Box length and error bars represent the interquartile range and 1.5
times the interquartile range, respectively. Outliers (high values extending
beyond 1.5 times and up to 3 times the interquartile range) are shown by circles
and extremes (high values extending beyond 3 times the interquartile range)
are shown by triangles. There were 25 articles with citation counts outside
the depicted range (3 randomized controlled trials and 1 review in 1991; 7
meta-analyses, 10 randomized controlled trials, 3 cohort studies, 1 review
in 2001). The thick lines in the boxes represent medians.
Patsopoulos NA, Analatos AA, Ioannidis JPA. Relative Citation Impact of Various Study Designs in the Health Sciences. JAMA. 2005;293(19):2362-2366. doi:10.1001/jama.293.19.2362
Author Affiliations: Clinical and Molecular
Epidemiology Unit and Clinical Trials and Evidence Based Medicine Unit, Department
of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina,
Greece (Drs Patsopoulos and Ioannidis and Mr Analatos); Department of Immunology
and Histocompatibility, Faculty of Medicine, University of Thessaly, Larissa,
Greece (Dr Patsopoulos and Mr Analatos); Institute for Clinical Research and
Health Policy Studies, Department of Medicine, Tufts-New England Medical Center,
Tufts University School of Medicine, Boston, Mass (Dr Ioannidis).
Context The relative merits of various study designs and their placement in
hierarchies of evidence are often discussed. However, there is limited knowledge
about the relative citation impact of articles using various study designs.
Objective To determine whether the type of study design affects the rate of citation
in subsequent articles.
Design and Setting We measured the citation impact of articles using various study designs—including
meta-analyses, randomized controlled trials, cohort studies, case-control
studies, case reports, nonsystematic reviews, and decision analysis or cost-effectiveness
analysis—published in 1991 and in 2001 for a sample of 2646 articles.
Main Outcome Measure The citation count through the end of the second year after the year
of publication and the total received citations.
Results Meta-analyses received more citations than any other study design both
in 1991 (P<.05 for all comparisons) and in 2001
(P<.001 for all comparisons) and both in the first
2 years and in the longer term. More than 10 citations in the first 2 years
were received by 32.4% of meta-analyses published in 1991 and 43.6% of meta-analyses
published in 2001. Randomized controlled trials did not differ significantly
from epidemiological studies and nonsystematic review articles in 1991 but
clearly became the second-cited study design in 2001. Epidemiological studies,
nonsystematic review articles, and decision and cost-effectiveness analyses
had relatively similar impact; case reports received negligible citations.
Meta-analyses were cited significantly more often than all other designs after
adjusting for year of publication, high journal impact factor, and country
of origin. When limited to studies addressing treatment effects, meta-analyses
received more citations than randomized trials.
Conclusion Overall, the citation impact of various study designs is commensurate
with most proposed hierarchies of evidence.
Several authors and organizations have proposed hierarchies of evidence,
based on the relative reliability of various types of study designs.1- 4 Although
many people recognize that expert opinions and nonsystematic reviews provide
the least reliable level of information,5,6 such
articles continue to have a massive influential presence.7 Controlled
studies assume higher places in hierarchies of evidence than uncontrolled
studies, and randomized trials are considered the gold standard for clinical
research.1- 4 However,
randomized trials cannot be conducted for all questions of interest8 and there is debate on whether they give different
results than nonrandomized studies.9- 14 Finally,
meta-analyses are becoming increasingly frequent in the literature. Meta-analyses
are often placed at the highest level of evidence,1- 4 despite
their critics.15,16 No hierarchy
of evidence is unanimously accepted.
An important issue is whether the impact of various studies is different
and changing over time. Impact on clinical practice and decision making is
difficult to measure comprehensively. However, one important measure of impact
is the use of citations in the published literature. Citations have limitations,17 but they provide an objective measurement of how
often scientists use a specific published work. One may ask: What is the relative
citation impact of published articles using various types of designs? Is this
impact commensurate with the proposed hierarchies of evidence? Has it changed
over time? We aimed to answer these questions using citation analysis.
We compared the citation impact across various study designs and between
studies published in 1991 and 2001. We searched the Institute for Scientific
Information (ISI) Science Citation Index at the Web of Science Database (www.isinet.com) for meta-analyses, randomized controlled trials (RCTs),
cohort studies, case-control studies, case reports, nonsystematic reviews,
and decision analysis or cost-effectiveness analysis records published in
1991 and 2001. These types of publications cover the major, readily identifiable
designs used in collecting and synthesizing medical information. Secondarily,
meta-analyses were also classified as meta-analyses including RCTs vs others.
