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5.7 References
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Review authors should define up front the reference standard(s) to be included in the
review. They should also explain whether variations or combinations of reference
standards will be considered acceptable for inclusion.
5.6 Chapter information
Authors: Mariska M. Leeflang (Department of Epidemiology and Data Science, University
of Amsterdam, The Netherlands), Clare Davenport (Institute of Applied Health Research,
University of Birmingham, UK), Patrick M. Bossuyt (Department of Epidemiology and
Data Science, University of Amsterdam, The Netherlands).
Sources of support: The authors declare no sources of support for writing this
chapter.
Declarations of interest: Mariska M. Leeflang and Clare Davenport are members of
Cochrane’s Diagnostic Test Accuracy Editorial Team. Mariska M. Leeflang is coof the Cochrane Screening and Diagnostic Tests Methods Group. The authors declare no
other potential conflicts of interest relevant to the topic of this chapter.
Acknowledgements: The authors thank Rob J. Scholten and Chris Hyde for contributions to a previous version of this chapter. The authors would like to thank Karen R.
Steingart and Ingrid Arevalo-Rodriguez for helpful peer review comments.
convenor
5.7 References
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existing diagnostic pathways. BMJ 2006; 332: 1089–1092.
Chalmers I, Bracken MB, Djulbegovic B, Garattini S, Grant J, Gülmezoglu AM, Howells DW,
Ioannidis JP, Oliver S. How to increase value and reduce waste when research priorities
are set. Lancet 2014; 383: 156–165.
Chuchu N, Takwoingi Y, Dinnes J, Matin RN, Bassett O, Moreau JF, Bayliss SE, Davenport C,
Godfrey K, O’Connell S, Jain A, Walter FM, Deeks JJ, Williams HC. Smartphone applications for triaging adults with skin lesions that are suspicious for melanoma. Cochrane
Database of Systematic Reviews 2018; 12: CD013192.
Dinnes J, Deeks JJ, Grainge MJ, Chuchu N, Ferrante di Ruffano L, Matin RN, Thomson DR,
Wong KY, Aldridge RB, Abbott R, Fawzy M, Bayliss SE, Takwoingi Y, Davenport C, Godfrey
K, Walter FM, Williams HC, Cochrane Skin Cancer Diagnostic Test Accuracy G. Visual
inspection for diagnosing cutaneous melanoma in adults. Cochrane Database of
Systematic Reviews 2018; 12: CD013194.
Dinnes J, Deeks JJ, Berhane S, Taylor M, Adriano A, Davenport C, Dittrich S, Emperador D,
Takwoingi Y, Cunningham J, Beese S, Dretzke J, Ferrante di Ruffano L, Harris IM, Price MJ,
Taylor- Phillips S, Hooft L, Leeflang MM, Spijker R, Van den Bruel A, Cochrane COVID- 19
Diagnostic Test Accuracy Group. Rapid, point- of- care antigen and molecular- based tests
for diagnosis of SARS- CoV- 2infection. Cochrane Database of Systematic Reviews 2021;
3:CD013705.
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Ferrante di Ruffano L, Takwoingi Y, Dinnes J, Chuchu N, Bayliss SE, Davenport C, Matin RN,
Godfrey K, O’Sullivan C, Gulati A, Chan SA, Durack A, O’Connell S, Gardiner MD, Bamber
J, Deeks JJ, Williams HC, Cochrane Skin Cancer Diagnostic Test Accuracy G. Computerassisted diagnosis techniques (dermoscopy and spectroscopy- based) for diagnosing
skin cancer in adults. Cochrane Database of Systematic Reviews 2018; 12: CD013186.
Gopalakrishna G, Langendam MW, Scholten RJPM, Bossuyt PMM, Leeflang MMG. Guidelines
for guideline developers: a systematic review of grading systems for medical tests.
Implementation Science 2013; 8: 78.
Gopalakrishna G, Langendam MW, Scholten RJPM, Bossuyt PMM, Leeflang MMG. Defining
the clinical pathway in Cochrane diagnostic test accuracy reviews. BMC Medical Research
Methodology 2016; 16: 153.
