Safety in FIH Trials

A Summary of the Symposium “Fatal Drug Trial in Phase 1: Understanding Risk, Subject Safety, Timelines, and Cost”

Howard E. Greenberg, Mattheus van Iersel, Mary L. Westrick, William Smith

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

A cross-section of clinical research professionals convened at the June 2016 Drug Information Association annual meeting in Philadelphia to discuss and critically analyze the first-in-human (FIH) clinical trial conducted by a French CRO with BIA 10-2474 (BIA) under development for pain relief by Bial-Portela & Ca., S.A., that resulted in 6 healthy volunteers hospitalized with serious adverse events, which resulted in 1 death. This paper summarizes the background, presentations, and discussion points of Symposium no. 107 in an effort to share the learnings of our symposium with others who conduct studies. Novel investigational products studied in phase 1 clinical trials propose a heightened risk of adverse events that may not be foreseeable when relying on animal studies to project outcomes in humans. Novelty of molecular structure, drug class, mechanism of action, proper dose selection, pharmacokinetics, and therapeutic window are all contributing factors that heighten risks when transitioning from animal to human trials. The potential for catastrophic events confronts every sponsor/investigator in clinical trials. Minimizing risks to subjects is an essential ethical and scientific mandate for all those involved in the clinical trials. A complex matrix of planning, conducting, and communicating preclinical and clinical observations need to be considered carefully by the Sponsor, Investigator and others during the planning, execution, and interpretation of FIH studies, in order to promote participant safety and study data integrity. Suggestions may be applied to FIH studies, which may provide a new or improved way to address complex system and prevent or mitigate situations such as what occurred with the Bial FIH trial, where seemingly a number of issues coincided in a “perfect storm” and the system failed to sound a warning or detect an issue before a life was tragically lost.

Original languageEnglish (US)
Pages (from-to)276-284
Number of pages9
JournalTherapeutic Innovation and Regulatory Science
Volume51
Issue number3
DOIs
StatePublished - May 1 2017

Fingerprint

Safety
Costs and Cost Analysis
Pharmaceutical Preparations
Clinical Trials
Research Personnel
Clinical Trials, Phase I
Molecular Structure
TimeLine
Healthy Volunteers
Pharmacokinetics
Learning
Pain
Research
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Pharmacology (medical)

Cite this

Safety in FIH Trials : A Summary of the Symposium “Fatal Drug Trial in Phase 1: Understanding Risk, Subject Safety, Timelines, and Cost”. / Greenberg, Howard E.; van Iersel, Mattheus; Westrick, Mary L.; Smith, William.

In: Therapeutic Innovation and Regulatory Science, Vol. 51, No. 3, 01.05.2017, p. 276-284.

Research output: Contribution to journalArticle

@article{02060610b9fd412d81b49f5080004524,
title = "Safety in FIH Trials: A Summary of the Symposium “Fatal Drug Trial in Phase 1: Understanding Risk, Subject Safety, Timelines, and Cost”",
abstract = "A cross-section of clinical research professionals convened at the June 2016 Drug Information Association annual meeting in Philadelphia to discuss and critically analyze the first-in-human (FIH) clinical trial conducted by a French CRO with BIA 10-2474 (BIA) under development for pain relief by Bial-Portela & Ca., S.A., that resulted in 6 healthy volunteers hospitalized with serious adverse events, which resulted in 1 death. This paper summarizes the background, presentations, and discussion points of Symposium no. 107 in an effort to share the learnings of our symposium with others who conduct studies. Novel investigational products studied in phase 1 clinical trials propose a heightened risk of adverse events that may not be foreseeable when relying on animal studies to project outcomes in humans. Novelty of molecular structure, drug class, mechanism of action, proper dose selection, pharmacokinetics, and therapeutic window are all contributing factors that heighten risks when transitioning from animal to human trials. The potential for catastrophic events confronts every sponsor/investigator in clinical trials. Minimizing risks to subjects is an essential ethical and scientific mandate for all those involved in the clinical trials. A complex matrix of planning, conducting, and communicating preclinical and clinical observations need to be considered carefully by the Sponsor, Investigator and others during the planning, execution, and interpretation of FIH studies, in order to promote participant safety and study data integrity. Suggestions may be applied to FIH studies, which may provide a new or improved way to address complex system and prevent or mitigate situations such as what occurred with the Bial FIH trial, where seemingly a number of issues coincided in a “perfect storm” and the system failed to sound a warning or detect an issue before a life was tragically lost.",
author = "Greenberg, {Howard E.} and {van Iersel}, Mattheus and Westrick, {Mary L.} and William Smith",
year = "2017",
month = "5",
day = "1",
doi = "10.1177/2168479017706404",
language = "English (US)",
volume = "51",
pages = "276--284",
journal = "Therapeutic Innovation and Regulatory Science",
issn = "2168-4790",
publisher = "SAGE Publications Inc.",
number = "3",

