CRISConceptnote
CRISConceptnote
CRISConceptnote
net/publication/264832812
CITATIONS READS
148 7,174
3 authors:
Manjula Datta
92 PUBLICATIONS 5,541 CITATIONS
SEE PROFILE
Some of the authors of this publication are also working on these related projects:
Isolation and Identification of Group A Streptococcal Infection Among Slum Children in the Age Group of 5-15 Years in Chennai - One Year Prospective Study View project
All content following this page was uploaded by Jogikalmat Krithikadatta on 08 September 2014.
Concept Note
Abstract
In vitro studies form a pivotal role in dental research contribution to a substantial evidence base. The reporting standards of these
studies are not uniform thus resulting in lacunae in evidence reported. The effort of this concept note is to propose a Checklist for
Reporting in vitro Studies (CRIS guidelines) that would promote quality and transparency in reporting in vitro studies.
Keywords: Reporting guidelines; in-vitro studies; quality; transparency
Nevertheless the acid test is how they translate in the studies are methods where required samples size can be
clinical situation. assembled without escalating the logistics of the study.
Results of in vitro studies are often applied in research and Meaningful difference between groups
development of dental material innovations, discovery of One of the information required to compute sample
new drugs and understanding material behavior. Published size in estimating mean is the “meaningful difference.”
in vitro studies enable the reader/clinician to analyze and Meaningful difference is the difference by which the
understand the variability affecting the outcome measure newer tested material is superior to the existing standard.
of a material, thus facilitating evidence based practice. For example, if the compressive strength of material A is
Systematic reviews of in vitro studies can be performed x MPa, then the newer material B should demonstrate a
to consolidate evidence about similar materials/technique. compressive strength of x+x’ MPa for it to be superior
This way, manufactures, clinicians and researchers rely to material A. Here, x’ is the meaningful difference and
on in vitro studies to deduce inferences. However lack of this measure can only be decided by the researcher. This
uniform methods and reporting hamper the meaningful difference is often set at a measure that would make a
comparisons of these studies. difference clinically or scientifically. Meaningful difference
is indirectly proportional to sample size. Greater the
CURRENT LACUNA IN REPORTING meaningful difference, lesser is the sample size. However, it
IN VITRO STUDIES is prudent to set this difference as close to clinical scenario
as possible. This is a significant step while recommending a
Most of the in vitro studies follow an experimental design. new material as a viable alternative to an existing standard.
In this design, hypothesis testing follows analytical inference
between the groups/materials tested. The structure of an in Sample preparation and handling
vitro study closely resembles that of a clinical trial, in other A detailed explanation about sample preparation and
words, it is a trial conducted in a lab. The merits of in vitro sample handling helps the reader to understand the
studies as compared to that of a trial include: Control over simplicity or complexity of the experiment conducted.
independent variables and unforeseen bias and ease of Information on sample loss at crucial steps would promote
operation. This improves internal validity of the results. transparency of the experiment and minimize bias. For
However, one of the major demerits is that it lacks external example there is a high risk of sample contamination in
validity and generalizability to clinical situations. Though a microbiological study. If this risk is calculated before
in vitro studies are relatively simpler to perform, they lack hand and additional number of samples included prior to
certain methodological rigor that clinical trials demonstrate. commencement of the study, then the bias related to loss
of sample could be minimized. This is similar to the clinical
Existing lacunae among in vitro studies that need to be trial where allowance of 10-15% is made to compensate
addressed to promote quality and transparency of evidence for drop-outs and loss to follow-up. Another area where
could include the reporting of: sample preparation is important is when we make multiple
samples from the same specimen. For example, samples
Sample size calculation created for micro-tensile bond strength or biofilm analysis
The significance of sample size is well-understood and on two halves of the same tooth. Technically speaking,
needless to say it has a huge impact on the results of the these are all samples from a single specimen and cannot
study. One of the main reasons for statistically insignificant be regarded as individual samples. The editor of operative
results could be a small sample size. However, most dentistry emphasized in one of the editorials that multiple
published in vitro studies do not include calculation of samples obtained from single tooth for micro-tensile bond
sample size as one of the steps in methodology. Instead of testing should be treated as an average for that tooth rather
choosing the required sample size to test the hypothesis, than using individual samples as such.[1] Or, they could be
we tend to choose a statistical method (nonparamentric treated as a cluster, and the appropriate correction made
tests) to analyze data sets from smaller sample sizes. In in sample size. This is relevant because, if we obtain five
the place of comparing mean value of the samples and its samples from each tooth, then three teeth will yield 15
distribution, we compare median and ranks of median. In samples. It will be an error to infer from three samples!
