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What Makes a Systematic Review Different from Other Types of Reviews?

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Reproduced from Grant, M. J. and Booth, A. (2009), A typology of reviews: an analysis of 14 review types and associated methodologies. Health Information & Libraries Journal, 26: 91–108. doi:10.1111/j.1471-1842.2009.00848.x

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Systematic, Scoping, and Other Literature Reviews: Overview

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What Is a Systematic Review?

Regular literature reviews are simply summaries of the literature on a particular topic. A systematic review, however, is a comprehensive literature review conducted to answer a specific research question. Authors of a systematic review aim to find, code, appraise, and synthesize all of the previous research on their question in an unbiased and well-documented manner. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) outline the minimum amount of information that needs to be reported at the conclusion of a systematic review project. 

Other types of what are known as "evidence syntheses," such as scoping, rapid, and integrative reviews, have varying methodologies. While systematic reviews originated with and continue to be a popular publication type in medicine and other health sciences fields, more and more researchers in other disciplines are choosing to conduct evidence syntheses. 

This guide will walk you through the major steps of a systematic review and point you to key resources including Covidence, a systematic review project management tool. For help with systematic reviews and other major literature review projects, please send us an email at  [email protected] .

Getting Help with Reviews

Organization such as the Institute of Medicine recommend that you consult a librarian when conducting a systematic review. Librarians at the University of Nevada, Reno can help you:

• Understand best practices for conducting systematic reviews and other evidence syntheses in your discipline
• Choose and formulate a research question
• Decide which review type (e.g., systematic, scoping, rapid, etc.) is the best fit for your project
• Determine what to include and where to register a systematic review protocol
• Select search terms and develop a search strategy
• Identify databases and platforms to search
• Find the full text of articles and other sources
• Become familiar with free citation management (e.g., EndNote, Zotero)
• Get access to you and help using Covidence, a systematic review project management tool

Doing a Systematic Review

• Plan - This is the project planning stage. You and your team will need to develop a good research question, determine the type of review you will conduct (systematic, scoping, rapid, etc.), and establish the inclusion and exclusion criteria (e.g., you're only going to look at studies that use a certain methodology). All of this information needs to be included in your protocol. You'll also need to ensure that the project is viable - has someone already done a systematic review on this topic? Do some searches and check the various protocol registries to find out. 
• Identify - Next, a comprehensive search of the literature is undertaken to ensure all studies that meet the predetermined criteria are identified. Each research question is different, so the number and types of databases you'll search - as well as other online publication venues - will vary. Some standards and guidelines specify that certain databases (e.g., MEDLINE, EMBASE) should be searched regardless. Your subject librarian can help you select appropriate databases to search and develop search strings for each of those databases.  
• Evaluate - In this step, retrieved articles are screened and sorted using the predetermined inclusion and exclusion criteria. The risk of bias for each included study is also assessed around this time. It's best if you import search results into a citation management tool (see below) to clean up the citations and remove any duplicates. You can then use a tool like Rayyan (see below) to screen the results. You should begin by screening titles and abstracts only, and then you'll examine the full text of any remaining articles. Each study should be reviewed by a minimum of two people on the project team. 
• Collect - Each included study is coded and the quantitative or qualitative data contained in these studies is then synthesized. You'll have to either find or develop a coding strategy or form that meets your needs. 
• Explain - The synthesized results are articulated and contextualized. What do the results mean? How have they answered your research question?
• Summarize - The final report provides a complete description of the methods and results in a clear, transparent fashion. 

Adapted from

Types of reviews, systematic review.

These types of studies employ a systematic method to analyze and synthesize the results of numerous studies. "Systematic" in this case means following a strict set of steps - as outlined by entities like PRISMA and the Institute of Medicine - so as to make the review more reproducible and less biased. Consistent, thorough documentation is also key. Reviews of this type are not meant to be conducted by an individual but rather a (small) team of researchers. Systematic reviews are widely used in the health sciences, often to find a generalized conclusion from multiple evidence-based studies. 

Meta-Analysis

A systematic method that uses statistics to analyze the data from numerous studies. The researchers combine the data from studies with similar data types and analyze them as a single, expanded dataset. Meta-analyses are a type of systematic review.

Scoping Review

A scoping review employs the systematic review methodology to explore a broader topic or question rather than a specific and answerable one, as is generally the case with a systematic review. Authors of these types of reviews seek to collect and categorize the existing literature so as to identify any gaps.

Rapid Review

Rapid reviews are systematic reviews conducted under a time constraint. Researchers make use of workarounds to complete the review quickly (e.g., only looking at English-language publications), which can lead to a less thorough and more biased review. 

Narrative Review

A traditional literature review that summarizes and synthesizes the findings of numerous original research articles. The purpose and scope of narrative literature reviews vary widely and do not follow a set protocol. Most literature reviews are narrative reviews. 

Umbrella Review

Umbrella reviews are, essentially, systematic reviews of systematic reviews. These compile evidence from multiple review studies into one usable document. 

