FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2066734273> ?p ?o ?g. }

• W2066734273 endingPage "748" @default.
• W2066734273 startingPage "736" @default.
• W2066734273 abstract "WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • After the TGN1412 incident in London, the European authorities reinforced the safety requirements for first‐entry‐into‐man (FIM) studies. Their recommendations on risk management included a risk minimization strategy based on clearly defined stopping rules. However to date, there are no approved grading scales for clinical adverse events or safety findings to support dose escalation and to define stopping rules in order to mitigate the risks for healthy subjects participating in FIM trials. WHAT THIS STUDY ADDS • This paper proposes standardized methods for the grading of safety data (adverse events, laboratory tests, electrocardiogram and vital sign findings) based on relevant criteria. The proposed grading scale provides support both for dose escalation and the design of stopping rules. The derived safety thresholds are applicable at either an individual subject level or at a cohort level, and are specifically adapted to young male healthy subjects, who represent the majority of the subjects participating in FIM trials. AIM To propose a relevant grading scale for clinical adverse events or laboratory results, electrocardiogram (ECG) and vital sign findings supporting both dose escalation and stopping decisions in first‐entry‐into‐man (FIM) studies conducted in young healthy subjects. METHODS A three‐level scale was used for the proposed grading system. The grading is directly derived from the observed severity of discontinuous variables, as are most of clinical adverse events. A ‘combined method’ based on normal ranges and spontaneous variation is suggested for grading the findings which are continuous variables mainly numerical in nature. One grade, at the subject level, and one algorithm, at the cohort level, support the proposed decision rules. This work was managed by a Club Phase I working group. RESULTS Examples of grade 1, 2 and 3 limits are given for the most frequent clinical adverse events and laboratory tests, ECG and vital sign findings. When available, the proposed NIH and FDA limits are also provided. The safety recommendation is to use the grade 2 at least as an alert for caution and the grade 3 as a maximum for stopping, applying the algorithm at the cohort level. CONCLUSIONS This paper proposes a safety grading system based on relevant criteria which might be used by investigators and sponsors to support and rationalize dose escalation decisions in healthy young subject FIM studies. These proposals are designed not to be a guideline but some ‘points to consider’ helping the dose escalation process. This paper supports the recent reinforcement of the safety requirements for FIM studies by European authorities." @default.
• W2066734273 created "2016-06-24" @default.
• W2066734273 creator A5004423469 @default.
• W2066734273 creator A5019359875 @default.
• W2066734273 creator A5051365872 @default.
• W2066734273 creator A5072900620 @default.
• W2066734273 date "2010-07-12" @default.
• W2066734273 modified "2023-10-18" @default.
• W2066734273 title "A safety grading scale to support dose escalation and define stopping rules for healthy subject first-entry-into-man studies" @default.
• W2066734273 cites W1966268750 @default.
• W2066734273 cites W1992157963 @default.
• W2066734273 cites W2042446689 @default.
• W2066734273 cites W2069292920 @default.
• W2066734273 cites W2073604271 @default.
• W2066734273 cites W2075453912 @default.
• W2066734273 cites W2101927226 @default.
• W2066734273 cites W2103185513 @default.
• W2066734273 cites W2141989396 @default.
• W2066734273 cites W2167805334 @default.
• W2066734273 cites W2227533634 @default.
• W2066734273 cites W2759991334 @default.
• W2066734273 cites W38847137 @default.
• W2066734273 cites W4293245940 @default.
• W2066734273 doi "https://doi.org/10.1111/j.1365-2125.2010.03741.x" @default.
• W2066734273 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2997314" @default.
• W2066734273 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21039768" @default.
• W2066734273 hasPublicationYear "2010" @default.
• W2066734273 type Work @default.
• W2066734273 sameAs 2066734273 @default.
• W2066734273 citedByCount "24" @default.
• W2066734273 countsByYear W20667342732012 @default.
• W2066734273 countsByYear W20667342732015 @default.
• W2066734273 countsByYear W20667342732017 @default.
