FPIN Journal Club
SYSTEMATIC REVIEW WORKSHEET
SPEAKER NOTES
Title: Low Dose Aspirin to Prevent Preeclampsia in High Risk Women
Journal Club Author: Laura Morris MD, MSPH, University of Missouri-Columbia
Journal Club Editor: Kate Rowland, MD, MS, Rush-Copley Medical Center
PURL Citation: Oyola S, Kirley K. Another good reason to recommend low-dose aspirin. J Fam
Pract. 2015 May;64(5):301-303.
Original Article: Henderson J, Whitlock E, O’Connor E, et al. Low-dose aspirin for prevention of
morbidity and mortality from preeclampsia: a systematic evidence review for the U.S.
Preventive Services Task Force. Ann Intern Med. 2014;160:695-703.
Definitions
Systematic review:
A review in which evidence on a topic or research question has been systematically identified,
appraised and summarized according to predetermined criteria.
Meta-analysis:
A statistical technique. Summarizes the results of several studies into a single estimate, giving
more weight to larger studies.
1. What question did the study attempt to answer?
Patients – Pregnant women at high risk for preeclampsia
Intervention – Daily low-dose (60-150mg) aspirin
Comparison – Usual care (no aspirin)
Outcome – Incidence of preeclampsia, Perinatal outcomes (fetal and maternal morbidity and
mortality, preterm birth, IUGR, low birth weight), potential harms of aspirin use
Did the study address an appropriate and clearly focused question
Yes
No
2. Determining relevance:
a. Did the authors study a clinically meaningful
and/or a patient oriented outcome?
b. The patients covered by the review similar to your population
Yes
Yes
No
No
3. Determining validity:
a. What type of studies are included in the review?
RCTs of various sizes plus two large, good quality observational studies (included for risk
of harms only)
b. The literature search is sufficiently rigorous to identify all the relevant studies?
Look for
Yes
No
· Which bibliographic databases were used
· Follow up from reference lists
· Personal contact with experts
· Search for unpublished as well as published studies
· Search for non-English language studies
c. Did the review’s authors do enough to assess the
quality of the included studies?
· The authors need to consider the rigor of the studies
they have identified. They used USPSTF methodology
d. If the results of the review have been combined, was it
reasonable to do so?
Consider whether
· The results were similar from study to study
· The results of all the included studies are clearly
displayed
· The results of the different studies are similar
· The reasons for any variations are discussed
Yes
No
Yes
No
4. What are the results?
a. What is the overall result of the review?
For women at elevated risk of preeclampsia, prophylaxis with low-dose aspirin (60 to 150 mg)
beginning after the first trimester of pregnancy reduced risk of preeclampsia and important
adverse perinatal health outcomes. Specifically, modestly reduced risks of preterm birth, IUGR,
and possibly perinatal mortality were supported by the evidence.
Among women who received low-dose aspirin, researchers noted a 14% risk reduction for
preterm birth (RR=0.86; 95% CI, 0.76-0.98); a 20% risk reduction for IUGR (RR=0.80; 95% CI,
0.65-0.99), and a 24% risk reduction for preeclampsia (RR=0.76; 95% CI, 0.62-0.95). The absolute
risk reduction for preeclampsia was estimated to be between 2% and 5%. There was no
increase in maternal postpartum hemorrhage or perinatal mortality, and no difference in
toddler’s development at 18 months.
b. Consider;
Are we clear about the reviews ‘bottom line’ results
Are the results presented with confidence intervals,
NNT, odds ratio, etc
5. Applying the evidence:
a. If the findings are valid and relevant, will this change
your current practice?
b. Is the change in practice something that can be done in
a medical care setting of a family physician?
c. Can the results be implemented?
d. Are there any barrier to immediate implementation?
e. How was this study funded? AHRQ for USPSTF
Yes
Yes
No
No
Yes
No
Yes
Yes
Yes
No
No
No
6. Teaching Points
Publication Bias
Occurs when the published research in a given topic area is not representative of the entire
body of work. In other words, readers may draw incorrect conclusions about research findings
because some are missing from the literature. Publication bias can be a threat to the validity of
a meta-analysis because meta-analytic techniques pool and summarize data—if the pool is
missing part of the data, then the conclusions may be incomplete or worse, wrong.
There are several possible sources of publication bias. Journals tend to publish positive findings,
leading to the “file drawer phenomenon,” where the no-effect or negative trials are left to fill
the publishers’ file drawers, or because authors, knowing this preference of journals to publish
positive findings, do not submit them. Or, findings from smaller or less well funded studies may
struggle to find a venue for publication. In the past, big pharma sponsors have been accused of
delaying or stopping publication of studies demonstrating adverse events or low efficacy. Only
after previously unpublished trials became available could scientists conclude that risks
outweighed benefits of a certain drug or that other costly treatments have little efficacy.
Funnel Plots
A funnel plot is a scatter plot of each study’s measure of effect against its size. Size goes on the
vertical axis and effect size on the horizontal axis. Small studies are less precise and should
scatter widely on the bottom of the figure, while larger studies that are more precise will cluster
more narrowly toward the top. In the absence of bias, the scatter plot will look like a reasonably
symmetrical inverted funnel. If there is publication bias, then the plot will be imbalanced (see
below). The absence of dots in the lower right hand quadrant indicates that small studies may
be missing.
Funnel plots are one method of assessment for publication bias. Negative or no-effect studies,
smaller studies, or less prominent studies may have more difficulty finding their way to
publication, aka the “file-drawer effect.” Other times publication bias could be intentional—
such as a large corporation stopping a negative study or “hiding” data.
In contrast, a symmetrical funnel plot (from another study) indicates publication bias is unlikely.
Dots are evenly and widely scattered.
From: BMJ 2011;343:d4002