Levels of Evidence
Levels of evidence (or hierarchy of evidence) is a system used to rank medical studies based on the quality and reliability of their design. Levels of evidence are commonly depicted in a pyramid model that illustrates both the quality and quantity of available evidence. The higher the position on the pyramid, the stronger the evidence.1 Each level draws on data and research previously developed in lower tiers.
Levels of evidence pyramids are often divided into two or three sections. The top section comprises filtered (secondary) evidence, including systematic reviews, meta-analyses, and critical appraisals. The section below includes unfiltered (primary) evidence, including randomized controlled trials, cohort studies, and case reports.1 Some models include an additional bottom segment for background information and expert opinion.
Systematic Review and Meta-Analysis
A systematic review synthesizes the results from all available studies of a particular health topic, answering a specific research question by collecting and evaluating all research evidence that fits the review’s selection criteria.2 The most well-known collection of systematic reviews is the Cochrane Database of Systematic Reviews.
Systematic reviews can include meta-analyses in which statistical methods are applied to evaluate and synthesize quantitative results from multiple studies.
Randomized Controlled Trial (RCT)
A randomized controlled trial (RCT) is a prospective study that measures the efficacy of an intervention or treatment. Subjects are randomly assigned to either an experimental or control group; the control group receives a placebo or sham intervention, while the experimental group receives the intervention being studied. Randomizing subjects is effective at removing bias, thus increasing the validity of the research. RCTs are frequently blinded so that neither the subjects (single blind), nor clinicians (double blind), nor the researchers (triple blind) know in which group the subjects are placed.3
A cohort study is a type of observational study, meaning no intervention is taken among the subjects. It is also a type of longitudinal study in which research subjects are followed over a period of time.4 A cohort study can be either prospective, which collects new data over time, or retrospective, which uses previously acquired data or medical records. This type of study examines a group of people who share a common trait or exposure and are assessed based on whether they develop an outcome of interest. An example of a prospective cohort study is a study that observes whether the subjects smoke and then many years later assesses the incidence of lung cancer in both smokers and non-smokers.
A case-control study is another type of observational study. It is also a type of retrospective study, which looks backwards in time to assess information. A case-control study compares people who have the specified condition or outcome being studied (known as the “cases”) with people who do not have the condition or outcome (known as the “controls”).5 An example of a case-control study is a study that assesses the lifetime smoking exposure of patients with and without lung cancer.
Case Series and Reports
A case report is a detailed report of the diagnosis, treatment, response to treatment, and follow-up after treatment of an individual patient. A case series is a group of case reports involving patients who were given similar treatment. A case series is observational and can be conducted either retrospectively or prospectively.
Also called a prevalence study, a cross-sectional study examines subjects at a single point in time. By definition, a cross-sectional study is only observational.6 An example of a cross-sectional study is a survey of a population to determine the prevalence of lung cancer.
Filtered vs. Unfiltered Information
Filtered (secondary) levels of evidence is information that has been previously collected and aggregated by expert analysis and review. Filtered levels of evidence are placed above unfiltered levels of evidence on the pyramid. Examples of filtered levels are meta-analyses and systematic reviews.
Unfiltered (primary) evidence includes original research studies, including randomized controlled trials (RCTs) and case-control studies. They are often published in peer-reviewed journals.7 However, these studies have not been subjected to additional analysis and review beyond that of the peer reviewers for each study. In most cases, unfiltered levels of evidence are difficult to apply in clinical decision-making.8
In 1972, Archibald Cochrane, a physician from Scotland, wrote Effectiveness and Efficiency, in which he argued that decisions about medical treatment should be based on a systematic review of clinical evidence. Cochrane proposed an international collaboration of researchers to systematically review the best clinical studies in each specialty.9
In 1979, the Canadian Task Force on the Periodic Health Examination published a ranking system for medical evidence, proposing four quality levels:10,11
- I: Evidence obtained from at least one properly randomized controlled trial
- II-1: Evidence obtained from a well-designed cohort or case-control analytic studies, preferably from more than one center or research group.
- II-2: Evidence obtained from comparisons between times or places with or without the intervention.
- III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
These levels were used to assign an alphabetic grade to the strength of individual recommendations or interventions. The U.S. Preventive Services Task Force (USPSTF) adopted a modified version of the Canadian Task Force’s categorization in 1988:12,13
- I: Evidence obtained from at least one properly designed randomized controlled trial.
