chambrone2016.pdf

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Journal of Periodontology; Copyright 2016 DOI: 10.1902/jop.2016.150554

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nonsurgical periodontal interventions (i.e., test vs control therapies), it was found that the

test therapy led to a statistically significant reduction (p = 0.01) in the mean number of

bleeding sites with periodontal probing depths [PD] 6 mm than the control therapy (e.g. 5

sites vs 15 sites). As a result, it might be concluded that the test treatment reduced the

number of sites that were candidates for surgical therapy (e.g., open-flap debridement).

SURROGATE VS. PERSON-CENTERED OUTCOMES

In clinical practice, it can be argued that person-centered outcomes (i.e., those that matter to

the individual) are the most important.14Clinical attachment level (CAL) and PD are not

considered true end points, but surrogate ones.3, 14Important person-centered orpatient-

reported outcomes include comfort, function, aesthetics and tooth retention. In any analysis

dealing with clinical relevance the success of a treatment approach should include patient-

centered outcomes.

An often neglected patient-centered outcome that is relevant to clinical practice is how

many teeth return to periodontal health after treatment. The number of teeth that return to

periodontal health after treatment might be a better primary outcome than the reduction innumber of inflamed/bleeding deep pockets. For example, an individual tooth presenting at

baseline with 3-4 deep/bleeding pockets may still have 1 residual deep/bleeding pocket at

the final examination (and remain unhealthy), thus additional therapy (e.g., open-flap

debridement) might be needed to successfully treat that tooth.

Interpretation of the clinical relevance of surrogate outcomes is exceptionally difficult. If

4 treatment approaches result in different average reductions in probing depth (e.g., 0.3 mm,

0.5 mm, 0.7 mm, and 1.00 mm) and all are statistically significant (P < 0.05) compared to

baseline values, which reductions (if any) are clinically important?Obviously, this is

difficult to answer, but it should be considered that the percentage of teeth that had a

questionable or hopeless diagnosis before therapy may inflate potential mean differences,independent of the type of therapy the patient received.15

Evidence is clear that the number of residual deep pockets (PD 6 mm) with bleeding

on probing (BOP) after periodontal therapy is important in the prediction of disease

progression,16, 17while the mean changes from baseline are important to establish the degree

of CAL gain. However, these can lead to another discussion such as what percentage of sites

or patients achieved a clinically significant end result (e.g., PD < 5 mm or CAL gain > 2

mm)? Additionally, the selection of the primary variable based on the inherent conditions

of the topic of interest seem of more clinical relevance, such as: a) sites/patients needed to

be treated (NNT) to have one site/patient with a desired outcome (e.g. CAL gain >2 mm for

a regenerative procedure); b) percentage of sites or patients achieving a clinically significant

end result (e.g., CAL gain > 2 mm for a regenerative procedure, 100% or 80% coverage for

a root coverage procedure, PD < 5 mm after a non- or surgical procedure); and combining

multiple different outcomes in the evaluation (e.g., CAL gain and radiographic gain for a

regenerative procedure, % coverage for a root coverage procedure and gain in keratinized

tissue (KT), PD < 5 mm and no BOP after a non- or surgical procedure).18, 19

Consequently, the number of teeth reaching a status of clinical periodontal health after

treatment (i.e., stable non-inflamed sites, with shallow probing depths) seems to be of better

clinical relevance than the number of residual pockets for the assessment of effect/success of

treatment (i.e. the primary outcome measure for the clinicians decision-making process). In

other words, it is essential to evaluate/interpret whether the different outcome measures

described in a study are relevant for clinical practice.10


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CLINICAL RELEVANCE

Different definitions can be applied to the terms clinical relevance or clinical significance,

such as, a way to determine the practical value of a treatment, as opposed to the

statistical significance,4 the minimally clinically important difference between

groups,7or a returning to normal functioning.6Jacobson et al.6have suggested two

criteria that are needed to establish the minimum requirements of a clinically significant

change: (1) The magnitude of the change has to be statistically reliable and (2) by the end

of therapy, clients/patients have to end up in a range that renders them indistinguishable

from well-functioning people.6In terms of periodontal therapy, the minimum requirements

of clinically significant outcomes include those associated with potential clinical

changes/improvements after therapy (e.g., gains in CAL and reduction in PD, BOP and

mobility) as well as patient-reported outcomes (e.g., comfort, better aesthetics and ability to

chew).

To reach these objectives, the following should be considered:

1 Clinicians judgment on whether a new therapy seems applicable in terms of clinicaloutcomes (Are the clinical improvements obtained with the tested therapy as effective as the

gold-standard established by the periodontal literature?);

2 Patient-centered outcomes and their importance in the implementation of novel

treatment approaches in the future (e.g., adverse effects [such as. discomfort, pain],

functional limitations [e.g., limitations on the chewing and deglutition of food], costs, and

patients preferences);5, 13, 20, 21

3 Long-term impact of treatment (Do the short-term results of therapy remain long-

term?);

4 The interpretation of the base of evidence from efficacy and effectiveness trials.

The use of statistical approaches has been also described to determine clinical relevance.

For instance, the Cohens effect size22computes the degree of the relationship between

outcome measures as well as the magnitude of the difference of the groups based on two

mean scores (one from each group) and the pooled standard deviation of the groups

(meanTest group mean Control group/SDpooled). However, the issue of clinical relevance is more

involved with aspects related to an ample group of conditions that have been studied by

evidence-based medicine/dentistry.

