(PRISMA) and observational studies

Report
Reporting systematic reviews and
meta-analyses (PRISMA) and
observational studies (STROBE)
Doug Altman
The EQUATOR Network
Centre for Statistics in Medicine, Oxford, UK
October 2012
Systematic review
 A systematic review is a scientific investigation
that focuses on a specific question and uses
explicit, prespecified scientific methods to identify,
select, assess, and summarise the findings of
similar but separate studies.
– A study of studies
 Objective is to summarize evidence from multiple
studies using explicit methods
 It may include a quantitative synthesis (metaanalysis), depending on the available data
2
Key characteristics of SR
 Focused well defined research question
 Clearly stated title and objectives
 Comprehensive strategy for identification of all relevant
studies (published & unpublished)
 Explicit (and justified) predefined inclusion & exclusion
criteria
 Critical appraisal of studies
 Clear analysis of the results of eligible studies
– Quantitative (meta-analysis)
– Qualitative
 Structured report
3
The QUOROM Statement
[Moher et al 1999]
 Guidance on what information should be included
in published reports of meta-analyses of
randomized trials
 Checklist of items which should be reported
 Also recommended a flow diagram showing flow of
studies through the review
– to be included in the published report
 Evidence-based, whenever possible
 QUOROM developed in 1996 and published in 1999
Moher et al. Improving the quality of reporting of meta-analyses of
randomised controlled trials: the QUOROM statement.
Lancet 1999;354:1896-1900
4
Checklist of items
5
Also recommended a flow diagram showing
flow of studies through the review
6
PRISMA: Preferred Reporting Items for
Systematic Reviews and Meta-Analyses
 Update of QUOROM
 Developed in 2005, Published in 2007
 Consists of a 27 item checklist and a flow diagram
 Reporting of systematic reviews and metaanalyses that evaluate healthcare interventions
 Includes long explanatory document
7
Slide 8 of 43
identification
eligibility screening
included
# of records identified through
database searching
# of additional records
identified through other
sources
Total # of duplicates removed
# of records screened
Total # of articles assessed
for eligibility
# of records
excluded
# of articles
excluded, with
reasons
Total # of studies included
in qualitative synthesis of
systematic review
# of studies included in
quantitative synthesis of
systematic review
9
Reporting vs conduct:
study methods
METHODS – each aspect of the methods
Done
well
Done
poorly
Not
done
Fully reported
(=reproducible)
Ambiguously or
incompletely reported
Not reported
10
PRISMA
Practical
11
 2 reviews in one article
 focus on progesterone
12
For each item …
 Is there text relating to the item?
 Does the text tell us what we need to know?
13
PRISMA: Item 6, eligibility criteria
METHODS
Eligibility criteria
 Specify study characteristics used as criteria for
eligibility, giving rationale
– PICOS
(participants, interventions, comparisons, outcomes and study design)
– Length of follow-up
 Specify report characteristics used as criteria for
eligibility, giving rationale
– Years considered
– Languages
– Publication status
Can you locate any text about this issue in the report?
14
Wyatt et al
 No explicit statement of study characteristics
 “… clinical trials of progesterone and progestogens in the
management of premenstrual syndrome.”
 Dates given in search criteria
 “All languages were included.”
15
PRISMA – item 8, search
 “Present full electronic search strategy for at least
one database, including any limits used, such that
it could be repeated”
Can you locate any text about this issue in the report?
Slide 16 of 43
Wyatt et al
Page 2, Methods, Trials
“MeSH terms used were premenstrual syndrome,
progesterone, and progestogen, as well as the individual
drug names, together with title and abstract searches
for keywords progesterone, progestogen, premenstrual
syndrome, premenstrual tension (PMT), late luteal phase
dysphoric disorder (LLPDD), premenstrual dysphoria
(PMD), and premenstrual dysphoric disorder (PMDD).”
