Inconsistencies and ambiguities in liver-disease-related contraindications: a systematic analysis of SmPCs/PI of Major Drug Markets

Liver disease is a common condition worldwide that can cause alterations in drug disposition and susceptibility to drug toxicities, with increased risk of adverse drug reactions. European Summaries of Product Characteristics (SmPCs) and United States Prescribing Information (US PI) should therefore be comprehensible to prescribers regarding their liver-associated contraindications to ensure safe prescribing. This study aimed to evaluate the ambiguity of terminology used in communicating liver-associated absolute contraindications in SmPCs/PI of commonly prescribed drugs in four major drug markets (Germany, Switzerland, the United Kingdom, and the United States) by assigning wordings to different categories and analyzing their clinical comprehensibility. For US PI, 79% did not contain liver-related contraindications, compared to 2, 13, and 6% of German, Swiss, and British SmPCs, respectively. Study findings indicate that out of 228 examined SmPCs/PI containing liver-related contraindications, 77, 79, 76, and 52% contained unclear wording in the German, Swiss, British, and American drug market, respectively. Only 40% (German), 52% (Swiss), 39% (British), and 29% (American) of SmPCs/PI included terms with explicit wording. Including more precise statements in SmPCs/PI based on laboratory parameters (such as albumin) or scores (e.g., the Child–Pugh score) to objectify the severity of liver disease may improve the clarity of SmPCs/PI and the safety of drug prescription

Us knows us in the UK: On director networks and CEO compensation

We analyze the relation between CEO compensation and networks of executive and non-executive directors for all listed UK companies over the period 1996-2007. We examine whether networks are built for reasons of information gathering or for the accumulation of managerial influence. Both indirect networks (enabling directors to collect information) and direct networks (leading to more managerial influence) enable the CEO to obtain higher compensation. Direct networks can harm the efficiency of the remuneration contracting in the sense that the performance sensitivity of compensation is then lower. We find that in companies with strong networks and hence busy boards the directors' monitoring effectiveness is reduced which leads to higher and less performance-sensitive CEO compensation. Our results suggest that it is important to have the 'right' type of network: some networks enable a firm to access valuable information whereas others can lead to strong managerial influence that may come at the detriment of the firm and its shareholders. We confirm that there are marked conflicts of interest when a CEO increases his influence by being a member of board committees (such as the remuneration committee) as we observe that his or her compensation is then significantly higher. We also find that hiring remuneration consultants with sizeable client networks also leads to higher CEO compensation especially for larger firms. © 2011 Elsevier B.V