False facts are highly injurious to the progress of science, for they often endure long but false views, if supported by some evidence, do little harm, for everyone takes a salutary pleasure in proving their falseness.

– Charles Robert Darwin

Evidence Based Orthodontics

Presented by – Parag S. Deshmukh

Contents:

• Introduction• Definition• History• Need for evidence based orthodontics• Evidence based orthodontic practice• Advantages and disadvantages• Clinical implications• Conclusion• References

Learning objective:Will learn what is EBOWill be familiar with EBO search tools and different types of

studies usedWill Understand the previlages of EBO approachWill know the stages in Evidence Based Practice

Orthodontists are challenged to manage sophisticated patient needs and demands. On the other hand keeping the advances in orthodontics and medical dental sciences up to date, following the current techniques and relevant literature and applying knowledge to daily practice is practicioner’s priority.

Glossary Relating to EBD:

Best evidence is a term that refers to information

obtained from randomized controlled clinical trials,

non-randomized controlled clinical trials, cohort studies, case-control

studies, crossover studies, cross-sectional studies, case studies or, in the absence of

scientific evidence, the consensus opinion of

experts in the appropriate fields of research or clinical

practice.

Case-control study involves identifying subjects with a clinical condition (cases)

and subjects free from the condition (controls), and investigating if the two groups have similar or

different exposures to risk indicator(s) or factor(s)

associated with the disease.

Case-series is a report on a series of patients with an outcome of interest. No

control group is involved.

Clinical practice guideline (parameter of care) is a

systematically developed statement designed to assist both practitioner and patient

with decisions about appropriate health care for specific clinical

circumstances.

Clinical protocol is a step-by-step decision-making tool that

describes how a health condition is diagnosed and

managed.

Randomized controlled clinical trial is a study in which

participants are randomly (i.e., by chance) assigned to either an experimental group or control group. The experimental group

receives the new intervention and the control group receives a

placebo or standard intervention. These groups are followed up for

the outcomes of interest.

Systematic review is a process of systematically locating, appraising

and synthesizing evidence from scientific studies in order to obtain a reliable overview. The aim is to ensure a review process that is comprehensive and unbiased.

Findings from systematic reviews may be used for decision-making about research and the provision

of health care

Controlled clinical trial is a study that uses the same design features

of a randomized controlled clinical trial,

but, for reasons beyond the control of the investigators, the subjects are assigned using a non-random

process into control or experimental groups.

Cross-sectional study is the observation of a

defined population at a single point in time or

in a specified time interval. Exposure and

outcome are determined

simultaneously.

Meta-analysis is a review that uses

quantitative methods to combine the

statistical measures from two or more

studies and generates a weighted average of

the effect of an intervention, degree of association between a

risk factor and a disease, or accuracy of

a diagnostic test.

Includes everything that is used to

reveal and determine

the truth, and therefore is

presumed to be true.

In scientific research, evidence

is accumulated through

observations of a phenomena or

which are created as experiments in

a laboratory or other controlled

conditions.

Scientific evidence usually

goes towards supporting or

rejecting a hypothesis.

Evidence based practice

What is Evidence Based Dentistry?

• Evidence-based dentistry is the practice of dentistry that integrates the best available evidence with clinical experience and patient preference in making clinical decisions.

Sutherland S., J Can Dent Assoc 2001; 67:204-6

• Evidence-based dentistry is an approach to oral health 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 preferences.

ADA Policy on Evidence-Based Dentistry

“a conscientious, explicit, and judicious use of current best evidence in conjunction with clinical experience to make decisions regarding patient care”

- David Sackett

Evidence based orthodontic practice is all about -

Doing the

right thing

to the right

patient

in the right way

at the right time

at the right cost

in the right place

History:

The Cochrane Legacy

Professor Archibald Leman Cochrane

(1909–1988)

His firm belief in finding evidence for the effectiveness of medical interventions resulted in the development of randomized clinical trials (RCTs) and systematic reviews of the scientific literature.

• Using evidence from the medical literature to answer questions, direct clinical action and guide practice was pioneered at McMaster University, Ontario, Canada in the 1980’s.

• The group was formed to organize medical research information in a systematic way to facilitate the choices that health professionals, patients, policy makers and others face in health interventions according to the principles of evidence-based medicine.