Both meta-analyses and RCTs were also classified according to their subject
or purpose (treatment effect [therapy or prevention], prognosis, diagnosis,
and etiology or association for meta-analyses; treatment effect and diagnosis
It is impractical to identify and analyze all the tens of thousands
of publications fitting in these study designs. Often it is impossible to
accurately classify the study design unless the whole article is carefully
scrutinized. Sometimes even this may not suffice. Thus we used a strategy
that aimed to yield an adequate number of relevant publications for each design
with high specificity in characterizing design. The search strategies for
each type of publication sought the appearance of the relevant study design
terms in the article title (TI). Meta-analysis was searched with TI = meta-analy* or metaanaly*,
randomized controlled trial with TI=random* AND TI=trial, decision analysis or cost-effectiveness analysis with TI=decision analy* OR TI=cost effectiveness analy* OR TI=cost-effectiveness
analy*, nonsystematic review with TI=review NOT TI=systemat*
NOT TI=meta-analy* NOT TI=overview NOT TI=case report*, case-control
study with TI=case control study, cohort study with TI=cohort study, and case report with TI=case report
NOT TI=review NOT TI=overview . When the search algorithm yielded an
excessive number of articles, we screened systematically 1:5 or 1:10 batches
of records, for study designs with 1200 to 3000 records and more than 3000
records retrieved in a year, respectively.
Two investigators (N.A.P. and A.A.A) independently screened both the
title and abstract of identified articles. Articles were eligible if they
represented applications of the type of study design under which they were
identified. We excluded ISI records without abstract; letters; editorials;
news and meeting abstracts; methodology-and-theory articles; and articles
not on human subjects or material, not on health, or both. Discrepancies were
discussed between investigators; a third investigator (J.P.A.I.) resolved
For each article eligible for citation analysis, we recorded total citations
until December 10, 2004; citations received up to the end of the second year
after publication (1991-1993 and 2001-2003, respectively); country of authors;
The main analyses addressed citation counts for 1991-1993 and 2001-2003
(early citations). Most articles are rarely cited, if at all, during the same
year in which they were published, but the citation count of the 2 subsequent
years is representative (it forms the basis of estimating journal impact factors).
Secondary analyses counted total citations until December 10, 2004 (long-term
impact); this time frame unavoidably differed between the 1991 and 2001 publication
Citation counts per publication type and year were summarized with medians
and interquartile ranges (citation distributions are left-skewed).18 Mann-Whitney U tests and Kruskal-Wallis analysis
of variance compared 2 or several groups, respectively.
We also identified articles that received more than 10 citations in
the first 2 years (approximately the top 10% most-cited ISI-indexed articles
in Clinical Medicine).19 Logistic regressions
addressed the year and type of publication (dummy variables) as predictors
of more than 10 citations in 2 years, adjusting also for country of authors
and high journal impact factor.
Analyses were conducted using SPSS statistical software version 12.0
(SPSS Inc, Chicago, Ill). P values are 2-tailed.
Statistical significance was considered at the .05 level.
We identified 17 813 articles (6052 from 1991, 11 761 from
2001) and screened 5769 of those for eligibility (1936 and 3833, respectively);
2646 articles (904 and 1742, respectively) were eligible for citation counting
Both in 1991 and in 2001, there was a significant difference in citation
counts between various study designs (P<.001).
Citation counts were statistically significantly higher in the 2001 publications
compared with the 1991 publications for all designs (P<.05),
except for cohort studies and decision and cost-effectiveness analyses (Table 1).
Both in 1991 and 2001, meta-analyses received the highest number of
citations and RCTs were second (Table 1).
For 1991, comparisons against other designs were always formally statistically
significant, with the exception of decision and cost-effectiveness analysis
publications (P = .11), and the difference
against RCTs was also modest (P = .04);
for 2001, P values were <.001 for meta-analyses
compared with any other design. Differences in citation counts for other designs
were more subtle, except for the case reports that always had negligible citation
Twenty-three meta-analyses (32.4%) published in 1991 received more than
10 citations within 2 years. This rose to 43.6% (116/266) for meta-analyses
published in 2001. Randomized controlled trials had the next highest impact
(23.2% [76/328] and 29.5% [78/264], respectively). Other designs had percentages
in the range of 10% to 25%, except for case reports for which less than 1%
received more than 10 citations (Figure 1).
In multivariable logistic regression, articles published in 2001 (odds ratio
[OR], 1.56; 95% confidence interval [CI], 1.23-1.99), having US authors (OR,
1.69; 95% CI, 1.37-2.08), and published in journals with impact factors greater
than 10 (OR, 12.8; 95% CI, 8.4-19.5) were more likely to be cited more than
10 times than articles published in 1991, without US authors, or in other
journals; and meta-analyses were significantly more likely to be cited more
than 10 times compared with all other designs (for RCTs, OR, 0.49; 95% CI,
0.36-0.68; for cohort studies, OR, 0.46; 95% CI, 0.34-0.63; for case-control
studies, OR, 0.37; 95% CI, 0.27-0.52; for case reports, OR, 0.01; 95% CI,
0.00-0.04; for nonsystematic reviews, OR, 0.47; 95% CI, 0.31-0.73; and for
decision or cost-effectiveness analysis articles, OR, 0.29; 95% CI, 0.16-0.51
Both in 1991 and in 2001, there was a statistically significant difference
in citation count between various designs (P<.001, Figure 2). For 1991, meta-analyses were statistically
significantly cited more times than all other designs (P<.05 for all comparisons). Conversely, RCTs had significantly more
citations only from case reports (P<.001) and
possibly decision or cost-effectiveness analysis articles (P = .05) but did not differ significantly in citation impact
vs other designs. Case reports were statistically significantly less cited
than anything else (P<.001 for all comparisons).
