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Comparative safety and efficacy of pharmacological and non-pharmacological interventions for the behavioral and psychological symptoms of dementia: Protocol for a systematic review and network meta-analysis

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Abstract

Background Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in patients with dementia. Both pharmacological and non-pharmacological strategies are commonly used to treat these symptoms, but their comparative safety and efficacy is unknown. Methods We will conduct a systematic review of the published and unpublished literature to retrieve all articles pertaining to outcomes of safety and efficacy associated with pharmacological and non-pharmacological treatments of BPSD for patients living in the community and institutionalized care settings. Our primary outcome of efficacy is a change in aggression. Our primary outcome of safety will be risk of fracture. These primary outcomes were chosen by stakeholders involved in the care of patients experiencing BPSD. Possible secondary outcomes of efficacy will include a change in agitation, depressive symptoms, and night-time behaviors. Possible secondary outcomes of safety will include the risk of stroke, falls, and mortality. All article screening, data abstraction, and risk of bias appraisal will be completed independently by two reviewers. If the assumption of transitivity is valid and the evidence forms a connected network, Bayesian random-effects pairwise and network meta-analyses (NMAs) will be conducted. Relative treatment rankings will be reported with mean ranks and the surface under the cumulative ranking curve. Discussion We will identify the safest and most efficacious treatment strategies for patients with BPSD from among our most highly ranked treatments. The results of this study will be used to guide decision-making and improve patient care. Systematic review registration PROSPERO registry number CRD42017050130. Electronic supplementary material The online version of this article (10.1186/s13643-017-0572-x) contains supplementary material, which is available to authorized users.
P R O T O C O L Open Access
Comparative safety and efficacy of
pharmacological and non-pharmacological
interventions for the behavioral and
psychological symptoms of dementia:
protocol for a systematic review and
network meta-analysis
Jennifer Watt
1,2
, Zahra Goodarzi
3
, Andrea C. Tricco
4,5
, Areti-Angeliki Veroniki
4
and Sharon E. Straus
1,4*
Abstract
Background: Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in patients with
dementia. Both pharmacological and non-pharmacological strategies are commonly used to treat these symptoms,
but their comparative safety and efficacy is unknown.
Methods: We will conduct a systematic review of the published and unpublished literature to retrieve all articles
pertaining to outcomes of safety and efficacy associated with pharmacological and non-pharmacological treatments of
BPSD for patients living in the community and institutionalized care settings. Our primary outcome of efficacy is a change
in aggression. Our primary outcome of safety will be risk of fracture. These primary outcomes were chosen by stakeholders
involved in the care of patients experiencing BPSD. Possible secondary outcomes of efficacy will include a change in
agitation, depressive symptoms, and night-time behaviors. Possible secondary outcomes of safety will include the risk of
stroke, falls, and mortality. All article screening, data abstraction, and risk of bias appraisal will be completed
independently by two reviewers. If the assumption of transitivity is valid and the evidence forms a connected network,
Bayesian random-effects pairwise and network meta-analyses (NMAs) will be conducted. Relative treatment rankings
will be reported with mean ranks and the surface under the cumulative ranking curve.
Discussion: We will identify the safest and most efficacious treatment strategies for patients with BPSD from among our
most highly ranked treatments. The results of this study will be used to guide decision-making and improve patient care.
Systematic review registration: PROSPERO registry number CRD42017050130.
Keywords: Behavioral and psychological symptoms of dementia (BPSD), Pharmacological treatments, Non-pharmacological
treatments, Dementia, Network meta-analysis, Systematic review, Knowledge synthesis
* Correspondence: sharon.straus@utoronto.ca
1
Department of Geriatric Medicine, University of Toronto, 27 Kings College
Circle, Toronto, ON M5S 1A1, Canada
4
Li Ka Shing Knowledge Institute, St. Michaels Hospital, 209 Victoria Street,
East Building, Room 716, Toronto, ON M5B 1W8, Canada
Full list of author information is available at the end of the article
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Watt et al. Systematic Reviews (2017) 6:182
DOI 10.1186/s13643-017-0572-x
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Background
Dementia is a progressive neurodegenerative disorder
characterized by both cognitive and functional impair-
ment [1]. In 2010, it was estimated that 35.6 million
people were living with dementia worldwide and this
number was projected to double over the subsequent
20 years [2]. Importantly, 75% of people with dementia
manifest behavioral and psychological symptoms of
dementia (BPSD) in a given month (e.g., aggression,
agitation, and apathy), which can lead to significant
distress for caregivers [35].
Numerous pharmacological and non-pharmacological
treatments have been proposed that target BPSD symp-
toms [6]. Exercise, animal therapy, and reminiscence ther-
apy are non-pharmacological approaches that are possible
interventions to improve the symptoms of BPSD [6, 7].
Commonly used pharmacological approaches for BPSD
include antipsychotics, antidepressants, and cholinesterase
inhibitors [8, 9]. In a study by Kales et al., it was found
that 28.8% of patients with dementia were prescribed
antipsychotics; however, these medications are associated
with several serious adverse events including fractures,
pneumonia, stroke, myocardial infarction, and acute
kidney injury [1015]. Except in the case of a patient
endangering self or others, many guidelines support the
use of non-pharmacological strategies prior to initiating a
pharmacological approach to symptom management [16].
This recommendation is not consistent across treatment
guidelines, which may relate to the lack of head-to-head
studies examining the comparative efficacy and safety of
these different interventions [9].
Given the concerns about drug safety in patients
with BPSD, it is critical to understand the compara-
tive safety and efficacy of pharmacological and non-
pharmacological interventions. To our knowledge, a
network meta-analysis describing the comparative
safety and efficacy of these two types of treatment
strategies has not been previously completed. As such,
our objective is to conduct a systematic review and
network meta-analysis on this topic.
Methods
This protocol is written in accordance with the Preferred
Reporting Items for Systematic Review and Meta-Analysis
Protocols (PRISMA-P) (see Additional file 1. PRISMA
Checklist) [17]. Any amendments to this protocol will be
reflected in an update to the PROSPERO registration. The
final publication of study findings will be written in
accordance with the PRISMA extension for network
meta-analyses and the International Society for Pharma-
coeconomics and Outcomes Research (ISPOR) Indirect
Treatment Comparison/Network Meta-Analysis Study
Questionnaire to Assess Relevance and Credibility to
Inform Health Care Decision-Making [18, 19].
