This document discusses evidence-based dentistry and randomized controlled trials (RCTs) in orthodontics. It defines evidence-based dentistry as integrating systematic assessments of scientific evidence with clinical expertise and patient preferences. RCTs are described as the gold standard for testing hypotheses as they minimize bias through randomization and blinding. However, RCTs can be challenging to conduct in orthodontics due to long treatment times and variability between patients. Recommendations for improving RCT quality include clearly defining the research question, proper randomization, sufficient sample sizes, and using valid and reliable methods.
4. Evidence-based Dentistry
ADA Definition - an approach to oral health care that requires
the judicious integration of systematic assessments of clinically
relevant scientific evidence, relating to the patient's oral and
medical condition and history, with the dentist's clinical
expertise and the patient's treatment needs and preference
6. Why is evidence-based dentistry
important?
To improve quality of health-care delivery
7. Why is evidence-based dentistry
important?
To improve quality of health-care delivery
By incorporating effective practices
8. Why is evidence-based dentistry
important?
To improve quality of health-care delivery
By incorporating effective practices
While eliminating those that are ineffective or inappropriate
10. The five steps of evidence-based
dentistry practice
1. Developing a clear, clinically focused
question
11. The five steps of evidence-based
dentistry practice
1. Developing a clear, clinically focused
question
2. Identifying, summarizing, and
synthesizing all relevant studies that
directly answer the formulated question
12. The five steps of evidence-based
dentistry practice
1. Developing a clear, clinically focused
question
2. Identifying, summarizing, and
synthesizing all relevant studies that
directly answer the formulated question
3. Appraising evidence in terms of validity
and applicability
13. The five steps of evidence-based
dentistry practice
1. Developing a clear, clinically focused
question
2. Identifying, summarizing, and
synthesizing all relevant studies that
directly answer the formulated question
3. Appraising evidence in terms of validity
and applicability
4. Combining research evidence with
clinical expertise and patients
characteristics
14. The five steps of evidence-based
dentistry practice
1. Developing a clear, clinically focused
question
2. Identifying, summarizing, and
synthesizing all relevant studies that
directly answer the formulated question
3. Appraising evidence in terms of validity
and applicability
4. Combining research evidence with
clinical expertise and patients
characteristics
5. Assessing the successful
implementation of previous steps
15.
16. Level Evidence
1++ High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
1- Meta-analyses, systematic reviews or RCTs, or RCTs with a high risk of bias
2++
High-quality systematic reviews of case-control or cohort studies or high-quality case-control or
cohort studies with a very low risk of confounding, bias, or chance and a high probability that
the relationship is causal
2+
Well-conducted case-control or cohort studies with a low risk of confounding, bias, or chance
and a moderate probability that the relationship is causal
2-
Case-control or cohort studies with a high risk of confounding, bias, or chance and a significant
risk that the relationship is not causal
3 Non-analytic studies, e.g., case reports, case series
4 Expert opinion
Scottish Intercollegiate Guidelines Network (SIGN)
Revised grading system for recommendations in
evidence-based guidelines
17. Level Evidence
1++ High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
1- Meta-analyses, systematic reviews or RCTs, or RCTs with a high risk of bias
2++
High-quality systematic reviews of case-control or cohort studies or high-quality case-control or
cohort studies with a very low risk of confounding, bias, or chance and a high probability that
the relationship is causal
2+
Well-conducted case-control or cohort studies with a low risk of confounding, bias, or chance
and a moderate probability that the relationship is causal
2-
Case-control or cohort studies with a high risk of confounding, bias, or chance and a significant
risk that the relationship is not causal
3 Non-analytic studies, e.g., case reports, case series
4 Expert opinion
Scottish Intercollegiate Guidelines Network (SIGN)
Revised grading system for recommendations in
evidence-based guidelines
18. Level Evidence
1++ High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
1- Meta-analyses, systematic reviews or RCTs, or RCTs with a high risk of bias
2++
High-quality systematic reviews of case-control or cohort studies or high-quality case-control or
cohort studies with a very low risk of confounding, bias, or chance and a high probability that
the relationship is causal
2+
Well-conducted case-control or cohort studies with a low risk of confounding, bias, or chance
and a moderate probability that the relationship is causal
2-
Case-control or cohort studies with a high risk of confounding, bias, or chance and a significant
risk that the relationship is not causal
3 Non-analytic studies, e.g., case reports, case series
4 Expert opinion
Scottish Intercollegiate Guidelines Network (SIGN)
Revised grading system for recommendations in
evidence-based guidelines
19. Level Evidence
1++ High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
1- Meta-analyses, systematic reviews or RCTs, or RCTs with a high risk of bias
2++
High-quality systematic reviews of case-control or cohort studies or high-quality case-control or
cohort studies with a very low risk of confounding, bias, or chance and a high probability that
the relationship is causal
2+
Well-conducted case-control or cohort studies with a low risk of confounding, bias, or chance
and a moderate probability that the relationship is causal
2-
Case-control or cohort studies with a high risk of confounding, bias, or chance and a significant
risk that the relationship is not causal
3 Non-analytic studies, e.g., case reports, case series
4 Expert opinion
Scottish Intercollegiate Guidelines Network (SIGN)
