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Between-study heterogeneity is common in meta-analysis because studies differ in their protocols, target populations, settings, and ages of included subjects. This type of heterogeneity provides evidence about potential variability in treatment effects. Therefore, heterogeneity is not a nuisance or an undesirable feature, but rather an important source of information to be carefully analyzed (Lau et al., 1998). Instead of eliminating heterogeneity by restricting study inclusion criteria or scope, which can limit the utility of the review, heterogeneity of effect sizes can be quantified, and related to aspects of study populations or design features through statistical techniques such as meta-regression, which associates the size of treatment effects with effect modifiers. Meta-regression is most useful in explaining variation that occurs from sources that have no effect within studies, but big effects among studies (e.g., use of randomization or dose employed). Except in rare cases, meta-regression analyses are exploratory, motivated by the need to explain heterogeneity, and not by prespecification in the protocol. Meta-regression is observational in nature, and if the results of meta-regression are to be considered valid, they should be clinically plausible and supported by other external evidence. Because the number of studies in a meta-regression is often small, the technique has low power. The technique is subject to spurious findings because many potential covariates may be available, and adjustments to levels of significance may be necessary (Higgins and Thompson, 2004). Users should also be careful of relationships driven by anomalies in one or two studies. Such influential data do not provide solid evidence of strong relationships.

As mentioned previously, a detailed discussion of meta-analysis methodology is beyond the scope of this report. There are many

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unresolved questions regarding meta-analysis methods. Fortunately, meta-analysis methodological research is vibrant and ongoing. Box 4-4 describes some of the research trends in meta-analysis and provides relevant references for the interested reader.

Meta-analysis entails combining information from different studies; thus, the data may come from very different study designs. A small number of studies in conjunction with a variety of study designs contribute to heterogeneity in results. Consequently, verifying that conclusions are robust to small changes in the data and to changes in modeling assumptions solidifies the belief that they are robust to new information that could appear. Without a sensitivity analysis, the credibility of the meta-analysis is reduced.

Results are considered robust if small changes in the metaanalytic protocol, in modeling assumptions, and in study selection do not affect the conclusions. Robust estimates increase confidence in the SR’s findings. Sensitivity analyses subject conclusions to such tests by perturbing these characteristics in various ways.

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Lynn Elber, Associated Press Lynn Elber, Associated Press

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LOS ANGELES — “Game of Thrones” roared back onto the Emmy battlefield, topping Thursday’s nominations with 22 bids but with a formidable opponent in last year’s winner “The Handmaid’s Tale,” while a streaming platform made history by earning the most bids for the first time.

Netflix’s 112 nominations took away the front-runner title that HBO held since 2001, giving cable and broadcast networks more reason to fear their future as the TV industry continues to change.

HBO is no piker: It claimed 108 bids. “Game of Thrones” helped boost the premium cable service’s total and became the most-nominated series of all time, with its 129 nods topping the 124 nominations earned by “ER.”

Donald Glover’s “Atlanta” was the top comedy series nominee with 16 bids, poised to take advantage of the absence this time around of three-time winner “Veep.” “Atlanta” will face newcomers including “The Marvelous Mrs. Maisel,” “GLOW” and “Barry.” Others in the category include “black-ish,” “Silicon Valley,” “Curb Your Enthusiasm” and “Unbreakable Kimmy Schmidt.”

The newbie comedies aced out long-time Emmy favorite “Modern Family,” a five-time winner and perennial nominee since it debuted in 2009 on ABC. Its absence leaves just one network contender for best comedy, ABC’s “black-ish,” which also earned nods for Tracee Ellis Ross and Anthony Anderson, who noted his urban California roots.

“Being a kid from Compton, one could only dream of moments like this, so it’s truly a humbling experience right now.”

“Being a kid from Compton, one could only dream of moments like this, so it’s truly a humbling experience right now,” Anderson said.

The short-lived revival of “Roseanne,” canceled because of star Roseanne Barr’s racist tweet, drew only one major nomination, a supporting actress nod for Laurie Metcalf. Another revival, “Will Grace,” got Emmy love for nominees Megan Mullally and Molly Shannon but the main stars and series itself were snubbed.

“Killing Eve” star Sandra Oh made history of her own, becoming the first actress of Asian descent to be nominated for lead acting honors in a drama series. Oh had earned five supporting bids for “Grey’s Anatomy.”



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