Grant, Maria J., and Andrew Booth. “A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies.” Health Information & Libraries Journal , vol. 26, no. 2, 2009, pp. 91-108. doi: 10.1111/j.1471-1842.2009.00848.x .

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Original Research

State-of-the-art literature review methodology: a six-step approach for knowledge synthesis.

• Jerusalem Merkebu
• Lara Varpio
• Jerusalem Merkebu , Department of Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, United States
• Lara Varpio , Department of Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, United States

Introduction Researchers and practitioners rely on literature reviews to synthesize large bodies of knowledge. Many types of literature reviews have been developed, each targeting a specific purpose. However, these syntheses are hampered if the review type’s paradigmatic roots, methods, and markers of rigor are only vaguely understood. One literature review type whose methodology has yet to be elucidated is the state-of-the-art (SotA) review. If medical educators are to harness SotA reviews to generate knowledge syntheses, we must understand and articulate the paradigmatic roots of, and methods for, conducting SotA reviews.

Methods We reviewed 940 articles published between 2014–2021 labeled as SotA reviews. We (a) identified all SotA methods-related resources, (b) examined the foundational principles and techniques underpinning the reviews, and (c) combined our findings to inductively analyze and articulate the philosophical foundations, process steps, and markers of rigor.

Results In the 940 articles reviewed, nearly all manuscripts (98%) lacked citations for how to conduct a SotA review. The term “state of the art” was used in 4 different ways. Analysis revealed that SotA articles are grounded in relativism and subjectivism.

Discussion This article provides a 6-step approach for conducting SotA reviews. SotA reviews offer an interpretive synthesis that describes: This is where we are now. This is how we got here. This is where we could be going. This chronologically rooted narrative synthesis provides a methodology for reviewing large bodies of literature to explore why and how our current knowledge has developed and to offer new research directions.

• Page/Article: 1-8
• DOI: 10.1007/S40037-022-00725-9
• Accepted on 27 Jul 2022
• Published on 5 Sep 2022
• Peer Reviewed

Libraries | Research Guides

Literature reviews, what is a literature review, learning more about how to do a literature review.

• Planning the Review
• The Research Question
• Choosing Where to Search
• Organizing the Review
• Writing the Review

A literature review is a review and synthesis of existing research on a topic or research question. A literature review is meant to analyze the scholarly literature, make connections across writings and identify strengths, weaknesses, trends, and missing conversations. A literature review should address different aspects of a topic as it relates to your research question. A literature review goes beyond a description or summary of the literature you have read. 

• Sage Research Methods Core Collection This link opens in a new window SAGE Research Methods supports research at all levels by providing material to guide users through every step of the research process. SAGE Research Methods is the ultimate methods library with more than 1000 books, reference works, journal articles, and instructional videos by world-leading academics from across the social sciences, including the largest collection of qualitative methods books available online from any scholarly publisher. – Publisher

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• Last Updated: Jan 17, 2024 10:05 AM
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Literature Reviews

• What is a literature review?
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What is a Literature Review?

A literature or narrative review is a comprehensive review and analysis of the published literature on a specific topic or research question. The literature that is reviewed contains: books, articles, academic articles, conference proceedings, association papers, and dissertations. It contains the most pertinent studies and points to important past and current research and practices. It provides background and context, and shows how your research will contribute to the field. 

A literature review should: 

• Provide a comprehensive and updated review of the literature;
• Explain why this review has taken place;
• Articulate a position or hypothesis;
• Acknowledge and account for conflicting and corroborating points of view

From  S age Research Methods

Purpose of a Literature Review

A literature review can be written as an introduction to a study to:

• Demonstrate how a study fills a gap in research
• Compare a study with other research that's been done

Or it can be a separate work (a research article on its own) which:

• Organizes or describes a topic
• Describes variables within a particular issue/problem

Limitations of a Literature Review

Some of the limitations of a literature review are:

• It's a snapshot in time. Unlike other reviews, this one has beginning, a middle and an end. There may be future developments that could make your work less relevant.
• It may be too focused. Some niche studies may miss the bigger picture.
• It can be difficult to be comprehensive. There is no way to make sure all the literature on a topic was considered.
• It is easy to be biased if you stick to top tier journals. There may be other places where people are publishing exemplary research. Look to open access publications and conferences to reflect a more inclusive collection. Also, make sure to include opposing views (and not just supporting evidence).

Source: Grant, Maria J., and Andrew Booth. “A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies.” Health Information & Libraries Journal, vol. 26, no. 2, June 2009, pp. 91–108. Wiley Online Library, doi:10.1111/j.1471-1842.2009.00848.x.

Meryl Brodsky : Communication and Information Studies

Hannah Chapman Tripp : Biology, Neuroscience

Carolyn Cunningham : Human Development & Family Sciences, Psychology, Sociology

Larayne Dallas : Engineering

Janelle Hedstrom : Special Education, Curriculum & Instruction, Ed Leadership & Policy ​

Susan Macicak : Linguistics

Imelda Vetter : Dell Medical School

For help in other subject areas, please see the guide to library specialists by subject .