Revised grading system for recommendations in
evidence-based guidelines
22. Features of RCT’s
Rarticipants are randomly assigned
Comparative - Treatment group compared with
control group with similar characteristics
23. Features of RCT’s
Rarticipants are randomly assigned
Comparative - Treatment group compared with
control group with similar characteristics
Allocation concealment
24. Features of RCT’s
Rarticipants are randomly assigned
Comparative - Treatment group compared with
control group with similar characteristics
Allocation concealment
Blinding
25. Features of RCT’s
Rarticipants are randomly assigned
Comparative - Treatment group compared with
control group with similar characteristics
Allocation concealment
Blinding
Is the most scientifically rigorous method of
hypothesis testing gold standard
26. Bias in RCT’s
Type of bias Prevention / elimination of bias
Selection bias Proper randomization
Performance bias
Blinding of participants and people
administering treatment
Detection bias Blinding of outcome assessors/analyzers
Attrition bias Intention-to-treat analysis
Publication bias Trial registration, no selective reporting
27. Bias in RCT’s
Type of bias Prevention / elimination of bias
Selection bias Proper randomization
Performance bias
Blinding of participants and people
administering treatment
Detection bias Blinding of outcome assessors/analyzers
Attrition bias Intention-to-treat analysis
Publication bias Trial registration, no selective reporting
28. Bias in RCT’s
Type of bias Prevention / elimination of bias
Selection bias Proper randomization
Performance bias
Blinding of participants and people
administering treatment
Detection bias Blinding of outcome assessors/analyzers
Attrition bias Intention-to-treat analysis
Publication bias Trial registration, no selective reporting
29. Bias in RCT’s
Type of bias Prevention / elimination of bias
Selection bias Proper randomization
Performance bias
Blinding of participants and people
administering treatment
Detection bias Blinding of outcome assessors/analyzers
Attrition bias Intention-to-treat analysis
Publication bias Trial registration, no selective reporting
30. Bias in RCT’s
Type of bias Prevention / elimination of bias
Selection bias Proper randomization
Performance bias
Blinding of participants and people
administering treatment
Detection bias Blinding of outcome assessors/analyzers
Attrition bias Intention-to-treat analysis
Publication bias Trial registration, no selective reporting
31. Bias in RCT’s
Type of bias Prevention / elimination of bias
Selection bias Proper randomization
Performance bias
Blinding of participants and people
administering treatment
Detection bias Blinding of outcome assessors/analyzers
Attrition bias Intention-to-treat analysis
Publication bias Trial registration, no selective reporting
34. Systematic Review
A research article that,
o Identify relevant studies
o Appraises their quality
35. Systematic Review
A research article that,
o Identify relevant studies
o Appraises their quality
o Summarizes their results
using scientific methodology
37. Meta-analysis
The use of statistical techniques to combine the results of studies
addressing the same question into a summary measure
Systematic
Review Systematic ReviewMeta-Analysis
38. Meta-analysis
The use of statistical techniques to combine the results of studies
addressing the same question into a summary measure
Increases the size of the `overall sample’ enhances statistical power
Systematic
Review Systematic ReviewMeta-Analysis
39. Meta-analysis
The use of statistical techniques to combine the results of studies
addressing the same question into a summary measure
Increases the size of the `overall sample’ enhances statistical power
Quantitative synthesis only when the studies to be combined are
clinically and statistically homogeneous
Systematic
