Practical risk management in early phase clinical trials
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1
Richmond Pharmacology Ltd., UK
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2
St George's University of London, Cardiovascular and Cell Sciences Research Institute, UK
Background: The use of adaptive design was shown to be time- and cost-effective, ethical and efficient in gathering relevant
data in early phase trials1. Risk management is a key component of adaptive integrated trials that allow performing entire early
phase programmes from First-Time-in-Human to Proof of Concept within one protocol. The update to the EMA’s first-inhuman
and early phase clinical trials guideline contains a framework for risk management and specifically for the setting of
toxicity rules.
Methods: Template toxicity rules were developed, using NCI CTCAE2 and a systematic, objective and consistent process, taking
into account severity, seriousness, frequency and reversibility of adverse drug reactions. These rules control decisions relating
to individual trial participants, decisions relating to dosing regimens and to dose escalation and/or progression to successive trial
parts. Template rules were adapted taking into account particulars of the Investigational Medicinal Products (IMP), non-IMP and their Reference Safety Information (RSI).
Results: Template toxicity rules have been successfully applied to early phase adaptive integrated trials that received regulatory
authorisation and were performed in the UK. Our poster shows examples of such rules and case studies of their trial specific and
strategic adaptations. We show how, based on standardised input factors, rule-based algorithms can be established to minimise
risk and ensure efficient study progression.
Conclusions: This work demonstrates how a systematic, objective and consistent approach to risk management of large
integrated trials can be simple yet robust, facilitating effective decision making and trial progression whilst safeguarding
participant safety.
References:
1. Lorch U, O’Kane M, Taubel J. Three steps to writing adaptive study protocols in the early phase clinical development of new
medicines. BMC Medical Research Methodology 2014, 14:84
2. Common Terminology Criteria for Adverse Events. Available from: https://evs.nci.nih.gov/ftp1/CTCAE/
CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf
Keywords:
Risk Management,
patient recruitment,
Exploratory clinical trials,
human pharmacology,
early phase drug development,
over-volunteering
Conference:
EUFEMED 2017, London, United Kingdom, 17 May - 19 May, 2017.
Presentation Type:
Oral and Poster
Topic:
EUFEMED 2017 CONFERENCE
Citation:
Coates
S,
Täubel
J and
Lorch
U
(2019). Practical risk management in early phase clinical trials.
Front. Pharmacol.
Conference Abstract:
EUFEMED 2017.
doi: 10.3389/conf.fphar.2017.62.00014
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Received:
29 Aug 2017;
Published Online:
25 Jan 2019.
*
Correspondence:
Dr. Simon Coates, Richmond Pharmacology Ltd., London, UK, s.coates@richmondpharmacology.com