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| SYSTEMATIC REVIEW |
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| Year : 2015 | Volume
: 6
| Issue : 4 | Page : 129-133 |
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Assessment of blinding success among dental implant clinical trials: A systematic review
Jafar Kolahi1, Saber Khazaei2
1 Independent Research Scientist, Founder and Managing Editor of Dental Hypotheses, Isfahan, Iran
2 Department of Research, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| Date of Web Publication | 27-Nov-2015 |
Correspondence Address:
Jafar Kolahi
N 24, Pardis, Shahin Shahr, Isfahan - 8317918981
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2155-8213.170636
Introduction: It is widely believed that blinding is a cornerstone of randomized clinical trials and that significant bias may result from unsuccessful blinding. However, it is not enough to claim that a clinical trial is single- or double-blinded and that assessment of the success of blinding is ideal. The aim of this study was to evaluate the prevalence of assessment of blinding success among dental implant clinical trials and to introduce methods of blinding assessment to the implant research community. Methods: In November 2014, PubMed was searched by blinded and experienced researchers with the query "implant AND (blind* OR mask*)" using the following filters: (1) Article type: clinical trial; (2) Journal categories: dental journals; (3) Field: title/abstract. Consequently, title/abstract was reviewed in all relevant articles to find any attempt to assess the success of blinding in dental implant clinical trials. Results: The PubMed search results yielded 86 clinical trials. The point of interest is that when "blind* OR mask*" was deleted from the query, the number of results increased to 1688 clinical trials. This shows that only 5% of dental implant clinical trials tried to use blinding. Disappointingly, we could not find any dental implant clinical trial reporting any attempt to assess the success of blinding. Conclusion: The current status of turning a blind eye to unblinding in dental implant clinical trials is not tolerable and needs to be improved. Researchers, protocol reviewers, local ethical committees, journal reviewers, and editors should make a concerted effort to incorporate, report, and publish such information to understand its potential impact on study results. Keywords: Blinding index, blinding success, clinical trial, dental implant
How to cite this article:
Kolahi J, Khazaei S. Assessment of blinding success among dental implant clinical trials: A systematic review. Dent Hypotheses 2015;6:129-33 |
| Introduction | |  |
According to the glossary of the U.S. National Institutes of Health, blinding (or masking) is defined as "A clinical trial design strategy in which one or more parties involved with the trial, such as the investigator or participant, do not know which participants have been assigned which interventions. Types of Masking include None, Open Label, Single Blind Masking, and Double Blind Masking" (http://clinicaltrials.gov/ct2/about-studies/glossary). It is widely believed that blinding is a cornerstone of randomized clinical trials and that significant bias may result from unsuccessful blinding. [1]
Human performance is influenced by what we know or have faith in. In clinical trials, there is a particular risk of anticipation influencing findings, most evidently when there is a specific subjectivity in assessment, leading to biased outcomes. [2] The importance of blinding is emphasized by well-known regulatory agencies, e.g., the United States Food and Drug Administration (FDA) and Consolidated Standards of Reporting Trials (CONSORT). [3]
Some researchers wonder whether the small effect size in many clinical trials might be totally explained by bias introduced through unblinding. [4] A meta-analysis showed that clinical trials described as double-blind in trial reports found 14% lower treatment effect than trials not claimed to be double-blind. [5] A good example is the small effect size in meta-analyses of antidepressant clinical trials, which is known as double blind random bluff. [6]
Blinding should not be limited to study participants. All of the following five categories of key trial persons should be blinded to treatment allocation:
- Participants,
- Healthcare providers,
- Data collectors,
- Outcome assessors, and
- Data analysts. [7]
Nevertheless, it is not enough to claim that a clinical trial is single- or double-blinded, and assessment of blinding success is crucial. Nowadays, effective methods and statistics, known as blinding indexes, [8],[9] are available to assess the success of blinding. [10],[11] Yet these methods are not well known among clinical research scientists, especially in young and rapidly growing fields, e.g., implant dentistry. Hrobjartsson et al. [12] reported 31 of 1599 medical blinded randomized clinical trials (2%) and Fergusson et al. [13] showed only 7 of 97 (7%) general medicine blinded randomized clinical trials and 8 of 94 (8%) psychiatric randomized clinical trials; overall, only 15 of the 191 (8%) provided evidence on the success of blinding.