Review Systematic ReviewMeta-Analysis
40. Meta-analysis
The use of statistical techniques to combine the results of studies
addressing the same question into a summary measure
Increases the size of the `overall sample’ enhances statistical power
Quantitative synthesis only when the studies to be combined are
clinically and statistically homogeneous
Systematic Review ≠ Meta-Analysis
Systematic
Review Systematic ReviewMeta-Analysis
49. What are Cochrane reviews?
The Cochrane Collaboration is an international
organization that aims to organize medical research
information in a systematic way promoting the
accessibility of systematic reviews of the effects of health-
care interventions
50. What are Cochrane reviews?
The Cochrane Collaboration is an international
organization that aims to organize medical research
information in a systematic way promoting the
accessibility of systematic reviews of the effects of health-
care interventions
Systematic reviews of primary research in human health
care and health policy, undertaken by members of The
Cochrane Collaboration adhering to a specific
methodology
53. This article is the result of a debate at the European Journal of
Orthodontics Open Session in 2013 in Reykjavik, Iceland
54. Part I: RCTs are for orthodontics
Lars Bondemark
55. Part I: RCTs are for orthodontics
The first published RCT 1948 ‘Streptomycin treatment
of pulmonary tuberculosis’
Lars Bondemark
56. Part I: RCTs are for orthodontics
The first published RCT 1948 ‘Streptomycin treatment
of pulmonary tuberculosis’
Orthodontic RCTs per year between 1990 and 2013
Lars Bondemark
58. Randomization
Ensures both known and unknown
determinants are evenly distributed
among the different study groups
59. Randomization
Ensures both known and unknown
determinants are evenly distributed
among the different study groups
Minimizes bias in assessment of
differences in effects between two
or more treatment alternatives
Confounding factors equally
distributed
60. Randomization
Ensures both known and unknown
determinants are evenly distributed
among the different study groups
Minimizes bias in assessment of
differences in effects between two
or more treatment alternatives
Confounding factors equally
distributed
Idea with randomization is that the
treatment will be the only thing that
will constitute a significant
difference between the patient
groups
61. Randomization
Ensures both known and unknown
determinants are evenly distributed
among the different study groups
Minimizes bias in assessment of
differences in effects between two
or more treatment alternatives
Confounding factors equally
distributed
Idea with randomization is that the
treatment will be the only thing that
will constitute a significant
difference between the patient
groups
Best if done by an independent
person
65. Recommendations
Create a relevant question use PICO
• P - population
• I - intervention
• C - control
• O - outcome
66. Recommendations
Create a relevant question use PICO
• P - population
• I - intervention
• C - control
• O - outcome
e.g. Is Quad-helix treatment (intervention) more cost-effective (outcome) than platal
expansion (control) in 8–10 year-old patients with unilateral posterior crossbite
(population)?
67. Recommendations
Create a relevant question use PICO
• P - population
• I - intervention
• C - control
• O - outcome
e.g. Is Quad-helix treatment (intervention) more cost-effective (outcome) than platal
expansion (control) in 8–10 year-old patients with unilateral posterior crossbite
(population)?
Use proper randomization
68. Recommendations
Create a relevant question use PICO
• P - population
• I - intervention
• C - control
• O - outcome
e.g. Is Quad-helix treatment (intervention) more cost-effective (outcome) than platal
expansion (control) in 8–10 year-old patients with unilateral posterior crossbite
(population)?
