Patient Safety, AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA.
Pharmacoepidemiol Drug Saf. 2012 Jun;21(6):589-96. doi: 10.1002/pds.2349. Epub 2012 Jan 30.
Disproportionality analysis is an important tool for interpreting spontaneous adverse event reports in pharmacovigilance. There exist a variety of disproportionality measures (DPMs) for use in safety signaling; however, it is not always clear which method is best suited for a particular need. A framework for comparing the various DPMs is necessary to fully understand the consequences of quantitative signal detection implementation decisions. Here, the mathematical relationship between these measures is explored through a comparison of the underlying equations and a shrinkage approach is adopted to further clarify these relationships.
Many DPMs take the form of a ratio of the number of observed (O) cases and the number of expected (E) cases (i.e., O/E). Because O is unchanged by the method selected, the method-specific E (E(DPM) ) is the fundamental difference between the values produced by these DPMs. Clarification of the relationship between these DPMs is pursued through the use of a shrinkage parameter (s).
It is demonstrated that any arbitrary DPM, which can be defined as O/E(DPM) , can also be expressed as a function of the reporting odds ratio (ROR) and s. This common equation allows for a straightforward comparison of the varying methods and the ability to clearly characterize the approaches according to their relative signal detection performance irrespective of the specific dataset to which the methods are applied. A novel DPM, the independent reporting ratio (IRR), provides an example of how the described framework can improve our understanding of disproportionality analyses and lead to the development of new methods.
Explicitly defining DPMs as RORs with applied shrinkage provides a convenient method for understanding their relative signal detection performance and insight into the relative contributions to DPM shrinkage.
比例失衡分析是药物警戒中解释自发不良事件报告的重要工具。存在多种用于安全信号检测的比例失衡测量方法（DPM）；然而，对于特定需求，哪种方法最合适并不总是很清楚。需要一个比较各种 DPM 的框架，才能充分理解定量信号检测实施决策的后果。在这里，通过比较基础方程来探索这些措施之间的数学关系，并采用收缩方法进一步澄清这些关系。
许多 DPM 采用观察到的（O）病例数与预期的（E）病例数之比的形式（即 O/E）。由于 O 不受所选方法的影响，因此特定于方法的 E（E(DPM)）是这些 DPM 产生的值之间的根本差异。通过使用收缩参数（s）来澄清这些 DPM 之间的关系。
证明任何任意的 DPM，可定义为 O/E(DPM)，也可以表示为报告比值比（ROR）和 s 的函数。这个通用方程允许对不同的方法进行直接比较，并能够根据其相对信号检测性能清晰地描述方法，而与方法应用的特定数据集无关。一种新的 DPM，即独立报告比（IRR），提供了一个例子，说明了描述的框架如何可以提高我们对比例失衡分析的理解，并导致新方法的发展。
将 DPM 明确定义为应用收缩的 ROR，提供了一种方便的方法来理解它们的相对信号检测性能，并深入了解 DPM 收缩的相对贡献。