Eligibility criteria
Population
Our study population will include all patients with a
diagnosis of dementia, as defined by study authors (e.g.,
medical history of dementia, diagnostic and statistical
manual (DSM) diagnosis of major neurocognitive dis-
order), residing in the community or an institutionalized
setting. There will be no restrictions based on patient
age, severity of dementia, or type of dementia [1].
Interventions
Any pharmacological or non-pharmacological treatment
strategy for the behavioral and psychological symptoms
of dementia (BPSD) will be considered for study inclu-
sion in our analyses for efficacy outcomes; however,
pharmacological treatments must have received final
approval by the Federal Drug Agency or Health Canada,
as of the date of our literature search. Given that some
treatments for BPSD (e.g., antipsychotics) are used in an
off-labelfashion, we do not want to exclude potential
interventions from our analyses of efficacy based on
their approved indications. We will limit our analyses of
safety to the following pharmacological interventions:
antipsychotics, antidepressants, sedative/hypnotics,
mood stabilizers, anticonvulsants, stimulants, cholin-
esterase inhibitors, and N-methyl-D-aspartate (NMDA)
receptor antagonists. We limited our systematic review
of safety outcomes for two reasons: (1) safety outcomes
were not consistently reported in studies of non-
pharmacological interventions in our preliminary
searches, and (2) many non-pharmacological interven-
tions, in particular, are used to treat conditions other than
BPSD in our patient population, which would have made
our systematic review unfeasible to carry out in a timely
manner. Examples of potential pharmacological and non-
pharmacological interventions are outlined in Table 1 [6].
Comparators
Eligible comparator groups within studies will include
usual care or another pharmacological or non-
pharmacological treatment strategy for BPSD.
Outcomes
Our primary outcomes were chosen by a convenience
sample of 12 stakeholders from Ontario and Alberta
with diverse experience in caring for patients with BPSD
(e.g., nurses, geriatricians, caregivers of patients with
dementia, and allied health professionals). Based on the
ranked preferences of these stakeholders, the primary
outcome of treatment efficacy will be patient aggression.
Other possible secondary outcomes of treatment efficacy
are outlined in Table 2 (e.g., depressive symptoms,
neuropsychiatric inventory total score). The primary out-
come of treatment safety will be the risk of fracture. The
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risk of fracture will be measured as a dichotomous out-
come (fracture versus no fracture). Overall estimates of
mortality will also be presented as secondary outcomes.
Other possible secondary outcomes of treatment safety
are outlined in Table 2 (e.g., falls, stroke).
Study designs
Only randomized controlled trials (RCTs) will be in-
cluded in our systematic review of efficacy outcomes.
The following study designs will be eligible for inclusion
in our systematic review of safety outcomes: RCTs,
quasi-randomized controlled trials, non-randomized
controlled trials, controlled-before-and-after studies,
interrupted time series, cohort studies, and case-control
studies. We plan to include observational studies in our
systematic review of safety outcomes because of their
importance in identifying adverse drug events in the
BPSD literature [20, 21]. Case series, case reports, and
qualitative studies will be excluded. Systematic reviews
related to the topic will be retained to search their
references for potential, eligible studies.
Information sources and search strategy
An information specialist developed a search strategy for
our clinical question (see Additional file 2. MEDLINE
search strategy), which was peer-reviewed by a second
information specialist using the Peer Review of
Electronic Search Strategies (PRESS) checklist [22]. The
following databases will be searched for citations
published in any language: MEDLINE, EMBASE, the
Cochrane Library, CINAHL, and PsycINFO. Searches of
the difficult to locate/unpublished (or gray) literature
will be conducted using websites (e.g., Government of
Canada website), search engines (e.g., Google Scholar,
the Turning Research into Practice (TRIP) database),
and thesis databases (e.g., Center for Research Libraries
Table 1 Examples of pharmacological and non-pharmacological
interventions for behavioral and psychological symptoms of
dementia (BPSD)
Pharmacological interventions
Antipsychotics (e.g., risperidone)
Antidepressants (e.g., citalopram)
Cholinesterase inhibitors (e.g., donepezil)
Memantine
Benzodiazepines (e.g., lorazepam)
Anticonvulsants (e.g., valproate)
Mood stabilizers (e.g., lithium)
Stimulants (e.g., methylphenidate)
Others (e.g., melatonin, quinidine)
Non-pharmacological interventions
Reminiscence therapy
Validation therapy
Simulated presence therapy
Light therapy
Animal therapy
Aromatherapy
Snoezelen room
Exercise
Cognitive training and rehabilitation
Table 2 Examples of outcomes associated with treatment of
behavioral and psychological symptoms of dementia (BPSD)
Outcomes of treatment efficacy
Aggression*
Agitation
Depression
Apathy
Anxiety
Night-time behaviors
Motor disturbances
Irritability
Disinhibition
Psychosis (delusions and hallucinations)
Appetite and eating abnormalities
Caregiver well-being
Overall quality of life (both patient and caregiver)
Improvement in function
Admission to skilled nursing facility
Outcomes of treatment safety
Fractures*
Falls
Stroke
Mortality
Prolonged QTc interval
Myocardial infarction
Pneumonia
Deterioration in cognition
Hyperprolactinemia
Weight gain
Somnolence
Hypotension
Edema
Cytopenia
Extrapyramidal side effects (e.g., tardive dyskinesia)
Hospitalization
Admission to intensive care unit (ICU)
*Primary outcome of interest
Watt et al. Systematic Reviews (2017) 6:182 Page 3 of 9
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Foreign Dissertation). Reference lists of included studies
and related systematic reviews will be scanned to iden-
tify additional studies for inclusion in our systematic re-
view. Content experts from Toronto and Calgary who
ranked the outcomes will be contacted via email for add-
itional relevant studies.