Islam N, Ebrahimzadeh S, Salameh JP, Kazi S, Fabiano N, Treanor L, Absi M, Hallgrimson Z,
Leeflang MM, Hooft L, van der Pol CB, Prager R, Hare SS, Dennie C, Spijker R, Deeks JJ,
Dinnes J, Jenniskens K, Korevaar DA, Cohen JF, Van den Bruel A, Takwoingi Y, van de
Wijgert J, Damen JA, Wang J, McInnes MD. Thoracic imaging tests for the diagnosis of
19. Cochrane Database of Systematic Reviews 2021; 3: CD013639.
COVID-
Korevaar DA, Gopalakrishna G, Cohen JF, Bossuyt PM. Targeted test evaluation: a frame-
work for designing diagnostic accuracy studies with clear study hypotheses. Diagnostic
and Prognostic Research 2019; 3: 22.
Leeflang MM, Debets-
Ossenkopp YJ, Wang J, Visser CE, Scholten RJ, Hooft L, Bijlmer HA,
Reitsma JB, Zhang M, Bossuyt PM, Vandenbroucke- Grauls CM. Galactomannan detection
for invasive aspergillosis in immunocompromised patients. Cochrane Database of
Systematic Reviews 2015; 12: CD007394.
Liu E, Nisenblat V, Farquhar C, Fraser I, Bossuyt PM, Johnson N, Hull ML. Urinary biomark-
ers for the non-
invasive diagnosis of endometriosis. Cochrane Database of Systematic
Reviews 2015; 12: CD012019.
Lord SJ, St John A, Bossuyt PM, Sandberg S, Monaghan PJ, O’Kane M, Cobbaert CM,
Röddiger R, Lennartz L, Gelfi C, Horvath AR. Setting clinical performance specifications
to develop and evaluate biomarkers for clinical use. Annals of Clinical Biochemistry 2019;
56: 527–535.
Niedermaier T, Balavarca Y, Brenner H. Stage- specific sensitivity of fecal immunochemical
tests for detecting colorectal cancer: systematic review and meta- analysis. American
Journal of Gastroenterology 2020; 115: 56–69.
Pepe MS, Janes H, Li CI, Bossuyt PM, Feng Z, Hilden J. Early- phase studies of biomarkers:
what target sensitivity and specificity values might confer clinical utility? Clinical
Chemistry 2016; 62: 737–742.
Randall M, Egberts KJ, Samtani A, Scholten R, Hooft L, Livingstone N, Sterling-
Levis K,
Woolfenden S, Williams K. Diagnostic tests for autism spectrum disorder (ASD) in
preschool children. Cochrane Database of Systematic Reviews 2018; 7: CD009044.
Schrecengost JE, LeGallo RD, Boyd JC, Moons KG, Gonias SL, Rose CE, Jr., Bruns DE.
Comparison of diagnostic accuracies inoutpatients and hospitalized patients of D-
dimer
testing for the evaluation of suspected pulmonary embolism. ClinicalChemistry 2003;
49: 1483–1490.
Shapiro AE, Ross JM, Yao M, Schiller I, Kohli M, Dendukuri N, Steingart KR, Horne DJ. Xpert
MTB/RIF and Xpert Ultra assays for screening for pulmonary tuberculosis and rifampicin
resistance in adults, irrespective of signs or symptoms. Cochrane Database of Systematic
Reviews 2021; 3: CD013694.
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Slaar A, Fockens MM, Wang J, Maas M, Wilson DJ, Goslings JC, Schep NW, van Rijn RR.
Triage tools for detecting cervical spine injury in pediatric trauma patients. Cochrane
Database of Systematic Reviews 2017; 12: CD011686.
Weiser K, Maayan N, Bergman H, Davenport C, Kirkham AJ, Grabowski S, Adams CE.
Soares-
First rank symptoms for schizophrenia. Cochrane Database of Systematic Reviews 2015;
1: CD010653.
Tamburrino D, Riviere D, Yaghoobi M, Davidson BR, Gurusamy KS. Diagnostic accuracy of
different imaging modalities following computed tomography (CT) scanning for
assessing the resectability with curative intent in pancreatic and periampullary cancer.
Cochrane Database of Systematic Reviews 2016; 9: CD011515.