• The group conducts systematic reviews of randomized controlled trials of health-care interventions and diagnostic tests, which it publishes in The Cochrane Library.

The Cochrane Oral Health Group

• Part of The Cochrane Collaboration • Established in the USA in 1994• Comprises an international network of researchers involved

in producing and disseminating systematic reviews of controlled RCTs in the field of oral health.

• Publishes summaries of the best quality research available to help people (patients, carers, clinicians, researchers and funders) make better informed decisions about oral healthcare choices.

The Graph shows the progress of the Oral Health Group since 1998, in terms of published reviews, protocols and review updates. There are now 118 published reviews, 61 updates and 78 published protocols as of the Cochrane LibraryEvidence-Based Care in Context : William Shaw Evidence-Based Orthodontics, First Edition.

Need for evidence based orthodontics???

“Simply because we, as health care professionals, owe it to our patients, to provide the currently best care available”

How does the Evidence based approach differ from what you already practice???

• Accessing new evidence on a regular basis

• Identification of new risk factors, analysis, continuous improvement in efficacy of care

• Patient centered approach

Systematic review:It is a process of systematically locating, appraising and synthesizing evidence from scientific studies in order to obtain a reliable overview.

The aim is to ensure a review process that is comprehensive and unbiased.

Findings from systematic reviews may be used for decision-making about research and the provision of health care.

STEPS IN PERFORMING SYSTEMATIC REVIEW

• FIRST STEP : Framing an important and well defined question that is relevant to patient care.

• Framing a question in a proper format and identifies four crucial “ PICO” elements. These elements are:

• Population or patient type • Intervention• Comparison • Outcome

SECOND STEP: • Determining inclusion and exclusion to select the

eligible studies. • Subcategory of outcome, exposure, confounder, effect

modifiers, intermediates, type of control as well as type of study design and other consideration.

THIRD STEP:

• Design a search strategy.

• Employed to search available studies include both electronic databases such as MEDLINE, EMBASE, Web of science, Cochrane, databases and manual searches.

Type I Resources:

• Resources that give you background and factual informationExamples - Text books, dictionaries, handbooks, drug information resourcesThese are the resources that you study to get your basic degrees

Type II Resources

• Resources related to current and old researchExamples - Journals, Indexes to Journals, Theses and Dissertations, Conference abstracts

Type III Resources:

• Resources that summarize Research Information from Type II resources and give you an analysis, evidence of what works, directions for patient management, information to compile guidelines or taking public health decisions

FOURTH STEP: • Involves application of the selection criteria identified in

step Two to the potential studies retrieved from both electronic and manual search strategies determined in step Three.

• This action will result in selection of the eligible studies for the review and appraising these studies.

FIFTH STEP:

• Performing a statistical summary of the abstracted data, or Meta- analysis.

• Data from different study designs are summarized with the purpose of the following six tasks:

i. Deciding whether to combine the data or defining what to combine

ii. Evaluating the statistically heterogeneity of the dataiii. Estimating a common effectiv. Exploring an explained heterogeneityv. Assessing the potential for biasvi. Presenting the results in the form of a table

FINAL STEP:

• INTERPRET THE EVIDENCE TO ANSWER THE RESEARCH QUESTION

Meta-analytic Procedures (MAPs)

It is a review that uses quantitative methods to combine the statistical measures from two or more studies and generates a weighted average of the effect of an intervention, degree of association between a risk factor and a disease, or accuracy of a diagnostic test.

Consequently, the evidence produced by MA can be considered the strongest possible.

Randomized control trials.+ = (MAPs)

Randomized control trials.

Meta-analyses are often, but not always, important components of a systematic review procedure.

Meta-analysis has the capacity to contrast results from different studies and identify patterns among study results, sources of disagreement among those results, or other interesting relationships that may come to light in the context of multiple studies.

Conducting meta-analyses…

Location of studies

Quality assessment

Calculating effect sizes

Checking for publication bias

Calculating effect sizes

Clinical trials commonly present their results as the frequency of some outcome in the intervention groups and the control group.

These are usually summarized as a ratio of the frequency of the events in the intervention to that in the control group.

In the past the most common summary measure of effect size was the odds ratio, but now the risk ratio (relative risk) can be given.

