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Systematic Review And Meta-Analysis In Oral Medicine-An Update

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 Journal of Rural Development Society
THE TRENDS IN SCIENCE AND TECHNOLOGY
(Published by : Rural Develeopment Society - Govt. Recognized R & D Institution)
www.rdsjournals.com

Systematic Review And Meta-Analysis In Oral

Medicine-An Update
Nallan Csk Chaitanya* , D.Reshma Priyanka, P.Karunakar, Komali Garlapati, Mamata Boringi,
Sujatha Mekala Mary, Sushma K,
*
Department of Oral Medicine and Radiology, Panineeya Institute of Dental Sciences and Research Centre, Hyderabad-500082,

Abstract-The amount of information being generated in medical
research is becoming overwhelming. Clinicians are finding it
nearly impossible to stay current, even in their own area of specialty
as new studies are constantly being published. Meta-analysis is a
review which is done systematically, following certain criteria,
with the pooling of results and quantitative analyzation. Valuable
information is provided by a well-designed meta-analysis for
researchers and clinicians. Systematic reviews (SRs) represent a
specific type of medical research in which the units of analysis are
the original primary studies. They are essential tools in
synthesizing available scientific information, increasing the
validity of the conclusions of primary studies, and identifying areas
for future research. They are also indispensable for the practice of
evidence-based medicine and the medical decision making
process. SRs are an essential tool in synthesizing available
scientific information; they enhance the validity of the findings
from individual studies and identify areas of uncertainty where
research is needed. They are essential to the practice of evidence-
based medicine. However, conducting high quality systematic
reviews is not easy and they can sometimes be difficult to interpret.
A strict methodology and applying quality control is to be
implemented in SRs to avoid biased conclusions. Regarding a
particular patient it is the clinician who must make decisions
and; SRs help us in making those decisions..
Keywords-Evidence based medicine, Meta-analysis, Precision,
Statistics, Systematic review..
I. INTRODUCTION
We live in the information age and the practice of medicine is
becoming increasingly specialized. The rapid advancement in the
field is attributed to integration of health care with research which
has paved way for proper protocols and update information on
various aspects of health care management.
With the myriad of problems, we can estimate the amount of
research work being carried out and the multiple small studies
(randomized control trials) being done. The results of most of the
studies are different, vary among same population and even
conflicting, which leads to difficulty in clinical decision-making
and puts the clinician in a helpless situation as to what to consider
and what to discard.
Evidence based medicine may be defined as the systematic,
quantitative, preferentially experimental approach to obtaining and
using medical information. Central role in evidence based medicine
is played by meta-analysis, which is a statistical procedure that
combines the results of all other studies conducted independently.
In the hierarchy of evidence, meta-analysis occupy the top position
where clinical evidence is ranked according to the strength of the
freedom from various biases. (1)
The terms "meta-analysis" and "systematic review" are
occasionally used interchangeably in the literature. However, they
are two different processes with complementary approach. A
systematic review is defined as a methodic review of the literature,
often accompanied by a scale or grading algorithm that assigns
values to the presence or absence of evidence (defined by the
publication of randomized trials, observational studies, and case
reports) that answers the question posed by the systematic review.(2)
Glass first defined meta-analysis in the social science literature
as "The statistical analysis of a large collection of analysis results
from individual studies for the purpose of integrating the findings".
(3)
In simpler words, when systematic review is subjected to
statistical analysis what we get is meta-analysis.
Meta-analysis systematically assesses the results of various
researches which are done previously to get to a definitive
conclusion regarding what the research hypothesis is. Most of the
studies included in meta-analysis fall into the category of
randomized, controlled clinical trials. (1)
RATIONALE
The available scientific literature on a particular research, enables

