Reference Safety Information (RSI) is the designated set of information used to determine the expectedness of a suspected adverse reaction in a clinical trial. It is not a safety report, but rather the benchmark for assessing whether the nature, severity, or outcome of a reaction is consistent with the known safety profile of the investigational medicinal product.<\/p>\n
In the context of a clinical trial, a serious adverse reaction is classified as unexpected if its nature, severity, or outcome is inconsistent with the Reference Safety Information. This classification is a core element in the assessment of a SUSAR. It requires a comparison with the pre-determined document rather than merely relying on the general knowledge of an investigator or sponsor.<\/p>\n
The Reference Safety Information must clearly identify which adverse reactions are considered expected, including their frequency and nature. This allows clinical teams to assess the same reaction based on a consistent, version-controlled safety status. A mere list of risks without a clear function as a reference makes a transparent decision on unexpectedness difficult.<\/p>\n
According to ICH E2F, the Investigator\u2019s Brochure in effect at the start of the reporting period generally serves as the Reference Safety Information. The DSUR specifies the document used for this purpose, including the version, if required by regional law. If no Investigator\u2019s Brochure is required, the applicable national or regional product information takes its place.<\/p>\n
The selection of a single reference document is the standard rule. For an investigational substance being studied both in combination and as monotherapy, multiple reference documents may be appropriate in exceptional cases. Safety-relevant changes during the reporting period are not silently incorporated into the initial benchmark; instead, they are identified in the DSUR as changes to the Reference Safety Information.<\/p>\n
The reference does not determine whether an event was actually caused by the investigational product. This question of causality is answered separately based on available medical information. Only once a suspected adverse reaction is assessed as a reaction is it checked against the RSI. Consequently, the same clinical diagnosis may be classified as expected or unexpected depending on the documented manifestation, severity, or outcome.<\/p>\n
For benefit-risk monitoring, this designation also serves a temporal function. It prevents a later-added adverse reaction from being automatically treated as known for the entire preceding reporting period. In the DSUR, safety changes within the period are reported separately; this ensures the historical basis for comparison in the tables remains verifiable.<\/p>\n
Reference Safety Information is not a development safety update report and does not summarize cases or signals. The related entry for the development safety update report refers to the periodic development report in which the sponsor evaluates new safety information. In contrast, the Reference Safety Information provides this report with the defined basis for comparison for tables and expectedness decisions.<\/p>\n
It is also not to be equated with the entire Investigator\u2019s Brochure document. The Investigator\u2019s Brochure may contain the Reference Safety Information; however, the regulatory function arises from the clearly identifiable section that defines expected reactions. Thus, the term Investigator\u2019s Brochure links the information source to the trial, while Reference Safety Information denotes its precise assessment function.<\/p>\n
The RSI thus translates the updated state of knowledge into a rule-based decision for individual reported reactions and their periodic presentation.<\/p>\n
In study practice, the version serving as the reference for each investigational product must be established before the safety assessment begins. For every serious reaction, the medical assessment of causality is documented separately from the check of expectedness against this version. Version changes during an ongoing study require controlled implementation to ensure that case processing, DSUR tables, and investigator information do not use conflicting comparison benchmarks.<\/p>\n
Full-service CROs like Mediconomics support Reference Safety Information through version control of the relevant section, verification of traceability in safety databases, and coordination with Medical Writing for DSUR tables. They can also document the approval pathways between the sponsor, pharmacovigilance, and the clinical project team so that the governing document remains identifiable for every expectedness decision.<\/p>\n
Does the Reference Safety Information alone decide a SUSAR?<\/strong><\/p>\n No. First, a suspected adverse reaction must be present and its severity must be assessed. The Reference Safety Information answers the additional question of whether the reaction is expected within the applicable safety status.<\/p>\n Can a new Investigator\u2019s Brochure be used retroactively for earlier cases?<\/strong><\/p>\n For periodic assessment, the version valid at the start of the reporting period is generally decisive according to ICH E2F. Changes are presented separately in the report rather than retroactively replacing the historical basis for comparison.<\/p>\n Why does the Investigator\u2019s Brochure require a clearly marked RSI section?<\/strong><\/p>\n The marking prevents users from using different parts of the document as a benchmark. It makes it transparent which reactions, manifestations, and frequencies are used for the expectedness assessment.<\/p>\n Reference Safety Information (RSI) is the designated set of information used to determine the expectedness of a suspected adverse reaction in a clinical trial. It is not a safety report, but rather the benchmark for assessing whether the nature, severity, or outcome of a reaction is consistent with the known safety profile of the investigational […]<\/p>\n","protected":false},"author":10,"featured_media":0,"parent":0,"template":"","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"glossary-cat":[23],"class_list":["post-8029","glossary","type-glossary","status-publish","hentry","glossary-cat-pharmakovigilanz"],"acf":[],"related_terms":"","external_url":"","internal_reference_id":"","_links":{"self":[{"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/glossary\/8029","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/glossary"}],"about":[{"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/types\/glossary"}],"author":[{"embeddable":true,"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/users\/10"}],"version-history":[{"count":0,"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/glossary\/8029\/revisions"}],"wp:attachment":[{"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/media?parent=8029"}],"wp:term":[{"taxonomy":"glossary-cat","embeddable":true,"href":"https:\/\/mediconomics.com\/en\/wp-json\/wp\/v2\/glossary-cat?post=8029"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Regulatory References<\/h2>\n
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