Evaluation of the methodologies used in clinical trials and effectiveness of chemo-mechanical caries removal with

ABSTRACT: This investigation aims to discuss the methodologies applied in clinical trials published about CarisolvTM, in order to assess the best scientific evidence concerning chemo-mechanical caries removal. Papers concerning the use of CarisolvTM were sought using a search strategy. The titles and abstracts of all the reports identified through the search were analyzed by a single reviewer. The inclusion criterion involved: clinical trials having CarisolvTM in one of the study groups. Then, those that fulfilled the inclusion criterion underwent methodology assessment and data extraction. Only 12 papers met the inclusion criterion. It was observed that none of these studies complied with all the evaluated research methodological principles required in order to have power of evidence generation. CarisolvTM proved to be effective in caries removal. Appointment mean time was greater, but the perceived time was shorter than that using conventional techniques due to patients’ perception of more comfort and a reduction of anesthesia needs. There were no adverse effect in long-term assessments. In studies with microbiological evaluation of the remaining dentine, it was observed that both the conventional and chemo-mechanical methods produced statistically significant reduction on counts of viable microorganisms. DESCRIPTORS: Dental caries/therapy; Effectiveness; Methods.


INTRODUCTION
Evidence-based medicine is the conscious, clear and cautious use of the current best evidence to make decisions when treating individual patients. 25Nowadays systematic reviews are considered the preferred method for identifying all of the available knowledge, determining which information is the best and summarizing it in a clinically useful manner. 2 Despite the caries prevalence decline 7 , carious tissue removal, still a challenge for researchers, is considered an unpleasant step of the restorative process, mainly because of the need for local anesthesia, drilling and noise. 1,5,6,9,12,15,18Furthermore, drilling results in a rapid and excessive removal of affected dentin 10 and may cause harmful thermal and pressure effects to the pulp. 1,5,12,15,18The advances in adhesive dentistry have changed the need for standard cavity designs allowing minimally invasive techniques. 6,14,17,18The chemo-mechanical caries removal system Carisolv TM has been developed with the purpose of removing all the infected tissue, preventing the removal of sound dentin, and is intended not to cause discomfort to the patient. 6,9The system is a gel constituted of 0.5% sodium hypochlorite and three amino acids, glutamic acid, leucin and lysine.Sodium hypochlorite has a non-specific proteolytic effect which dissolves organic substances as a result of the action of chlorine, which breaks collagen net links.Thanks to the amino acids present in Carisolv TM , there is a reduction of this effect, allowing selective caries removal by differentiating sound, bacteria-free tissue from the infected, disnatured and irretrievable dentin. 9ecause of the variety of papers involving Carisolv TM , the present investigation aimed to discuss the methodologies applied in the clinical trials published about this system in order to assess the best scientific evidence concerning the efficacy and safety of chemo-mechanical caries removal.The key question stated was: "Is Carisolv TM effective in caries removal?And is it more comfortable compared to conventional methods?"

MATERIAL AND METHODS
This methodology followed the format of a systematic review. 4

Search strategy for identification of studies
Papers concerning the use of the chemo-mechanical caries removal system Carisolv TM (Medi Team, Gothenburg, Sweden) published until May 2005 were searched.The following databases were examined: PubMed, Cochrane Library and Bireme.The descriptors typed were: Carisolv or chemomechanical and caries and removal.The idioms were restricted to Portuguese and English.Titles and abstracts of all reports identified through the searches were analyzed by a single reviewer.The inclusion criterion involved: Clinical trials having Carisolv TM in one of the study groups.Studies that fulfilled the inclusion criterion underwent meth-odology assessment and data extraction by full text analysis. 4Selected papers references were also examined.No attempt to identify grey literature or unpublished data was done.

Studies analysis
The same reviewer assessed each complete study regarding methodological aspects in order to assess its power of evidence generation.The following principles were considered in the assessment: sample size, well defined inclusion and exclusion criteria, randomization, control group, calibration, examiner blinding, statistical analysis and long-term follow-up.Data extraction comprised the studies' main characteristics and analysis of the results and its arrangement in tables.

RESULTS
Only 12 papers fulfilled the inclusion criterion: clinical trial having Carisolv TM in one of the study groups.One clinical trial primarily selected was excluded during methodology assessment because Carisolv TM had been used associated with air-abrasion. 24able 1 presents the 12 selected studies, their respective authors, and methodology features.Table 2 presents the 12 selected studies, their respective authors, and their main features.Table 3 presents the 12 selected studies, their respective authors, and their main results.