Nallan Csk Chaitanya, D.ReshmaPriyanka, P.Karunakar, Komali Garlapati, Mamata Boringi, Sujatha Mekala Mary And Sushma K,
"Systematic Review And Meta-Analysis In Oral Medicine-An Update,"Journal of Rural Development Society
The Trends in Science And Technologies, Volume 1, Issue 1, November - 2017, ISSN No:……….
www.rdsjournals.com Page No : 35
us to get to a simplified clinical decision which is based on the
evidence available, helping us to get a good clinical outcome and
also in reducing the cost of the treatment.
Meta-analysis has the advantage of detecting small but clinically
important effects, as it encompasses large subject numbers. It also
helps us to find significant inter-study differences which may
generate new hypotheses for future research, and analyzing of
group/subset effects increases precision. (2)
Meta-analysis also helps in establishing whether scientific
findings are consistent in various studies which can be generalized
across populations, settings, and treatment variations, or whether
findings vary by particular subsets. It enhances precision, provides
robust estimates, and answers
calculatedquestions that single trials are under-powered or were
not designed to address. (4)
Explicit methods used in Meta -analysis limit bias and help
improve the reliability (precision) and accuracy (validity) of
conclusions. As data is available from more than one study the
'sample size' increases leading to increase in "power". In clinical
trials and cohort studies, it helps in observing more events of interest
in different groups considered. So, when incidence or mortality is
rare, meta-analysis helps in giving combined estimates which are
likely to be more precise. (5)
Supporting arguments for performing a meta-analysis include
the increase in power and precision of the estimates, quantification
of effect sizes, and the assessment of the consistency of results
across trials. The most convincing reason for conducting meta-
analysis is when similar clinical studies are present with results of
different effect sizes. (2)
Finally, meta-analysis identifies various questions which have
not been adequately addressed with past research. Thus it
documents the need for a major clinical trial. Similarly, it also confirms
the sufficiency of available literature on a particular topic. Thus, it
helps to avoid the time and expense of conducting another clinical
trial. It has been estimated that for any clinical setting which involves
a 10% risk of an event, 10,000 patients need to be randomized to
demonstrate a 25% reduction in the risk with a more than 90% power
and a p value less than 0.01. (6)
How to conduct meta-analysis in medicine?
The flow chart shows the methodology of a systematic review
of RCTs. Thus any such methodology in oral medicine should
include:
State objectives of the review and outline eligibility criteria
 stressed upon. This is done by inspecting the graphical display
Comprehensively search for trials that meet eligibility criteria
 is heterogeneity, it is not proper to pool such results. (7)
Tabulate each of the characteristics and assess the methodology
 Following a systematic review, data from individual studies
Apply eligibility criteria and justify exclusion
Nallan Csk Chaitanya, D.ReshmaPriyanka, P.Karunakar, Komali Garlapati, Mamata Boringi, Sujatha Mekala Mary And Sushma K,
"Systematic Review And Meta-Analysis In Oral Medicine-An Update,"Journal of Rural Development Society
The Trends in Science And Technologies, Volume 1, Issue 1, November - 2017, ISSN No:……….
www.rdsjournals.com

