The INTEGRATE Study: Integrated Pharmacogenetics, TDM and Active Pharmacovigilance as Innovative Tools for the Optimisation and Appropriateness of Drug Therapy (INTEGRATE)

Pharmacogenetics, Therapeutic Drug Monitoring (TDM) and Active Pharmacovigilance as Innovative Tools Aimed at the Optimisation/ Appropriateness of Drug Therapy and the Minimisation of the Risks of ADRs in Clinical Practice: a Multidisciplinary Approach Exportable at National Level

The primary goal of this observational study is to evaluate the feasibility of implementing a multidisciplinary approach based on pharmacogenetics, TDM (Therapeutic Drug Monitoring) and MedReview into the clinical practice in order to optimize the appropriateness of drugs prescription and to minimise the risk of Adverse Drug Reactions (ADRs) in adult cancer patients and in pediatric patients affected by chronic inflammatory diseases. This approach of active pharmacovigilance will also allow a better definition of the causality assessment of ADRs through the direct implementation of data quality in the reporting forms. The study may therefore constitute an example of an approach for both the prevention of ADRs and the optimization of drug use, and for the integration of pharmacogenetics, TDM, and the MedReview data into the National Pharmacovigilance Reports for an improved and innovative evaluation of adverse events, aiming at the implementation of this approach in the regional context.

Study Overview

• Status: Active, not recruiting
• Conditions: Adverse Drug Reaction (ADR)
• Intervention / Treatment: Other: Pharmacogenetics, TDM and MedReview

Detailed Description

Primary aim of the study:

To implement the use of pharmacogenetics, TDM, and MedReview at the regional level supporting their utility through an observational approach to assess the effects of these innovative methods, already active in IRCCS, for the optimization of appropriate drug use and minimization of ADR risk in adult and pediatric oncology patients, as well as pediatric patients with chronic inflammatory diseases. Specifically, the aim is to evaluate the incidence of ADRs in patients treated based on pharmacogenetics, TDM, and MedReview compared to historical cases treated according to the standard of care before the implementation of the proposed innovative methodologies.

Secondary aims of the study:

1. To evaluate the "Causality Assessment" between ADR and drug based on the enhanced data quality deriving from the integration of pharmacogenetics, TDM and MedReview into the Pharmacovigilance report.
2. To propose the systematic integration of the results related to pharmacogenetics, TDM, and MedReview within the existing fields of the current ADR reporting form. This aims to develop a proposal for updating AIFA procedures related to the inclusion of this type of evidence-based information in the National Pharmacovigilance Network (RNF), with a potential update of the reporting form.

• Study Type: Observational
• Enrollment (Estimated): 450

Contacts and Locations

Study Locations

• Italy
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Centro di Riferimento Oncologico di Aviano (CRO)
  • Trieste
    • Trieste, Trieste, Italy, 34137
      • IRCCS materno infantile Burlo Garofolo di Trieste

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who are candidates for therapy with: Abemaciclib, Palbociclib, Ribociclib, Letrozole, Tamoxifen, Olaparib, Infliximab, Cyclophosphamide, Methotrexate, Irinotecan, Capecitabine, 5-Fluorouracil, Noraparib, Adalimumab, Imatinib, Regorafenib, Lenvatinib, Sorafenib, Sunitinib, Rucaparib, 6-MP/ Azathioprine

Description

Inclusion Criteria:

Patients who are candidates for therapy with:

• Abemaciclib,
• Palbociclib,
• Ribociclib,
• Letrozole,
• Tamoxifen,
• Olaparib,
• Niraparib,
• Rucaparib,
• Imatinib,
• Sunitinib,
• Sorafenib,
• Regorafenib,
• Lenvatinib,
• Irinotecan,
• Capecitabine,
• 5-Fluorouracil,
• Infliximab,
• Cyclophosphamide,
• Methotrexate,
• Adalimumab,
• 6-Mercaptopurine/Azathioprine

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult patients; Adult cancer patients	Other: Pharmacogenetics, TDM and MedReview; Patients will undergo pharmacogenetics, TDM and MedReview analyses according to the study protocol
Pediatric patients; Pediatric patients with chronic inflammatory diseases	Other: Pharmacogenetics, TDM and MedReview; Patients will undergo pharmacogenetics, TDM and MedReview analyses according to the study protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients treated with study drugs tested with pharmacogenetic and TDM analysis	Percentage of patients treated with study drugs tested with pharmacogenetic and TDM analysis on total patients treated	Up to 2 years
MedReview reports	Number of MedReview reports	Up to 2 years
ADRs in patients treated on the basis of pharmacogenetics, TDM and MedReview	Incidence of ADRs in the study cohorts	Up to 2 years
Comparison of ADRs in patients treated on the basis of pharmacogenetics, TDM and MedReview and retrospective data	Difference in incidence of ADRs in the prospective cohort will be tested against historical data with binomial test	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proposal for updating the pharmacovigilance reporting forms including Pharmacogenetics, TDM and MedReview information in the National Network of Pharmacovigilance	Frequencies of new reports sent to the National Pharmacovigilance Network, including pharmacogenetics, TDM, and drug interaction data	Up to 2 years
Costs of ADRs management	Median and interquartile range of costs	Up to 2 years
Concordance between plasmatic concentration measured with conventional methods and with new methods such as Dried Blood Spot (DBS)	Lin's correlation coefficient between plasmatic concentration and DBS estimation	Up to 2 years
Correlation between pharmacogenetic profile and drug exposure (TDM)	Difference in drug exposure measured as Cmin for different pharmacogenetic profiles	Up to 2 years
Correlation between ADRs, TDM and pharmacogenetics analyses	Frequencies of ADRs in different subgroups of patients defined by TDM and pharmacogenetic profiles	Up to 2 years
Correlation between ADRs, TDM and pharmacogenetics analyses	Frequencies of severe ADRs in different subgroups of patients defined by TDM and pharmacogenetic profiles	Up to 2 years
Integration of pharmacogenetics, TDM and MedReview information in the existing tool for the evaluation of "Causality assessment" between ADR and specific drug	Change of Causality Assessment. The change is evaluated as the number of "definite" and "probable" associations between ADRs and suspected drugs compared with historical data	Up to 2 years
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 v3	The EORTC QLG Core Questionnaire (EORTC QLQ-C30) is a 30-item instrument designed to measure quality of life in all cancer patients. The possible answers to the questionnaire range from a minimum value ("not at all") to a maximum value ("very much"). Higher values indicate a worse quality of life. Mean and standard deviation of scores at EORTC QLQ-C30 v3 questionnaire will be evaluated.	Up to 2 years

Collaborators and Investigators

• Sponsor: Direzione centrale salute, politiche sociali e disabilità
• Collaborators: Centro di Riferimento Oncologico - Aviano; IRCCS Burlo Garofolo
• Investigators: Principal Investigator: Erika Cecchin, Centro di Riferimento Oncologico di Aviano (CRO) - IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2022
• Primary Completion (Actual): December 31, 2025
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: February 7, 2025
• First Submitted That Met QC Criteria: February 7, 2025
• First Posted (Actual): February 12, 2025

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Health Services; Health Care Facilities Workforce and Services; Preventive Health Services; Genetic Testing; Genetic Techniques; Genetic Services; Diagnostic Services; Pharmacogenomic Testing
• Other Study ID Numbers: CRO-2022-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No