Periodically, UT Libraries runs a workshop covering the basics and library support for literature reviews. While we try to offer these once per academic year, we find providing the recording to be helpful to community members who have missed the session. Following is the most recent recording of the workshop, Conducting a Literature Review. To view the recording, a UT login is required.

• October 26, 2022 recording
• Last Updated: Oct 26, 2022 2:49 PM
• URL: https://guides.lib.utexas.edu/literaturereviews

Targeted literature review of the burden of illness in patients with chronic kidney disease and type 2 diabetes

Affiliation.

• 1 University of Tennessee Health Science Center, 965 Court Avenue, Room 222, Memphis, TN 38163. Email: [email protected].
• PMID: 34019359
• DOI: 10.37765/ajmc.2021.88660

Objectives: Chronic kidney disease (CKD) is increasingly prevalent among patients with type 2 diabetes (T2D). CKD is associated with increased mortality rates, clinical and humanistic burden, and substantial health care costs in the T2D population. The objective of this review was to summarize the burden of illness among patients with CKD and T2D, including the profile of patients, incidence, prevalence, mortality, progression, diagnosis and screening rates, and cardiovascular (CV) events.

Methods: A targeted literature review of published studies was conducted using Embase; Medline; Medline In-Process Citations, Daily Update, and Epub Ahead of Print; Igaku Chuo Zasshi databases; and 7 websites. Methods recommended by the Cochrane collaboration handbook, the Centre for Reviews and Dissemination, and the Joanna Briggs Institute critical appraisal checklist were employed.

Results: A total of 1290 full-text articles were reviewed for eligibility and 73 were included in this analysis. Patient profiles indicated older age was associated with more severe disease and number of comorbidities. The definition of kidney disease varied between studies reporting incidence and prevalence, with reported values up to 37.0% and 43.5% for incidence and prevalence, respectively. CKD among patients with T2D contributed to higher mortality rates. Higher disease progression rates were associated with higher albuminuria and lower estimated glomerular filtration rate levels. The available literature suggested annual screening rates for CKD declined over time. CV events were reported to have a substantial effect on morbidity and resource use.

Conclusions: This review highlights the burden of CKD among patients with T2D and underscores a need for new treatment alternatives to reduce the burden of disease.

Publication types

• Research Support, Non-U.S. Gov't
• Cost of Illness
• Diabetes Mellitus, Type 2* / complications
• Diabetes Mellitus, Type 2* / epidemiology
• Glomerular Filtration Rate
• Renal Insufficiency, Chronic* / epidemiology

• Research Process

Systematic Literature Review or Literature Review?

• 3 minute read
• 39.8K views

Table of Contents

As a researcher, you may be required to conduct a literature review. But what kind of review do you need to complete? Is it a systematic literature review or a standard literature review? In this article, we’ll outline the purpose of a systematic literature review, the difference between literature review and systematic review, and other important aspects of systematic literature reviews.

What is a Systematic Literature Review?

The purpose of systematic literature reviews is simple. Essentially, it is to provide a high-level of a particular research question. This question, in and of itself, is highly focused to match the review of the literature related to the topic at hand. For example, a focused question related to medical or clinical outcomes.

The components of a systematic literature review are quite different from the standard literature review research theses that most of us are used to (more on this below). And because of the specificity of the research question, typically a systematic literature review involves more than one primary author. There’s more work related to a systematic literature review, so it makes sense to divide the work among two or three (or even more) researchers.

Your systematic literature review will follow very clear and defined protocols that are decided on prior to any review. This involves extensive planning, and a deliberately designed search strategy that is in tune with the specific research question. Every aspect of a systematic literature review, including the research protocols, which databases are used, and dates of each search, must be transparent so that other researchers can be assured that the systematic literature review is comprehensive and focused.

Most systematic literature reviews originated in the world of medicine science. Now, they also include any evidence-based research questions. In addition to the focus and transparency of these types of reviews, additional aspects of a quality systematic literature review includes:

• Clear and concise review and summary
• Comprehensive coverage of the topic
• Accessibility and equality of the research reviewed

Systematic Review vs Literature Review

The difference between literature review and systematic review comes back to the initial research question. Whereas the systematic review is very specific and focused, the standard literature review is much more general. The components of a literature review, for example, are similar to any other research paper. That is, it includes an introduction, description of the methods used, a discussion and conclusion, as well as a reference list or bibliography.

A systematic review, however, includes entirely different components that reflect the specificity of its research question, and the requirement for transparency and inclusion. For instance, the systematic review will include:

• Eligibility criteria for included research
• A description of the systematic research search strategy
• An assessment of the validity of reviewed research
• Interpretations of the results of research included in the review

As you can see, contrary to the general overview or summary of a topic, the systematic literature review includes much more detail and work to compile than a standard literature review. Indeed, it can take years to conduct and write a systematic literature review. But the information that practitioners and other researchers can glean from a systematic literature review is, by its very nature, exceptionally valuable.