EVIDENCE-BASED DECISION MAKING: HOW STATISTICALSIGNIFICANCE SHOULD MEET CLINICAL RELEVANCE

For more than a decade, systematic reviews (SR) of efficacy studies have been designed to

identify the best treatment options in periodontology, but theseper semay not be clearly

designed to translate the current evidence into practical decision guidances for common

daily clinical scenarios.21Efficacy is only one dimension of evidence-based dentistry and

adoption of a specific technology requires more than this line of evidence. Efficacy

refers to the probability of benefit to individuals in a defined population from an

intervention administered under ideal conditions, whereas effectiveness is the impact in

real-world situations by assessing the benefit of an intervention provided to typical

individuals by the average practitioner under ordinary conditions.23

Systematic reviews of RCTs are important tools that are primarily designed to determine

differences in treatment approaches in interventional studies and provide implications forfuture research and practice.18The calculation of pooled estimates from different trials is


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certainly a critical issue due to inherent conditions related to the protocol of the study [i.e.,

adherence to the study design, sample of patients treated, expertise of clinician(s) providing

treatment], and the number of studies included in the analysis.15, 20, 21Meta-analyses

reporting, or not reporting, statistical differences assist the clinician in rendering a treatment

plan, but they do not certify that one therapy is much better than the other. It should be noted

that factors associated with the periodontal diagnosis, sample size, and the applied inclusioncriteria may make the pooling of data from different trials a critical issue. For instance, the

inclusion of studies with mean PD > 6 mm can increase the impact of outcome change by

promoting greater differences between baseline and follow-up means (i.e. baselinemean follow-

upmean = outcome change), an element that may impact the estimates of meta-analyses.

Thus, it is expected that studies should be combined into meta-analyses according their

baseline characteristics in order to generate more accurate evaluations.18, 20, 21Moreover,

both RCTs and systematic reviews may not answer key questions regarding uncommon

conditions where an adequate sample of patients may not be easily available for analysis, or

for clinical outcomes of interest that could not be reproduced in humans due to ethical

aspects. Thus, information gathered from private-practice studies should assist in answering

some research questions.

Effectiveness is a very significant question, which has not been explored to the same

extent that efficacy has, and the idea of effectiveness is based on outcome of therapy by

average clinicians in the community and not by research experts.21Most practitioners are not

used to designing research protocols or conducting/running clinical studies, and only a few

will ever present the results of their work as case reports/series.21These factors are

important and deserve distinction, because often there is a gap between protocols

investigated by experts and those carried out in clinical practice.21As a result, other

assessment tools/criteria that take into account the available clinical evidence and expert

opinions might be considered. An example of such an assessment tool is the one defined by

the U.S. Preventive Services Task Force (USPSTF) adapted by the American DentalAssociation in 2013,24with the intent that it may guide the strength of recommendation of a

procedure as follows: a) strong evidence strongly supports providing this intervention; b)

in favor evidence favors providing this intervention; c) weak evidence suggests

implementing this intervention after alternatives have been considered; d) expert opinion for

evidence is lacking; the level of certainty is low (expert opinion guides this

recommendation); e) expert opinion against evidence is lacking; the level of certainty is

low (expert opinion suggests not implementing this intervention); and f) against evidence

suggests not implementing this intervention or discontinuing ineffective procedures.24

In other words, new or alternative procedures should be used when definitive

information is scarce and evidence based on clinical experience must be used to fill the gap

in knowledge until strong evidence becomes available.

CONCLUDING REMARKS

The findings of a study should allow for the balanced interpretation of both the statistical

significance and clinical relevance of the data followed by a thoughtful assessment of their

clinical applicability in a practical setting.1The use of P-values is important, but other useful

estimates/tools such as confidence intervals (CIs) can quantify the amount of differences

between groups. For instance, an honest way to evaluate the balance between significance

and relevancy relies on the following question proposed by Saiani11: Are any of the values

within the 95% CI big enough to care about? If the answer is no, then the effect is clinically

insignificant and statistical significance is immaterial.


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Without a doubt the use of statistical analysis is certainly important and necessary for

clinical research. However, statistically significant differences alone between two

procedures may not be sufficient to support the use of a new therapy in private practice. An

evidence-based clinical practice clearly requires the data generated by clinical research, and

statistical analysis of the data provides a basis for the development of treatment strategies

and helps in the decision-making process. However, cost-benefit analyses and magnitude-of-change determinations of any treatment approach depend on how much of the statistical

differences can be translated into clinically useable tools for daily practice.

CONFLICT OF INTEREST

The authors report no conflict of interest related to this commentary.

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Contact : Leandro Chambrone, Rua Antonio Pinto Guedes, 626, Mogi das Cruzes, SP,

08820-430 Brazil e-mail: [email protected]

Submitted September 10, 2015; accepted for publication December 22, 2015.
http://www.ncbi.nlm.nih.gov/pubmed/16235343http://www.ncbi.nlm.nih.gov/pubmed/16235343http://www.ncbi.nlm.nih.gov/pubmed/16625546http://www.ncbi.nlm.nih.gov/pubmed/16625546http://www.ncbi.nlm.nih.gov/pubmed/16625546http://www.ncbi.nlm.nih.gov/pubmed/16625546http://www.ncbi.nlm.nih.gov/pubmed/16235343http://www.ncbi.nlm.nih.gov/pubmed/16235343

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