For 2001, meta-analyses had greater impact than all other designs (P<.001 for all comparisons) and RCTs were cited significantly more
times than all the remaining designs (P<.05 for
all comparisons). Case reports had once again a very low impact (P<.001 for all comparisons). All other comparisons of designs were
not statistically significant.
Citations of subgroups of meta-analyses and RCTs are shown in Table 2. There were no statistically significant
differences in the citations received by meta-analyses including or not including
RCTs, both in 1991 and 2001 and both for the 2 years and for the long term
(P>.19 for all analyses). Similarly, citations did
not differ significantly for meta-analyses of different purpose or subject
(P>.58 for all analyses). Meta-analyses addressing
treatment effects tended to receive more citations than RCTs of treatment
effects in 1991 (P = .08 for 2-year citations, P = .10 for long-term citations), and the difference
became more clear in 2001 (P = .001 and P = .001, respectively).
The citation impact of various study designs follows the order proposed
by most current theoretical hierarchies of evidence.1- 3 On
average meta-analyses currently receive more citations than any other type
of study design. Meta-analyses have clearly surpassed in citation impact both
decision or cost-effectiveness analysis articles and RCTs, against which they
had mostly modest differences, if any, in the early 1990s. Although RCTs have
become the second most cited study design, decision or cost-effectiveness
analysis has not followed this growth. Epidemiological studies are now lagging
behind randomized research; however, this was not as evident for articles
published in 1991. Nonsystematic reviews continue to have a citation impact
similar to that of epidemiological studies. Finally, case reports have negligible
The superiority in citation impact of meta-analyses and secondarily
RCTs is consistent with the prominent role given to these designs by evidence-based
medicine,1- 4 despite
the criticisms leveled against both designs.15,20 The
further dissemination of hierarchies of evidence may further increase the
citations for meta-analyses and RCTs. If the proposal that each study should
start and end when a meta-analysis is adopted,21 meta-analyses
may become even more highly cited. Interestingly, high citations for meta-analyses
extend to meta-analyses of nonrandomized research. Of course, we acknowledge
that primary studies are required for quantitative syntheses ever to be performed.
The relative impact of epidemiological research has lost ground recently.Perhaps
there is increasing uncertainty due to the refutation of several key cohort
studies on important questions such as vitamins or hormone therapy.11 Decision or cost-effectiveness analysis has also
not managed to keep a high impact. Nevertheless, many important questions
simply cannot be answered with randomized research.
Also many nonsystematic reviews continue to be published. In our study,
we excluded nonquantitative reviews that seemed to use some systematic approaches.
Empirical evaluations of orthopedic and general medical journals have shown
that systematic reviews received double the number of citations compared with
nonsystematic ones.22,23 Efforts
to enhance the accuracy and usefulness of all reviews are important because
even nonsystematic expert reviews are still extensively read by practitioners.24
Some caveats should be discussed. First, higher citation rates in articles
published in 2001 than in those published in 1991 probably reflect simply
the increase of journals worldwide (especially journal articles listed by
ISI). Second, we excluded several types of reports such as nonhuman studies
and hybrid designs (eg, reports describing both cohort and case-control studies).
However, we wanted to focus sharply on the key study designs. Third, we did
not exclude self-citations. Fourth, we used very strict screening criteria
to ensure high specificity for characterizing study designs. Most studies
probably still do not mention their design in their title. It is unknown whether
among studies having the same design, those that state it in the title would
get more citations or less. Nevertheless, even if such differences exist,
they probably would not affect selectively some study designs over others.
Finally, a citation does not guarantee the respect of the citing investigators.
Occasionally a study may be cited only to be criticized or dismissed. Nevertheless,
citation still means that the study is active in the scientific debate. Moreover,
we should acknowledge that citation impact does not necessarily translate
into clinical or scientific impact, but this is extremely difficult to measure
and could vary on a case-by-case basis. Allowing for these caveats, our evaluation
provides empirical evidence on the relative impact of various study designs
in the literature.
Corresponding Author: John P. A. Ioannidis,
MD, Department of Hygiene and Epidemiology, University of Ioannina School
of Medicine, Ioannina 45110, Greece (email@example.com).
Author Contributions: Dr Ioannidis had full
access to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Study concept and design: Ioannidis, Patsopoulos.
Acquisition of data: Ioannidis, Patsopoulos,
Analysis and interpretation of data: Ioannidis,
Drafting of the manuscript: Ioannidis, Patsopoulos.
Critical revision of the manuscript for important
intellectual content: Analatos.
Statistical analysis: Ioannidis, Patsopoulos,
Study supervision: Ioannidis.
Financial Disclosures: None reported.
Acknowledgment: We thank Tom Trikalinos, MD,
for help in retrieving articles and Anastasios E. Germenis, MD, for encouragement.