This is not to diminish the value of the standard literature review. The importance of literature reviews in research writing is discussed in this article . It’s just that the two types of research reviews answer different questions, and, therefore, have different purposes and roles in the world of research and evidence-based writing.

Systematic Literature Review vs Meta Analysis

It would be understandable to think that a systematic literature review is similar to a meta analysis. But, whereas a systematic review can include several research studies to answer a specific question, typically a meta analysis includes a comparison of different studies to suss out any inconsistencies or discrepancies. For more about this topic, check out Systematic Review VS Meta-Analysis article.

Language Editing Plus

With Elsevier’s Language Editing Plus services , you can relax with our complete language review of your systematic literature review or literature review, or any other type of manuscript or scientific presentation. Our editors are PhD or PhD candidates, who are native-English speakers. Language Editing Plus includes checking the logic and flow of your manuscript, reference checks, formatting in accordance to your chosen journal and even a custom cover letter. Our most comprehensive editing package, Language Editing Plus also includes any English-editing needs for up to 180 days.

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Biomimetic Design Method for Innovation and Sustainability pp 45–49 Cite as

Literature Review Conclusions and Definition of Research Target

• Yael Helfman Cohen 3 &
• Yoram Reich 4  
• First Online: 02 July 2016

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While in formation, the biomimetic discipline still lacks a clear theoretical and applicative framework of reference that could address the main challenge of the biomimetic process. In this chapter, we present our literature review conclusions, the research gap, and suggest directions to address it.  We indicate some knowledge bases that have not been exhausted yet, such as the TRIZ knowledge base, patterns in general and structure-function patterns in particular. We suggest to harness a system view and to integrate a sustainability framework within the biomimetic core design process. We point a lacuna of transfer methods and conclude with our research target: develop a biomimetic design method for innovation and sustainability based on these research gaps.

• System View
• Research Target
• Conceptual Design Stage
• Sustainability Framework
• Abstraction Method

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Cohen, Y.H., Reich, Y. (2016). Literature Review Conclusions and Definition of Research Target. In: Biomimetic Design Method for Innovation and Sustainability. Springer, Cham. https://doi.org/10.1007/978-3-319-33997-9_4

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Literature Review vs Systematic Review

• Literature Review vs. Systematic Review
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Definitions

It’s common to confuse systematic and literature reviews because both are used to provide a summary of the existent literature or research on a specific topic. Regardless of this commonality, both types of review vary significantly. The following table provides a detailed explanation as well as the differences between systematic and literature reviews. 

Kysh, Lynn (2013): Difference between a systematic review and a literature review. [figshare]. Available at:  http://dx.doi.org/10.6084/m9.figshare.766364

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• NPJ Schizophr

Diverse definitions of the early course of schizophrenia—a targeted literature review

Richard newton.

1 Austin Health, University of Melbourne, Melbourne, VIC Australia

7 Present Address: Peninsula Health, Frankston, VIC Australia

Alice Rouleau

2 Lundbeck SAS, Paris, France

Anna-Greta Nylander

3 H. Lundbeck A/S, Copenhagen, Denmark

Jean-Yves Loze

4 Otsuka Pharmaceutical Europe Ltd., Wexham, UK

Henrike K. Resemann

5 Costello Medical Consulting Ltd, Cambridge, UK

Sara Steeves

Benedicto crespo-facorro.

6 Department of Medicine & Psychiatry, University Hospital Marqués de Valdecilla, IDIVAL, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Santander, Spain

Associated Data

No datasets were generated or analysed during the current study.

Schizophrenia is a debilitating psychiatric disorder and patients experience significant comorbidity, especially cognitive and psychosocial deficits, already at the onset of disease. Previous research suggests that treatment during the earlier stages of disease reduces disease burden, and that a longer time of untreated psychosis has a negative impact on treatment outcomes. A targeted literature review was conducted to gain insight into the definitions currently used to describe patients with a recent diagnosis of schizophrenia in the early course of disease (‘early’ schizophrenia). A total of 483 relevant English-language publications of clinical guidelines and studies were identified for inclusion after searches of MEDLINE, MEDLINE In-Process, relevant clinical trial databases and Google for records published between January 2005 and October 2015. The extracted data revealed a wide variety of terminology and definitions used to describe patients with ‘early’ or ‘recent-onset’ schizophrenia, with no apparent consensus. The most commonly used criteria to define patients with early schizophrenia included experience of their first episode of schizophrenia or disease duration of less than 1, 2 or 5 years. These varied definitions likely result in substantial disparities of patient populations between studies and variable population heterogeneity. Better agreement on the definition of early schizophrenia could aid interpretation and comparison of studies in this patient population and consensus on definitions should allow for better identification and management of schizophrenia patients in the early course of their disease.