A ratio of 2 implies that the defined outcome happens about twice as often in the intervention group as in the control group; an odds ratio of 0.5 implies around a 50% reduction in the defined event in the treated group compared with the controls.

The findings from individual studies can be combined using an appropriate statistical method.

Checking for publication bias:

A key concern is publication bias, as clinical trials that obtain negative findings (that is, no benefit of treatment) are less likely to be published than those that conclude the treatment is effective.

To examine a funnel plot.

Display the studies included in the meta analysis in a plot of effect size against sample size

In the absence of publication bias, it assumes that the largest studies will be plotted near the average, and smaller studies will be spread evenly on both sides of the average, creating a roughly funnel-shaped distribution. Deviation from this shape can indicate publication bias

Presenting the findings:Forest plots:

It is a graphical display of estimated results from a number of scientific studies addressing the same question, along with the overall results.

Heterogeneity:

A major concern about meta-analyses is the extent to which they mix studies that are different in kind.

‘a statistical analysis which combines or integrates the results of several independent clinical trials considered by the analyst to be “combinable”

To get a precise answer to a specific question, only studies that exactly match the question should be included.

Meta-analyses should test for the existence of heterogeneity.

Meta-regressionWhen heterogeneity is detected, it is important to investigate what may have caused it.

Meta-regression is a technique which allows researchers to explore which types of patient-specific factors or study design factors contribute to the heterogeneity.

The simplest type of metaregression uses summary data from each trial, such as the average effect size, average disease severity at baseline, and average length of follow-up.

It struggles to identify which patient features are related to the size of treatment effect.

Advantages:• Results can be generalized to a larger population• The precision and accuracy of estimates can be improved as

more data is used. This, in turn, may increase the statistical power to detect an effect.

• Inconsistency of results across studies can be quantified and analyzed.

• Moderators can be included to explain variation between studies.

• The presence of publication bias can be investigated

Disadvantages:

• Over simplifying the results of a research area• Errors in classifying the studies and estimating effect

sizes• The small number of studies available in certain

research topics• The low quality and heterogeneous results

• Published MAs in medical research are 8418 articles,

• Only 13 orthodontic-related MAs were cited in Cochrane library for the same period!!

Few Facts…1966 to 2002

RANDOMISED CONTROL TRIALS• An experimental study on patients with a particular disease or

disease free subjects in which the individuals are randomly assigned to either an experimental intervention or a control group to determine the ability of an agent or a procedure to diminish symptoms, to decrease risk of disease during follow up period.

• Provide strongest evidence causation of evidence.• The RCT is often considered the gold standard for a clinical

trial.

The first published RCT in medicine appeared in the 1948 paper entitled "Streptomycin treatment of pulmonary tuberculosis", which described a Medical Research Council investigation.

One of the authors of that paper was Austin Bradford Hill, who is credited as having conceived the modern RCT.

As of 2004, more than 150,000 RCTs were in the Cochrane Library.

Classification

By study design:

Parallel group – each participant is

randomly assigned to a group, and all the participants in the

group receive (or do not receive) an intervention.

Crossover – over time, each

participant receives (or does not receive) an intervention in a random sequence.

Cluster – pre-existing groups of

participants (e.g., villages, schools) are randomly selected to

receive (or not receive) an

intervention.

Factorial – each participant is randomly assigned to a

group that receives a particular combination of

interventions or non-interventions (e.g., group 1

receives vitamin X and vitamin Y, group 2 receives

vitamin X and placebo Y, group 3 receives placebo X and vitamin Y, and group 4

receives placebo X and placebo Y).

• An analysis of the 616 RCTs indexed in PubMed during December 2006 found that 78% were parallel-group trials, 16% were crossover, 2% were cluster, and 2% were factorial.

By outcome of interest (efficacy vs. effectiveness)

Explanatory RCTs test efficacy in a research setting with highly selected

participants and under highly controlled conditions.

Pragmatic RCTs test effectiveness in everyday practice with relatively

unselected participants and under flexible conditions; in this way,

pragmatic RCTs can "inform decisions about practice."

RCTs can be classified as "explanatory" or "pragmatic.“

Superiority trials, in which one intervention is hypothesized to be

superior to another in a statistically significant way.

Noninferiority trials "to determine whether a new

treatment is no worse than a reference

treatment."

Equivalence trials in which the hypothesis is that two

interventions are indistinguishable from

each other.