However, results of a survey showed that only 12% of dental implant clinical trials incorporated blinding in the assessment of outcome. [14] Yet there are no data about the success of blinding. The aim of this study was to evaluate the prevalence of assessment of blinding success in dental implant clinical trials and to introduce methods of blinding assessment to the implant research community.
| Methods | | |
A multilayered search strategy was used to identify any attempt to assess the success of blinding in dental implant clinical trials published by November of 2014 in any language.
PubMed was searched with the query "implant AND (blind* OR mask*)" using the following filters:
- Article type: Clinical trial;
- Journal categories: Dental journals;
- Field: Title/abstract. The asterisk (*) was used as a truncation symbol.
In addition, we used another search strategy to be more specific and sensitive. We tried to find all relevant dental implant clinical trials using relevant key words in the index list of PubMed advanced search. We searched PubMed with a full query [Appendix 1 [Additional file 1]] in November 2014.
All searches were conducted in November 2014 by blinded and experienced researchers (JK and SKH). Consequently, title/abstract was reviewed in all relevant articles to find any attempt to assess the success of blinding in dental implant clinical trials.
| Results | | |
The first search strategy for PubMed showed 86 clinical trials in the results. The point of interest is that when "blind* OR mask*" was deleted from the query, the number of results increased to 1688 clinical trials. This shows that only 5% of dental implant clinical trials tried to use blinding. The second search strategy for PubMed resulted in 29 clinical trials. Disappointingly, we could not find any dental implant clinical trial reporting any attempt to assess the success of blinding.
| Discussion | | |
These results are not surprising. A recent systematic review has revealed that 88% of dental implant clinical trials have weak design features and exhibit numerous methodological weaknesses or limitations: Only 37% showed a random sequence generation at a low risk of bias, 75% did not provide information on allocation concealment, only 12% performed a correct sample size calculation, and the examiner was blinded in only 42% of the studies where blinding was feasible. [15] Assessment of bias in methodology showed that reporting of randomization procedures and blinding in outcome assessment for most implant randomized clinical trials was inadequate. The method of randomization was explicit in 51% of the trials, but only 12% incorporated blinding in the assessment of outcome. [14] Another quality assessment revealed that no attempt at blinding was reported in 72% of dental implant trials. [16] Likewise, the quality of methodological reporting on descriptive studies [17] and experimental research [18] in implant dentistry is low.
