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In the United States, clinical data management (CDM) has been accelerating from a single focus on collecting and preparing clinical trial data for study analysis to a multi-pronged endeavor. This endeavor emphasizes quality data from inception or planning of study design to collection, coding, analysis, reporting, and sharing of all applicable and available data. In this article the influence of legislation and scientific expertise in the collection and analysis of valid, sound data is detailed. FDA requirements as well as academic and technical developments have led to better, more precise and reliable methods in CDM. As such, the perspectives of industry, academia, and non-profits are presented. The role of CDM, at the center of the clinical data explosion, is described, demonstrating how data managers coordinate and build on expertise from all stakeholders. The dependence of biomedical research on CDM and quality data for breakthroughs in diagnostics, drugs, biologics and vaccines is examined. The state of current educational programs is detailed and suggestions are made for new interdisciplinary programs that can provide technical support for all clinical research endeavors. In the article, CDM is viewed through the lens of providing leadership in clinical research and striving to overcome obstacles in communicating the latest technological changes to all stakeholders.&nbsp

The DIA Clinical Data Management Community created a committee to develop a model standard operating procedure (SOP) for writing a data management plan. The goal of the committee was to develop a plan that could be used by industry and academic institutions. The model was based on contributed examples from committee members and their experiences with current practices and technologies. It is understood that as new clinical trial technology is implemented, the SOP will require modification. The model SOP and associated templates are presented as a starting point, and each company or institution will need to modify them to meet its individual needs. The model DMP SOP produced addresses most data management issues that are present in any phase clinical trial while providing a flexible framework.

Purpose Standardised MedDRA Queries (SMQs) have been developed since the early 2000’s and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA) and Biologics License Application (BLA) submissions to the United States Food and Drug Administration (USFDA). Methods We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs) of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed. Results A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with “narrow terms” to enhance specificity over strategies using “broad terms” to increase sensitivity, while some involved modification of search terms. A majority (59%) of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18%) of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated). Most searches (75% of 227 searches) with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process. Conclusions SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.

A novel dimeric lignan, bispicropodophyllin glucoside (1) and a highly oxygenated new withanolide, coagulin S (2) were isolated from the ethanolic extract of Withania coagulans. The structures were established on the basis of the spectroscopic data and have been identified as (5S*,5aR*,8aR*,9S*,15S*,15aS*,18aS*,19S*)-9,19-di-β-D-glucopyranosyl-5,8a,9,15,15a,18,18a,19-octahydro-5,15-bis(3,4,5-trimethoxyphenyl)bis([1,3]dioxolo[4′,5′:6,7]naphtho)[2,3-c:2,3-h][1,6]dioxecin-6,16(5aH,8H)-dione (1) and (20S*,22R*)-5α,6β,14α,15α,17β,20,27-heptahydroxy-1-oxowith-24-enolide (2), respectively.

Three new withanolides, coagulins M, N, and 0 were isolated from the whole plant of Withania coagulans. Their structures were established as (14R,17R,20ξ,22R)-5α,6β,27-trihydroxy-14,20-epoxy-1-oxo-witha-24-enolid (1), (14R,17S,20ξ,22R)-15α,17-dihydroxy-14,20-epoxy-3β-(O-β-D-glucopyranosyl)-1-oxo-witha-5,24-dienolide (2) and (14R,20ξ,22R)-14,20-dihydroxy-3β-(O-β-D-glucopyranosyl)-1-oxo-witha-5,24-dienolide (3) respectively, by extensive spectroscopic studies.

Four bioactive withanolides withalactone (1), withaoxylactone (2), quresimine-A (4β-hydroxy, 3β-methoxy-5β, 6β-epoxy-(22R)-witha-24-enolide) (3) and quresindne-B (4β, 27 dihydroxy-3β-methoxy-5β, 6β-epoxy-(22R)-witha-24-enolide (4) have been isolated from the herbs of Withania somnifera, Dunal (Solanaceae). The elucidation of their structures is based on extensive spectroscopic studies, such as1H-NMR, COSY-45°, HMBC, HMQC HOHAHA, E.I., FAB (+ ve), and HR MS, etc.

Two new withanolides (steroidal lactones) named coagulin F [27-hydroxy-14,20-epoxy-1-oxo-(22R)-witha-3,5,24-trienolide] (1) and coagulin G [17beta,27-dihydroxy-14,20-epoxy-1-oxo-(22R)-witha-2,5, 24-trienolide] (2) were isolated from the whole plant of Withania coagulans, and their structures were deduced by spectral analysis.