Use proper randomization
Plan and coordinate the trial carefully - have patience since it takes time to run an RCT
69. Recommendations
Create a relevant question use PICO
• P - population
• I - intervention
• C - control
• O - outcome
e.g. Is Quad-helix treatment (intervention) more cost-effective (outcome) than platal
expansion (control) in 8–10 year-old patients with unilateral posterior crossbite
(population)?
Use proper randomization
Plan and coordinate the trial carefully - have patience since it takes time to run an RCT
Have sufficient sample size – if small, greater risk of unknown or confounding factors that
may interfere the outcomes
70. Recommendations
Create a relevant question use PICO
• P - population
• I - intervention
• C - control
• O - outcome
e.g. Is Quad-helix treatment (intervention) more cost-effective (outcome) than platal
expansion (control) in 8–10 year-old patients with unilateral posterior crossbite
(population)?
Use proper randomization
Plan and coordinate the trial carefully - have patience since it takes time to run an RCT
Have sufficient sample size – if small, greater risk of unknown or confounding factors that
may interfere the outcomes
Use valid and reliable methods
71. Recommendations
Create a relevant question use PICO
• P - population
• I - intervention
• C - control
• O - outcome
e.g. Is Quad-helix treatment (intervention) more cost-effective (outcome) than platal
expansion (control) in 8–10 year-old patients with unilateral posterior crossbite
(population)?
Use proper randomization
Plan and coordinate the trial carefully - have patience since it takes time to run an RCT
Have sufficient sample size – if small, greater risk of unknown or confounding factors that
may interfere the outcomes
Use valid and reliable methods
Follow the CONSORT statement
72. Recommendations
Create a relevant question use PICO
• P - population
• I - intervention
• C - control
• O - outcome
e.g. Is Quad-helix treatment (intervention) more cost-effective (outcome) than platal
expansion (control) in 8–10 year-old patients with unilateral posterior crossbite
(population)?
Use proper randomization
Plan and coordinate the trial carefully - have patience since it takes time to run an RCT
Have sufficient sample size – if small, greater risk of unknown or confounding factors that
may interfere the outcomes
Use valid and reliable methods
Follow the CONSORT statement
Use blinding if possible
73. Recommendations
Create a relevant question use PICO
• P - population
• I - intervention
• C - control
• O - outcome
e.g. Is Quad-helix treatment (intervention) more cost-effective (outcome) than platal
expansion (control) in 8–10 year-old patients with unilateral posterior crossbite
(population)?
Use proper randomization
Plan and coordinate the trial carefully - have patience since it takes time to run an RCT
Have sufficient sample size – if small, greater risk of unknown or confounding factors that
may interfere the outcomes
Use valid and reliable methods
Follow the CONSORT statement
Use blinding if possible
Use the Intention-to-treat (ITT)analysis to evaluate the results
76. Part II: RCTs are not for orthodontics
New EBM ideology - RCTs may minimize, but do not eliminate
bias
Sabine Ruf
77. Why RCTs are not ‘working’ for crucial
clinical orthodontic questions?
78. Why RCTs are not ‘working’ for crucial
clinical orthodontic questions?
Primary goal of RCT test whether an intervention works
by comparing it to a control condition
79. Why RCTs are not ‘working’ for crucial
clinical orthodontic questions?
Primary goal of RCT test whether an intervention works
by comparing it to a control condition
o No treatment
o A placebo treatment
o An alternative treatment
80. Why RCTs are not ‘working’ for crucial
clinical orthodontic questions?
Primary goal of RCT test whether an intervention works
by comparing it to a control condition
o No treatment
o A placebo treatment
o An alternative treatment
Orthodontics is a device-driven specialty not a series of
pills that can be administered at random and evaluated
blindly
81. Why RCTs are not ‘working’ for crucial
clinical orthodontic questions?
