Quality expectations and tolerance limits of trial master files (TMF) - Developing a risk-based approach for quality assessments of TMFs.

This article addresses the question of when a trial master file (TMF) can be considered sufficiently accurate and complete: What attributes does the TMF need to have so that a clinical trial can be adequately reconstructed from documented data and procedures? Clinical trial sponsors face significant challenges in assembling the TMF, especially when dealing with large, international, multicenter studies; despite all newly introduced archiving techniques it is becoming more and more difficult to ensure that the TMF is complete. This is directly reflected in the number of inspection findings reported and published by the EMA in 2014. Based on quality risk management principles in clinical trials the authors defined the quality expectations for the different document types in a TMF and furthermore defined tolerance limits for missing documents.

Moderate hyperkalemia in hospitalized patients with cirrhotic ascites indicates a poor prognosis.

Objective: Development of ascites in patients with liver cirrhosis is an ominous sign with a poor outcome. A liver transplantation must be considered, and it then becomes important to know if there are any factors indicating a worsened prognosis.

Material And Methods: We used official registers for a follow-up study of at least 5 years considering the prognosis of 155 prospectively recruited in-patients with cirrhotic ascites from medical units at nine Swedish university hospitals.

Abdominal tenderness in ascites patients indicates spontaneous bacterial peritonitis.

Background: Spontaneous bacterial peritonitis (SBP), which has been reported to be present in 10-30% of patients with cirrhotic ascites, may easily be overlooked. An important aim of our study was to determine whether there are any clinical signs which, in clinical practice, may predict or exclude SBP.

Methods: We studied 133 patients with cirrhotic ascites from medical units at nine Swedish university hospitals where there had been at least one diagnostic ascites tap with analysis of polymorphonuclear leukocytes in the ascites fluid.

Comparative judgments with missing information: a regression and process tracing analysis.

We had participants decide which one of two applicants was better qualified for a scholarship. They also judged the difference between them (comparative judgment). The applicants were described by features (grades) in different subjects (dimensions).

Non-invasive resting magnetocardiographic imaging for the rapid detection of ischemia in subjects presenting with chest pain.

Background: Early diagnosis of ischemia is complicated by the poor sensitivity of standard tests and contraindication for stress testing in unstable angina patients. Magnetocardiography (MCG) imaging can be used for the rapid, non-invasive detection of ischemia at rest.

Methods: We studied 125 patients with presumed ischemic chest pain.