situations when we can use actual sample size that allows It would be better to use the five samples from the same
comparison of mean and the distribution between groups, tooth to record the variations within the tooth.
we are ethically bound to do so. In the event of procuring
samples due to cost or feasibility is difficult, a smaller Allocation sequence, randomization
sample size with appropriate statistical method to analyze and blinding
data could be performed. For example, shear bond strength When an experiment is conducted, it is often a single
testing of bonding agents or dentin tubule disinfection researcher who prepares the samples, allocates them to
groups, conducts the study and assesses the outcome. In review.[12] These guidelines urge the investigator to report
the last 5 years there is a change in the method of outcome the study in concurrence to an itemized checklist. The
assessment among many researchers. There are usually need for standard reporting of clinical trials first started in
two independent observers who assess the outcome of the early 1990s and by 1996, the first version of CONSORT
the experiment to promote transparency of the results. was formulated. This underwent modifications in 2001 and
However there could be a potential for bias in allocating 2010.[5] The premise of CONSORT has paved way for other
the samples to the groups. A person independent of checklists, which are primarily an adaptation of CONSORT
the experiment could also do this step. This could be a to suit their respective needs.[11] The checklist however
lab assistant or clerical staff. These methods (allocation does not aim to improve the quality of the study but
concealment and outcome assessment) of blinding can helps to satisfy certain standard requirements that allow
minimize bias. Next is the method of allocating the samples comparability across several studies.[9] The success of these
to the groups. Several manuscripts refer to this step as guidelines has ensured transparency of clinical studies
“randomly allocated to groups”, however, randomization and has improved evidence based patient care. Systematic
itself is an important and a systematic step in clinical reviews and meta-analyses have also become more
trials. Randomization refers to the equal and independent comprehensive and meaningful. CONSORT guideline has
possibility of a sample entering any group. The sequence been accepted by over 400 journals since its introduction in
of samples allotted to groups is often predetermined using 1996. International Committee of Medical Journal Editors
a randomization chart or a computer generated random
(ICMJE) endorses this guideline.[13] There is convincing
sequence table. Randomization:
evidence that journals using CONSORT guideline has
a Balances known and unknown factors and eliminates
improved the quality of reports of clinical trials.[14-16]
bias,
b Permits the use of probability theory that the likelihood
Extrapolation of a similar guideline to suit in vitro studies
of a difference in outcome between groups is by
would immensely improve the quality of reporting across
chance, and
in vitro studies. As of now, there has been no validated
c Maintains a certain degree of blinding of samples.[2-4]
guidelines or check list for reporting in vitro studies. The
prime focus of this concept note is to sensitize the research
Statistical analysis
fraternity regarding this lacuna and propose the concept
The statistical method for analyzing data is often a crucial
to develop standardized guidelines for conducting and
step while rejecting hypothesis in both clinical and in-
vitro research. While most authors address analysis for the reporting in vitro dental research.
primary objective, the same for the secondary objective
is often not reported. There have also been reports on This checklist for in vitro studies would be an adaptation the
misuse of statistical methods in dental literature.[5,6] The CONSORT guidelines since the methodological structure
results of certain studies have completely changed when of in vitro study and clinical trial are similar. The checklist
correct statistics were applied.[7] The editorial published in would help to address most of the above mentioned
the International Endodontics Journal provided statistical lacunae. Apart from this, clear guidelines for reporting
guidelines for manuscript submissions.[8] It is important to would be recommended in the Introduction, Materials
understand that statistical significance is not the deciding and methods, Results and Discussion (IMRAD) format of
factor in a study; rather it gives the researcher a direction manuscript preparation. Although items like sample size
towards what the results indicate. Hence to look in the calculation, meaningful difference, and randomization
right direction, we need to use the right statistics and apply are not featured in a conventional structure of an in vitro
statistics to both primary and secondary objective if any. study it is obvious that these would make the in vitro study
reporting robust and significant. In turn the designing of
Need for CRIS Guidelines for in-vitro dental experiments, and their comparability would improve.
