When evaluating the causality of an adverse event

#WHEN EVALUATING THE CAUSALITY OF AN ADVERSE EVENT REGISTRATION#
#WHEN EVALUATING THE CAUSALITY OF AN ADVERSE EVENT TRIAL#

None of them were medical oncologists, but they received trainings in different aspects of oncology and were medical monitors in various oncology clinical studies. Their medical background included internal medicine, infectious diseases, pediatric, and intensive care.

At the time of evaluation, the experts were not aware of the investigatorвЂ™s and sponsorвЂ™s assessments.Д®xperts were CRO medical monitors. They also provided the reasons for their evaluation.

Previous information on the drug and adverse experience: yes/noД®xperts assessed each criterion and also made an overall causality assessment of вЂњrelatedвЂќ or вЂњnot related.вЂќ Events were considered related if a relationship cannot be ruled out.

Rechallenge: positive/negative/not available.

Dechallenge: positive/negative/not available.

Time to onset: incompatible/compatible/highly suggestive.

The investigatorвЂ™s assessment was deleted from the narrative, so the experts were unaware whether or not the AE was assessed by the investigator as an ADR.ДЇor each drug-event pair, the questionnaire asked the experts to assess causal relationship based on the following criteria: The information for the SAEs was summarized in narratives, which included demography data, medical history, concomitant medications, study treatment with dates (the name of the study drug was blinded), the course of the AE, and the list of expected AEs for the particular study drug. Among the 37 cases from the placebo-controlled trial, 17 of the patients (46%) received the study drug and chemotherapeutic agent and 20 (54%) were administered the placebo and chemotherapeutic agent. All patients from the open-label studies received an investigational drug as a part of their chemotherapeutic regimen. All patients, including those from the placebo arm, received one or two chemotherapeutic agents. One of three trials was a placebo-controlled one and two studies were open-label. The studies involved in patients with locally-advanced (inoperable) or metastatic non-small cell lung cancer (NSCLC). MethodsДЇour drug safety experts, who were not medical oncologists, but had experience monitoring oncology trials independently, analyzed 50 consecutive (in terms of time of registration) blinded serious adverse events (SAE) from three Phase II-III clinical trials conducted in 2014-2015.

#WHEN EVALUATING THE CAUSALITY OF AN ADVERSE EVENT TRIAL#

Herein, we compared the assessments of 50 ADRs made by four experts from a clinical research organization (CRO medical monitors) and clinical trial investigators, analyzing the reasons for different evaluations. 3,4,5 These reports mainly compared judgments made by physicians or experts without analysis of possible reasons for disagreements. Such disagreements have been reported previously and ranged from 51% to 95%. Experts may evaluate similar ADRs differently. Such scales have proved their validity, but have a general disadvantage-they are based on individualsвЂ™ medical judgment and thus subjective. It is a combined assessment taking into account the clinical-pharmacological aspects of the case history and the quality of the documentation of the observation. The WHO-UMC assessment scale is meant as a practical tool for the assessment of case reports. This makes assessment of causal relationship a key factor, as underestimation may subject potential patients to an unexpected and unnecessary risk, while overestimation might narrow indications and therapeutic use, or lead to dose modification (e.g., decreased dosage), which may lead to decreased efficacy. All available information about ADRs observed with the drug is captured in the InvestigatorвЂ™s Brochure, and once the drug is approved for use-in the package insert. 1 Not all ADRs are attributed to the study drug and one of the key characteristics of every ADR is causal relationship, or causality-whether the event under question is obviously related to the study drug, or at least such relationship cannot be ruled out.

#WHEN EVALUATING THE CAUSALITY OF AN ADVERSE EVENT REGISTRATION#

It is based on registration and assessment of adverse drug reactions (ADRs), defined as noxious and unintended responses to a medicinal product related to any dose. Safety surveillance is one of the core objectives of every clinical trial.

When evaluating the causality of an adverse event