Relationship Between Adverse Drug Reactions and Unlicensed/ Off-label Drug Use in Hospitalized Children

Completed

• Conditions: Hospitalized Children

• Registration Number: NCT02852590
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

Medications are the most commonly used clinical intervention and complications associated with their use are one of the most common causes of adverse events in health care. Adverse Drug Reactions (ADR) are a major cause of morbidity and pose a substantial burden on limited health care resources.

Many drugs used to treat children in hospitals are either not licensed for use in children or are prescribed outside the terms of their product license (off-label prescribing). This is mainly due to the lack of clinical trials in this vulnerable population, and both practical difficulties and ethical considerations arising from involving children in clinical research.

Drugs used within the specifications of the product license might be less likely to cause ADR compared to drugs that are either unlicensed or off-label for use in children. Few studies have shown a significant association between pediatric off-label drug use and ADR.

To compare the probability of ADR after a licensed drug prescription versus the probability of ADR after prescribing a drug off-label in children, we are conducting a multi-center prospective observational study in different pediatric hospital wards in France.

The availability of electronic health records made this study feasible. An automatic data extraction from hospital information systems has been implemented. A computer algorithm for determining pediatric drug labelling (i.e. off-label or unlicensed use) using the French summaries of product characteristics available in Thériaque® database has been developed. Detection of ADRs is carried out by health care professionals and research groups using a trigger tool and patients' electronic health records. The causality between ADRs and suspected medications is evaluated using the Naranjo and the French methods by regional pharmacovigilance centers. An independent pharmacovigilance board validates ADR evaluations, assesses both of their severity and avoidability, and indicates therapeutic alternatives to suspected medications.

This is, to our knowledge, the first large multi-center and prospective study in France that evaluates the relationship between adverse drug reactions and unlicensed/ off-label drugs use in hospitalized children. The results of this study will provide more information on the prescription practice and the amplitude, nature and consequences of unlicensed/off-label drug use in hospitalized children. It will also help identify the risk factors of ADR that could be used to implement preventive actions, and guide future research in the field. An indirect benefit is represented by the increase of physicians' awareness in detecting and declaring ADRs and by communicating the results to the health professionals and to the public. This study is funded by ANSM (the French Medicine Agency).

Detailed Description

Not available

Study Timeline

• Study Start: 2013-11
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2016-07
• Study First Submitted: 2016-07-28
• Study First Submitted QC: 2016-07-28
• Last Update Submitted: 2016-07-28
• Study First Posted: 2016-08-02
• Last Update Posted: 2016-08-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6227

Inclusion Criteria

• Children from 0 to 15 years old [0 ; 15[ (including term and preterm newborn infants).
• Hospitalised for at least 3 days.
• Receiving at least one medication.

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Exclusion Criteria

• Children aged 15 to 18 years old [15 ; 18]
• Children hospitalized for an Adverse Drug Reaction or undergoing voluntary drug detoxification.
• Children who did not take any drugs during their hospital stay.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
occurrence of an adverse drug reaction (ADR)	up to one month	To compare the probability of occurrence of an adverse drug reaction (ADR) after a licensed prescription drug versus the probability of occurrence of an ADR after prescribing a drug off-label or unlicensed in patients aged 0-15 years hospitalized at least 3 days.

Secondary Outcome Measures

Name	Time	Method
severity of ADRs	up to one month	Physician Assessment
Identify the factors influencing the risk of developing ADRs after prescribing a drug	up to one month	These factors may include (but are not limited to) : age, gender, severity of the disease, concomitant treatments, number of administered medications, parenteral nutrition, prematurity, etc.
causality of ADRs	up to one month	Physician Assessment
proportion of pediatrics inpatients presenting at least one ADR	up to one month	Compare the proportion of pediatrics inpatients presenting at least one ADR among inpatients with at least one off-labels or unlicensed prescription drug with the proportion of inpatients presenting at least one ADR among inpatients with all licensed prescription drugs
indications for which drugs are prescribed in term of licensed/ unlicensed/ off-label manner by age group	up to one month
avoidability of ADRs	up to one month	Physician Assessment

Trial Locations

Locations (1)

Pediatric Clinical Research and Investigation Centre CIC 1407 Inserm-UMR 5558 CNRS Lyon University & Hospices Civils de Lyon; 🇫🇷 Lyon, France