Primary goal of RCT test whether an intervention works
by comparing it to a control condition
o No treatment
o A placebo treatment
o An alternative treatment
Orthodontics is a device-driven specialty not a series of
pills that can be administered at random and evaluated
blindly
Even ‘invisible’ appliances are visible to the pt & operator
82. Why RCTs are not ‘working’ for crucial
clinical orthodontic questions?
Primary goal of RCT test whether an intervention works
by comparing it to a control condition
o No treatment
o A placebo treatment
o An alternative treatment
Orthodontics is a device-driven specialty not a series of
pills that can be administered at random and evaluated
blindly
Even ‘invisible’ appliances are visible to the pt & operator
Excludes the possibility of orthodontic placebo treatments
at least for the majority of the questions
84. Effect of Informed Consent
RCT by Bergmann et al. in 1994,
shortly before informed consent
became mandatory in France
85. Effect of Informed Consent
RCT by Bergmann et al. in 1994,
shortly before informed consent
became mandatory in France
Aim: Effect of informed consent on
analgesic activity of pain killers
86. Effect of Informed Consent
RCT by Bergmann et al. in 1994,
shortly before informed consent
became mandatory in France
Aim: Effect of informed consent on
analgesic activity of pain killers
49 consecutively hospitalized patients
with mild to moderate cancer pain
87. Effect of Informed Consent
RCT by Bergmann et al. in 1994,
shortly before informed consent
became mandatory in France
Aim: Effect of informed consent on
analgesic activity of pain killers
49 consecutively hospitalized patients
with mild to moderate cancer pain
Uninformed group - 25 received both
treatments without any information
88. Effect of Informed Consent
RCT by Bergmann et al. in 1994,
shortly before informed consent
became mandatory in France
Aim: Effect of informed consent on
analgesic activity of pain killers
49 consecutively hospitalized patients
with mild to moderate cancer pain
Uninformed group - 25 received both
treatments without any information
Informed-consent group - 24 had a
complete information about the trial;
6 refused to participate 18 pt’s
89. Effect of Informed Consent
RCT by Bergmann et al. in 1994,
shortly before informed consent
became mandatory in France
Aim: Effect of informed consent on
analgesic activity of pain killers
49 consecutively hospitalized patients
with mild to moderate cancer pain
Uninformed group - 25 received both
treatments without any information
Informed-consent group - 24 had a
complete information about the trial;
6 refused to participate 18 pt’s
VAS score of pain before and 30, 60,
120 and 180 min after the intake of
naproxen and placebo were
recorded
90. Changes (mm) in VAS pain levels after naproxen or placebo intake in patients
with and without informed consent
91. Changes (mm) in VAS pain levels after naproxen or placebo intake in patients
with and without informed consent
Pain reduces with the drug in the
non-informed group
Pain increases after receiving the
placebo in the non-informed group
92. Changes (mm) in VAS pain levels after naproxen or placebo intake in patients
with and without informed consent
Pain reduces in both the
drug and placebo in the
informed consent group
93. First described in the 1950s by Henry A. Landsberger after experiments conducted at the
Hawthorne works electric company to determine if increasing or decreasing the amount of
light workers received would have an effect on worker productivity
Employee productivity seemed to increase due to the changes, but then decreased at
after the experiment was over
Researchers suggested that productivity increased due to attention from the research team
and not because of changes to the experimental variables
Lansdberger defined the Hawthorne effect as a short-term improvement in performance
caused by observing workers
94. All orthodontic treatment modalities requiring cooperation cannot be
tested reliably using a RCT design, at least not if we are seeking clinically
relevant truth. And that is maybe ‘why RCTs in orthodontics have not
achieved their intended objective
95. Drawbacks of RCT’s
High costs
Ethical problems
Informed consent
Bias problems
Clinicians/patients preference for certain treatment
Recruiting sufficient patients
96. Final Thoughts
Lack of evidence does not necessarily imply lack of effect
Instead, there is need for further relevant evaluations. Clearly,
new well-designed RCTs and non-randomized studies can
achieve important support to reliable evidence in orthodontics