}

TY - JOUR

T1 - Safety in FIH Trials

T2 - A Summary of the Symposium “Fatal Drug Trial in Phase 1: Understanding Risk, Subject Safety, Timelines, and Cost”

AU - Greenberg, Howard E.

AU - van Iersel, Mattheus

AU - Westrick, Mary L.

AU - Smith, William

PY - 2017/5/1

Y1 - 2017/5/1

N2 - A cross-section of clinical research professionals convened at the June 2016 Drug Information Association annual meeting in Philadelphia to discuss and critically analyze the first-in-human (FIH) clinical trial conducted by a French CRO with BIA 10-2474 (BIA) under development for pain relief by Bial-Portela & Ca., S.A., that resulted in 6 healthy volunteers hospitalized with serious adverse events, which resulted in 1 death. This paper summarizes the background, presentations, and discussion points of Symposium no. 107 in an effort to share the learnings of our symposium with others who conduct studies. Novel investigational products studied in phase 1 clinical trials propose a heightened risk of adverse events that may not be foreseeable when relying on animal studies to project outcomes in humans. Novelty of molecular structure, drug class, mechanism of action, proper dose selection, pharmacokinetics, and therapeutic window are all contributing factors that heighten risks when transitioning from animal to human trials. The potential for catastrophic events confronts every sponsor/investigator in clinical trials. Minimizing risks to subjects is an essential ethical and scientific mandate for all those involved in the clinical trials. A complex matrix of planning, conducting, and communicating preclinical and clinical observations need to be considered carefully by the Sponsor, Investigator and others during the planning, execution, and interpretation of FIH studies, in order to promote participant safety and study data integrity. Suggestions may be applied to FIH studies, which may provide a new or improved way to address complex system and prevent or mitigate situations such as what occurred with the Bial FIH trial, where seemingly a number of issues coincided in a “perfect storm” and the system failed to sound a warning or detect an issue before a life was tragically lost.

AB - A cross-section of clinical research professionals convened at the June 2016 Drug Information Association annual meeting in Philadelphia to discuss and critically analyze the first-in-human (FIH) clinical trial conducted by a French CRO with BIA 10-2474 (BIA) under development for pain relief by Bial-Portela & Ca., S.A., that resulted in 6 healthy volunteers hospitalized with serious adverse events, which resulted in 1 death. This paper summarizes the background, presentations, and discussion points of Symposium no. 107 in an effort to share the learnings of our symposium with others who conduct studies. Novel investigational products studied in phase 1 clinical trials propose a heightened risk of adverse events that may not be foreseeable when relying on animal studies to project outcomes in humans. Novelty of molecular structure, drug class, mechanism of action, proper dose selection, pharmacokinetics, and therapeutic window are all contributing factors that heighten risks when transitioning from animal to human trials. The potential for catastrophic events confronts every sponsor/investigator in clinical trials. Minimizing risks to subjects is an essential ethical and scientific mandate for all those involved in the clinical trials. A complex matrix of planning, conducting, and communicating preclinical and clinical observations need to be considered carefully by the Sponsor, Investigator and others during the planning, execution, and interpretation of FIH studies, in order to promote participant safety and study data integrity. Suggestions may be applied to FIH studies, which may provide a new or improved way to address complex system and prevent or mitigate situations such as what occurred with the Bial FIH trial, where seemingly a number of issues coincided in a “perfect storm” and the system failed to sound a warning or detect an issue before a life was tragically lost.

UR - http://www.scopus.com/inward/record.url?scp=85018423806&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018423806&partnerID=8YFLogxK

U2 - 10.1177/2168479017706404

DO - 10.1177/2168479017706404

M3 - Article

VL - 51

SP - 276

EP - 284

JO - Therapeutic Innovation and Regulatory Science

JF - Therapeutic Innovation and Regulatory Science

SN - 2168-4790

IS - 3

ER -