Introduction

Schizophrenia can be a debilitating psychiatric disorder, with the majority of patients experiencing significant comorbidity throughout the course of their illness. Studies have reported cognitive and psychosocial deficits already at the onset of disease, 1 and a negative impact of longer time of untreated psychosis on treatment outcomes. 2 , 3 Despite continued development of pharmacological, psychosocial and other treatment modalities over the last 5 decades, many patient outcomes often remain poorly managed, especially with regards to negative symptoms and cognitive impairment. 4

Current evidence suggests that individuals with schizophrenia are not only at considerable psychosocial risks, but also at risk of biological harm that may be associated with relapse. 5 Research has further proposed that treating patients during the earlier stages of schizophrenia reduces the likelihood or frequency of relapse, reduces disease burden and provides patients with more favourable outcomes, including in the long term. 3 , 6 – 8

The lack of standardised definitions of early schizophrenia allows for considerable variation of patient groups between studies and limits analysis of comparative effectiveness of the interventions used. There is therefore an increasing interest for consensus regarding definitions of early stage disease. The aim of this targeted literature review was to map definitions currently used to describe patients with a recent diagnosis of schizophrenia who are early in the disease course (‘early course’ schizophrenia), as reported in clinical guidelines and as used in study inclusion criteria.

Literature search and study characteristics

1845 articles from MEDLINE/MEDLINE in-process and 656 records from clinical trial registries were identified and reviewed for relevance. From these records, 466 primary studies used some form of early schizophrenia terminology. A total of 17 relevant treatment guidelines were identified and included in the review. Across all studies included in the review, a large proportion of studies were conducted in Europe ( n  = 177). Further, 66 studies from North America were identified, 19 studies from Australia and 204 studies from elsewhere in the world (Table ​ (Table1). 1 ). Most included studies were cross-sectional observational studies ( n  = 279), with further featured study designs including longitudinal observational studies ( n  = 92), randomised controlled trials ( n  = 50) and other interventional studies ( n  = 45).

Summary of primary studies identified in the review

a Other regions included Asia ( n  = 175), Middle East ( n  = 10), Central/South America ( n  = 8), Africa ( n  = 3) or encompassed multiple regions ( n  = 8)

Terminology used in treatment guidelines

Most of the 17 identified treatment guidelines divided the patient population into those with a first episode of psychosis and those with recurrent episodes, and did not provide additional definitions of early schizophrenia. 9 – 25 Three guidelines also included alternative terminology for patients with early schizophrenia as distinct from first-episode schizophrenia. 26 – 28 In 2011, the American Psychiatric Association defined 'early course' as the period after recovery from a first episode of schizophrenia and extending up to the subsequent 5 years. 26 Llorca et al. ( 2013 ) considered 'early course' to apply to patients who had been newly diagnosed with schizophrenia and who had had no previous antipsychotic treatment. 27 The Schizophrenia Patient Outcomes Research Team (2010) used the term “recent onset schizophrenia”, but no associated definition was specified. 28

Definitions used in primary studies

Across the 466 primary studies using some form of early schizophrenia definition, three main definition types were identified (Fig. ​ (Fig.1): 1 ): episode-based definitions ( n  = 401), duration-based definitions ( n  = 147) and symptom severity-based definitions ( n  = 23). Episode-based definitions included those selecting patients on the basis of the number of psychotic episodes they have experienced. Duration-based definitions were definitions based on time since the start of illness, such as time since symptom onset, diagnosis or start of treatment. Symptom severity-based definitions included definitions based on current severity of symptoms and/or referring to the staging of schizophrenia as detailed in treatment guidelines.

Summary of definitions used in primary studies ( N  = 466) identified in the literature review

There were 370 (79%) studies which used a single definition type, while the remaining 96 (21%) studies used overlapping definitions (e.g. first-episode and a duration-based definition). Stratifying these groups by study location revealed broadly similar patterns, with slightly higher proportions of European studies using single rather than overlapping definition types (Fig. ​ (Fig.2). 2 ). No substantial differences between the proportion of single and overlapping definitions were seen when stratifying by study design (Fig. ​ (Fig.2 2 ).

Proportion of studies ( N  = 466) using single vs overlapping early schizophrenia definitions; stratified by a study location and b design

Episode-based definitions

Of the 401 studies using episode-based definitions, 98% ( n  = 392) used ‘first-episode’ to define the enroled schizophrenia patient population. Nine studies did include multi-episode patients within a definition of early schizophrenia, but definitions were variable. Of these studies, three defined early schizophrenia in patients who had experienced <3 episodes. 29 – 31 A further three studies selected early schizophrenia in patients who had experienced ≥1 episode with duration of illness ≤5 years, 32 – 34 while an additional three studies defined early schizophrenia in patients who had experienced ≥2 episodes of relapse, again with an upper disease duration limit of 5 years, 35 – 37 one of which required patients to have been hospitalised for those relapses. 37

