univariate sensitivity analysis1Level-I through IV studies may be graded downward on the basis of study quality, imprecision, indirectness, or inconsistency between studies or because the effect size is very small; these studies may be graded upward if there is a dramatic effect size. For example, a high-quality randomized controlled trial (RCT) should have >80% follow-up, blinding, and proper randomization. The Level of Evidence assigned to systematic reviews reflects the ranking of studies included in the review (i.e., a systematic review of Level-II studies is Level II). A complete assessment of the quality of individual studies requires critical appraisal of all aspects of study design.2Investigators formulated the study question before the first patient was enrolled.3In these studies, “cohort” refers to a nonrandomized comparative study. For therapeutic studies, patients treated one way (e.g., cemented hip prosthesis) are compared with those treated differently (e.g., cementless hip prosthesis).4Investigators formulated the study question after the first patient was enrolled.5Patients identified for the study on the basis of their outcome (e.g., failed total hip arthroplasty), called “cases,” are compared with those who did not have the outcome (e.g., successful total hip arthroplasty), called “controls.”6Sufficient numbers are required to rule out a common harm (affects >20% of participants). For long-term harms, follow-up duration must be sufficient.