research
Evidence is categorical in clinical research, whichstates A good beginning would be to create a checklist with
“Assessment of health care interventions can be misleading leads from the CONSORT and to validate the checklist
unless investigators ensure unbiased comparisons. Random for its effectiveness. A Delphi group needs to be called to
allocation to study groups remains the only method that identify items in the CONSORT that need to be retained or
eliminates selection and confounding bias.”[9] This has modified. Focus group discussions and consensus meetings
led to formulation of checklists for reporting clinical with interested collaborators is mandatory in creating
studies. These include; CONSORT guidelines for clinical a comprehensive checklist. This checklist then needs to
trials[9], STROBE guidelines for observational studies[10], be validated. The J Conserv Dent proposes to undertake
STRAD guidelines for studies involving diagnostic tests,[11] the formation and validation of a Checklist for Reporting
and PRISMA guidelines for meta-analysis and systematic In vitro Study (CRIS guidelines).
CONCLUSION 9. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ,
et al. CONSORT 2010 Explanation and Elaboration: Updated guidelines
for reporting parallel group randomised trials. BMJ 2010;340:c869.
CRIS guidelines could standardize the reporting of in vitro 10. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC,
Vandenbroucke JP. STROBE Initiative. The Strengthening the Reporting
experimental studies in dentistry thereby promoting of Observational Studies in Epidemiology (STROBE) statement:
transparency and quality of these studies. Guidelines for reporting observational studies. J Clin Epidemiol
2008;61:344-9.
11. Bossuyt PM, Reitsma JB. Standards for reporting of diagnostic accuracy.
ACKNOWLEDGEMENT The STARD initiative. Lancet 2003;361:71.
12. Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group (2009).
Preferred reporting items for systematic reviews and meta-analyses: The
The authors thank Dr. Spoorthy Reddy, Sr. Lecturer, Dept of PRISMA Statement. BMJ 2009;339:b2535.
Conservative Dentistry, Meenakshi Ammal Dental College, 13. Davidoff F. News from the International Committee of Medical Journal
Chennai for providing information during manuscript preparation. Editors. Ann Intern Med 2000;133:229-31.
14. Hopewell S, Dutton S, Yu LM, Chan AW, Altman DG. The quality of
reports of randomised trials in 2000 and 2006: Comparative study of
REFERENCES 15.
articles indexed in PubMed. BMJ 2010;340:c723.
Plint AC, Moher D, Morrison A, Schulz K, Altman DG, Hill C, et al. Does
the CONSORT checklist improve the quality of reports of randomised
1. Platt JA. Decades of bond strength. Oper Dent 2010;32:13-38. controlled trials? A systematic review. Med J Aust 2006;185:263-7.
2. Schulz KF. Randomized controlled trials. Clin Obstet Gynecol 1998;41:245-56. 16. Egger M, Jüni P, Bartlett C. Value of flow diagrams in reports of
3. Greenland S. Randomization, statistics, and causal randomized controlled trials. JAMA 2001;285:1996-9.
inference. Epidemiology 1990;1:421-9.
4. Armitage P. The role of randomization in clinical trials. Stat
Med 1982;1:345-52.
5. Vähänikkilä H, Nieminen P, Miettunen J, Larmas M. Use of statistical How to cite this article: Krithikadatta J, Gopikrishna V, Datta M.
methods in dental research: Comparison of four dental journals during a CRIS Guidelines (Checklist for Reporting In-vitro Studies):
10-year period. Acta Odontol Scand 2009;67:206-11.
6. Krithikadatta J, Valarmathi S. Research methodology in dentistry: Part II A concept note on the need for standardized guidelines for
- The relevance of statistics in research. J Conserv Dent 2012;15:206-13. improving quality and transparency in reporting in-vitro studies
7. Lucena C, Lo´pez JM, Abalos C, Robles V, Pulgar R. Statistical errors
in microleakage studies in operative dentistry. A survey of the literature
in experimental dental research. J Conserv Dent 2014;17:301-4.
2001–2009. Eur J Oral Sci 2011;119:504-10.
8. Souza E. Research that matters: Setting guidelines for the use and Source of Support: Nil, Conflict of Interest: None declared.
reporting of statistics. Int Endodon J 2014;47:115-9.
Announcement