Online information discrepancies regarding safety of medicine use during pregnancy and lactation: an IMI ConcePTION study.

Background: Inconsistencies in information on safety of medicine use during pregnancy and lactation can result in sub-optimal treatment for pregnant and lactating women, risks to the fetus or child and unnecessary weaning off breastfeeding. The objective of this study was to analyze information discrepancies regarding medicine use during pregnancy and lactation between on-line sources for patients and health care professionals (HCPs) in four European languages.Research design and methods: The medicines analyzed were ibuprofen, ondansetron, olanzapine, fingolimod, methylphenidate and adalimumab. Recommendations were classified into different data source categories, for patients and for HCPs, and compared between the data source categories for each medicine and language.Results: For patients, 11/24 (46%) and 4/24 (17%) comparisons of the pregnancy and lactation recommendations, respectively, were consistent between all sources. The corresponding figures for HCP-sources were 13/24 (54%) and 5/24 (21%). Regulatory sources had generally more restrictive recommendations. Teratology Information Services (TIS) centers' recommendations for medicine use during pregnancy and lactation were consistent in 25/27 (93%) and 15/22 (68%) of cases respectively.Conclusion: Discrepancies between online information sources regarding medicine use during pregnancy and lactation are common, especially for lactation. TIS centers recommendations were more aligned. Additional work is needed to harmonize information within and between countries to avoid conflicting messages.

Structured benefit-risk evaluation for medicinal products: review of quantitative benefit-risk assessment findings in the literature.

A favorable benefit-risk profile remains an essential requirement for marketing authorization of medicinal drugs and devices. Furthermore, prior subjective, implicit and inconsistent ad hoc benefit-risk assessment methods have rightly evolved towards more systematic, explicit or "structured" approaches. Contemporary structured benefit-risk evaluation aims at providing an objective assessment of the benefit-risk profile of medicinal products and a higher transparency for decision making purposes. The use of a descriptive framework should be the preferred starting point for a structured benefit-risk assessment. In support of more precise assessments, quantitative and semi-quantitative methodologies have been developed and utilized to complement descriptive or qualitative frameworks in order to facilitate the structured evaluation of the benefit-risk profile of medicinal products. In addition, quantitative structured benefit-risk analysis allows integration of patient preference data. Collecting patient perspectives throughout the medical product development process has become increasingly important and key to the regulatory decision-making process. Both industry and regulatory authorities increasingly rely on descriptive structured benefit-risk evaluation and frameworks in drug, vaccine and device evaluation and comparison. Although varied qualitative methods are more commonplace, quantitative approaches have recently been emphasized. However, it is unclear how frequently these quantitative frameworks have been used by pharmaceutical companies to support submission dossiers for drug approvals or to respond to the health authorities' requests. The objective of this study has been to identify and review, for the first time, currently available, published, structured, quantitative benefit-risk evaluations which may have informed health care professionals and/or payor as well as contributed to decision making purposes in the regulatory setting for drug, vaccine and/or device approval. PLAIN LANGUAGE SUMMARY: Quantitative evaluation of the benefit-risk balance for medicinal products The review of the benefits and the risks associated with a medicinal product is called benefit-risk assessment. One of the conditions for a medicinal product to receive marketing authorization is to demonstrate a positive benefit-risk balance in which the benefits outweigh the risks. In order to enhance the transparency and consistency in the assessment of benefit-risk balance, frameworks and quantitative methods have been developed for decision making purposes and regulatory approvals of medicinal products. This article considers published quantitative benefit-risk evaluations which may have informed health care professionals and/or payor as well as contributed to decision making purposes in the regulatory setting for drug, vaccine and/or device approval.

Bleeding in patients with Budd-Chiari syndrome.

BACKGROUND & AIMS: Anticoagulation therapy is recommended for patients with Budd-Chiari syndrome (BCS). This study aimed to assess the incidence, severity, and risk factors of major bleeding in patients with Budd-Chiari syndrome (BCS) receiving anticoagulation therapy. METHODS: We evaluated 94 consecutive BCS patients. Major bleeding required hospitalization, and/or transfusion of ≥ 2 red blood cell units, and/or was located intracranially, and/or retroperitoneally, and/or was fatal. RESULTS: After a median follow-up of 43 months, 47 patients had 92 major bleeding episodes (22.8 per 100 patient-years). Forty episodes were related to invasive therapy for BCS. The origin of the 52 other episodes was gastrointestinal in 26 (including 15 related to portal hypertension) and genital in 10; 26 were spontaneous and 26 provoked. Excess anticoagulation was identified in 13 (27%) out of 49 documented episodes. Bleeding was managed by interrupting or reducing anticoagulation in 34 episodes, surgery in 18, endoscopy in 12, and radiological intervention in 8. The presence of esophageal varices was an independent predictor of bleeding unrelated to invasive therapy for BCS. Bleeding contributed to death in five patients and caused neurological complications in two. These poor outcomes were associated with more severe liver disease at baseline. CONCLUSIONS: Major bleeding is common in BCS patients receiving anticoagulation therapy. Invasive procedures and portal hypertension are major factors, while excess anticoagulation plays a secondary role. Baseline BCS severity is the main determinant of prognosis at bleeding. Reducing anticoagulation intensity during invasive therapy and reinforced prophylaxis for portal hypertension could improve the benefit-risk ratio of anticoagulation.

Levels and initial course of serum alanine aminotransferase can predict outcome of patients with Budd-Chiari syndrome.

BACKGROUND & AIMS: Patients with Budd-Chiari syndrome can present with acute, subacute, or chronic disease; the definitions and significance of these variants have been disputed. An increased level of serum alanine aminotransferase (ALT) is an objective marker for acute liver injury. We analyzed the significance of changes in ALT levels in Budd-Chiari syndrome patients. METHODS: We performed a retrospective analysis of data from 96 consecutive Budd-Chiari syndrome patients. RESULTS: A threshold peak ALT level that was 5-fold the upper limit of normal distinguished 2 groups of patients: patients with high levels of ALT (40% of patients) presented with more severe liver disease, less frequent liver fibrosis, and more frequent liver cell necrosis, compared with those with ALT levels below this threshold. Patients with levels of ALT that started out high but slowly declined (<50% of starting concentration within 3 days) had significantly lower odds of survival than those with a rapid decline and those with low levels of ALT (40 months transplantation-free survival, 31%, 63%, and 71%, respectively). When ALT level and the velocity of its decline are used as criterion, these data add significant prognostic information to Child-Pugh, to Clichy, and to Rotterdam Budd-Chiari syndrome scores. CONCLUSIONS: Determination of ALT levels at patient presentation allows 2 variants of Budd-Chiari syndrome to be distinguished. High levels of ALT reflect acute, severe, but potentially reversible, ischemic liver cell necrosis. High levels of ALT that decrease slowly predict a poor outcome for patients and might justify rapid aggressive management.