- II-1: Evidence obtained from well-designed controlled trials without randomization.
- II-2: Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group.
- II-3: Evidence obtained from multiple time series designs with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.
- Level III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
The physician Gordon Guyatt, who in 1991 coined the term “evidence-based medicine,” proposed another approach to classifying the strength of recommendations for use in evidence-based-medicine.14 In "Users' Guides to the Medical Literature," Guyatt expanded the Canadian Task Force’s categorization to account for new systematic procedures for combining results from different studies.15 Referencing Guyatt’s paper, Trisha Greenhalgh summarized his revised hierarchy as follows:16
- Systematic reviews and meta-analyses
- Randomized controlled trials with definitive results (confidence intervals that do not overlap the threshold of clinically significant effect)
- Randomized controlled trials with non-definitive results (a point estimate that suggests a clinically significant effect but with confidence intervals overlapping the threshold for this effect)
- Cohort studies
- Case-control studies
- Cross sectional surveys
- Case reports
Evidence level definitions can vary based on the clinical question being asked (i.e. the categorization of evidence for a medical treatment may differ from evidence for determining disease prevalence). For example, The Centre for Evidence-Based Medicine and American Society of Plastic Surgeons published tables specific to therapeutic, diagnostic, and prognostic studies.17,18
- Hassan Murad, M.; Asi, N.; Alsawas, M.; Alahdab, F. “New evidence pyramid.” BMJ Evidence Based Medicine, 21(4) (2016): 125-127.
- University of Canberra Library. “Evidence-Based Practice in Health.” (2020, last update.)
- Hariton, E.; Locascio, J.J. “Randomised controlled trials—The gold standard for effectiveness research.” BJOG: An International Journal of Obstetrics and Gynaecology, 125(13) (2018): 1716.
- Barrett, D.; Noble, H. “What are cohort studies?” Evidence Based Nursing, BMJ, 22(4) (2019): 95-96.
- Himmelfarb Health Sciences Library. “Study design 101: Case control study.” (2019).
- Singh Setia, M. “Methodology Series Module 3: Cross-sectional Studies.” Indian Journal of Dermatology, 61(3) (2016): 261-264.
- Northern Virginia Community College. “Evidence-based practice for health professionals.” (2021, last update).
- Kendall, S. “Evidence-based resources simplified.” Canadian Family Physician, 54(2) (2008): 241-243.
- Stavrou, A.; Challoumas, D.; Dimitrakakis, G. “Archibald Cochrane (1909–1988): the father of evidence-based medicine.” Interactive Cardiovascular and Thoracic Surgery, 18(1) (2014): 121-124.
- Spitzer, W. et al. The periodic health examination. Canadian Task Force on the Periodic Health Examination. (1979). Canadian Medical Association journal, 121(9), 1193–1254.
- Burns, P. B. ; Rohrich, R. J.; Chung, K. C. “The Levels of Evidence and their Role in Evidence-Based Medicine.” Plastic and Reconstructive Surgery, 128(1) (2010): 305-310.
- U.S. Preventive Services Task Force. (2018, current as of). “Grade definitions.”
- U.S. Preventive Services Task Force. Guide to Clinical Preventive Services: Report of the U.S. Preventive Services Task Force. DIANE Publishing, 1989. ISBN 1568062974.
- Guyatt, G. H.; Sackett, D. L.; Sinclair, J. C.; Hayward, R.; Cook, D. J.; Cook, R. J. "Users’ guides to the medical literature IX. A method for grading health care recommendations." JAMA, 274 (22) (1995): 1800-1804.
- Zimerman, A. L. “Evidence-Based Medicine: A Short History of a Modern Medical Movement.” AMA Journal of Ethics, 15(1) (2013): 71-76.
- Greenhalgh T. How to read a paper. Getting your bearings (deciding what the paper is about). BMJ. 1997;315(7102):243-246. doi:10.1136/bmj.315.7102.243
- Sullivan D, Chung KC, Eaves FF 3rd, Rohrich RJ. The level of evidence pyramid: indicating levels of evidence in Plastic and Reconstructive Surgery articles. Plast Reconstr Surg. 2011 Jul;128(1):311-314. doi:10.1097/PRS.0b013e3182195826. PMID: 21701349.
- Oxford Centre for Evidence-Based Medicine: Levels of Evidence. March 2009. CEBM.
Moira Tannenbaum, MSN; Stacy Sebastian, MD
Published: August 17, 2021