Data collection and analysis
Study selection
Two levels of screening will be completed independ-
ently using Synthesi.SR (proprietary online software
developed by the Knowledge Translation Program of
St Michaels Hospital, Toronto, Canada, http://
www.breakthroughkt.ca/login.php). Two reviewers will
independently review the title and abstract of articles
retrieved from the literature search to determine if a
study is eligible for inclusion. At the initiation of
article screening, a calibration exercise will occur
whereby each reviewer will independently screen 10%
of a random sample of articles to ensure appropriate
inter-rater agreement (at least 80% agreement).
Discrepancies between the two reviewers will be
resolved by consensus; otherwise, a third reviewer will
be available to make a final decision about an articles
inclusion. The full-text of articles retained from level
one screening will then be reviewed to confirm each
articles eligibility for inclusion. If a conference abstract
is retained for level two screening, study authors will be
contacted for further information as to whether a related
manuscript has subsequently been published or to ensure
the study meets our outlined eligibility criteria, as
required. Whenever it is unclear if a study meets our
outlined eligibility criteria, authors will be contacted for
further information.
Data abstraction
Prior to data abstraction, we will complete a charting
exercise to better inform the structure of our data
abstraction form in terms of: (1) types of studies
retrieved, (2) outcomes reported, and (3) effect
measures used by study authors [23]. All data will be
abstracted independently by two reviewers from those
studies retained in level two screening using a data
abstraction form. The form will be piloted by each
team member on a random sample of five included
studies to ensure adequate inter-rater reliability (at
least 80% agreement). The form will be modified as
necessary to ensure clarity for reviewers based on our
charting exercise. Disagreements will be resolved by a
third person. When multiple studies report data from
the same study population (e.g., companion reports),
the study with the primary outcome of interest (frac-
tures or aggression) or the largest sample size will be
considered the major publication and the others will
be retained for supplementary material only.
Information to be abstracted as potential effect modi-
fiers will include study characteristics (e.g., year of study
publication, authorship, location(s) of study, journal of
publication, study sponsorship), patient characteristics
(e.g., average (mean or median) age of study population,
proportion of female patients, care setting, type(s) of
dementia, severity of dementia, and standard of care in
each care setting), and intervention characteristics (e.g.,
to whom the intervention was directed (e.g., patient,
caregiver, clinician, and surrounding environment), and
details of the intervention (e.g., intervention protocol or
medication dosing schedule)).
Primary and secondary arm- or trial-level outcomes
associated with intervention safety and efficacy (Table 2)
will be extracted from included studies. Outcomes of
efficacy and safety will be extracted at short-term
(30 days), medium-term (31364 days), and long-term
(>364 days) follow-up because many interventions have
been evaluated at many different time-points in our
preliminary searches [7, 24, 25]. All doses and schedules
of drug administration will be extracted from included
studies.
Node formation
We expect this review to identify numerous interventions
for BPSD. There is no established taxonomy for classifying
interventions for BPSD; however, we will begin with the
broad categories of patient-, care provider-, and
environment-oriented interventions [6]. In order to build
a framework, we propose a qualitative consensus-based
categorization procedure [26]. This will involve the follow-
ing four steps by two researchers at each step: (1) identify-
ing, coding and defining all interventions from the
systematic review, (2) independent categorization of inter-
ventions into relevant domains (e.g., all interventions
coded as relating to a multi-sensory intervention would be
sorted into this domain), (3) resolving any discrepancies in
the categorization of interventions through discussion,
and (4) emailing a representative group of stakeholders
(e.g., clinicians, caregivers, allied health professionals) to
review, reach consensus through discussion, and finalize
the domains. This will provide feedback and ensure stake-
holder validation of the proposed domains. At the initi-
ation of step one, a calibration exercise will occur whereby
each reviewer will independently identify, code, and define
interventions from 10% of a random sample of articles to
ensure appropriate inter-rater agreement (at least 80%
agreement). This process ensures a rigorous approach to
the categorization of interventions by using a qualitative
method of independent multiple coding of the interven-
tions and a consensus approach integrating the stake-
holders early in the analysis.
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Risk of bias and quality assessment
Risk of bias assessment of each included study will be
completed independently by two reviewers. If there is
disagreement between reviewers, a third reviewer will be
available. In the case multiple outcomes are reported in
a single study, we will use the hierarchy outlined by
Kirkham et al., to establish our order of preference for
selecting an outcome on which to complete our assess-
ment of bias [27].
The risk of bias of included clinical trials will be
assessed as per the methodology of the Cochrane Hand-
book for Systematic Reviews of Interventions [28]. The
quality assessment of observational studies will be
assessed with the Newcastle-Ottawa scale [29]. In the
assessment of case-control and cohort studies, a control
patient might also be living in an institutional setting, in
which case the study would still be awarded a star for an
appropriate selection of control group. The most
important confounder to adjust for in an observational
study would be age, but other important confounders
will include sex, comorbidities, dementia severity,
caregiver availability, care setting, and other current or
prior treatments for BPSD. For certain outcomes of
intervention efficacy (e.g., change in aggression or
agitation), the symptom may be present at the start of
the study, but still be awarded a star if a change from
baseline is reported. An appropriate length of follow-
up for safety outcomes could be as little as 30 days,
while most studies of efficacy outcomes would be
expected to last at least 4 to 6 weeksmany are
10 weeks or longer [24, 30]. We plan to assess other
study designs with the Cochrane Effective Practice
and Organization Care Risk-of-Bias Tool [31].
Measures of treatment effect
If studies consistently report continuous data outcomes
that are measured on the same scale, then mean differ-
ences (MDs) will be used. An odds ratio (OR) will be
used if studies report an outcome as dichotomous data.
To derive summary effect measures that combine both
dichotomous and continuous effect measures, MDs or
standardized mean differences (SMDs) will be trans-
formed to OR estimates [28, 32, 33]. For outcomes that
are reported with a number of different scales across
studies, the SMD will be derived and will be transformed
into an OR to facilitate the outcomes interpretation by
knowledge users [34]. The order of preference for
selecting source data, when multiple options are
reported by study authors (e.g., 2 × 2 tables, adjusted
andunadjustedORs,MDs,SMDs)isdescribedin
Additional file 3 (Additional file 3. Order Preference
for Combining Data Types). In the case where
authors report several scales for the same outcome,
we will use our charting exercise to better inform our
choice of scale used in the derivation of our summary
effect measures. If a cluster design is reported,
outcome measures will be extracted from the primary
study that account for the clustering; however, if
thesedataarenotavailable,thenthemethodofRao
and Scott will be used to account for the correlation
in these data [28, 35, 36]. For the presentation of
results, the summary relative effect sizes (e.g., MDs
or ORs) and associated 95% credible intervals (CrIs)
for each possible pairwise comparison will be used.