DISCUSSION
A clinical trial is a planned experiment, strictly on human subjects, which is conducted with a view to investigate the efficacy of one or more treatments for a given condition. 22This kind of research offers us the most trustworthy evidence.All selected papers in this review are clinical trials.In vitro studies can serve as hypothesis generators and indicators of possible correlations but have the uncertainty of extrapolating results to physiological effects in humans, thus presenting weak evidence. 16For that reason they have been excluded in this review.
Investigators are interested in the effect of some "intervention" or "treatment" in a particular target population.It is possible to use statistical techniques to make inferences about the population of patients who will present to a practitioner in the future by using information obtained from a sample of patients in a trial. 22Considering infer-ence ability, all the assessed studies in this review carried out adequate statistical analysis.
Selection bias occurs when the individuals in the study are not representative of the population of interest.This may be avoided by ensuring that a random method of selection is used rather than relying on purposive or judgment sampling, where investigators include in their samples those individuals who they believe are typical or representative of the population. 20In this review it was observed that all the clinical trials evaluated used a convenience sample.This could have an implication on the results since people that have access to dental treatment may differ from the target population in terms of caries activity and psychological profile.
The aim in designing a study is to control α and β.Since they both increase as the sample size of the study decreases, all other relevant factors remain-ing constant, estimating sample size becomes an integral part of study design. 23From the analyzed studies, only Nadanovsky et al. 18 (2001) mentioned to have calculated the necessary sample size.
Clinicians may have a preconceived notion related to the effectiveness of a new treatment and this will influence the way in which the patients are allocated to various treatments.This might result in the more severely ill patients being allocated to the standard treatment, or vice-versa, even if the clinician's intention is to be fair, and this in turn would result in a biased estimate of the treatment effect.In order to avoid the possibility of this happening, the patients are randomly assigned treatments. 22If the size of the sample is enough, randomization guarantees that some results determinants known and unknown by the researcher are randomly distributed between test and control groups.Not randomized trials of ef- fectiveness are inevitably limited in its ability of distinction between useful and useless or even harmful therapies. 11The great majority of the investigated studies distributed patients or teeth into test or control groups by chance, except that of Munshi et al. 17 (2001).
A group which does not receive the test therapy is the reference to assess superiority or equivalence. 22Clinical trials in dentistry normally use two types of study design: parallel and split mouth.The parallel group design relies on comparisons which are made between groups of subjects.Split-mouth has the advantage of avoiding variation among individuals, because it uses individuals as their own controls, but cannot be utilized for conditions which do not remain stable in the study period or which can be cured by the treatments being administered, when there is a carry-over effect from one treatment to another, or when the response to treatment is prolonged. 21From the 12 analyzed papers, nine 3,6,9,13,15,18 used the conventional technique of caries removal by burs and or hand instruments as control group for Carisolv TM .Concerning study design, the great majority of studies used a parallel model 5,6,8,9,13,14,17 while others 1,3,12,15,18 used a split mouth model.Calibration aims to guarantee the uniformity of interpretation and application of adopted criteria by examiners both in relation to themselves and to the other examiners. 26Ideally, reproducibility should be calculated by Cohen's Kappa coefficient, in order to deduct agreements by chance. 19Interexaminers calibration was demonstrated by Kavvadia et al. 13 (2004) and Nadanovsky et al. 18 (2001).
Both the patient receiving treatment and the assessor of the response to treatment may have preconceived notions about the superiority of one treatment over another.If either is aware of which treatment the patient is receiving, this may influence the assessor's evaluation of the response and lead to a biased result. 22In trials where patient and operator can not be blinded, the examiner who assesses the results must be. 11Bergmann et al. 3 (2005), Ericson et al. 6 (1999), Fure et al. 9 (2000), Fure, Lingström 8 (2004), Kakaboura et al. 12 (2003) and Nadanovsky et al. 18 (2001) all mentioned examiner's blinding.
A long-term follow-up is essential to evaluate a drug or technique safety.Longitudinal studies are the best ones regarding ability of evaluating later symptoms or adverse effects, although they present a high cost and a great possibility of individual drop outs. 21Maragakis et al. 15  Cavities restorative treatment is a wide issue in cariology, and there is no particular technique which is useful in all situations.Intrinsic differences of each patient, including cooperation level, oral health appraisal and general health conditions make the consensus about a therapy more difficult.Based on the available clinical trials results, Carisolv TM demonstrated to be effective in caries removal. 1,3,6,9,12,13,18Appointment mean time was greater 3,6,8,9,12,13,15 but due to patient perception of more comfort 3,5,8,9,12,17 and reduced anesthesia necessity 6,9,12,13,15,18 , the perceived time was shorter than that observed using conventional techniques. 6,9he system was considered adequate for pediatric use because it did not affect child cooperation 13,17 .However, in the study by Maragakis et al. 15 (2001), the majority of pediatric patients preferred the conventional technique because it was faster and did not produce an unpleasant flavor.There were no adverse effects in long-term assessments. 3,6,8,9,15,17n studies involving a microbiological evaluation of the remaining dentine, it was observed that both the conventional and the chemo-mechanical methods produced a statistical significant reduction on counts of viable microorganisms. 1,14

CONCLUSIONS
Based on the available clinical trials related to Carisolv TM , it was observed that none of the studies complied with all research methodological principles.However, the best available evidence concerning Carisolv TM suggests that it is effective in caries removal and ensures higher patient comfort than does conventional drilling, although it involves a longer appointment.