By hypothesis (superiority vs. noninferiority vs. equivalence)

Superiority trials, noninferiority trials and equivalence trials, which differ in methodology and reporting.

Randomization:

Choosing a randomization procedure to generate an unpredictable sequence of allocations; this may be a simple random assignment of patients to any of the groups at equal probabilities, it may be "restricted," or may be "adaptive."

Allocation concealment, which refers to the stringent precautions taken to ensure that the group assignment of patients are not revealed prior to definitively allocating them to their respective groups.

Non-random "systematic" methods of group assignment, such as alternating subjects between one group and the other, can cause "limitless contamination possibilities" and can cause a breach of allocation concealment.

Blinding:An RCT may be blinded, (also called "masked") by "procedures that prevent study participants, care givers, or outcome assessors from knowing which intervention was received.“

Sometimes inappropriate or impossible to perform in an RCT.

Advantages:

RCTs are considered by most to be the most reliable form of scientific evidence in that they influences healthcare policy and practice because RCTs reduce spurious causality and bias.

Drawbacks:

• Raise ethical concerns in control groups• Costly and time consuming to implement• Because of the strict eligibility criteria and loss to

follow-up, RCT sample size requirements are difficult to attain and maintain.

COHORT STUDIES

An observational study that follows an exposed cohort compared to an unexposed cohort to determine the incidence of given outcome.

Obtain evidence to try to refute the existence of a suspected association between cause and effect; failure to refute a hypothesis often strengthens confidence in it.

The study groups follow a group of people who do not have the disease for a period of time and see who develops the disease.

It is a longitudinal observation of the individual through time

• A "prospective cohort" defines the groups before the study is done

A “Retrospective cohort", defines the grouping after the data is collected.

• Well designed cohort study provides strong support for causation

• Non concurrent cohort studies are relatively weaker because they rely on existing records.

Disadvantages : • Require large sample size• Take a long follow-up time to generate useful data. Length of the

studies result in misclassification in outcome status• Expensive to conduct.• Are sensitive to attrition

CASE CONTROL STUDIES

An observational epidemiological study of persons with the disease (or another outcome variable) of interest and a suitable control group of persons without the disease (comparison group, reference group) [Porta’s dictionary of epidemiology]

These are observational studies where in cases with a particular outcome and controls that do not have the same outcome are first selected and exposure assessment is done retrospectively.

Quick, relatively inexpensive

Appropriate in studying rare diseases

Assessment of multiple risk factors for a particular disease within the same study

Advantages:

Quick and cheap. Excellent for rare condition.

Disadvantages:

Potential recall bias. Confounding of exposure variable. Matching control to cases is challenge.

CASE REPORT AND CASE SERIES

• Document unusual occurrences of outcomes • First clues of a new diseases or adverse effects of exposure• Case series are an extension of case reports

Decision making….

EBDM is the formalized process and structure for learning these skills with the purpose of closing the gap between what is known and what is practiced in

order to improve patient care based on informed decision-making.

Evidence Based Decision Making(EDBM)

Clinical decision making will be based on:

• CLINICAL EXPERTISE = Knowledge + Experience • May be out of

date • Increasingly

difficult to keep up with New ideas and concepts

• Acquisition of new knowledge is slow and haphazard

• May be limited Subject to personal bias

• May out weigh knowledgeDrawback

s

Evidence based decision making

The Need for EBDM• Forces driving the need to improve the quality of

care include:

Variations in practice,

Slow translation and assimilation of the scientific evidence

into practice.

Managing the information overload, and changing

educational competencies that require students to

have the skills for lifelong learning

• Convert information needs/problems into clinical questions so that they can be answered

• Conduct a computerized search with maximum efficiency for finding the best external evidence with which to answer the question

• Critically appraise the evidence for its validity and usefulness (Clinical applicability).

• Apply the results of the appraisal, or evidence, In Clinical practice.

• Evaluate the process and your performance.

Skills needed to apply the EBDM Process

Surgically facilitated orthodontic treatment: A systematic reviewEelke J. Hoogeveen, Johan Jansma, and Yijin Ren; April 2014; Vol 145; Issue 4.• A systematic review was performed to evaluate the evidence supporting that the

corticotomy and dental distraction shorten orthodontic treatment duration in adolescent and adult patients.

