How To Write A Systematic Review
How To Write A Systematic Review
Medicine
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Evidence-based medicine utilizes the available medical literature to guide clinical decision making and assess the
strength of clinical recommendations. When diagnosing
and treating patients, practitioners employ evidence-based
guidelines to advocate for or against an intervention. Metaanalyses and systematic reviews critically appraise and
formally synthesize the best existing evidence to provide
a statement of conclusion that answers specific clinical
questions. Conduct of performance of this type of investigation is transparent, with explicit selection, evaluation, and
reporting of the analyzed evidence.
*Address correspondence to Joshua D. Harris, MD, The Methodist
Orthopedics and Sports Medicine Center, 6560 Fannin Street, Scurlock
Tower, Suite 400, Houston, TX 77030 (e-mail: joshuaharrismd@
gmail.com).
y
The Methodist Orthopedics and Sports Medicine Center, Houston,
Texas.
z
Sports Medicine Center, The Ohio State University, Columbus, Ohio.
1
Downloaded from ajs.sagepub.com at UNIVERSITAETSSPITAL on July 5, 2014
Harris et al
GETTING STARTED
Harris et al
SEARCH METHODOLOGY
The search strategy should be strictly focused on the
PICOS criteria. Before beginning the search, the authors
need to be aware that a PRISMA flowchart (Figure 3 and
Appendices 1-3 [available in the online version of this article at http://ajsm.sagepub.com/supplemental]) should be
created to illustrate study identification, screening, eligibility, inclusion, and analysis. There are several nonmutually exclusive electronic databases publicly available (free
of charge) for the extraction of studies to be included in systematic review analyses. Pay-per-use databases are also
accessible. Use of only a single database is insufficient.
PubMed is a free database that utilizes the MEDLINE
database maintained by the United States National
Library of Medicine of the National Institutes of Health.
As of December 31, 2012, there are 22.4 million citations
in the PubMed database. Embase is a subscription-based
database maintained by Elsevier BV, with more than
25.2 million citations (as of May 13, 2012). Embase contains all MEDLINE records and 5 million citations not
included in MEDLINE (including more than 2000 exclusively Embase-indexed journals). The Embase database is
growing by more than 1 million citations annually. PEDro
(Physiotherapy Evidence Database) is a free database
maintained by the Centre for Evidence-Based Physiotherapy. It contains more than 23,000 randomized controlled
trials, systematic reviews, and clinical practice management guidelines.
The Cochrane Library is a collection of 6 unique databases maintained by John Wiley & Sons Ltd. Included in
the Cochrane Library is the Cochrane Database of Systematic Reviews (CDSR), which contains 7626 systematic
reviews as of December 1, 2012. The reviews in the latter
are excellent examples upon which to guide a novice
author of systematic reviews. The Cochrane Central Register of Controlled Trials (CENTRAL) contains more than
680,000 controlled trials, most of which are concurrently
found in MEDLINE, Embase, Cochrane Review Groups
specialized registers, and hand-search results register.
SciVerse Scopus is a subscription-based database that contains 41 million records of peer-reviewed journals, books,
conferences, and scientific web pages.
Other commonly used databases for the identification of
studies relevant to the investigation for systematic reviews
include CINAHL (Cumulative Index to Nursing and Allied
Health Literature), SPORTDiscus, and Google Scholar.
Several publications have documented the necessity of utilizing at least 2 databases and, in certain circumstances,
hand-searching important selected journals.16,27,34 Nevertheless, in reference to sports medicine/orthopaedic surgery
meta-analyses, recall rates (defined as the proportion of primary studies analyzed within orthopaedic meta-analyses
that are indexed in either MEDLINE or Embase) of 90%
and 81% for MEDLINE and Embase were obtained individually for all primary studies included in the meta-analyses,
respectively.25 Combining MEDLINE and Embase
increased recall rates to 91%, and the addition of Cochrane
databases increased recall rates to 97%.25
Regardless of the database(s) used, the initial searchs
specificity must not compromise the sensitivity. In other
words, it is better to manually review more journal title(s),
abstract(s), and full-text article(s) in the database than to
be too specific and omit potentially inclusive studies. The
entire take-home point of the review, its results and conclusions, is based on the studies that it analyzes. Thus, it is
imperative to ensure that all of the relevant studies are
included. It may take a longer amount of time to perform
manual searching; however, this is absolutely necessary.
In addition to studies identified from the database(s)
searched, all reference lists from these studies should be
analyzed for the potential inclusion of studies omitted
from the initial search. A minimum of 2 reviewers should
perform the initial study identification, secondary study
screening, and final determination of eligibility and study
inclusion. Although the inclusion of conference abstracts
reduces publication bias, the bias introduced by the lack
of a formal rigorous peer-review process (and the oftenpresent differences between conference abstracts and final
published articles) often warrants the exclusion of
abstracts from high-quality systematic reviews.
Once the database review of study titles, abstracts, and
full-text articles has commenced, the investigator must be
sure to eliminate duplicate patient populations found in
different studies. This is applicable when authors publish
more than one article on the same group of patients, usually with different lengths of follow-up or with analysis
and reporting of a different primary or secondary outcome.
The easiest way to identify duplicate patient populations is
in the articles Methods section, which reports the dates of
patient enrollment. If 2 separate studies with the same
authors and the same intervention have overlapping dates
of patient enrollment, then only one study may be inclusive. In this situation, the reviewer should select the study
with the higher level of evidence, greater number of
patients, longer follow-up, or more thorough reporting of
the primary outcome of interest.