Duration-based definitions

Across primary studies using duration-based definitions to select patients, nearly half did not specify the disease onset definition used (71/147; 48%). 32 , 36 , 38 – 106 The remaining 52% ( n  = 76) of studies used a variety of definitions for disease onset, including five studies that used multiple onset definitions: 29 studies referred to time since symptom onset; 107 – 135 14 studies referred to time since first episode or acute phase; 33 , 34 , 136 – 147 17 studies referred to time since first presentation to mental health services, hospitalisation or admission; 138 , 148 – 163 17 studies referred to time since schizophrenia diagnosis; 37 , 108 , 137 , 164 – 177 and 5 studies referred to time since treatment had first been initiated. 35 , 108 , 109 , 149 , 178

In total, 142 of these studies selected patients with disease duration of less than a particular period of time to define early schizophrenia. 32 – 36 , 38 – 58 , 60 – 75 , 77 – 139 , 141 – 175 , 177 , 178 Durations ranged from <1 month to <10 years, while 1, 2 or 5 years were the most common duration cut-offs used with duration-based criteria (Fig. ​ (Fig.3). 3 ). 91% (129/142) of studies did not provide a rationale for the duration cut-offs used. Of the remaining 9% (13/142) that did specify a rationale for their duration-based definitions, six established their definitions on prior experience and evidence, 34 , 90 , 93 , 150 , 152 , 164 while seven studies provided study-specific rationale (Table ​ (Table2 2 ). 32 , 42 , 45 , 52 , 63 , 154 , 169

Distribution of cut-offs used with duration-based criteria, stratified by disease onset definition ( n ). Footnote: studies with multiple definitions were repeated under each category ( n  = 5)

Rationale provided in primary studies for the selection of patients with disease duration under a particular threshold

Finally, seven studies selected patients with disease duration between two periods of time to define early schizophrenia, ranging from 6 months to 7 years in length, starting from 1 month since diagnosis to as late as 24 months thereafter. 35 , 37 , 59 , 74 , 76 , 140 , 176 Two of these studies had also used ‘less than’ disease duration definitions with cut-offs of <1 year and <2 years, respectively, to define a separate subgroup of schizophrenia patients with earlier disease. 35 , 74

Symptom severity-based definitions

The review identified 22 relevant studies that incorporated symptom severity-based definitions (e.g. requiring patients to be in an acute phase of the disease or in a stable phase or remission). 30 , 32 , 36 , 37 , 40 , 48 , 67 , 76 – 78 , 100 , 137 , 172 , 173 , 178 – 185 All of these studies used the symptom severity criteria in combination with a duration or episode-based definition. It should be noted that in many of the first-episode studies it was often implied that these patients were in the acute phase of an episode, however as symptom severity was not a formal patient selection criterion these studies were therefore not included under this definition type. One additional study employing the 5-stage model proposed by McGorry et al. to describe the onset of psychiatric disorders for the purposes of selecting patients for the study was identified. This study included patients who fulfilled the criteria for stage 2 (first episode of psychosis). 42

Early schizophrenia terminology

The most commonly used terminology for early schizophrenia included ‘first-episode’, ‘recent-onset’, ‘early-phase’, ‘early course’, ‘early’ and ‘early stage’ schizophrenia. Terminology varied somewhat between studies using the duration, episode and/or severity definitions. In particular, the terms ‘first-episode’ and ‘recent-onset’ were more frequently used in studies that included disease duration or severity definitions, whereas studies with multi-episode definitions tended to use terms such as ‘early phase’ or ‘early course’. However, there was no clear association of particular terms with specific definitions.

From the results of this literature review it is clear that a wide variety of definitions are being used to describe patients with early schizophrenia, likely based on the different study types represented in the review and their objectives for patient inclusion. The majority of guidelines used the terminology ‘first-episode psychosis’ when discussing patients early in the course of the disease, while in primary studies, the most commonly used criterion to define early schizophrenia, was for patients to be in their first episode of schizophrenia, followed by application of disease duration limits, frequently disease duration less than 1, 2 or 5 years. Only a small number of studies used multi-episode or symptom severity/staging criteria to select patients with early schizophrenia. The majority of studies did not use a combination of definitions, with many studies simply identifying patients being in their first episode of schizophrenia.

The onset of psychosis has been found to be difficult to determine, as onset may be rapid or more subtle, and may be preceded by months to years of prodromal disease. 186 Further, although in the majority of cases time of symptom onset is obtained from parents or close relatives, in some cases it may rely on patients’ recollection only, causing additional variability. There were wide variations in definitions used to mark the onset of schizophrenia in studies identified in this review as using duration-based definitions, with a large proportion of studies not specifying when illness or disease was considered to start. Of the studies that did provide a definition, the most common was to refer to time since symptom onset, however no studies provided clear information on how the first occurrence of symptoms was detected. As a result, there may be variation in how the definition was applied between patients, and also between studies. The next most common definitions of onset were first presentation to mental health services, hospitalisation or admission, and first diagnosis. While these may be more objectively measured than symptom onset, by this stage patients have already developed psychotic symptoms, and therefore it could be argued that the onset of schizophrenia occurred some time before this point.