Assemble most comprehensive data set

Analyze results of RCT using statistics

Compare alternative analyses if appropriate and possible

Prepare critical summary, stating aims, materials and results (7)
Generally one has to follow certain prescribed format of
questionnaire when contemplating on a systematic review in any
subject such as those given as outline below.
1. Did the review address a clearly focused question?
2. Did the review include the right type of the study?
3. Did the reviewers try to identify all relevant studies?
4. Did the reviewers assess the quality of all the studies included?
5. If the results of the study were combined, was it reasonable?
6. How the results presented and what are main results?
7. How precise are the results?
8. Can results be applied to local population?
9. Were all important outcomes considered?
10. Should policy or practice change as a result of the evidence?(8)
ASSESSMENT OF TRIAL METHODOLOGY
a) Searching data base for relevant studies in question -
A single data base may not effectively provide all the studies
in question equally. Dickersin et al showed that only 30-80%
of all known published RCTS were identifiable using
MEDLINE. (9)Thus a comprehensive search is important to
reduce selection bias. Article search should not be limited to
English language and those indexed in MEDLINE.
b) Quality assessment of trials -
There should be a predetermined method of assessment
including eligibility and quality of studies. At least two
reviewers should independently assess the quality of included
studies to minimize the risk of selective bias. (10)
c) Result pooling -
Determine whether the pooling was reasonable. A clinical
judgment should be made about whether it was reasonable
for the studies to be combined based on the individual trials
differed considerably in population studies, interventions and
comparisons used or outcome achieved. The Meta analytic
validity looking for homogeneity of outcome should be
of results looking for similarities in direction of results. If there
d) Meta-analysis:
may be pooled quantitatively and reanalyzed using established
statistical methods.(11) This technique is called meta-analysis.
Page No : 36
 It is done by combining the samples of individual studies, the
overall sample size thus increase improving the statistical power
of the studies as well as the precision of the estimates of
treatment effects. (12)
It is a two stage process.
e) Stage 1: Involves the calculation of the measure of the treatment
effect with its 95% confidence intervals for each individual
study. The summary statistics used to measure treatment effect
include odds ratio (OR) relative risk (RR).
f) Stage 2: Over all treatment effect is calculated as a weighted
average of individual summary statistics. (13)Greater weights
are given to the results from studies providing more
information because they are likely to be closer to true effect
of estimate. It is thus taken as inverse of variance. The typical
graph to display this data is called "forest plot". (14)(Figure 1)
g) The picture below is a typical representation of forest plot.
The alphabets of the left side of the graph represent first author
of the primary study. The black squares represent the odds
ratio of individual studies. The horizontal lines their 95%
confidence intervals. The area of black space reflects the
weight the each trial contributed to meta-analysis. The 95%
confidence interval represents the true underlying effect in 95
% of the occasion if the study was repeated again and again.
The solid vertical line represents to no effective treatment,
with p Value (P<0.05). The overall treatment effect calculated
as weighted average of individual odds from meta-analysis
and its CI at bottom represents a diamond. The center of the
diamond represents combined effect. If the diamond shape is
present towards left of the line it shows lesser change in results
and if on right side of the line, it shows no change of the
results. If it touches the line at Centre, it is considered as no
effect. (OR=1) that is p is not significant.
Methods of expression of results can be done using odds
ratio, relative risk and mean differences. If the result is two
ways, for example, no effect Vs effect, presence of infection Vs
no infection, odds ratio or relative risks are used. If the result is
a continuous variable (like blood glucose), mean differences
may be used.
What is ODDS and ODDS ratio :
ODD-it is calculated as number of patients in a group who
achieved end point ÷ number of patients who did not.
Example: Treatment with vitamin a reduces mucositis in 6 of
10 patients: ODD is here 6:4=1.5. In control group the odds may
be 3:7 = 0.43.
The ODDS ratio is the ratio of odds of treatment group to odds
of control group. (1.5÷0.43).
What is risk and relative risk?
Risk- here number of patients who received treatment and found
effective to total number of patients. (6÷10= 0.6)
Risk ratio is a risk of two groups ratio = 6/10÷3/10= 0.6/0.3
Nallan Csk Chaitanya, D.ReshmaPriyanka, P.Karunakar, Komali Garlapati, Mamata Boringi, Sujatha Mekala Mary And Sushma K,
"Systematic Review And Meta-Analysis In Oral Medicine-An Update,"Journal of Rural Development Society