STATISTICAL ASSIMILATION
OF DATA (META-ANALYSIS)
Once all studies data have been extracted, a brief tabular
narrative of each investigation may be presented for publication within the article.12 Columnar data usually include
the (1) year of publication, (2) lead author, (3) number of
study participants, (4) participant group(s), (5) intervention(s), (6) follow-up period, and (7) outcomes. Unique
study details may warrant the addition of further study
details in a tabular/graphical form.14 Additional tables
may be added to illustrate complications and reoperations14 and study limitations/biases.13 After each study
has been critically evaluated, the decision must be made
to quantitatively group the data with like outcome tools
together (meta-analysis).15 Homogeneous studies allow
for the assimilation of separate studies results and the creation of a forest plot, which is an illustration that displays
the relative strength (effect size) of an individual studys
results that evaluate the same intervention with the
same outcome measure. Effect size analysis allows for
a direct numerical comparison between different studies.
Performance of a meta-analysis is not always possible
because of heterogeneity among studies. Heterogeneity
may be assessed in 1 of 2 ways. One is visually with the
eyeball test, published by the CEBM in 2005.31 This
test simply seeks to find the overlap of CIs of the trials
with the summary estimate on the forest plot. A second
method involves a quantitative assessment of statistical
heterogeneity via tests such as the Cochrane Q (x2) test,
index test (I2), or t2 test (or T2). It is recommended to
seek the assistance of a biostatistician who is experienced
in meta-analyses early in the timeline of the investigation.37 Additionally, it is important to understand, identify,
and directly report the difference between statistical significance and clinical relevance within the individual
TABLE 1
Relevant Information Sought to Be Extracted
From Individual Trialsa
Study details
Study author(s)
Journal
Year of publication
Years of patient enrollment
Presence, absence, or lack of reporting of financial COI
Level of evidence
Study design (RCT, prospective, retrospective, etc)
Single vs multicenter
Country of study performance
Key study statements
Primary and secondary purposes
Hypothesis(es)
Study inclusion and exclusion criteria
Intended primary and secondary outcome measures
Evaluation of study methodological quality
Cochrane Bone, Joint and Muscle Trauma Groups methodological
quality score
CLEAR-NPT
Delphi list
Detsky Quality Assessment Scale
Coleman (and modified) methodology score
Quality appraisal tool
Jadad score
CONSORT
STROBE statement
Newcastle-Ottawa Quality Assessment Scale
Participants
Number of patients enrolled
Blinded? Yes/no
Number of male/female patients
Number of body parts analyzed (eg, knees)
Number of right vs left sides
Number of dominant vs nondominant
Number of surgical interventions (eg, total knee arthroplasty)
Patient age, mean 6 SD
Clinical follow-up, mean 6 SD
% follow-up (eg, .80%)
Radiographic follow-up (if applicable), mean 6 SD
Duration of symptoms warranting an intervention, mean 6 SD
Length of treatment before intervention, mean 6 SD
Number of prior surgical procedures, mean 6 SD
Other treatments performed
Interventions
Number of interventions performed in each group, mean 6 SD
Number of providers performing the intervention
Blinded? Yes/no
Comparators
Number of patients in control or comparator groups
Description of treatment in the control or comparator groups
Outcomes
Explicit description of all outcome measures and scores utilized
Preintervention score
1-year score
2-year score
5-year score
Etc
Number of complications
Number of reinterventions
Independent blinded evaluator/assessor?
Were study conclusions based on study results?
a
CLEAR-NPT, Checklist to Evaluate and Report a Non-Pharmacologic
Trial; COI, conflict of interest; CONSORT, Consolidated Standards of
Reporting Trials; RCT, randomized controlled trial; SD, standard deviation;
STROBE, Strengthening the Reporting of Observational Studies in
Epidemiology.
Harris et al
TABLE 2
Pearls and Pitfalls for the Conduct of a High-Quality Systematic Reviewa
Pearls
Pitfalls
Answerable question
Does the review improve significantly upon existing reviews?
PICOS strategy protocol
PROSPERO registration
PRISMA guidelines, checklist, and flowchart
Thorough data extraction
Quantitative synthesis of studies data (if applicable, meta-analysis)
Grade the evidence and strength of recommendations (eg, SORT,
GRADE)
Explicit statement of the reviews take-home point
a
GRADE, Grading of Recommendations Assessment, Development, and Evaluation; PICOS, Participants, Interventions, Comparisons/
Controls, Outcomes, and Study Design; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses; SORT, Strength
of Recommendation Taxonomy.
EVALUATION OF STUDY
METHODOLOGICAL QUALITY
The quality of a systematic review (Table 2) is only as good
as the studies that it analyzes. Thus, a review of only randomized controlled trials with level I evidence is a level I
review. Further, a review of multiple level I randomized
trials and multiple level III retrospective case comparison
studies is a level III review. In addition to level of evidence
ratings (updated by the CEBM in 2011),32 there are several
different study methodological quality scores available to
numerically grade the quality of a trial (Table 1). Some
questionnaires are designed as guides to help improve
the conduct and reporting of trials and are not intended
to generate a quantitative result (eg, CONSORT). When
intended to numerically grade the quality of an investigation, these scores simply grade the quality of study reporting and not necessarily the quality of study performance
and conduct. It is important to recognize that, just as the
review search and study selection be performed by at least
2 reviewers, it is also important to assess study quality
with at least 2 reviewers as well. These quality evaluation
tools describe the potential sources of bias within studies
(eg, selection, performance, transfer, detection, publication, study design). The reviewers must be aware that
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