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Systematic Data Monitoring and Analysis of Cardiovascular Off-label Prescriptions in Pediatrics: Focus on Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Beta Blockers

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Abstract

Introduction

Many efforts have been made to stimulate clinical trials (CTs) in pediatrics but most of the drugs are still authorized only in adults and used off-label in the pediatric population.

Aim

To assess how widespread is the off-label prescription in Italy and to identify areas of unmet medical need by applying a model for the systematic collection and analysis of data.

Methods

A study was performed using 2015 data from the Italian Medicines Utilization Monitoring Centre Health Database (OsMed). A study sample of 3,726,583 pediatric patients, was considered. Cardiovascular drugs were selected for this study. Assessment of the off-label use, the analysis of the pharmacovigilance signals, a bibliographic research and the analysis of ongoing CTs were carried out.

Results

In 2015, 8,544 pediatric patients received treatment with a cardiovascular drug. Angiotensin converting enzyme inhibitors (ACE-I) followed by beta blockers agents are the most prescribed molecules. Eight molecules were selected and an in-depth analysis conducted. The PhV network showed only one record of adverse reaction as off-label in 2015. The results show several therapeutic areas of use in pediatrics.

Conclusion

Off-label in pediatrics is largely widespread in Europe and US and our results show it is also present in Italy. Molecules selected are used off-label for therapeutic areas such as oncologic, hematological and rare diseases. Results of pharmacovigilance suggests underreporting. The analysis carried out in this study could be an open track for a systematic monitoring activity and of interest for prescribers, pediatricians and other healthcare professionals during the clinical practice.

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Acknowledgements

The Authors would like to thank Professor Alfredo Vannacci, Dr. Giada Crescioli and Dr. Alessandra Bettiol (University of Florence, Florence, Italy) for their contribution in the present study as experts in the field of clinical pharmacology and pharmacoepidemiology. The Authors would like to thank Dr. Anna Rosa Marra and Dr. Loriana Tartaglia for their contribution for the pharmacovigilance data and Dr. Agnese Cangini for the raw data Osmed. The Authors would like to thank Marta Toma (AIFA) for the English revision.

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Authors and Affiliations

  1. Italian Medicines Agency (AIFA), Via del Tritone, 181, 00187, Rome, Italy

    S. M. Cammarata & G. Capone

  2. Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence, Italy

    S. M. Cammarata, N. Lombardi & A. Mugelli

  3. Department of Psychiatry and Behavioral Sciences, University of Miami, School of Medicine, Miami, FL, 33136-1015, USA

    L. Pani

Authors
  1. S. M. Cammarata
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  2. G. Capone
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  3. N. Lombardi
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  4. L. Pani
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Corresponding author

Correspondence to S. M. Cammarata.

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Funding and Competing Interests

There are no competing interests to declare. The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Availability of data and material (data transparency)

The data that support the findings of this study are available from corresponding author. Restrictions apply to the availability of these data, which were used under license for this study.

Disclosure

The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the Italian Medicines Agency or their Committee. LP has consulted for AbbVie USA; Acadia USA; BCG Switzerland; Boehringer Ingelheim International GmbH; Compass Pathways, UK; Ferrer Spain, EDRA-LSWR Publishing Company, Italy; Inpeco SA Lab Automation Company, Switzerland; Johnson & Johnson USA; NeuroCog Trials USA; Otsuka USA, Pfizer Global USA; PharmaMar Spain; Takeda, USA and VeraSci USA.

Authors’ contributions

SMC carried out the analysis on the Osmed Database data, the bibliographical search, screened studies for inclusion, recorded the motivation for the exclusion of any study considered, performed data extraction and analysis, and drafted the manuscript; GC participated in the discussion related to the selection process in case of discrepancies, checked the forms containing the data extraction, revised the manuscript. NL revised the manuscript. LP and AM provided methodological advice and revised the manuscript. All authors read and approved the final manuscript.

Ethics Statement

Given the nature (not clinical) of the study, exclusively based on the administrative anonymous data with no disclosure of confidential/sensitive information, approval by an ethics committees and informed consent were not required, in accordance with the local legislation and institutional requirements.

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Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 62 KB)

Appendix

Appendix

See Tables 1, 2, 3, 4 and 5.

Table 1 Age and gender distribution in the study sample
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Table 2 Most commonly prescribed medications in the study sample, belonging to ATC C
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Table 3 Number of pediatric patients treated divided per molecule, gender and age
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Table 4 Most prescribed active substances belonging to ATC C divided according to gender
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Table 5 Research of published studies on ACE-I and on beta blockers agents
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Cammarata, S.M., Capone, G., Lombardi, N. et al. Systematic Data Monitoring and Analysis of Cardiovascular Off-label Prescriptions in Pediatrics: Focus on Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Beta Blockers. High Blood Press Cardiovasc Prev 29, 169–195 (2022). https://doi.org/10.1007/s40292-021-00499-x

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  • DOI: https://doi.org/10.1007/s40292-021-00499-x

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