Level of Evidence

DEFINITIONS

THERAPEUTIC STUDIES investigate the results of treatment on patient outcomes and complications.

PROGNOSTIC STUDIES investigate the natural history of a disease or disorder, and they evaluate the effect of a patient characteristic on the outcome of the disease.

DIAGNOSTIC STUDIES evaluate the effectiveness of a diagnostic test or outcome instrument.

ECONOMIC/DECISION ANALYSIS OR MODELLING STUDIES explore costs and alternatives or may even develop or assess the effectiveness of decision models.

SYSTEMATIC REVIEWS AND META-ANALYSES are assigned a level of evidence equivalent to the lowest level of evidence used from the manuscripts analysed.

A PROSPECTIVE STUDY is defined as a study in which the research question was developed (and the statistical analysis for determining power was developed) before data were collected.

A RETROSPECTIVE STUDY is defined as a study in which the research question was determined after the data were collected (even for studies where the authors collected general data prospectively).

 

STUDY TYPE QUESTION LEVEL I LEVEL II LEVEL III LEVEL IV LEVEL V
DIAGNOSTIC Is this (early detection) test worthwhile?

 

Randomised controlled trial Prospective  cohort  study Retrospective cohort study Case series Mechanism-based reasoning
Is this diagnostic or monitoring test accurate? Testing of previously developed diagnostic criteria (consecutive patients with consistently applied reference standard and blinding) Development of diagnostic criteria (consecutive patients with consistently applied reference standard and blinding Case-control  study

Non-consecutive patients

No consistently applied reference standard

Poor or non-independent reference standard  Mechanism-based reasoning
PROGNOSTIC What is the natural history of the condition? Inception cohort study (all patients enrolled at an early, uniform point in the course of their disease) Prospectivecohort study (patients enrolled at different points in their disease)

Control arm of randomized trial

Retrospective cohortstudy

 

Case-control  study

Case series Mechanism-based reasoning
THERAPEUTIC Does this treatment help? What are the harms?7 Randomised controlled trial Prospectivecohort  study

Observational study with dramatic effect

Retrospectivecohort study

Case-control study

Case series

Historically controlled study

Mechanism-based reasoning
ECONOMIC Does the intervention offer good value for € 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 years (QALYs) and uncertainty examined using probabilistic sensitivity analyses Computer simulation model (Monte Carlo simulation, Markov model) with inputs derived from Level-II studies, lifetime time duration, outcomes expressed in dollars per QALYs and uncertainty examined using probabilistic sensitivity analyses Computer simulation model (Markov model) with inputs derived from Level-II studies, relevant time horizon, less than lifetime, outcomes expressed in dollars per QALYs and stochastic multilevel sensitivity analyses Decision tree over the short time horizon with input data from original Level-II and III studies and uncertainty is examined by univariate sensitivity analyses Decision tree over the short time horizon with input data informed by prior economic evaluation and uncertainty is examined by univariate sensitivity analyses