Adverse events special interest

Adverse Events of Special Interest and Potential Toxicities... 

This section specifies the list of adverse events (AEs) of special interest for the product as well as potential toxicities that should be considered for all products. The potential toxicities that should be explicitly considered for... 

Generally speaking, the safety evaluat ion of new drugs is intended to detect quantifiable effects in as many organs and bodily systems as possible, hence the expression casting a wide net. However, in the domain of cardiovascular safety, hypothesis-testing approaches are employed to investigate cardiovascular adverse events of special interest. 

The previous chapter provided examples of statistical analyses that are used to assess efficacy in clinical trials. In this and the following chapter, the focus moves to assessments of safety. As will be seen in the first part of this chapter, general safety assessments are conducted quite differently from those for efficacy, in that descriptive statistics are used as opposed to hypothesis testing. However, in the domain of cardiovascular safety, hypothesis-testing approaches are employed to investigate the potential occurrence of specific cardiac and cardiovascular adverse events. In the language introduced in this chapter, these can be regarded as adverse events of special interest. 

The varying nomenclature used to describe safety data in clinical trials can be confusing. Terms used include adverse events, adverse experiences, adverse drug reactions, side effects, severe adverse events, significant adverse events, tteattnent-emeigent adverse events, adverse events of special interest, and toxidties. We therefore endeavor to bring some consistency to this terminology. 

In the domain of proarrhy thmic cardiac safety, QT prolongation can be regarded as an adverse event of special interest, and therefore an inferential (hypothesis-testing) statistical approach is taken. Three statistical methodologies are applicable here the first two, the intersection-union test and the union-intersection test, are discussed in this section concentration- esponse modeling is then discussed in the following section. 

Ross SA (2015) A multipUcity of targets evaluating composite endpoint studies of the GLP-1 receptor agonists in type 2 diabetes. Curr MedRes Opin 31 125-135 RovieUo G, Sigala S, Danes R et al (2016) Incidence and relative risk of adverse events of special interest in patients with castration resistant prostate cancer treated with CYP-17 inhibitors a meta-analysis of published trials. Crit Rev Oncol Hematol 101 12-20 Sankoh AJ, Li H, D Agostino RB Sr (2016) Use of composite endpoints in cUnical trials. Stat Med 35 319-320... 

Girard PM, CampbeU TB, Grinsztejn B, Hartikainen J, RachEne A, Nijs S, et al. Pooled week 96 results of the phase III DUET-1 and DUET-2 trials of etravirine further analysis of adverse events and laboratory abnormaEties of special interest. Hiv Med 2012 13(7) 427-35. 

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