Slide 17 of 43
PRISMA: Reporting search strategy
 We realize that journal restrictions vary and
that having the search strategy in the text of
the report is not always feasible
– Expensive real estate
 We strongly encourage all journals, however,
to find ways, such as a ‘‘Web extra,’’
appendix, or electronic link to an archive, to
make search strategies accessible to readers
 We also advise all authors to archive their
searches so that:
– others may access and review them (e.g., replicate
them or understand why their review of a similar topic
did not identify the same reports)
– future updates of their review are facilitated
PRISMA: Item 9, study selection
METHODS
Study selection
 State the process for selecting studies
– Screening
– Eligibility
– Included in systematic review and, if applicable, included in
meta-analysis
Can you locate any text about this issue in the report?
19
Wyatt et al
 “We searched medical databases for reports of published
clinical trials of progesterone and progestogens in the
management of premenstrual syndrome.”
 “References cited in all trials were searched iteratively to
identify missing studies. All languages were included.”
 “We included trials that investigated the effect of
progesterone or progestogens on premenstrual symptoms
if they were randomised, placebo controlled, double blind
studies that included patients with a pretreatment
diagnosis of premenstrual syndrome, for which all data
from the trials could be acquired.”
20
PRISMA
Item 11, Data items
METHODS
Data items
11 List and define all variables for which data were
sought (e.g., PICOS, funding sources) and any
assumptions and simplifications made.
(PICOS = participants, interventions, comparisons,
outcomes and study design)
Can you locate any text about this issue in the report?
21
Wyatt et al
“We collected data on the dosage and preparation of
treatment. The main outcome measure was a reduction in
overall symptoms of premenstrual syndrome. Combined or
overall symptoms was chosen in an attempt to overcome the
clinical heterogeneity associated with the measurement and
scoring of symptoms used in individual trials.”
22
PRISMA – item12,
Risk of bias in individual studies
 “Describe methods used for assessing risk of bias of
individual studies (including specification of whether
this was done at the study or outcome level), and how
this information is to be used in any data synthesis”
– Can you locate any text about this issue in the report?
Slide 23 of 43
Wyatt et al
Page 2, Methods, Quality assessment
 “We assessed trial quality using a scale developed by Jadad
et al,11 which assesses the randomisation, double blinding,
reports of drop outs, and withdrawals for the trials
 ... our own quality scale, which assesses the quality of the
trials for study design, reproducibility, and statistical
analysis. This eight point scale comprised the following:
confirmation that no other medications or oral
contraceptives were being taken; a power calculation to
justify patient numbers or more than 65 participants in each
arm (enabling detection of a small effect size of 0.3, see
below); a single, clearly stated dose of drug; reproducible
measurement of premenstrual symptoms; clear
presentation of results; a description of the number and
reason for trial withdrawals; exclusion of, or a separate
analysis of, participants with a major psychiatric disorder;
and whether or not the trial was supported by independent
funding.”
Slide 24 of 43
Reporting risk of bias
 “Authors should report how they assessed risk of bias;
whether it was in a blind manner; and if assessments
were completed by more than one person, and if so,
whether they were completed independently. Similarly,
we encourage authors to report any calibration
exercises among review team members that were done.
Finally, authors need to report how their assessments of
risk of bias are used subsequently in the data synthesis
(see Item 16).”
Slide 25 of 43
Wyatt et al
Page 2, Methods, Quality assessment
 “We awarded one point for each category present in
the trial.
 Each trial was independently scored by two
investigators and the third investigator arbitrated on
any disagreements.
 We used predetermined criteria for the recognition of
the highest quality trials. A score of 3 or more was
required in the Jadad score for the trial to be
designated “high quality” and included in the metaanalysis11; a score of less than 3 meant that the trial
was designated “low quality.”
Slide 26 of 43
PRISMA
Item 17
RESULTS
Trial flow
17 Give numbers of studies screened, assessed for
eligibility, and included in the review, with reasons
for exclusions at each stage, ideally with a flow
diagram.
Can you locate any text about this issue in the report?
27
Page 2, Results
 “We identified 14 published trials that assessed the
efficacy of progesterone in the management of
premenstrual syndrome. We excluded four: two
because of their low quality score on the Jadad
scale, one because the data could not be extracted,
and one because the trial failed to make a
prospective diagnosis of premenstrual syndrome
before randomisation. Ten trials remained ........”