Missing data
Where adjusted summary effect measures are reported,
study-level data as provided by study authors will be
included in our analyses. The type of data imputation
method used for missing data will be noted on our data
abstraction form so that the quality assessment of each
study will reflect the appropriateness of the data imput-
ation method used to account for missing data. For
example, attrition in a trial for dementia treatments may
be related to side effects of the treatment, and using the
last observation carried forward approach can introduce
important bias favoring the treatment, as outcomes tend
to deteriorate with time. Informative missing odds ratios
(IMORs) for dichotomous outcomes and informative
missingness difference of means (IMDoM) for continu-
ous outcomes will be derived to capture the uncertainty
in our estimates from missing data under the missing at
random assumption [37, 38]. For continuous outcomes
that are not reported as means with associated standard
deviations, imputation methods will be used to derive
approximate effect measures [28, 39]. Study authors will
be contacted for further information prior to applying
data imputation methods, as needed.
Assessment of transitivity
The assumption of transitivity will be assessed to
ensure that potential effect modifiers described above
are balanced on average across treatment comparisons
[40, 41]. Treatment groups receiving the standard of
care (or placebo) will be evaluated to ensure they are
similar across pairwise comparisons [42].
Data synthesis
Included studies will be summarized descriptively based
on study characteristics, study-level patient covariates,
interventions and outcomes studied, and our assessment
of risk of bias. If quantitative synthesis is not appropri-
ate, we will narratively describe the findings of our
systematic review. In our pairwise and network meta-
analyses of treatment efficacy and safety, we will pool ef-
fect measures across all types of dementia because stud-
ies in the BPSD literature frequently include patients
with any type of dementia, to derive overall effect
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estimates based on the totality of the evidence; however,
in our secondary analysis of treatment efficacy we will
not assume exchangeability of priors for between-study
heterogeneity across dementia subtypes given their well-
described differences in presentation and clinical course
[1, 30, 43]. We will further test our findings in subgroup
analyses based on dementia subtype.
Direct treatment comparisons
Bayesian random-effects models using vague priors for
all trial baselines (N(0,1000)), treatment effects
(N(0,1000)), and between-study standard deviations
(σ~N(0,100) for σ>0) will be used to derive summary
effect measures with associated 95% credible intervals
when two or more studies report data that can be
included in the analysis [44].
Indirect and mixed treatment comparisons
Outcomes of treatment efficacy will be modeled as
described in Dias et al., if the assumption of transitivity
is valid and the evidence forms a connected network
[45, 43]. A three-level hierarchical model as described in
Schmitz et al., will be used to model outcomes of
treatment safety given that we will be including both
randomized and non-randomized study designs [43].
Random-effects models are most appropriate given the
anticipated clinical and methodological heterogeneity
among pooled studies [28]. We will assume vague prior
distributions for all trial baselines (N(0,1000)), treatment
effects (N(0,1000)), and between-study standard
deviations (σ~N(0,100) for σ>0). We will use a minim-
ally informative prior for between-study type standard
deviations (N(0,1) for γ>0), which is consistent with
priors used in previous Bayesian 3-level hierarchical
NMA models [21, 43].
Model convergence will be assessed using the
Brooks-Gelman-Rubin diagnostic and goodness of
model fit will be assessed with the deviance informa-
tion criterion [46]. These analyses will be completed
using JAGS software [47]. Relative treatment rankings
will be reported with mean ranks and the surface
under the cumulative ranking curve [48]. We will
present tables in our final manuscript that contain
the rank probabilities of each intervention and
associated efficacy and safety outcomes given the
uncertainty related to the interpretation of interven-
tion rankings [49]. Number needed to treat for an
additional beneficial outcome (NNTB) and number
needed to treat for an additional harmful outcome
(NNTH) will be estimated for each intervention [28,
50]. Rank-heat plots will be used to display the treat-
ment rankings across multiple outcomes [51].
Assessment of inconsistency
Global consistency of the entire network will be
assessed with the design-by-treatment interaction
model [52]. If inconsistency is found within the
network, local inconsistency of the loops within each
network will then be assessed with the loop-specific
approach to generate an inconsistency factor with an
associated 95% CI [5355].
Exploring sources of heterogeneity or inconsistency with
subgroup analyses and meta-regression
Subgroup analyses will be undertaken to explore the
influence of potential effect modifiers further. If
there are a sufficient number of studies identified
reporting study-level data to assess our hypothesized
effect modifiers, we will perform analyses based on
subgroups of the following effect modifiers: age, sex,
severity of dementia, dementia type, care setting,
availability of caregiver, specialty of treating clinician,
and number of prior treatments trialed. Network
meta-regression will be used to explore the effect of
study year if more than 10 studies are available.
Sensitivity analyses
The robustness of our study findings will be tested
with the following sensitivity analyses (in addition to
the aforementioned sensitivity analyses) incorporating
only data from the following studies into the network
estimates: (1) RCTs (outcomes of safety only), (2)
RCTs and cohort studies reporting effect measures
that are adjusted for important confounders
(outcomes of safety only), (3) studies at low risk of
bias based on the two components of our risk of bias
assessment found to be the greatest threat to study
validity [4], studies at low or moderate risk of bias
based on the two components of our risk of bias
assessment found to be the greatest threat to study
validity, and [5] studies where study authors use a
standardized method for the diagnosis of dementia.
Our choice of priors on the between-study standard
deviation will be tested in sensitivity analyses with the fol-
lowing vague priors: σ~U(0,10) and log(σ)~N(0,1000).
Assessment of publication bias and small-study effects
We will use contour-enhanced funnel plots for each
treatment comparison separately to assess for publica-
tion bias if there are 10 or more studies reporting on
a particular outcome [28, 56]. Within each funnel
plot, we will distinguish cohort studies from RCTs
and we will also illustrate study quality by using
distinct symbols. Small-study effects will be tested
within a network meta-regression model that distin-
guishes studies based on their size [57].
