Levodopa-carbidopa intestinal gel in advanced Parkinson's: Final results of the GLORIA registry.

Background The Safety Planning, Evaluation and Reporting Team (SPERT) was formed in 2006 by the Pharmaceutical Research and Manufacturers of America.Purpose SPERT’s goal was to propose a pharmaceutical industry standard for safety planning, data collection, evaluation, and reporting, beginning with planning first-in-human studies and continuing through the planning of the post-product-approval period.Methods SPERT’s recommendations are based on our review of relevant literature and on consensus reached in our discussions.Results An important recommendation is that sponsors create a Program Safety Analysis Plan early in development. We also give recommendations for the planning of repeated, cumulative meta-analyses of the safety data obtained from the studies conducted within the development program. These include clear definitions of adverse events of special interest and standardization of many aspects of data collection and study design. We describe a 3-tier system for signal detection and analysis of a...

Recommendations for safety planning, data collection, evaluation and reporting during drug, biologic and vaccine development: a report of the safety planning, evaluation, and reporting team

SummaryObjective
Perampanel, a selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, is indicated for adjunctive treatment of partial seizures in patients ≥12 years based on three phase III clinical studies. The perampanel U.S. Prescribing Information includes a boxed warning for serious psychiatric and behavioral adverse reactions. To provide context for this warning, detail on psychiatric and behavioral safety data from perampanel clinical studies is presented.

Methods
An analysis of pooled safety data from three phase III studies in patients with partial seizures is presented. Data from phase I and phase II studies in patients with and without epilepsy were also analyzed. Psychiatric and behavioral treatment-emergent adverse events (TEAEs) were evaluated according to Medical Dictionary for Regulatory Activities (MedDRA) terms, using “narrow” and “narrow-and-broad” standardized MedDRA queries (SMQs) for TEAEs suggestive of hostility/aggression.

Results
From the three phase III partial-seizure studies, the overall rate of psychiatric TEAEs was higher in the 8 mg (17.2%) and 12 mg (22.4%) perampanel groups versus placebo (12.4%). In the “narrow” SMQ, hostility/aggression TEAEs were observed in 2.8% for 8 mg and 6.3% for 12 mg perampanel groups, versus 0.7% of placebo patients. “Narrow-and-broad” SMQs for hostility/aggression TEAE rates were 12.3% for 8 mg and 20.4% for 12 mg perampanel groups, versus 5.7% for placebo; rates for events resulting in discontinuation were perampanel = 1.6% versus placebo = 0.7%. For events reported as serious AEs (SAEs), rates were perampanel = 0.7% versus placebo = 0.2%. In nonepilepsy patients, psychiatric TEAEs were similar between patients receiving perampanel and placebo. In phase I subjects/volunteers, all psychiatric TEAEs were mild or moderate. These analyses suggest that psychiatric adverse effects are associated with use of perampanel.

Significance
Patients and caregivers should be counseled regarding the potential risk of psychiatric and behavioral events with perampanel in patients with partial seizures; patients should be monitored for these events during treatment, especially during titration and at higher doses.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/epi.13054

Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel.

Randomised placebo-controlled trial of cytisine for smoking cessation.

Medical Dictionary for Regulatory Activities (MedDRA), as the ICH approved standard terminology for all drug regulatory activities, is in many aspects different from previously used terminologies, mainly in size, specificity, structure, rules and conventions. All these aspects impact on retrieval strategies, analysis and presentation of the coded data. After shortly describing the key features of MedDRA and their theoretically anticipated impact on data analysis and presentation, two examples for display of MedDRA coded data are described, one from a clinical study project and one from spontaneous reporting. The first example compares the adverse drug reaction (ADR) profile of the same data coded in WHO Adverse Reaction Terminology (WHO-ART) and recorded in MedDRA; the second example demonstrates different ways of presenting the ADR profile of an antibacterial, using different elements in MedDRA with the aim of presenting the ADR profile in a way that best transports the medical concepts reported with this drug. Based on some results obtained from these examples and based on analysis of the content of MedDRA version 6.0, the following limitations of MedDRA for data analysis have been identified: (i) the Preferred Term level is generally too granular, bearing the danger of underestimating risks, and the midlevels are currently not a robust, consistent and non-ambiguous level for data aggregation; and (ii) the rules relating to multiaxiality add complexity for data aggregation because related medical concepts may be split into different System Organ Classes, which may mislead frequency analysis. In the absence of guidance from regulatory agencies and with the growing need for analysis of MedDRAencoded data, there is a risk of diminishing the benefits of MedDRA as a standard terminology through the use of user-specific and non-standardised data analysis and presentation strategies. MedDRA would benefit from a redesign of the group terms (High Level Group Terms/High Level Terms) to become a robust, consistent and non-ambiguous level for data analysis and aggregation. This should be done in an interdisciplinary effort coordinated by the MedDRA Maintenance Supply and Support Organisation (MSSO).

Medical Dictionary for Regulatory Activities (MedDRA)

The Medical Dictionary for Regulatory Activities (MedDRA) is a dictionary of medical terms which covers signs and symptoms; diseases; diagnoses; therapeutic indications; names and qualitative results of indications; surgical and medical procedures; and medical, social, and family history. Until now, the pharmaceutical industry was only obligated to use MedDRA for submissions of individual case safety reports. Neither the MedDRA Maintenance and Support Services Organization nor regulatory bodies provided any recommendations on the use of MedDRA for analyses and reporting of clinical trial data. As the pharmaceutical industry introduces MedDRA in its day-to-day processes, there is an urgent need to fill this gap. The Biometry Subgroup of the German Association of Research-Based Pharmaceutical Companies has established a working group which will provide recommendations on the use of MedDRA in reporting and labeling. This paper aims to start a discussion about the use of MedDRA in the analysis of clinical trials.

Adverse Event Analysis and MedDRA: Business as Usual or Challenge?*:

Medical Dictionary for Regulatory Activities (MedDRA), as the ICH approved standard terminology for all drug regulatory activities, is in many aspects different from previously used terminologies, mainly in size, specificity, structure, rules and conventions. All these aspects impact on retrieval strategies, analysis and pre- sentation of the coded data. After shortly describing the key features of MedDRA and their theoretically anticipated impact on data analysis and presentation, two examples for display of MedDRA coded data are described, one from a clinical study project and one from spontaneous reporting. The first example compares the adverse drug reaction (ADR) profile of the same data coded in WHO Adverse Reaction Terminology (WHO-ART) and recorded in MedDRA; the second example demonstrates different ways of presenting the ADR profile of an antibacterial, using dif- ferent elements in MedDRA with the aim of presenting the ADR profile in a way that best transports the medical concepts reported with this drug. Based on some results obtained from these examples and based on analysis of the content of MedDRA version 6.0, the following limitations of MedDRA for data analysis have been identified: (i) the Preferred Term level is generally too granular, bearing the danger of underestimating risks, and the midlevels are currently not a robust, consistent and non-ambiguous level for data aggregation; and (ii) the rules relating to multiaxiality add

Jürgen Kübler

Papers

Medical Dictionary for Regulatory Activities (MedDRA)

Adverse Event Analysis and MedDRA: Business as Usual or Challenge?*:

Data Retrieval and Presentation