• MATERIAL AND METHODS:Articles regarding corticotomy -facilitated orthodontics or dental distraction in

healthy adolescent or adult patients without periodontal disease were considered.

Randomized controlled trials (RCT), controlled clinical trials (CCT), and case series (CS) with sample sizes of 5 or more patients were eligible for inclusion in this review.

Studies needed to focus on the velocity of tooth movement or treatment time reduction, tissue health or complications, or comparisons between different surgical techniques to be included.

Only full-length articles were considered.

• The studies were assessed for eligibility and graded by 2 observers

• A 3-point grading system, as described by the Swedish Council on Technology Assessment in Health Care and the Centre for Reviews and Disseminations (York), was used to rate the methodologic quality of the articles

• Surgically facilitated orthodontics is characterized by a temporary phase of accelerated tooth movement; this might effectively shorten the duration of treatment, but careful treatment planning, early activation of appliances, and short intervals between checkups are recommended.

• Surgically facilitated orthodontics is not associated with complications such as loss of tooth vitality, periodontal problems, or severe root resorption.

• However, the level of evidence is limited owing to shortcomings in methodologies and the small numbers of patients in the studies.

• Due to a lack of comparative data, it is unclear which surgical protocol is preferable regarding treatment efficiency and safety.

Treatment effectiveness of Fränkel function regulator on the Class III malocclusion: A systematic review and meta-analysisXianrui Yang, Chunjie Li, Ding Bai, Naichuan Su, Tian Chen, Yang Xu , Xianglong Han; August 2014Volume 146, Issue 2, Pages 143–154 Aim:To assess the effectiveness of the FR-3 in treating patients with Class III malocclusion in the growth and development period.Methods:Medline (via PubMed), Cochrane Central Register of Controlled Trials, Embase, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Scirus, Lilacs, Scopus, and World Health Organization International Clinical Trials Registry Platform were searched electronically. Relevant journals and reference lists of included studies were manually searched. The quality of the included studies was assessed with the Newcastle-Ottawa scale. The meta-analysis was carried out using RevMan (version 5.2; Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark).

Results:

• Seven high-quality cohort studies were included. • The meta-analysis showed that SNA changes did not differ in the short (mean

difference, 0.43°; 95% CI, −0.52°-1.39°) and long (mean difference, 0.37°; 95% CI, −0.29°-1.03°) terms. However, SNB changes significantly differed in the short (mean difference, −1.62°; 95% CI, −2.62° to −0.62°) and long (mean difference, −1.50°; 95% CI, −2.12° to −0.88°) terms.

• By contrast, MPA changes did not differ in the short term (mean difference, 0.55°; 95% CI, −0.74°-1.84°).

Conclusions:

Clinical evidence suggests that the FR-3 might restrict mandibular growth but not stimulate forward movement of the maxilla. Further high-quality studies are necessary to confirm the effectiveness of the FR-3.

• The objective of this randomized controlled trial was to investigate the effects of facemask protraction combined with alternating rapid palatal expansion and constriction (RPE/C) vs rapid palatal expansion (RPE) alone in the early treatment of maxillary retrusive patients.

Methods:Patients with a midface deficiency were recruited and randomly allocated into either the control group (RPE) or the intervention group (RPE/C).

Eligibility criteria = Age 7 to 13 years old, Class III malocclusion, Anterior crossbite, ANB less than 0°, Wits appraisal less than −2 mm and No cleft of lip or palate.

Effect of maxillary protraction with alternating rapid palatal expansion and constriction vs expansion alone in maxillary retrusive patients: A single-center, randomized controlled trialWeitao Liu, Yanheng Zhou, Xuedong Wang, Dawei Liu, Shaonan Zhou; October 2015; Volume 148, Issue 4, Pages 641–651.

• The primary outcome was the degree of maxillary forward movement after treatment.• The secondary outcomes were the changes of the other cephalometric variables after

treatment and the treatment time. • Simple randomization was carried out using a random number table at the beginning

of the study. • Envelopes containing the grouping information were used to ensure allocation

concealment from the researchers. • Blinding was applicable for cephalometric analysis only. • Hyrax palatal expanders and facemask maxillary protraction were used in all patients.• Patients in the RPE group were treated with rapid palatal expansion for 1 week.• Patients in the RPE/C group were treated with RPE/C for 7 weeks. • The expansion or constriction rate was 1 mm per day. • Comparison of the pretreatment and posttreatment cephalometric radiographs were

made. • Independent t tests were used to compare the data between the 2 groups.