Vaarwerk B, Breunis WB, Haveman LM, de Keizer B, Jehanno N, Borgwardt L, van Rijn RR,
van den Berg H, Cohen JF, van Dalen EC, Merks JH. Fluorine-
18- fluorodeoxyglucose
(FDG) positron emission tomography (PET) computed tomography (CT) for the detection
of bone, lung, and lymph node metastases in rhabdomyosarcoma. Cochrane Database of
Systematic Reviews 2021; 11: CD012325.
Wijedoru L, Mallett S, Parry CM. Rapid diagnostic tests for typhoid and paratyphoid
(enteric) fever. Cochrane Database of Systematic Reviews 2017; 5: CD008892.
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Searching forand selecting studies
René Spijker, Jacqueline Dinnes, Julie Glanville and Anne Eisinga
KEY POINTS
Review teams should include an information specialist or at least one co- author with
•
expertise in searching.
Search strategies should be developed by the information specialist in close collaboration
•
with review authors with clinical and technical knowledge of, and expertise in, the
index test(s) and target condition(s) under investigation.
Test accuracy questions can be complex and the optimal search strategy may use
•
several combinations of key concepts combined into one overall database query
stranded) to capture the different ways in which relevant studies may be
(multi described.
Methodological search filters should not be added to the final set of search results,
•
as they may result in studies being missed. They could, however, be used within the
search as part of a multiIn addition to MEDLINE and Embase, a range of bibliographic databases including
•
subjectshould be searched. The references of retrieved studies, forward citation searches,
the ‘similar articles’ feature in electronic databases, grey literature and
searches should also be considered.
The proposed search strategy for at least one database should be included in the
•
protocol of the review to enable peer review at an early stage in review production.
Full details of the search process should be reported in the final review, including the
•
full details of each search as conducted. Complex searches should be explained in a
narrative way so that the logic of their construction is clear.
specific (e.g. DiTA (physiotherapy), CINAHL) and regional databases (e.g. LILACS)
stranded approach.
internet
This chapter should be cited as: Spijker R, Dinnes J, Glanville J, Eisinga A. Chapter6: Searching for and selecting
studies. In: Deeks JJ, Bossuyt PM, Leeflang MM, Takwoingi Y, editors. Cochrane Handbook for Systematic Reviews
of Diagnostic Test Accuracy. 1st edition. Chichester (UK): John Wiley &Sons, 2023: 97–130.
Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy, First Edition. Edited by
Jonathan J. Deeks, Patrick M. Bossuyt, Mariska M. Leeflang and Yemisi Takwoingi.
© 2023 The Cochrane Collaboration. Published 2023 by John Wiley & Sons Ltd.
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6.1 Introduction
Conducting an effective search for studies to determine the diagnostic accuracy of
tests is a crucial and challenging task in preparing a systematic review of test accuracy. Search strategies for test accuracy studies can be particularly complex and
knowledge of a range of resources may be needed. This chapter is designed to help
review authors gain a better understanding of the search process as a whole and of
the key role played by the information specialist on the review team. An online technical supplement to Chapter4 of the Cochrane Handbook for Systematic Reviews of
Interventions, aimed at those actually carrying out the search process, provides more
detail on searching methods (Lefebvre 2021). It is accompanied by an appendix listing
a wide range of potential resources to search and search tools to aid in the review
process. This is regularly updated. To support decisions on how best to optimize
searching, there is further evidencelished research, on the SuRe Info portal (www.sites.google.com/york.ac.uk/sureinfo/
home), which is updated twice a year. There is a specific section dedicated to diagnostic test accuracy.
This chapter provides an overview of approaches for searching for test accuracy studies. It starts with the general principles for searching for studies and sources to search,
followed by considerations for designing search strategies and documenting and
reporting the search process. The process of selecting relevant studies and a summary
of future developments completes the chapter.
based information, including appraisals of pub-
6.2 Searching forstudies
The aim of the literature search is to generate as extensive a list as possible of studies
that may be suitable for answering the review question, within available resource
constraints. Key decisions include the type of literature that may be relevant, the
identification of relevant sources of literature and the design of a search strategy that
will identify as many relevant reports as possible in the most efficient way, without
creating an unmanageable volume of records for title and abstract screening.
The literature typically encompasses published and unpublished study reports,
including journal articles, dissertations, conference proceedings and reports (see
Chapter 7), the importance of which will vary depending on the review question.
