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

Hospitalized Children Clinical Trial

— EREMI  

Official title:

Relationship Between Adverse Drug Reactions and Unlicensed/ Off-label Drug Use in Hospitalized Children: an Observational Multicenter Prospective Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02852590
• Other study ID #: D21530
• Status: Completed
• Phase: N/A
• First received: July 28, 2016
• Last updated: July 28, 2016
• Start date: November 2013
• Est. completion date: January 2016

Study information

• Verified date: July 2016
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Commission nationale de l'informatique et des libertés
• Study type: Observational

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6227
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 15 Years

Eligibility

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.

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Drug-Related Side Effects and Adverse Reactions
• Hospitalized Children

Locations

Country	Name	City	State
France	Pediatric Clinical Research and Investigation Centre CIC 1407 Inserm-UMR 5558 CNRS Lyon University & Hospices Civils de Lyon	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	occurrence of an adverse drug reaction (ADR)	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.	up to one month	No
Secondary	proportion of pediatrics inpatients presenting at least one ADR	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	up to one month	No
Secondary	indications for which drugs are prescribed in term of licensed/ unlicensed/ off-label manner by age group		up to one month	No
Secondary	Identify the factors influencing the risk of developing ADRs after prescribing a drug	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.	up to one month	No
Secondary	causality of ADRs	Physician Assessment	up to one month	No
Secondary	severity of ADRs	Physician Assessment	up to one month	No
Secondary	avoidability of ADRs	Physician Assessment	up to one month	No