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Clinical evidence

– not all evidence is created equal

Scientific research and clinical evidence on probiotcs
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Levels of evidence

The quality of scientific evidence is typically dependent on the study design that was implemented. Thus, study designs are ranked based on the quality of data that can be obtained, i.e. ‘levels of evidence’.1

Many different models of evidence hierarchy exist.2 Evidence from higher up the hierarchy is not necessarily high-quality, for instance, a randomized controlled trial (RCT) may not have been conducted, or reported, optimally. The RCT design is not applicable in all situations, such as in providing evidence in the contexts of surgery, prognosis of a disease, or in some public health contexts (due to the ethical implications), therefore, study designs further down the evidence hierarchy are not automatically inferior.2, 3

Grading the level of quality

The Oxford Centre for Evidence-Based Medicine

The evidence hierarchy from the Centre for Evidence-Based Medicine acknowledges that, in addition to study design, the quality of data must be considered, for example, it classifies a poorly designed randomized controlled trial as providing the same level of evidence as a cohort study.2, 4

Grading systems for assessing the quality of evidence

Therefore, it is not enough to rely on study design when weighting quantitative studies; it is also important to assess the quality of the evidence at each level of the given hierarchy. Several systems exist to aid with grading the quality of evidence and for making recommendations and deciding on clinical practice.2

GRADE (Grading of Recommendations, Assessment, Development and Evaluations) is a transparent framework for developing and presenting summaries of evidence and provides a systematic approach for grading quality of evidence and making clinical practice recommendations.5, 6, 7 GRADE is used to rate the body of evidence at the outcome level rather than the study level and provides a reproducible and transparent framework for grading certainty in evidence.8 The system is employed by Cochrane Reviews.

To read more about grading systems and how they have been used to assess evidence in the field of probiotics, click here.

Be confident when making recommendations

When reviewing scientific and clinical evidence, the level of the evidence is important, and, typically, randomized controlled trials and meta-analyses provide the best evidence.

As an RCT is the more rigorous scientific method for evaluating the effectiveness of health care interventions, it is generally recommended that HCPs only advise patients on products that are supported by evidence obtained from RCTs. It is important to remember that not all Level 4 evidence should be ignored and not all Level 1 evidence should be accepted as fact. The levels of evidence provide a guide, and the reader needs to be cautious when interpreting these results.2

Levels of evidence within probiotics

Level 1

Randomized controlled trials are experimental studies that compare groups to establish the effectiveness or efficacy of a specific intervention. RCTs involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups. The treatments to be administered are selected by a random process.

Systematic reviews combine evidence from relevant RCT studies. Extracted data from all of the included studies are combined to develop a broader picture of the evidence.

Meta-analyses are systematic reviews that use quantitative methods to summarize the results.


Level 2

Cohort studies are observational studies that identify participants who are exposed (or not exposed) to a particular risk factor. Participants are then followed forward in time to determine if they develop the disease under investigation.

Systematic reviews combine evidence from relevant cohort studies. Extracted data from all of the included studies are combined to develop a broader picture of the evidence. In Level 2, low quality RCTs are also included.


Level 3

Case-control studies are studies in which patients with a certain outcome or disease and an appropriate, often matched, group of controls without the outcome or disease are selected and then information is obtained on whether the subjects have been exposed to the factor under investigation.

Systematic reviews combine evidence from relevant case-control studies. Extracted data from all of the included studies are combined to develop a broader picture of the evidence.


Level 4

Case series are studies that tracks participants with a known exposure, such as participants who have received a similar treatment. In Level 4, low-quality cohort and case-control studies are also included.


Level 5

Expert opinions are views or interpretations without explicit critical appraisal, and are not based on physiology, bench research or “first principles”.


The article is provided for informational purposes regarding probiotics and is not meant to suggest that any substance referenced in the article is intended to diagnose, cure, mitigate, treat, or prevent any disease.

Reference list

1. National Cancer Institute. NCI Dictionary of Cancer Terms: Levels of evidence. US DHHS-National Institutes of Health.
2. Burns PB, et al. The levels of evidence and their role in evidence-based medicine. Plast Reconstr Surg. 2011;128(1):305-10. (PubMed)
3. West SG, et al. Alternatives to the randomized controlled trial. Am J Public Health. 2008;98(8):1359-66. (PubMed)
4. OCEBM Levels of Evidence Working Group. The Oxford 2011 Levels of Evidence. Oxford Centre for Evidence-Based Medicine; 2011.
5. Guyatt G, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383-94. (PubMed)
6. Guyatt GH, et al. What is "quality of evidence" and why is it important to clinicians? BMJ. 2008;336(7651):995-8. (PubMed)
7. Guyatt GH, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-6. (PubMed)
8. Mustafa RA, et al. The GRADE approach is reproducible in assessing the quality of evidence of quantitative evidence syntheses. J Clin Epidemiol. 2013;66(7):736-42; quiz 42.e1-5. (PubMed)

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