• W2066734273 countsByYear W20667342732019 @default.
• W2066734273 countsByYear W20667342732020 @default.
• W2066734273 countsByYear W20667342732021 @default.
• W2066734273 countsByYear W20667342732022 @default.
• W2066734273 countsByYear W20667342732023 @default.
• W2066734273 crossrefType "journal-article" @default.
• W2066734273 hasAuthorship W2066734273A5004423469 @default.
• W2066734273 hasAuthorship W2066734273A5019359875 @default.
• W2066734273 hasAuthorship W2066734273A5051365872 @default.
• W2066734273 hasAuthorship W2066734273A5072900620 @default.
• W2066734273 hasBestOaLocation W20667342732 @default.
• W2066734273 hasConcept C12174686 @default.
• W2066734273 hasConcept C126322002 @default.
• W2066734273 hasConcept C127413603 @default.
• W2066734273 hasConcept C141071460 @default.
• W2066734273 hasConcept C147176958 @default.
• W2066734273 hasConcept C160735492 @default.
• W2066734273 hasConcept C162324750 @default.
• W2066734273 hasConcept C197934379 @default.
• W2066734273 hasConcept C2777286243 @default.
• W2066734273 hasConcept C2779328685 @default.
• W2066734273 hasConcept C2993012660 @default.
• W2066734273 hasConcept C38652104 @default.
• W2066734273 hasConcept C41008148 @default.
• W2066734273 hasConcept C50522688 @default.
• W2066734273 hasConcept C535046627 @default.
• W2066734273 hasConcept C71924100 @default.
• W2066734273 hasConceptScore W2066734273C12174686 @default.
• W2066734273 hasConceptScore W2066734273C126322002 @default.
• W2066734273 hasConceptScore W2066734273C127413603 @default.
• W2066734273 hasConceptScore W2066734273C141071460 @default.
• W2066734273 hasConceptScore W2066734273C147176958 @default.
• W2066734273 hasConceptScore W2066734273C160735492 @default.
• W2066734273 hasConceptScore W2066734273C162324750 @default.
• W2066734273 hasConceptScore W2066734273C197934379 @default.
• W2066734273 hasConceptScore W2066734273C2777286243 @default.
• W2066734273 hasConceptScore W2066734273C2779328685 @default.
• W2066734273 hasConceptScore W2066734273C2993012660 @default.
• W2066734273 hasConceptScore W2066734273C38652104 @default.
• W2066734273 hasConceptScore W2066734273C41008148 @default.
• W2066734273 hasConceptScore W2066734273C50522688 @default.
• W2066734273 hasConceptScore W2066734273C535046627 @default.
• W2066734273 hasConceptScore W2066734273C71924100 @default.
• W2066734273 hasIssue "5" @default.
• W2066734273 hasLocation W20667342731 @default.
• W2066734273 hasLocation W20667342732 @default.
• W2066734273 hasLocation W20667342733 @default.
• W2066734273 hasLocation W20667342734 @default.
• W2066734273 hasOpenAccess W2066734273 @default.
• W2066734273 hasPrimaryLocation W20667342731 @default.
• W2066734273 hasRelatedWork W1975087469 @default.
• W2066734273 hasRelatedWork W2009332870 @default.
• W2066734273 hasRelatedWork W2108745537 @default.
• W2066734273 hasRelatedWork W2185661708 @default.
• W2066734273 hasRelatedWork W2404156760 @default.
• W2066734273 hasRelatedWork W2590979198 @default.
• W2066734273 hasRelatedWork W3011885879 @default.
• W2066734273 hasRelatedWork W4293775409 @default.
• W2066734273 hasRelatedWork W4383226634 @default.
• W2066734273 hasRelatedWork W2187073112 @default.
• W2066734273 hasVolume "70" @default.
• W2066734273 isParatext "false" @default.
• W2066734273 isRetracted "false" @default.
• W2066734273 magId "2066734273" @default.
• W2066734273 workType "article" @default.