Sources include a range of electronic bibliographic databases, web- based topic- specific
resources (such as the Cochrane COVID- 19 Study Register (www.covid- 19.cochrane.
org)) and other search approaches such as handsearching journals, citation tracking
and contacting experts, other research groups and test manufacturers (Section6.4).
The selection of sources to search, particularly when resources are scarce, should be
guided by evidence whenever possible from information retrieval research and systematic reviews of similar topics. Although publication bias is a more complex issue in
systematic reviews of test accuracy than in intervention reviews (see Section6.4.7 and
Chapter 12, Section 12.3.1.5), a well- planned search strategy, for example including
searching conference abstracts, trials registries and checking for test accuracy study
protocols, may provide information about unpublished evidence and mitigate potential
publication or reporting bias (Zarei 2018, Glanville 2021).
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Box 6.2.a Performance measures forsearch strategies
Search recall (search sensitivity) is defined as the number of relevant records identified by a search strategy divided by the total number of relevant records on a given topic.
It is a measure of the comprehensiveness of the search method. Strategies with high
recall tend to have low levels of precision and the other way round. The challenge in
estimating the effectiveness of search recall is that we rarely know how many relevant
records are available to be identified.
Precision is defined as the number of relevant records identified by a search strategy
divided by the total number of records identified. It is a measure of the ability of a search
to exclude irrelevant reports. Its inverse (1/precision) represents the number of records
we need to read to find one relevant report (number needed to read, NNR).
Source: Adapted from Bachmann 2002.
Search strategies need as an aim to identify all relevant records, but without retrieving too many irrelevant records. Therefore we need to balance optimum recall with
manageable precision; see Box6.2.a. Another term for recall is (search) sensitivity.
However, as this handbook is about systematic reviews of test accuracy, and sensitivity
is also a performance measure of tests, we use the term recall instead of (search) sensitivity in this chapter.
Depending on the research question (see Chapter5) and the possible ways in which
relevant studies have been designed and described (see Chapter3), strategies for identifying test accuracy studies may use a number of different combinations of concepts
from the research question. The starting point for most reviews will be to structure the
search using terms related to two key concepts: the test(s) of interest (index test) and
the condition to be detected (target condition). Other concepts, including the population to be tested, the reference standard or accuracy measures, may also be used in
combination with either one or both of these key concepts. Depending on how exactly
they will be combined, these additions may increase search recall (to minimize the risk
of missing relevant studies) or may be used to improve precision (to minimize the
retrieval of irrelevant records) if a simple two- concept search is producing unmanageable numbers of records.
For some topics, a combination of several search queries may be needed, each representing different combinations of key concepts (Whiting 2006). To determine the optimal approach, review authors need to explore how relevant test accuracy studies have
been reported in the literature and indexed in databases (see Section 6.3 and
Section6.4). Reporting guidelines for studies of diagnostic test accuracy (STARD) have
been developed (Bossuyt 2015, Cohen 2017), including standards designed for specific
subject areas, such as diagnostic accuracy studies in dementia (Noel- Storr 2014) and
those evaluating tests that make use of artificial intelligence (STARD- AI) (Sounderajah
2021). These standards, if adhered to, should help to make studies more discoverable by
systematic searches. There is some evidence that adoption of the STARD reporting
guideline for diagnostic accuracy studies (Bossuyt 2015) has begun to improve reporting standards (Korevaar 2014b, Korevaar 2015), but abstracts can still be poorly
reported, leading to inadequate indexing (Cohen 2019, Gurung 2020). Search strategies
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therefore should not only rely on subject headings assigned by database indexers, but
include text word searches of the record title, abstract and authors’ keywords. These
search options can differ across databases, so a good working knowledge of the features of the major databases as well as search query design is essential (Section6.4.7).
6.2.1 Working inpartnership
There are many advantages for systematic review teams that include review authors
with a range of expertise. Ideally, review author teams should include an information
specialist or at least one author with equivalent experience of systematic review searching. This expertise includes more than just an extensive knowledge of possible search
terms. Knowledge of the types of documents that may contain the required evidence
and knowledge of the databases and other places where these documents may be
found are needed to design and execute good search strategies. Planning, designing
and conducting the complete search process constitute a team effort. Although the
electronic searching will typically be carried out by one individual with experience in
designing electronic search strategies, other search types, such as manually checking
reference lists or identifying grey literature, may be done by other review authors.