A potential problem in persons who perform dental implant clinical trials is lack of knowledge and awareness about methods of blinding in nonpharmacological clinical trials. [19] Well-known methods, such as use of the sham procedure, blinding to study hypothesis, and blinded centralized assessment of the primary outcome, can be used effectively in dental implant clinical trials. For example, according to "Extending the CONSORT Statement to Randomized Trials of Nonpharmacologic Treatment," [20] in a trial assessing an implant surgical procedure, even if the surgeon cannot be blinded, the outcome assessor must be blinded to the study hypothesis and treatment allocation, and contact with the surgeon should be avoided, thus limiting the risk for performance bias. In some clinical trials, this might need more creative but practical blinding techniques, such as digitally altering radiographs to mask the type of implant. [21],[22] Moreover, researchers can always blind the person who performs statistical analysis by merely labelling the groups with nonidentifying terms (such as A and B). [7] Although this seems instinctive, surprisingly few researchers adopt the principle of blinding the data analysts in their clinical trials. [21] Such unblinding perhaps occurs because of misunderstandings about the objectivity of biostatisticians. Data analysts make several semisubjective decisions about some topics, e.g., handling missing data, transforming variables, conducting subgroup analysis, and selecting covariates. These decisions can better be made without the analyst's knowledge of how treatment groups are allocated. [23]
Nevertheless, a vast majority of dental implant clinical trials do not report tests or sufficient evidence for the success of blinding. This methodological failing may result from lack of knowledge and awareness about methods of assessment of blinding success. However, the methods are not difficult. Subjects could be asked to guess their treatment assignment ("active," "placebo," or "do not know"). Alternatively, the certainty of the guess could be rated on a 5-point scale:
- Strongly believe the treatment is active,
- Somewhat believe the treatment is active,
- Somewhat believe the treatment is placebo,
- Strongly believe the treatment is placebo, and
- Do not know. [10],[11] Specialized statistical approaches for blinding assessment, i.e., blinding indexes, and protocols to interpret blinding data are now available. [1]
James et al. [8] proposed a blinding index, as a variation of the kappa coefficient, that is sensitive not to the degree of agreement but to the degree of disagreement, by placing the highest weight on "do not know" responses. Bang et al. [9] proposed a new blinding index that can be directly interpreted as the proportion of the potential unblinding in each trial arm and has the ability to detect different behaviors in different treatment groups.Computing modules for the two blinding indexes have been available for Stata (StataCorp LP, College Station, TX, USA) since March 2008, and can be referred to at http://ideas.repec.org/c/boc/bocode/s456898.html.
| Conclusion | | |
The current status of turning a blind eye to unblinding in dental implant clinical trials is not tolerable and needs to be improved. Researchers, protocol reviewers, local ethical committees, journal reviewers, and editors should make a concerted effort to incorporate, report, and publish such information to understand its potential impact on study results.
Considering the principles of evidence-based clinical decision-making, clinicians have a duty to note the blinding status of dental implant clinical trials and its potential effect on trial findings before incorporating the results into their routine clinical practice.
Guidelines for future implant clinical trials
To increase the quality of blinding in implant clinical trials, consideration of the following items is greatly recommended:
- What is the method of blinding? The following items would be good examples:
- Use of the sham procedure, for example in case of usage of low-level laser,
- Blinding to study the hypothesis, and blinded centralized assessment of the primary outcome,
- Blinded data analyst, and
- Digitally altering radiographs to mask the type of implant. [19],[20],[21],[22]
- Who is blinded and tested for success of blinding? All of the following five categories of key trial persons could be considered:
- Participants,
- Healthcare providers,
- Data collectors,
- Outcome assessors, and
- Data analysts. [7]
- What is the method of assessment of blinding success? Subjects could be asked to guess their treatment assignment ("active," "placebo," or "do not know"). Alternatively, the certainty of the guess could be rated on a 5-point scale:
- Strongly believe the treatment is active,
- Somewhat believe the treatment is active,
- Somewhat believe the treatment is placebo,
- Strongly believe the treatment is placebo, and
- Do not know.
Specialized statistical approaches for blinding assessment, i.e., blinding indexes by James et al. and Bang et al., and protocols to interpret blinding data are available these days. [1],[10],[11] Readers may find good methodological examples provided by Kolahi et al. [10] - Timing: We recommend assessment of blinding before the trial by the third party for independent credibility, for example in case of digitally altering radiographs to mask the type of implant, in the early stage of the trial with great caution for credibility at the specific trial setting, and at the end of the trial for overall assessments of blinding success. [10]
As a final point, we suggest that well-known international organizations, such as CONSORT, the International Committee of Medical Journal Editors (ICMJE), the World Association of Medical Editors (WAME), pay more attention to the negative results of unblinding in clinical trial outcomes.
Acknowledgment
We would like to thank Prof. Heejung Bang (New York, United States) for her valuable advices about this study.
Financial support and sponsorship
Nil.
Conflicts of interest
Both authors have editorial involvement with Dent Hypotheses.
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