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Dissemination of study findings
Early stakeholder involvement improves knowledge
dissemination, as stakeholders are engaged from question
formation to the end of study activities [58]. Given the
complexity of BPSD management and the need to improve
care at the bedside, the early involvement of stakeholders
will potentially improve the impact of this research.
As such, we aim to use an integrated knowledge trans-
lation approach, with early participation and engagement
of knowledge/end users in the research process in the
following ways: (1) surveying of knowledge/end users to
identify their preferences for primary efficacy and safety
outcomes, (2) integrating a qualitative consensus-based
categorization procedure (as described in Node Forma-
tion) into our verification process for ensuring the
proper categorization of interventions, and (3) discussing
study findings with stakeholder groups to understand
the broader social context of our findings given the
importance of social constructs such as gender in the
caregiving role of patients with BPSD and to identify key
messages for study findings [26, 59, 60].
For dissemination, we will pursue open access publica-
tion(s) and presentation of results at several local,
national, and international meetings. Local dissemin-
ation will take place in two provinces (Ontario and
Alberta). We will engage with patient advocacy groups
through our stakeholder linkages to disseminate our
results through their media platforms and create a
research brief to post on the St. Michaels Hospital
Knowledge Translation Program website.
Discussion
There will be two main anticipated challenges in com-
pleting this systematic review and network meta-
analysis: (1) incorporating both randomized and non-
randomized study designs into our network meta-
analyses for safety outcomes, and (2) ensuring the treat-
ment comparisons in our networks maintain transitivity
in our network meta-analyses while also remaining clin-
ically meaningful to knowledge users. The decision to
incorporate both randomized and non-randomized study
designs into the network meta-analyses for safety out-
comes will provide knowledge users (e.g., clinicians,
caregivers) with a better understanding of the risks asso-
ciated with possible treatment strategies given the sig-
nificant number of publications in the observational
literature on this topic; however, there are methodo-
logical concerns about the possibility of unknown con-
founders that could affect the validity of our findings
[44, 61]. It is also important to further explore the find-
ings of industry-sponsored studies in a real-world setting
to capture adverse drug events that RCTs are not pow-
ered to detect, which is often done with observational
study designs [62].
Optimal organization of our treatment nodes within
our networks will also be a challenge. Integrating non-
pharmacological interventions into our network meta-
analysis will require input from both researchers and
knowledge users, which is why we will utilize a qualitative
consensus-based categorization procedure [26]. Complex
non-pharmacological interventions have previously
been integrated into network meta-analyses [63, 64].
We hope that by including non-pharmacological
interventions into our network meta-analyses of effi-
cacy outcomes that we can help knowledge users to
make informed health care decisions concerning the
management of BPSD.
Additional files
Additional file 1: PRISMA Checklist. (DOCX 36 kb)
Additional file 2: MEDLINE Search Strategy. (DOCX 16 kb)
Additional file 3: Order Preference for Combining Data Types. (DOCX 14 kb)
Abbreviations
BPSD: Behavioral and psychological symptoms of dementia; CIHR: Canadian
Institutes for Health Research; IMDoM: Informative missingness difference in
means; IMOR: Informative missing odds ratios; ISPOR: International Society for
Pharmacoeconomics and Outcomes Research; MD: Mean difference;
NMA: Network meta-analysis; NMDA: N-methyl-D-aspartate; NNTB: Number
needed to treat; NNTH: Number needed to harm; OR: Odds ratio; PRESS: Peer
Review of Electronic Search Strategies; PRISMA-P: Preferred reporting items for
systematic review and meta-analysis protocols; RCT: Randomized controlled
trial; SMD: Standardized mean difference; TRIP: Turning Research into Practice
Acknowledgements
We would like to thank Jessie McGowan for developing the literature search
strategy and Becky Skidmore for completing the PRESS Checklist associated
with this literature search strategy. We would also like to thank Alissa
Epworth for conducting the literature searches.
Funding
This study is funded through a Late Life Issues Team Grant (LLI01001) from
the Critical Care Strategic Clinical Network and Canadian Institutes of Health
Research (CIHR). JW is funded by the Eliot Phillipson Clinician Scientist Training
Program and the CIHR Canada Graduate Scholarships-Masters Program. ZG has
funding from the M.S.I Foundation, Hotchkiss Brain Institute, and Canadian
Consortium on Neurodegeneration in Aging. ACT is funded by a Tier 2 Canada
Research Chair in Knowledge Synthesis. AAV is funded by the CIHR Banting
Postdoctoral Fellowship Program. SES is funded by a Tier 1 Canada Research
Chair in Knowledge Translation. The funders played no role in the development
of this protocol.
Availability of data and materials
Not Applicable.
Authorscontributions
JW drafted the manuscript. JW, ZG, ACT, AAV, and SES designed the study and
edited the manuscript. All authors read and approved the final manuscript prior
to its submission. All authors had full access to all of the data (including
statistical report and table) in the protocol and can take responsibility for the
integrity of the data and the accuracy of the data analysis.
Ethics approval and consent to participate
Not Applicable.
Consent for publication
Not Applicable.
Watt et al. Systematic Reviews (2017) 6:182 Page 7 of 9
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Competing interests
ACT and AAV are associate editors of Systematic Reviews; otherwise,
protocol authors have no conflicts of interest to declare.
PublishersNote
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Author details
1
Department of Geriatric Medicine, University of Toronto, 27 Kings College
Circle, Toronto, ON M5S 1A1, Canada.
2
Institute for Health Policy
Management and Evaluation, University of Toronto, 4th Floor, 155 College
Street, Toronto, ON M5T 3M6, Canada.
3
Section of Geriatric Medicine,
Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
4
Li
Ka Shing Knowledge Institute, St. Michaels Hospital, 209 Victoria Street, East
Building, Room 716, Toronto, ON M5B 1W8, Canada.
5
Epidemiology Division,
Dalla Lana School of Public Health, University of Toronto, Health Sciences
Building, 155 College Street, 6th floor, Toronto, ON M5T 3M7, Canada.