A number of review articles have discussed the validity of using episode-based definitions in schizophrenia, particularly ‘first-episode’ definitions, highlighting difficulties including the lack of a consensus definition of ‘first-episode schizophrenia’, 187 , 188 and the fact that first-episode samples may still show great heterogeneity due to potential uncertainty of a schizophrenia diagnosis at the first episode and variation in illness duration. 8 , 188 , 189 Use of multi-episode definitions is further complicated by the need to define when one episode has ended and the next has started. The lack of a standardised definition of ‘relapse’ has been highlighted in a systematic review of observational studies, 190 and few studies using multi-episode definitions identified in the present review specified a definition for relapse. The majority of studies that did define relapse in this review used hospitalisation as a proxy for identifying it, which may be problematic as patients could be hospitalised for reasons other than a worsening of symptoms and conversely, patients may suffer a worsening of symptoms but not be hospitalised. This is particularly true in countries where crisis management teams have been implemented in the community setting. Other studies used a symptom severity scale as part of the definition for relapse, but there was variation in the scales used as well as the cut-off scores used with those scales. Only one of the studies using multi-episode definitions identified in this review defined how subsequent episodes were measured, defining these as relapses requiring psychiatric hospitalisation. 37

With regards to definitions using symptom severity, an article by Francey et al. ( 2010 ) suggested that use of symptom severity alone may not be sufficient in defining first-episode schizophrenia, particularly when determining whether antipsychotic medications should be used. 189 Further, duration-based definitions are flawed by limitations such as difficulties in reliably measuring symptom duration, especially retrospective estimation of the duration of untreated psychosis, 191 as well as heterogeneity between patients, particularly when a long disease duration is allowed.

Although no clear differences in the types of definition used were seen when stratifying studies by study design, a somewhat higher proportion of cross-sectional studies used overlapping definitions, whereas other study designs tended to use single definitions. This may indicate that cross-sectional studies, many of which were imaging studies, tended to require a more homogeneous patient population, whereas for other studies broader definitions may have been more appropriate in order to achieve a larger sample size.

In addition to the lack of consensus in definitions identified in this review, terminology used to refer to ‘early schizophrenia’ is equally heterogeneous. The term ‘early schizophrenia’ itself is problematic since it may be used both to refer to patients early in the course of the disease and to patients who have disease onset at an early age. As a result definitions such as ‘recent onset’, ‘early phase’, ‘early course’ and ‘early stage’, were more commonly used in the literature. As identified from the review of treatment guidelines, the term ‘first-episode psychosis’ is often used in place of ‘first-episode schizophrenia’. This is in part because at the time of presenting with a first psychotic episode it can be challenging to establish a diagnosis of schizophrenia as opposed to other psychiatric diagnoses or other underlying causes. 16 , 19 , 26 An added factor relates to the stigma attached to the term ‘schizophrenia’ which may influence the timing of applying a schizophrenia ‘label’. 192 , 193 Consequently, the use of ‘first-episode schizophrenia’ as a term may be more applicable in settings where the definition can be applied retrospectively, for example when reviewing the history of a patient with a confirmed diagnosis of schizophrenia but no longer in their first episode of psychosis. 187

From this literature review, there does not appear to be a single ‘best’ definition of early schizophrenia. Taking the most commonly used definitions in this review, the most ‘standard’ definition is for patients to be in their first episode of schizophrenia, identified due to a first contact with health services or hospitalisation. For further refinement, the most common additional criterion used was to add a disease duration limit of 1, 2 or 5 years from illness onset.

Establishing a consensus definition of early schizophrenia is important for several reasons. First, when applied in clinical practice it can aid prediction of the outcome of different treatment approaches. For example, it is well established that patients treated earlier have a better prognosis, but that those earlier in the disease course can also be more sensitive to treatment side-effects as they typically have limited prior exposure to antipsychotic agents. 19 , 23 In this setting the priority should be on establishing a definition that is both straightforward to apply and clinically meaningful. In the context of clinical studies, establishing a consensus definition depends somewhat on the study design and objectives. For ease of comparing results across studies, the emphasis should be on definitions that can be applied consistently to minimise heterogeneity in the included populations. Thus, we propose that the onset of early schizophrenia should be set as the point at which patients first develop symptoms severe enough to be considered a psychotic episode. Regarding the end of early schizophrenia, we suggest that disease duration of <5 years encompasses previous definitions of the critical period for early intervention. 194 Within this broad definition, it may be possible to identify further subgroups, taking into account early symptom severity, age of onset and time to treatment, which have all been found to be prognostic factors for schizophrenia outcome. 195 – 197 Further investigation of the impact of these factors through trajectory modelling could help refine the definition of early schizophrenia, while a consensus panel on this topic is required to drive forward consistency in the way in which early schizophrenia is defined.

