41. LEVELS OF EVIDENCE

Question 1

1. What are the Levels of Evidence based on?

Answer 1

• they are based on the Oxford Center for Evidence
  based Medicine (2009)
• there is no gold standard rule on the levels of evidence
• they are changed and revised over time
• other organisations have slightly different levels

Question 2

2. What are the Levels?

Answer 2

1a
1b
1c
2a
2b
3a
3b
4
5

NB:
- the strongest and most reliable studies are the at the
top of the list

Question 3

3. What is the type of study related with:
   Evidence Level 1a?

Answer 3

• Systematic Reviews and Meta-Analysis
• of Randomised Controlled Trials (RCT)

Question 4

4. What are the strengths related with:
   Evidence Level 1a?

Answer 4

1. IT IS AN INTERVENTIONAL STUDY
   - this means that the exposure is assigned to the
   participants
   - the exposure is not assessed
2. IT HAS HIGH INTERNAL VALIDITY
   
   • very low Random Error
   • very low Bias and Confounding
3. IT HAS HIGH EXTERNAL VALIDITY
   
   • this is assuming that the samples are representative
   • and that there are no drop outs
4. IT CAN PROVE TEMPORALITY IS ASSOCIATIONS
5. IT IS THE STRONGEST EVIDENCE
   - that proves that an exposure causes an outcome

Question 5

5. What are the Limitations related with:
   Evidence Level 1a?

Answer 5

1. IT DEPENDS ON THE QUALITY OF THE INCLUDED
   STUDIES
   - if the original studies are poorly conducted
   - this cannot be fixed

Question 6

6. What is the type of study related with:
   Evidence Level 1b?

Answer 6

• High Quality Randomised Controlled Trials
• that are individual studies

THESE STUDIES:
- have narrow confidence intervals
- they have a low drop out rate
- random allocation takes place

Question 7

7. What are the strengths related with:
   Evidence Level 1b?

Answer 7

1. IT IS AN INTERVENTIONAL STUDY
   - this means that the exposure is assigned to the
   participants
   - the exposure is not assessed
2. IT HAS HIGH INTERNAL VALIDITY
   
   • very low Random Error
   • very low Bias and Confounding
3. IT CAN PROVE TEMPORALITY IS ASSOCIATIONS
4. IT IS A STUDY THAT CAN INFER CAUSALITY
   - this proves that an exposure causes an outcome
   - but this has to be assumed with caution
   - since we are only looking at a single study

Question 8

8. What are the Limitations related with:
   Evidence Level 1b?

Answer 8

• this is only a single study
• the External Validity could be low
• this is definitely the case if the study sample is too
  specific
• this means that it will not be representative

Question 9

9. What type of study is related with:
   Evidence Level 1c?

Answer 9

• high quality studies
• they are not randomised
• they are not controlled
• they are individual studies

THESE STUDIES HAVE:
- a low drop out rate
- a narrow confidence interval

Question 10

10. What are the strengths related with:
    Evidence Level 1c?

Answer 10

1. IT IS AN INTERVENTIONAL STUDY
   - this means that the exposure is assigned to the
   participants
   - the exposure is not assessed
2. IT HAS MODERATE INTERNAL VALIDITY
   
   • it has a lower bias than in Observational Studies
3. IT CAN PROVE TEMPORALITY IS ASSOCIATIONS

Question 11

11. What are the limitations related with:
    Evidence Level 1c?

Answer 11

1. IT IS PRONE TO CONFOUNDING
   - this is because of the lack of Randomisation
2. THE EXTERNAL VALIDITY IS LOW
   • since we are dealing with a single study
   • the study can be too specific
   • this means that it is not representative

Question 12

12. What is the type of study related with:
    Evidence Level 2a?

Answer 12

• Systematic reviews and Meta-Analysis
• of Cohort Studies

Question 13

13. What are the strengths related with:
    Evidence Level 2a?

Answer 13

1. IT HAS AN ACCEPTABLE INTERNAL VALIDITY
   
   • very large sample
   • low Random error
2. IT CAN PROVE TEMPORALITY IS ASSOCIATIONS
3. HIGH EXTERNAL VALIDITY
   - only if we assume that the samples are representative