 No flow diagram
Slide 28 of 43
Caughey AB, Sundaram V, Kaimal AJ, Gienger A, Cheng YW, McDonald KM, Shaffer BL, Owens DK, Bravata DM. Systematic
Review: Elective Induction of Labor Versus Expectant Management of Pregnancy. Annals of Internal Medicine 2009;151:
252-263
Slide 29 of 43
PRISMA
Item 18
RESULTS
Study characteristics
18 For each study, present characteristics for which
data were extracted (e.g., study size, PICOS,
follow-up period) and provide the citations.
Can you locate any text about this issue in the report?
30
Wyatt et al
31
Wyatt et al
Problems in Table 1
 Crossover trials – not mentioned in text
 Comparator not stated
 Variation in outcome measures – how combined or
chose one?
 Some statements disagree with Figure
 No details of elements of “quality” scores
 Unclear how handled trial with 3 arms
32
PRISMA – item 15,
Risk of bias across studies
 Specify any assessment of risk of bias that may
affect the cumulative evidence (e.g., publication
bias, selective reporting within studies).
Can you locate any text about this issue in the report?
Slide 33 of 43
Page 2, methods, statistical analysis
 “We used the method of Egger et al to detect bias
(such as publication and location bias) in the included
trials with a funnel plot. We assessed the asymmetry
of the funnel plot quantitatively by plotting a linear
regression of the standard normal deviate
(standardised mean difference divided by SE) against
precision (inverse of SE). A regression line that passes
through the origin of the plot (within error limits)
indicates symmetry and hence the absence of bias.”
Slide 34 of 43
PRISMA
Item 20
RESULTS
Results of individual studies
20 For all outcomes considered (benefits or harms)
present, for each study: (a) simple summary data
for each intervention group, (b) effect estimates
and confidence intervals, ideally with a forest plot.
35
36
Altman & Cates complained about absence of
any numerical results (BMJ rapid response)
 “There are several aspects of this review that readers
cannot assess without summary data from each study.
 For example, we would wish
– to assess the strange heterogeneity P values for Figures 1 and 2
(the quoted P values of 0.999 are implausible given the clear
graphical heterogeneity);
– to gain some insight into how the cross-over trials were included in
the analysis (about which the authors say nothing at all) and
whether the crossover and parallel group trials differed in their
findings;
– to seek an explanation for the apparent discrepancy for three trials
(references 19, 31 and 32) between the ‘reported results’ in Table 1
and the results shown in Figures 1 and 2;
– to assess the claim that random and fixed models give the same
answer in the face of graphical heterogeneity;”
– … and 5 more points
37
Altman & Cates complained about
the absence of any numerical results
 “In addition, we note that the authors make no comment about
the varied nature of the outcome measures in these trials,
nor do they say which outcome was used for those trials that
presented more than one. It is hard to believe that all of
the scales can be considered equally valid assessments
of symptoms.
 Also, we wonder if they can clarify the meaning in the figure
legends of ‘standardised mean difference … for
proportion of patients who showed improvement …’. We
are puzzled by this terminology as the SMD gives no direct
information about proportions of patients improving.”
38
Authors’ reply
 “We have found this personal attack unpleasant and
upsetting and have to question the use of unsupported
attacks in the Rapid Response forum.”
 “We have considerable experience in PMS (clinically as
well as though our research) and believe ourselves
competent to judge the clinical appropriateness of
combining trial data.”
 The only question they addressed was one we had not
asked!
 A 2nd request for the data to be provided went
unanswered!