Received: 27 February 2017 Accepted: 22 August 2017
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... We registered and published our protocol, which contains details of the literature search strategy. 19 Our systematic review and NMA manuscript is written in accordance with the Preferred Reporting Items for Systematic Reviews and Metaanalyses (PRISMA) extension statement for reporting systematic reviews incorporating NMA. 20 Data sources and searches We searched Medline, Embase, the Cochrane Library, CINAHL, and PsycINFO for citations published in any language from inception to 15 October 2020. ...
... 20 Data sources and searches We searched Medline, Embase, the Cochrane Library, CINAHL, and PsycINFO for citations published in any language from inception to 15 October 2020. 19 We also searched grey literature and reviewed reference lists of included studies and related systematic reviews. 19 study selection Eligible studies for inclusion were randomised controlled trials of drug and nondrug interventions used to treat symptoms of depression in people with dementia experiencing depression as a neuropsychiatric symptom of dementia or with a diagnosis of a major depressive disorder. ...
... 19 We also searched grey literature and reviewed reference lists of included studies and related systematic reviews. 19 study selection Eligible studies for inclusion were randomised controlled trials of drug and nondrug interventions used to treat symptoms of depression in people with dementia experiencing depression as a neuropsychiatric symptom of dementia or with a diagnosis of a major depressive disorder. Dementia (eg, medical history of dementia or Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSMV)) and major depressive disorder (eg, DSMV) were defined by study authors. ...
Article
Full-text available
Objective To describe the comparative efficacy of drug and non-drug interventions for reducing symptoms of depression in people with dementia who experience depression as a neuropsychiatric symptom of dementia or have a diagnosis of a major depressive disorder. Design Systematic review and meta-analysis. Data sources Medline, Embase, the Cochrane Library, CINAHL, PsycINFO, and grey literature between inception and 15 October 2020. Eligibility criteria for study selection Randomised trials comparing drug or non-drug interventions with usual care or any other intervention targeting symptoms of depression in people with dementia. Main outcome measures Pairs of reviewers screened studies, abstracted aggregate level data, and appraised risk of bias with the Cochrane risk of bias tool, which facilitated the derivation of standardised mean differences and back transformed mean differences (on the Cornell scale for depression in dementia) from bayesian random effects network meta-analyses and pairwise meta-analyses. Results Of 22 138 citations screened, 256 studies (28 483 people with dementia) were included. Missing data posed the greatest risk to review findings. In the network meta-analysis of studies including people with dementia without a diagnosis of a major depressive disorder who were experiencing symptoms of depression (213 studies; 25 177 people with dementia; between study variance 0.23), seven interventions were associated with a greater reduction in symptoms of depression compared with usual care: cognitive stimulation (mean difference −2.93, 95% credible interval −4.35 to −1.52), cognitive stimulation combined with a cholinesterase inhibitor (−11.39, −18.38 to −3.93), massage and touch therapy (−9.03, −12.28 to −5.88), multidisciplinary care (−1.98, −3.80 to −0.16), occupational therapy (−2.59, −4.70 to −0.40), exercise combined with social interaction and cognitive stimulation (−12.37, −19.01 to −5.36), and reminiscence therapy (−2.30, −3.68 to −0.93). Except for massage and touch therapy, cognitive stimulation combined with a cholinesterase inhibitor, and cognitive stimulation combined with exercise and social interaction, which were more efficacious than some drug interventions, no statistically significant difference was found in the comparative efficacy of drug and non-drug interventions for reducing symptoms of depression in people with dementia without a diagnosis of a major depressive disorder. Clinical and methodological heterogeneity precluded network meta-analysis of studies comparing the efficacy of interventions specifically for reducing symptoms of depression in people with dementia and a major depressive disorder (22 studies; 1829 patients). Conclusions In this systematic review, non-drug interventions were found to be more efficacious than drug interventions for reducing symptoms of depression in people with dementia without a major depressive disorder. Systematic review registration PROSPERO CRD42017050130.
... Our protocol was registered (Prospero: CRD42017050130) and published [14]. We report our findings in accordance with the PRISMA extension statement for reporting systematic reviews incorporating NMA [8]. ...
... We report our findings in accordance with the PRISMA extension statement for reporting systematic reviews incorporating NMA [8]. We discuss protocol deviations in Additional file 1 [14]. ...
... We asked 12 dementia care partners (e.g. nurses, physicians, a caregiver) to rank commonly reported safety outcomes associated with the treatment of neuropsychiatric symptoms in dementia [14,15]. Risk of fracture was selected as our primary outcome. ...
Article
Full-text available
Background: Prescribing trends suggest that pharmacologic alternatives to antipsychotics are gaining in popularity, but randomized trial (RCT) data of their comparative safety is scarce. Our objective was to describe the comparative safety of pharmacologic interventions for treating neuropsychiatric symptoms in dementia. Methods: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO, from inception to May 28, 2019, for studies of pharmacologic interventions used to treat neuropsychiatric symptoms in dementia. Dementia care partners selected fracture risk as our primary outcome. Pairs of reviewers, working independently, conducted all study screening, data abstraction, and risk of bias appraisal. We conducted Bayesian random-effects network meta-analyses (NMAs) using data from RCTs to derive odds ratios (ORs). In secondary analyses, we conducted frequentist random-effects NMAs using data from RCTs and Bayesian three-level hierarchical random-effects NMAs incorporating data from RCTs and non-randomized studies. Results: Our systematic review included 209 randomized and non-randomized studies (889,378 persons with dementia). In NMAs of data from randomized trials, there were no increased odds of fracture associated with any intervention in primary analyses; however, data were sparse. We found increased odds of cerebrovascular events associated with antipsychotics (odds ratio [OR] 2.12, 95% credible interval [CrI] 1.29 to 3.62; number needed to harm [NNH] = 99) and increased odds of falls associated with dextromethorphan-quinidine (OR 4.16, 95% CrI 1.47 to 14.22; NNH = 55) compared to placebo in persons with dementia. In a subgroup of persons with Alzheimer disease, antipsychotics were associated with increased odds of fracture compared to anticonvulsants (OR 54.1, 95% CrI 1.15 to 38,300; NNH = 18). In older persons (mean age ≥ 80 years) with dementia, anticonvulsants were associated with increased odds of death compared to placebo (OR 8.36, 95% CrI 1.17 to 203.4; NNH = 35) and antipsychotics were associated with increased odds of death compared to antidepressants (OR 5.28, 95% CrI 1.06 to 3.51; NNH = 47). Conclusion: Although antipsychotics were associated with greater harm than antidepressants and anticonvulsants in subgroups of persons with dementia, medications used in lieu of antipsychotics for treating neuropsychiatric symptoms in dementia, such as anticonvulsants and dextromethorphan-quinidine, were also associated with harm. Decision-making concerning treatments prescribed in lieu of antipsychotics should include potential harms. Prospero registration: CRD42017050130.