Question 14

14. What are the limitations related with:
    Evidence Level 2a?

Answer 14

1. PRONE TO BIAS AND CONFOUNDING
   
   • this is because of the Methodological limitations
   • the study is observational
2. CAUSALITY CAN NOT BE INFERRED
   - we can not state that the outcome is caused by the
   Exposure

Question 15

15. What is the type of study related with:
    Evidence Level 2b?

Answer 15

1. These studies can be high quality Cohort studies
   
   • these studies are individual

THESE STUDIES:
- have narrow confidence intervals
- they have low drop out rates
- they have accurate assessments
- they are adjusted for confounding

2. These studies can be low Quality Randomised Control
   Trials (RCTs)
   
   • they are individual studies

THESE STUDIES HAVE:
- wide confidence intervals
- they have a high drop out rate
- random allocation is not maintained

Question 16

16. What are the strengths related with:
    Evidence Level 2b?

Answer 16

1. IT HAS AN ACCEPTABLE INTERNAL VALIDITY
   
   • the sample is large
   • random error is low
   • this applies only for the Cohort Studies
2. IT CAN PROVE TEMPORALITY IS ASSOCIATIONS

Question 17

17. What are the limitations related with:
    Evidence Level 2b?

Answer 17

1. IT IS PRONE TO BIAS AND CONFOUNDING
   
   • this is due to the methodological limitations
     of the included studies
2. CAUSALITY CAN NOT BE INFERRED
   - we can not state that the outcome is caused by the
   exposure

Question 18

18. What type of study is related with:
    Evidence Level 3a?

Answer 18

• Systematic Reviews and Meta-Analysis
• of Case-Control studies

Question 19

19. What are the strengths related with:
    Evidence Level 3a?

Answer 19

1. A VERY LARGE SAMPLE IS USED
   - the Random Error is low
2. IT HAS HIGH EXTERNAL VALIDITY
   • assuming that the sample is representative

Question 20

20. What are the limitations related with:
    Evidence Level 3a?

Answer 20

1. LOW INTERNAL VALIDITY
   - there is Bias present
   - there is Confounding
2. CANNOT PROVE TEMPORALITY IN ASSOCIATIONS
3. CAUSALITY CANNOT BE INFERRED
   - we cannot state that the outcome is caused by the
   exposure

Question 21

21. What type of study is related with:
    Evidence Level 3b?

Answer 21

• high quality Case Control studies
• they are individual cases

THESE STUDIES HAVE:
- narrow confidence intervals
- accurate assessments
- no serious recall bias
- adjustments for Confounding

Question 22

22. What are the strengths related with:
    Evidence Level 3b?

Answer 22

1. THE SAMPLE IS LARGE
   - random error is low

Question 23

23. What are the limitations related with:
    Evidence Level 3b?

Answer 23

1. LOW INTERNAL VALIDITY
   - there is bias present
   - there is Confounding
2. CANNOT PROVE TEMPORALITY IN ASSOCIATIONS
3. CAUSALITY CANNOT BE INFERRED
   - cannot state that the outcome is caused by the
   exposure

Question 24

24. What type of study is related with:
    Evidence Level 4?

Answer 24

1. CASE-SERIES
   - this is the follow-up of patients that receive specific
   treatments
   - we look at their prognosis
2. CROSS-SECTIONAL STUDIES
3. LOW QUALITY COHORT AND CASE-CONTROL STUDIES
   - they have a wide confidence interval
   - they have a high bias
   - they are affected by Confounding

Question 25

25. What are the strengths related with: Evidence Level 4?

Answer 25

1. IT IS EASY TO CONDUCT 2. IT IS CHEAP 3. IT CAN GENERATE A HYPOTHESES - this can be used for further and higher quality research

Question 26

26. What are the limitations related with: Evidence Level 4?

Answer 26

1. IT HAS A VERY LOW INTERNAL VALIDITY - random error - bias - confounding 2. IT CANNOT PROVE TEMPORALITY IN ASSOCIATIONS - except for Cohort studies 3. CAUSALITY CANNOT BE INFERRED - we cannot state that the outcome is caused by the exposure 4. THE EXTERNAL VALIDITY IS LOW