39
40
Observational studies
 Transparent reporting is particularly important for
observational studies
– Vulnerable to bias and confounding
– Findings are often over-interpreted
– Findings often generate health scares
41
41
42
Scope of STROBE
 Epidemiological research comprises several study
designs and multiple topic areas
 Initial restriction to three major areas
– cohort, case-control, and cross-sectional studies
 Later extensions to other study designs
– STREGA for genetic association studies (published 2009)
– STROBE-ME for molecular epidemiology
– etc
43
Final STROBE checklist
TITLE and ABSTRACT
INTRODUCTION
RESULTS
Background/rationale
Objectives
METHODS
Study design
Setting
Participants
Variables
Data sources/measurement
Bias
Study size
Quantitative variables
Statistical methods
Participants
Descriptive data
Outcome data
Main results
Other analyses
DISCUSSION
Key results
Limitations
Interpretation
Generalisability
OTHER INFORMATION
Funding
22 (34)
items
44
44
Design-specific items




Participants
Statistical methods
Descriptive data
Outcome data
45
45
STROBE Statement
 Guidance on how to report observational studies well
– Focus on 3 main study designs: cohort, case-control, crosssectional studies
 Published in Oct 2007: short paper and E&E
 Adopted by many journals
Find it on:
www.equator-network.org
www.strobe-statement.org
46
Case-control studies
 Patients with a certain outcome or disease and an
appropriate group of controls without the outcome
or disease are selected
– (usually with careful consideration of choice of controls,
possibly with matching)
 Information is obtained on whether the
participants have been exposed to the factor under
investigation
47
STROBE exercise
48
49
50
STROBE
Item 5. Setting
Describe the setting, locations, and relevant dates,
including periods of recruitment, exposure, followup, and data collection
Can you locate any text about this issue in the
report?
51
STROBE
Item 5. Setting
Qiu et al
“This case-control study was conducted at the Materno
Perinatal Institute of Lima and the Dos de Mayo Hospital
in Lima, Peru, from May 2004 through October 2005.
Both institutions are operated by the Peruvian
government and are primarily responsible for providing
maternity services to low income women residing in
Lima.”
52
STROBE
Item 6a. Participants
Give the eligibility criteria, and the sources and
methods of case ascertainment and control
selection. Give the rationale for the choice of cases
and controls
Can you locate any text about this issue in the
report?
53
STROBE
Item 6a. Participants
Qiu et al
“Cases were selected from those women with a diagnosis of
preeclampsia. Potential preeclampsia cases were
identified by daily monitoring of all new admissions to
antepartum wards, emergency room wards, and labor and
delivery wards of the study hospitals. Study subjects were
recruited during their hospital stay. Study personnel made
periodic visits to each ward in a fixed order for the
purposes of identifying potential cases and controls for the
present study. Preeclampsia was defined by …”
“Controls were women with pregnancies uncomplicated by
pregnancy-induced hypertension or proteinuria. Each day
during the enrollment period, controls were numbered in
the order in which they were admitted and identified.
Subsequently, they were approached in the order in which
research personnel identified them.”
54
STROBE
Item 10. Study size
Explain how the study size was arrived at
Can you locate any text about this issue in the
report?
55
STROBE
Item 10. Study size
Qiu et al
?
56
STROBE
Item 13. Participants
(a) Report numbers of individuals at each stage of
study—e.g. numbers potentially eligible, examined
for eligibility, confirmed eligible, included in the
study, completing follow-up, and analysed
(b) Give reasons for non-participation at each stage
(c) Consider use of a flow diagram
57
What we’d like
to see:
What do they
give us?
58
58
Qiu et al
59
STROBE
Item 19. Limitations
Discuss limitations of the study, taking into
account sources of potential bias or imprecision.
Discuss both direction and magnitude of any
potential bias
Can you locate any text about this issue in the
report?
60
Qiu et al
“First, our analyses are based on cross-sectionally collected data, which
may be subject to recall bias. There has been one longitudinal study
of Finnish women [6]; however, more longitudinal studies are needed to
re-examine the potential causal relation between maternal experience of
depression and preeclampsia risk in different populations.
Second, we used a depression screening instrument to categorize
participants according to depression/depressive symptoms. Participants
did not have formal diagnostic examinations. As a result, some
misclassification is possible. ... In addition, our assessment of
maternal depression and depressive symptoms was limited to the
duration of the pregnancy.
Last, although we adjusted for multiple confounding factors, as with all
observational studies, we cannot exclude the possibility of some
residual confounding.”
61
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Closing Comments on Checklists
 They help AUTHORS ensure that they have
addressed important issues in the report of their
study
 They help PEER REVIEWERS and EDITORS by
reminding them what issues should be addressed
 “Necessary but not sufficient!”
63
Closing Comments on Checklists
 They help AUTHORS ensure that they have
addressed important issues in the report of their
study
 They help PEER REVIEWERS and EDITORS by
reminding them what issues should be addressed
 “Necessary but not sufficient!”
64

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