The Trends in Science And Technologies, Volume 1, Issue 1, November - 2017, ISSN No:……….
www.rdsjournals.com
The "3" stands for the control group in the example.
Interpretation:
If the ODDS ratio and relative risk are greater than 1, it indicates
increased likelihood of good intervention in group. If it is less than
1, then it indicates decreased change with intervention. If it is equal
to 1, then there is no change.
More widely placed confident intervals show us that there is
less precision outcome. If the confidence interval for relative risk
or odds ratio for an estimate includes 1, then there is no statistic al
significance between the groups compared. (7)
Advantages of doing a meta-analysis: (15)
The main advantage is we can able to detect small but clinically
relevant effects of an intervention. Diverse groups of subjects are
present across studies, which permits a transparent solution to a
question or hypothesis. The conclusion has the potential advantage
of being based on most, if not all, existing evidence from relevant
studies. If the evidence from studies are available which are
statistically well handled, then meta-analysis provides a conclusive
result and helps in avoiding time and expense of doing a large
study for confirmatory purpose.
For many studies as the data is too old or too expensive to
retrieve, meta-analysis helps in collecting the data needed. The
statistical tools are such that most sources of bias and heterogeneity
can be statistically examined. Sensitivity of statistically significant
results can be measured. The statistical techniques to analyze results
from meta-analyses are generally not new and many standard
techniques apply. The resources to help accomplish a systematic
review of studies to be included in the meta-analysis are available.
For Eg., To know the association of HPV with oral cancer, whether
it is just an incidental finding or a sole etiologic factor one can have
a look into the "Systematic meta analysis on association of human
papilloma virus and oral cancer"(16) where it was concluded that,
there was definite prevalence of HPV in cancer group patients when
compared to control group but that association wasn't clearly proven
to be existing.
Some of the more prominent issues facing Meta analyses include:
(17)
An assumption that the evaluation techniques carried out in
doing meta-analysis are consistent across various studies. There is
something called as "file-drawer" effect- that is difficulty in locating
all the articles needed. Some statistics must be adjusted accordingly
leading to bias. Heterogeneity in the studies leads to inconsistent
coding of variables. Moreover, the exact source of heterogeneity is
not detected. Because the study is the unit of analysis, the adequacy
of statistical power of any meta-analysis may be in question.
Sometimes the data available may be inconsistent leading to
difficulty in interaction and trends. When combining studies for
analysis, appropriate weights and scoring must be considered.
Apart from these, there are some statistical issues which have to be
addressed to overcome the limitations of a well-designed Meta
analysis.eg. If Bayesian approach is being considered, then an
Page No : 37
experienced statistician should be consulted to eliminate the al. (eds.), Evidence-Based Practice: Toward Optimizing Clinical
misinterpretation of a study. Outcomes,Springer-Verlag Berlin Heidelberg 2010.
16. Chaitanya NC, Allam NS, Gandhi Babu DB, Waghray S, Badam RK,
CONCLUSIONS Lavanya R. Systematic meta-analysis on association of human papilloma
The traditional basis of medical practice has changed by the virus and oral cancer. J Can Res Ther, vol 12, pp 969-74, 2016.
use of randomized, blinded, multicenter clinical trials and meta- 17. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic
analysis, leading to the widely used term "evidence-based Reviews of Interventions Version 5.0.2 [updated September 2009]. The
medicine". Any field can benefit from well conducted small research Cochrane Collaboration, 2009.Available from www.Cochrane-
handbook.org.
and compilation of the same in the form of meta-analysis when
large studies are missing.
Single studies, whether meta-analytic or not, will not provide
the precise understanding of responses to treatment, diagnostic tests,
or risk factors that influence the disease process. Meta-analytic
approaches offer benefits such as addressing the limitations of study
size, including diverse populations along with the opportunity to
evaluate new hypotheses than any single study.
At last, we can conclude that systematic reviews and meta-
analysis are definitely a major contribution to the research studies
conducted in area of Medicine, and much more are required for
benefit of the clinician [1].
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Nallan Csk Chaitanya, D.ReshmaPriyanka, P.Karunakar, Komali Garlapati, Mamata Boringi, Sujatha Mekala Mary And Sushma K,
"Systematic Review And Meta-Analysis In Oral Medicine-An Update,"Journal of Rural Development Society
The Trends in Science And Technologies, Volume 1, Issue 1, November - 2017, ISSN No:……….
www.rdsjournals.com Page No : 38

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