Question 27

27. What types of studies are related with: Evidence Level 5?

Answer 27

1. INDIVIDUAL EXPERT OPINIONS AND REPORTS 2. EXPERT COMMITTEE OPINIONS AND REPORTS 3. CLINICAL EXPERIENCES OF RESPECTED AUTHORITIES

Question 28

28. What are the strengths related with: Evidence Level 5?

Answer 28

1. VERY EAST TO CONDUCT 2. CHEAP TO CONDUCT 3. CAN GENERATE A HYPOTHESIS - that can be used for higher quality research

Question 29

29. What are the limitations related with: Evidence Level 5?

Answer 29

1. DO NOT QUALIFY AS SCIENTIFIC RESEARCH 2. NOT BASED ON EMPIRICAL RESEARCH FINDINGS - it is just based on clinical observations 3. THE INTERNAL VALIDITY IS EXTREMELY LOW 4. THE EXTERNAL VALIDITY IS EXTREMELY LOW 5. CANNOT INFER CAUSALITY AT ALL - we cannot state that the outcome is a result of the exposure

Question 30

30. What are the four factors that determine the Strength of Recommendation?

Answer 30

1. The Quality of Evidence 2. The balance between the desirable and undesirable effects 3. Values and preferences - such as the patients, the professionals, the paymasters and the public 4. Cost - how the available resources are utilised

Question 31

31. Does strong level evidence always mean strong recommendations?

Answer 31

- no

Question 32

32. What can be said about RCT results and Observational Study results?

Answer 32

- always believe the RCT results

Question 33

33. What do we use the "GRADE" guidelines to establish?

Answer 33

- we use them to establish the Quality of Evidence - it grades the strength of recoomendations

Question 34

34. What do the "GRADE" guidelines analyse?

Answer 34

1. IMPRECISION - this is done by using the 95% Confidence Interval 2. LIMITATIONS IN THE STUDY DESIGN (BIAS): - this looks at the quality 3. INCONSISTENCY OF RESULTS - this looks at the Heterogeneity 4. PUBLICATION BIAS - this looks at the Publication Bias 5. INDIRECTNESS OF EVIDENCE - this looks at the generalisability of the data

Question 35

35. Why do we rate the Certainty in the Evidence and the Strength of the Recommendations?

Answer 35

1. IT HELPS US TO JUDGE THE EVIDENCE - and the recommendations in Healthcare 2. CLINICAL ACTIONS - are likely to differ - this depends on whether one concludes that the evidence is high or low 3. TO DECIDE WHETHER THE HEALTH BENEFITS - are worth the additional costs 4. HELPS TO IMPROVE COMMUNICATION - of the practice guidelines

Question 36

36. What kind of studies are given a High Quality Rating based on the GRADE System?

Answer 36

- Randomised Trials (RCT) - Double Upgraded Observational Studies

Question 37

37. What kind of studies are given a Moderate Quality Rating based on the GRADE System?

Answer 37

- Downgraded Randomised Trials (RCT) - Upgraded Observational Studies

Question 38

38. What kind of studies are given a Low Quality Rating based on the GRADE System?

Answer 38

- Double Downgraded Randomised Trials (RCT) - Observational Studies

Question 39

39. What kind of studies are given a Very Low Quality Rating based on the GRADE System?

Answer 39

- Triple Downgraded Randomised Trials (RCT) - Downgraded Observational Studies - Case Series - Case Reports

Question 40

40. What are factors that can decrease the Quality level of data evidence?

Answer 40

1. Limitations in the design 2. Limitations in the implementation of the studies 3. Bias 4. Indirect Population 5. Indirect Intervention 6. Indirect Control 7. Indirect Outcomes 8. Unexplained Heterogeneity 9. Inconsistency of Results 10. Problems with subgroup analyses 11. Imprecision of Results 12. Wide Confidence Intervals 13. High probability of Publication Results

Question 41

41. What are factors that can increase the Quality Level of data evidence?

Answer 41

1. Large Magnitude of Effect 2. All possible confounding is adjusted for 3. There is a dose-response gradient