Box6.2.b provides examples of the type of information that might be provided by review
authors with clinical and technical knowledge and the contributions that can be
provided by an information specialist. Above all, the involvement of an information
specialist in the review should improve the quality of various aspects of the search
process (Rethlefsen 2015, Meert 2016, Metzendorf2016).
Box 6.2.b Range ofreview author roles forsystematic review searching
Review authors with clinical and technical knowledge about the index test(s) and target
condition(s) can:
●
explain and clearly describe each of the key concepts of the review;
●
advise on terminology, for example where tests may have different names or can be
referred to using different abbreviations, or if the names for diseases have changed
over time;
●
provide known relevant studies to help develop search strategies and validate search
results;
●
suggest specialized sources (such as journals, databases, registries, etc.) to search;
●
provide advice on the relevance of records retrieved during search iterations or when
responding to peer reviewer comments to clarify whether proposed search terms are
appropriate;
●
identify related systematic reviews for information on helpful sources to search, terminology used and potentially relevant citations;
●
provide information about potentially eligible commercial tests or test manufacturers; and
●
provide any other information relevant to searching the literature, such as advice on
different uses of clinical terms, how far back to search, which study authors or research
groups are known experts in the topic area, etc.
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Information specialists can:
●
provide feedback on the clarity or scope of the review question in relation to the
reports expected to be found;
●
provide feedback and advice on the types of reports to be included;
●
support the team by providing insight on types of report likely to be found and how
this relates to the question and the types of report the team may wish to identify;
●
select sources to search;
●
design, develop, test, adapt and run search strategies in each selected database;
●
provide a draft search narrative to include search sources and master strategy and any
key outputs/deliverables (e.g.search narrative and EndNote file of search results) for
off before beginning the definitive searches;
sign-
●
save search results;
●
remove duplicates;
●
send results to the team in a format compatible with the team’s chosen reference management software where possible;
●
provide a detailed search log to assist with fully documenting and reporting the search
process;
●
assist in locating the full text of documents; and
●
contribute to writing the review, with specific emphasis on writing up the search
methods and search results.
6.2.2 Advice forreview teams that do not include aninformation specialist
If for any reason it is not possible to include an information specialist on the review
team, author teams can contact an information specialist or medical/healthcare librarian at their own institution. Many university (medical) libraries and specialized research
institutes employ qualified staff who will have experience in systematic review search
approaches. Alternatively, the team can contact resources such as Cochrane task
exchange (taskexchange.cochrane.org) or independent search specialist services.
6.3 Sources tosearch
6.3.1 Bibliographic databases
Thousands of electronic bibliographic databases exist. Some, such as MEDLINE and
Embase, cover a wide range of areas of health care and index journals from around the
world, while others index journals from specific regions, focus on specific areas of
health care or on specific document types.
Choosing the most appropriate databases to search is an essential component of
designing a search. Review authors with topic expertise should share with the information specialist any knowledge they have regarding specialized sources of research that
may be useful, as these may yield relevant studies not held in mainstream databases.
Topic experts should also provide a list of relevant journals in the field, as these can be
used to make an informed decision about the bibliographic databases to be searched.
Sources such as Ulrichsweb (www.ulrichsweb.serialssolutions.com) list all the
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bibliographic databases that index a specific journal. The online technical supplement
to the Cochrane Handbook for Systematic Reviews of Interventions provides a selective
list of possible resources that can be searched, together with a regularly updated
appendix of additional resources (Lefebvre 2021).
There is overlap between different databases with regard to the journals indexed and
the records retrieved. For example, Embase now includes all MEDLINE records.
Differences in the way in which the two databases index records, using different indexing systems and rules, mean that some articles that are difficult to identify from one
database may be retrieved more easily from the other. In addition, database providers
of MEDLINE and Embase present different search interfaces with differing functionality,
which may also explain why some records may be retrieved from one interface to the
database and not another. Because of the overlap between databases, one of the first
steps of the selection process is deduplication of the retrieved articles. This can often be
automated, but needs to be checked by a human (see online technical supplement,
Section4.3in Lefebvre 2021).
MEDLINE, PubMed and Embase
6.3.1.1
MEDLINE, the US National Library of Medicine’s database of citations and abstracts,
currently indexes over 5200journals in about 40languages. Its subject scope is biomedicine and health. MEDLINE is available free via PubMed, on subscription from a
number of online database providers, such as Ovid, or can be accessed through Embase
(see later). The Ovid search interface and others offer advanced search facilities that
can help increase search precision.
