A course held by Dr. P. Iannone, Emergency Department, Tigullio Hospital, Genova, Italy.
The Institute of Medicine (2011) defines guidelines as “statements that include recommendation intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options”. Since the 1970’s a growing number of organizations have employed various systems to grade the quality (level) of evidence and the strength of recommendations. Some grading approach consider the study design alone without include an explicit evaluation of other important factors which influence the quality of evidence. Some other systems are too complex. Unfortunately, different organisations use different systems to grade the quality of evidence and the strength of recommendations. The same evidence and recommendation could be graded as II-2, B; C+, 1; or strong evidence, strongly recommended depending on which system is used. This is confusing and impedes effective communication.
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group began in the year 2000 and has developed a common, sensible and transparent approach to grading the quality of evidence and strength of recommendations, in order to reduce unnecessary confusion arising from multiple systems for grading.
The advantages of GRADE over other systems are (Guyatt et al., 2008):
- Developed by a widely representative group of international guideline developers.
- Clear separation between quality of evidence and strength of recommendations.
- Explicit evaluation of the importance of outcomes of alternative management strategies.
- Explicit, comprehensive criteria for downgrading and upgrading quality of evidence ratings.
- Transparent process of moving from evidence to recommendations.
- Explicit acknowledgment of values and preferences.
- Clear, pragmatic interpretation of strong versus weak recommendations for clinicians, patients, and policy makers.
- Useful for systematic reviews and health technology assessments, as well as guidelines.
GRADE classifies the quality of evidence in one of four levels:
- High: We are very confident that the true effect lies close to that of the estimate of the effect;
- Moderate: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different;
- Low: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect;
- Very low: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
GRADE system defines the strength of a recommendation as the extent to which one can be confident that the desirable consequences of an intervention outweigh its undesirable consequences.
GRADE classifies recommendations as strong or weak. Strong recommendations mean that most informed patients would choose the recommended management and that clinicians can structure their interactions with patients accordingly. Weak recommendations mean that patients’ choices will vary according to their values and preferences, and clinicians must ensure that patients’ care is in keeping with their values and preferences.
GRADE’s primary criterion for judging precision is to focus on the 95% confidence interval (CI) around the difference in effect between intervention and control for each outcome.
GRADE requires a rating of confidence in effect estimates (quality of evidence) for each outcome. Guideline developers using GRADE will subsequently make an overall rating of confidence in effect estimates across all outcomes based on those outcomes they consider critical to their recommendation. In particular, the GRADE approach suggests that guideline developers should consider the quality of evidence across outcomes as that associated with the critical outcome with the lowest quality evidence.
GRADE has chosen a simple four-category classification of recommendations. Panel may make a strong or weak recommendation for (desirable outweighs undesirable) or against (undesirable outweighs desirable) an intervention. Using the GRADE approach, guideline authors make a strong recommendation when they believe that all or almost all informed people would make the recommended choice for or against an intervention. In contrast, guideline panels using GRADE make a weak recommendation when they believe that most informed people would choose the recommended course of action, but a substantial number would not.
In the GRADE approach, four factors influence the strength of recommendations:
- Magnitude of the difference between the desirable and undesirable consequences: if desirable consequences of following the recommendation clearly outweigh (or closely balanced) the undesirable consequences, it is more likely that the recommendation will be strong (or weak);
- Quality of the available supporting evidence: the higher the quality of evidence, the higher the likelihood that a strong recommendation is warranted (however this is not a rule);
- Certainty about values and preferences of patients: the greater the uncertainty in values and preferences, the higher the likelihood that a weak recommendation is warranted;
- The resource expenditure associated with the compared management options: the greater the resources consumed, the lower the likelihood that a strong recommendation is warranted.
Simona Arcuti works at the Casa Sollievo della Sofferenza, Department of Neurology, Giovanni Rotondo, Italy
