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Erschienen in:
The Role and Potential of Surrogate Outcomes in Clinical Trials: Have We Made Any Progress in the Past Decade? Kapitel lesen Erstes Kapitel lesen

2013 | OriginalPaper | Buchkapitel

Identifying and Addressing Safety Signals in Clinical Trials: Some Issues and Challenges

verfasst von : Thomas R. Fleming

Erschienen in: Proceedings of the Fourth Seattle Symposium in Biostatistics: Clinical Trials

Verlag: Springer New York

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Abstract

Reliable evidence is needed from clinical research about whether the interventions used in clinical practice are safe as well as effective. Regarding risk, safety is not established by failure to establish excess risk, such as obtaining confidence intervals for the relative risk of safety events that include unity. Absence of evidence is not evidence of absence. Rather, safety is established if available data about safety are sufficiently favorable and reliable to rule out the threshold for unacceptable risk, where this threshold should be determined by considering the strength of the evidence for efficacy.
Important insights about safety usually will be provided before marketing through Phase 1, 2, and 3 clinical trials. These insights, especially regarding risks associated with long-term use of the intervention and risks of rare but clinically compelling events, are enhanced by post-marketing active and passive surveillance, and especially by large, long-term randomized trials that provide the most reliable approach for identifying and addressing safety signals. The integrity of these randomized trials is enhanced by preventing irregularities in the quality of trial conduct that would reduce their sensitivity to detecting clinically meaningful safety risks caused by the experimental regimen.
After considering approaches to identifying and addressing safety risks and discussing performance standards to improve the quality of conduct of safety trials, we will consider further the vulnerability to undetected safety risks when evidence for efficacy has been limited to documentation of effects on surrogate endpoints such as biomarkers, and then discuss important considerations regarding cardiovascular safety trials conducted in the setting of type 2 diabetes mellitus.

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Vorheriges Kapitel Quantitative Risk/Benefit Assessment: Where Are We?
Nächstes Kapitel Past, Present, and Future of Drug Safety Assessment
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Metadaten
Titel
Identifying and Addressing Safety Signals in Clinical Trials: Some Issues and Challenges
verfasst von
Thomas R. Fleming
Copyright-Jahr
2013
Verlag
Springer New York
Buch
Proceedings of the Fourth Seattle Symposium in Biostatistics: Clinical Trials

Print ISBN: 978-1-4614-5244-7

Electronic ISBN: 978-1-4614-5245-4

Copyright-Jahr: 2013

DOI
https://doi.org/10.1007/978-1-4614-5245-4_9