MEDLINE is the primary component of PubMed (www.pubmed.ncbi.nlm.nih.gov), a
search engine supporting the retrieval of literature from MEDLINE. PubMed also includes
records from journals that are not indexed for MEDLINE and records considered ‘out of
scope’ from journals that are only partially indexed for MEDLINE. Using PubMed is free
of charge and does not require registration, which is why many review authors use
PubMed as their primary way to search MEDLINE. However, PubMed does not currently
have advanced search techniques such as proximity operators, genuine phrase searching, wildcards and the ability to limit truncation, which are useful tools to optimize the
balance between search recall and precision in information retrieval.
Embase, a biomedical and pharmacological bibliographic database published by
Elsevier, indexes over 8200journals in over 30languages. Embase also includes conference abstracts from 2010 onwards. Embase includes records from MEDLINE from 1966
to date, thus allowing both databases to be searched simultaneously. Embase is only
available by subscription and can be accessed through a number of interfaces, including Ovid and Embase.com.
Both Embase and MEDLINE have an indexing system (also known as a ‘controlled
vocabulary’): EMTREE for Embase and Medical Subject Headings (MeSH) for MEDLINE.
These indexing systems are topic based and use a preferred term to describe a concept
that might be described by authors in many different ways using many different terms.
This can help to increase recall, for example if a record does not mention a specific
term. The preferred term is assigned by the indexer to all the records covering that concept, irrespective of how the authors have described the concept in the article. Every
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article is labelled with multiple indexing terms to describe concepts such as the population,
disease or condition, outcomes and tests. Other indexing terms are used to retrieve
particular publication types such as letters and comments, and still others are designed
to retrieve particular types of study design, for example test accuracy studies (see
Section6.5.2).
The PubMed and Ovid interfaces also have ‘similar articles’ or ‘find similar’ features,
where an algorithm is used to find articles that may be similar in subject to the studies
already retrieved. This can be a useful tool when building a set of relevant articles to
help design and test a search strategy (see Section6.4.7).
National andregional databases
6.3.1.2
Country- or region- specific databases, such as the Latin American and Caribbean Health
Sciences Literature (LILACS) database or China National Knowledge Infrastructure
(CNKI), record the literature produced in these geographical areas and often include
publications not indexed elsewhere. Record abstracts may be in English or other languages, in which case searches need to be performed in the region- specific language(s).
Many such databases are available free of charge on the internet, while others are available by subscription or on a ‘pay- as- you- go’ basis. The complexity and consistency of
database indexing vary by database, as does the sophistication of the search interface.
Examples are included in the online technical supplement of the Cochrane Handbook
for Systematic Reviews of Interventions and an extensive list is given in the supplementary appendix of resources (Lefebvre 2021).
Region- specific databases can be an important source of additional studies, particularly as tests are not always used in the same way across countries and regions, and test
pathway. A case study by Cohen and colleagues compared two systematic reviews of
anti- cyclic citrullinated peptide for diagnosing rheumatoid arthritis (Cohen 2015). One
review, which included Chinese databases in its search strategy, resulted in the identification of 100 additional studies compared to the other review. Supplementing a search
of MEDLINE and Embase with databases from other regions may therefore be particularly important for systematic reviews of test accuracy.
6.3.1.3 Subject- specific databases
Subject- specific databases index literature according to fields of research, for example
CINAHL indexes nursing and allied health literature, PsycINFO covers psychology and
psychiatry, and BIOSIS Previews covers biological sciences and related areas. Searching
subject- specific databases may add unique records from journals not indexed in
MEDLINE or Embase (Whiting 2008, Rice 2016). For example, PsycINFO may include
additional studies on the measurement of instrument performance.
Evidence of the impact of searching extensively, for example including subjectspecific databases compared to restricting the search to one or two main biomedical
sources, on the estimates of sensitivity and specificity in syntheses of test accuracy is
sparse (van Enst 2014, Glanville 2021) or has not been conducted as part of exploratory
studies to improve search efficiency (Preston 2015). Searching for test accuracy studies
in subject- specific databases should be considered as part of a careful search strategy
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