CNS Clinical Trials Suicidality and Data Collection: Workshop Summary (2010) / Chapter Skim
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3 Data Analysis
3 Data Analysis
Pages 25-34
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From page 25... ...
They focused primarily on the limitations of metaanalysis as a study design and the multiple alternative explanations for the apparent findings.
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From page 26... ...
There were 87 cases reporting suicide behavior or ideation, assessed retrospectively. The graphic depiction used in the FDA's meta-analysis, the forest plot, revealed that only one study of antidepressants and suicidality found a significant relationship, the TADS (Treatment of Adolescents with Depression Study)
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From page 27... ...
Observational studies invite alternative explanations to explain their findings. Alternative explanations abound in the FDA data, according to presentations by Greenhouse and Robert Gibbons of the University of Illinois at Chicago.
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. Using statistical modeling techniques, another study of the selection effect in antidepressant trials found that more restrictive inclusion/exclusion criteria of an RCT generates greater
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From page 29... ...
To examine this possibility, he presented an illustrative example of a person-time logistic regression analysis of the relationship between antiepileptic drugs and suicide attempts in patients with bipolar illness. This permitted a comparison of suicide attempt rates in treated and untreated patients, adjusting for the natural decay in suicide rates over time from the index episode (Gibbons et al., 2009)
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From page 30... ...
, is useful, but it is far from ideal because of heightened media reporting and the lack of a denominator (AERS only gives how many individuals receiving the drug report adverse events, not the total number of people receiving the drug)
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From page 31... ...
He asked the generic question of whether propensity to withdraw stemmed from susceptibility to drug-related adverse events (or lack of therapeutic effect in placebo subject) , drug effect on tolerability of adverse events, and/or the
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From page 32... ...
His bottom line was that both withdrawals from the RCT and statistical models affect meta-analysis findings, and the impact may be greater given the rarity of completed suicide. During the workshop's discussion period devoted to methodological limitations of RCTs and their use in meta-analysis, FDA's Tom Laughren acknowledged that every method of study has its flaws.
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From page 33... ...
Although such studies are almost universally deemed to be of lesser validity than RCTs, observational studies may be better suited to studying rare clinical outcomes in real-world settings, where patients are more ill and more complicated. The foremost benefit of observational studies is the sample size and thus generalizability.
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From page 34... ...
The system does have drawbacks: lack of severity data, unmeasured covariates, and unvalidated outcomes, among others. Valuck and colleagues, drawing from another dataset, conducted a large nested case-control study of suicide attempts using claims data from managed care organizations (Valuck et al., 2009)
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