Limitations of the review

Limitations of this literature review include single-reviewer screening and extraction of articles, restriction of searches to articles published from 2005 onwards and including only articles written in the English language, while no geographical restrictions were applied. The search strategy did not include terms for ‘first-episode psychosis’, which may have resulted in some studies including schizophrenia subgroups within this broader population being missed. Further, the results of this review are limited by use of search terms related to ‘early’, rather than searching for all studies conducted in schizophrenia. While we attempted to mitigate this by running iterative searches to include additional terminology identified through the review, there is the potential for over- or under-representation of the terms identified in the results depending on whether they were used as search terms themselves. Additionally, the lack of clarity provided in some publications regarding diagnoses may mean that some studies with mixed schizophrenia disorder populations were inadvertently included in the review. For example, studies using the term ‘DSM-IV for schizophrenia’ despite later referring to a mixture of schizophrenia, schizoaffective disorder and schizophreniform patients were excluded, whereas those simply stating ‘DSM-IV for schizophrenia’ were included.

The focus on definitions used for participants with diagnosed schizophrenia in itself means that findings from this review cannot be extrapolated to broader populations diagnosed with schizophrenia spectrum disorders. Given the difficulty in establishing a diagnosis at the early stages of schizophrenia, there may be value in a broader review of the literature in this expanded population. Nevertheless, since there are differences in the interventions that are licensed for patients diagnosed with schizophrenia versus other schizophrenia spectrum disorders, a review of definitions to guide therapy in this specific population is still relevant.

Finally, determination of the frequency of definitions used was limited by weighting each included study equally, irrespective of population number. A series of small studies using the same definition may thus have had a higher weighting than a single larger study.

Conclusions

A wide variety of definitions have been used to identify patients with early schizophrenia, with no apparent consensus. First-episode schizophrenia is the most frequently reported terminology in studies of patients with early schizophrenia, in line with the clinical guidelines, but even this common terminology is accompanied by a variety of definitions, including disease duration or symptom severity, and neither the terminology nor the definitions used are without limitations. When not referring specifically to first-episode patients, ‘recent-onset’ was the next most frequently used term, while the duration-based definitions most frequently used duration less than 1, 2 or 5 years. Better agreement on the definition of early schizophrenia could aid interpretation and comparison of studies in this patient population and consensus on definitions should allow for better identification and management of schizophrenia patients in the early course of their disease.

Search strategy and selection of studies

For this targeted literature review, searches for published studies, clinical trial entries and guidelines were conducted between 14.08.2015 and 21.10.2015 using MEDLINE and MEDLINE In-Process (via PubMed), the Australian New Zealand Clinical Trials Registry, ClinicalTrials.gov, the EU Clinical Trials Register, the International Standard Randomised Controlled Trial Number database, and Google (Data Supplement Table 1 – 7 ). Searches for published studies and clinical trial records were conducted iteratively, adding in any new terminology for ‘early schizophrenia’ from identified studies as new search terms, until no further new terminology was identified. The searches for relevant guidelines were updated in May 2016.

Studies were eligible for inclusion (Data Supplement Table 8 ) if they were written in the English language and conducted in humans, included a distinct population of patients with early schizophrenia or discussed definitions of early schizophrenia, and were published from January 1st 2005. Case studies were excluded, but there was no other restriction on study design. No limits were applied regarding interventions, comparators or outcomes. Articles were reviewed against the eligibility criteria by a single reviewer. Where the applicability of the eligibility criteria was unclear, the article was assessed by a second reviewer.

Data extraction and analysis

Information extracted from relevant studies relating to the search objectives was input into pre-specified Excel workbooks. Data extraction was performed by a single individual for each included study and any uncertainties were reviewed by a second individual.

Electronic supplementary material

Acknowledgements.

This study was initiated and sponsored by Lundbeck SAS and Otsuka Pharmaceutical Europe Ltd. Medical writing services were provided by Ms. Sara Steeves and Dr. Henrike Resemann of Costello Medical Consulting Ltd., and were funded by Lundbeck SAS. This study was funded by Lundbeck SAS and Otsuka Pharmaceutical Europe Ltd.

Author contributions

Study concept and design: A.R., A.-G.N., J.-Y.L., and S.S. Acquisition, analysis, or interpretation of data: all authors. Drafting of the manuscript: all authors. Critical revision of the manuscript for important intellectual content: all authors. Obtained funding: A.R., and A.-G.N. Administrative, technical, or material support: A.R., A.-G.N., S.S., and H.K.R. Study supervision: A.R., A.-G.N., and S.S. Additional contributions: the authors acknowledge Kate Hanman and Amy Buchanan-Hughes (Costello Medical Consulting Ltd.) for assistance in data acquisition.

Data availability

Competing interests.

A.R. and A.-G.N. are employees of Lundbeck SAS and H. Lundbeck A/S, respectively. J.-Y.L. is an employee of Otsuka Pharmaceutical Europe Ltd. S.S. and H.K.R. are employees of Costello Medical Consulting and were supported by a grant from Lundbeck SAS for this study. R.N. and B.C.-F. received an honorarium from Lundbeck SAS for their participation in the study, but did not receive remuneration for their contribution to the development of this manuscript.

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Supplementary information accompanies the paper on the npj Schizophrenia website (10.1038/s41537-018-0063-7).