Results:

• A total of 44 patients were randomized to either the RPE group or the RPE/C group in a 1:1 ratio.

• One subject in the RPE group was lost to follow-up during the treatment. Per-protocol analysis was used. All the other 43 patients reached the treatment completion criteria and were analyzed (RPE group: n = 21; RPE/C group: n = 22).

• The average protraction time was 10.84 months in the RPE group, which was significantly longer than that in the RPE/C group (9.06 months).

• Maxillary forward movement increased by 3.04 mm in the RPE/C group, which was significantly greater than that in the RPE group (2.11 mm).

• The counterclockwise rotation of the palatal plane was 1.73° in the RPE/C group, which was significantly greater than that in the RPE group (0.83°).

• The degree of mandibular downward and backward rotation was significantly smaller in the RPE/C group (P <0.05).

• No serious harm was observed during treatment and research.

• A survey consisting of 35 questions pertaining to the use of scientific evidence in orthodontics was sent to 4771 members of the American Association of Orthodontists in the United States.

• Each respondent’s age, attainment of a master’s degree, and whether he or she was currently involved with teaching were ascertained. To minimize bias, the survey questions were phrased as an examination of the use of scientific literature in orthodontics.

Asha Madhavji et al (Am J Orthod Dentofacial Orthop 2011;140:309-16)

Attitudes, awareness, and barriers toward evidence-based practice in orthodontics

Results:A total of 1517 surveys were received. • Most respondents had positive attitudes toward, but a poor

understanding of, evidence-based practice.

• Younger orthodontists were more aware, had a greater understanding, and perceived more barriers than did older orthodontists.

• Orthodontists involved in teaching were more aware, had a greater understanding, and reported fewer barriers than those not involved with teaching.

• Those with master’s degrees had a greater understanding of evidence-based practice than those without degrees.

Differing view..• PCSO ( Seattle Washington) member wrote at the

end of the survey that “evidence-based research and treatment modalities are a joke in orthodontics.” Well, that may be true, but the joke is really on us.

• Orthodontics is dentistry’s first specialty, and yet we have poor scientific support for many of our treatments.

Making the case for evidence-based orthodontics, Greg J. Huang AJODO:2004:11.018

• A common criticism is that the findings of clinical trials are not relevant to patients in private practice, because the operators in trials are working to such tight protocols that their treatment bears no resemblance to the real world.

The excuse…

Dr. David L. TurpinEditor Emeritus, Former editor in chief AJODO

“Every time I hear this statement, I nod my head and say that is exactly why an evidence-

based approach was developed—to systematically evaluate information from

many studies to determine what seems to be the best approach, treatment, or

intervention.”

In the land of no evidence, is the salesman king? AJO-DO September 2010

Take home message

Up till date, the American Association of Orthodontists has been very careful to state that an evidence-based approach does not set a standard of care, and that the treatment for

each patient should be based on a combination of the doctor’s clinical expertise, the patient’s needs and preferences, and the evidence.

It's not necessarily the amount of time you spend at practice that counts; it's what you put into the practice, which will be best done bye doing Evidence Based Practice - Eric londros.

REFRENCES1. Making the case for evidence- based orthodontics- Greg J Huang (AJODO 2004; 125: 405-

6)2. Putting the evidence first- David L Turpin (AJODO 2005; 128: 415)3. Fasten your seat belts for the bumpy ride to evidence-based practice. Greg

J.Huang(AJODO,Volume 127,Number 1)4. Understanding science and evidence-based decision making in orthodontics-Donald J

Rinchuse,Emily M.Sweitzer,Daniel J.Rinchuse,Dara L.Rinchuse,AJODO,Volume 127,Number 5)

5. Model of Evidence-Based Dental Decision Making, Janet Baeuer, Sue Spackman, Francesco Chiappelli, Paolo Prolo (Journal of Evidence-Based Dental Practice 2005;5:189-97)

6. Evidence-Based therapy: An Orthodontic dilemma- Anthony Gianelly (AJODO, Volume 129,Number 5)7. Evidence-Based Care in Context : William Shaw

Thank You