... Twelve dementia care partners (nurses, allied health professionals, physicians, and a caregiver) selected our study outcomes (18) by independently ranking a group of commonly reported neuropsychiatric symptoms (for example, aggression, agitation, and sleep disturbances) in descending order of importance. The care partners selected change in aggression as our main outcome and change in agitation as our secondary outcome. ...
Article
Background: Both pharmacologic and nonpharmacologic interventions are used to treat neuropsychiatric symptoms in persons with dementia. Purpose: To summarize the comparative efficacy of pharmacologic and nonpharmacologic interventions for treating aggression and agitation in adults with dementia. Data sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO between inception and 28 May 2019 without language restrictions; gray literature; and reference lists scanned from selected studies and systematic reviews. Study selection: Randomized controlled trials comparing interventions for treating aggression and agitation in adults with dementia. Data extraction: Pairs of reviewers independently screened studies, abstracted data, and appraised risk of bias. Data synthesis: After screening of 19 684 citations, 163 studies (23 143 patients) were included in network meta-analyses. Analysis of interventions targeting aggression and agitation (148 studies [21 686 patients]) showed that multidisciplinary care (standardized mean difference [SMD], -0.5 [95% credible interval {CrI}, -0.99 to -0.01]), massage and touch therapy (SMD, -0.75 [CrI, -1.12 to -0.38]), and music combined with massage and touch therapy (SMD, -0.91 [CrI, -1.75 to -0.07]) were clinically more efficacious than usual care. Recreation therapy (SMD, -0.29 [CrI, -0.57 to -0.01]) was statistically but not clinically more efficacious than usual care. Limitations: Forty-six percent of studies were at high risk of bias because of missing outcome data. Harms and costs of therapies were not evaluated. Conclusion: Nonpharmacologic interventions seemed to be more efficacious than pharmacologic interventions for reducing aggression and agitation in adults with dementia. Primary funding source: Alberta Health Services Critical Care Strategic Clinical Network. (PROSPERO: CRD42017050130).
... [6][7][8] In turn, these options may compromise the conclusions of the systematic review. 9 Statistical modeling of MOD has received little attention in systematic reviews with two (for example, the works of Ejere et al, 10 Mayo-Wilson et al, 11 and Virgili et al 12 ) or more interventions (for example, the works of Watt et al 13 and Veroniki et al 14 ). As opposed to imputation or exclusion, modeling MOD comprises an elegant framework that adjusts for bias due to MOD and fully acknowledges the uncertainty about the scenarios considered for the missingness mechanism. ...
Article
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Objectives: To investigate the implications of addressing informative missing binary outcome data (MOD) on network meta‐analysis (NMA) estimates while applying the missing at random (MAR) assumption under different prior structures of the missingness parameter. Methods: In three motivating examples, we compared six different prior structures of the informative missingness odds ratio (IMOR) parameter in logarithmic scale under pattern‐mixture and selection models. Then, we simulated 1000 triangle networks of two‐arm trials assuming informative MOD related to interventions. We extended the Bayesian random‐effects NMA model for binary outcomes and node‐splitting approach to incorporate these 12 models in total. With interval plots, we illustrated the posterior distribution of log OR, common between‐trial variance (τ²), inconsistency factor and probability of being best per intervention under each model. Results: All models gave similar point estimates for all NMA estimates regardless of simulation scenario. For moderate and large MOD, intervention‐specific prior structure of log IMOR led to larger posterior standard deviation of log ORs compared to trial‐specific and common‐within‐network prior structures. Hierarchical prior structure led to slightly more precise τ² compared to identical prior structure, particularly for moderate inconsistency and large MOD. Pattern‐mixture and selection models agreed for all NMA estimates. Conclusions: Analyzing informative MOD assuming MAR with different prior structures of log IMOR affected mainly the precision of NMA estimates. Reviewers should decide in advance on the prior structure of log IMOR that best aligns with the condition and interventions investigated.
... Furthermore, collaborative care, a multi-professional, structured approach to depression management and enhanced communication and follow-up [11], can encompass both combined psychotherapy and anti-depressant usage. Such treatments-anti-depressants, psychotherapies and collaborative care-have all been investigated in recent RCTs in patients with CAD, have been combined in other pairwise and network meta-analyses [11,31,32], and should therefore be comparable for NMA. While exercise is an established treatment for depression [15], as outlined above, it is usually encompassed in (heterogeneous) cardiac rehabilitation programmes, but where it studied alone it could be compared to other interventions. ...
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Background: Depression is common in patients with coronary artery disease (CAD) and is associated with poorer outcomes and higher costs. Several randomised controlled trials (RCTs) targeting depression, of various modalities (including pharmacological, psychotherapeutic and other approaches), have been conducted and summarised in pairwise meta-analytic reviews. However, no study has considered the cumulative evidence within a network, which can provide valuable indirect comparisons and information about the relative efficacy of interventions. Therefore, we will adopt a review of review methodology to develop a network meta-analysis (NMA) of depression interventions for depression in CAD. Methods: We will search relevant databases from inception for systematic reviews of RCTs of depression treatments for people with CAD, supplementing this with comprehensive searches for recent or ongoing studies. We will extract data from and summarise characteristics of individual RCTs, including participants, study characteristics, outcome measures and adverse events. Cochrane risk of bias ratings will also be extracted or if not present will be conducted by the authors. RCTs that compare depression treatments (grouped as pharmacological, psychotherapeutic, combined pharmacological/ psychotherapeutic, exercise, collaborative care) to placebo, usual care, waitlist control or attention controls, or directly in head-to-head comparisons, will be included. Primary outcomes will be the change in depressive symptoms (summarised with a standardised mean difference) and treatment acceptability (treatment discontinuation: % of people who withdrew). Secondary outcomes will include change in 6-month depression outcomes, health-related quality of life (HRQoL), mortality, cardiovascular morbidity, health services use and adverse events. Secondary analyses will form further networks with individual anti-depressants and psychotherapies. We will use frequentist, random effects multivariate network meta-analysis to synthesise the evidence for depression intervention and to achieve a ranking of treatments, using Stata. Rankograms and surface under the cumulative ranking curves will be used for treatment ranking. Local and global methods will evaluate consistency. GRADE will be used to assess evidence quality for primary outcomes. Discussion: The present review will address uncertainties about the evidence in terms of depression management in CAD and may allow for a ranking of treatments, including providing important information for future research efforts. Systematic review registration: PROSPERO CRD42018108293 Keywords: Depression, Coronary artery disease, Network meta-analysis, Systematic review, Randomised controlled trial, Intervention,
... The World Health Organization estimates that around 50 million people worldwide are suffering from dementia with 10 million new cases diagnosed every year [1]. Approximately 75% of patients diagnosed with dementia will exhibit at least one behavioural and psychological symptom such as agitation, lethargy, oppositional behaviour or aggression in a given month [2,3]. Episodes of aggressivity in dementia can appear spontaneously or be triggered by physical illness or pain, unfamiliar surroundings or medical examinations. ...
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: Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central's Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols--PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols.
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This paper reviews the use of Bayesian methods in meta-analysis. Whilst there has been an explosion in the use of meta-analysis over the last few years, driven mainly by the move towards evidence-based healthcare, so too Bayesian methods are being used increasingly within medical statistics. Whilst in many meta-analysis settings the Bayesian models used mirror those previously adopted in a frequentist formulation, there are a number of specific advantages conferred by the Bayesian approach. These include: full allowance for all parameter uncertainty in the model, the ability to include other pertinent information that would otherwise be excluded, and the ability to extend the models to accommodate more complex, but frequently occurring, scenarios. The Bayesian methods discussed are illustrated by means of a meta-analysis examining the evidence relating to electronic fetal heart rate monitoring and perinatal mortality in which evidence is available from a variety of sources.
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Non-randomized studies aim to reveal whether or not interventions are effective in real-life clinical practice, and there is a growing interest in including such evidence in the decision-making process. We evaluate existing methodologies and present new approaches to using non-randomized evidence in a network meta-analysis of randomized controlled trials (RCTs) when the aim is to assess relative treatment effects. We first discuss how to assess compatibility between the two types of evidence. We then present and compare an array of alternative methods that allow the inclusion of non-randomized studies in a network meta-analysis of RCTs: the naïve data synthesis, the design-adjusted synthesis, the use of non-randomized evidence as prior information and the use of three-level hierarchical models. We apply some of the methods in two previously published clinical examples comparing percutaneous interventions for the treatment of coronary in-stent restenosis and antipsychotics in patients with schizophrenia. We discuss in depth the advantages and limitations of each method, and we conclude that the inclusion of real-world evidence from non-randomized studies has the potential to corroborate findings from RCTs, increase precision and enhance the decision-making process. Copyright © 2017 John Wiley & Sons, Ltd.
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Considering the ample evidence of involvement of the glutamate system in the pathophysiology of depression, pre-clinical and clinical studies have been conducted to assess the antidepressant efficacy of glutamate inhibition, and glutamate receptor modulators in particular. This review focuses on the use of glutamate receptor modulators in unipolar depression.
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Background: Ranking of interventions is one of the most appealing elements of network meta-analysis. There is, however, little evidence about the reliability of these rankings. Purpose: To empirically evaluate the extent of uncertainty in intervention rankings from network meta-analysis. Data sources: Two previous systematic reviews that involved searches of the Cochrane Library, MEDLINE, and Embase up to July 2012 for articles that included networks of at least 3 interventions. Study selection: 58 network meta-analyses involving 1308 randomized trials and 404 interventions with available aggregated outcome data. Data analysis: Each network was analyzed with a Bayesian approach. For each intervention, the surface under the cumulative ranking curve (SUCRA) and its 95% credible interval (95% CrI) were estimated. Through use of the SUCRA values, the interventions were then rank-ordered between 0% (worst) and 100% (best). Data synthesis: The median width of the 95% CrIs of the SUCRA was 65% (first to third quartile, 38% to 80%). In 28% of networks, there was a 50% or greater probability that the best-ranked treatment was actually not the best. No evidence showed a difference between the best-ranked intervention and the second and third best-ranked interventions in 90% and 71% of comparisons, respectively. In 39 networks with 6 or more interventions, the median probability that 1 of the top 2 interventions was among the bottom 2 was 35% (first to third quartile, 14% to 59%). Limitation: This analysis did not consider such factors as the risk of bias within trials or small-study effects that may affect the reliability of rankings. Conclusion: Treatment rankings derived from network meta-analyses have a substantial degree of imprecision. Authors and readers should interpret such rankings with great caution. Primary funding source: Cochrane France.
Article
Objective: To present a novel and simple graphical approach to improve the presentation of the treatment ranking in a network meta-analysis (NMA) including multiple outcomes. Study design and settings: NMA simultaneously compares many relevant interventions for a clinical condition from a network of trials, and allows ranking of the effectiveness and/or safety of each intervention. There are numerous ways to present the NMA results, which can challenge their interpretation by research users. The rank-heat plot is a novel graph that can be used to quickly recognize which interventions are most likely the best or worst interventions with respect to their effectiveness and/or safety for a single or multiple outcome(s), and may increase interpretability. Results: Using empirical NMAs, we show that the need for a concise and informative presentation of results is imperative, particularly as the number of competing treatments and outcomes in a NMA increases. Conclusions: The rank-heat plot is an efficient way to present the results of ranking statistics, particularly when a large amount of data is available, and it is targeted to users from various backgrounds.