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The value of software that provides clinically relevant information on drug interactions
EJINME-02966; No of Pages 2 European Journal of Internal Medicine xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letter to the Editor The value of software that provides clinically relevant information on drug interactions Keywords: Drug interactions Aged Polypharmacy Computerised prescription support system
Letter to the Editor Potential drug–drug interactions (pDDIs) are critical issues in the management of the elderly. The development of multiple diseases with increasing age leads to therapies based upon many concomitant drugs, a risk factor for severe pDDIs [1]. Pharmacological interactions may affect patient health by leading to adverse drug reactions and more hospitalisations [2–4], so that they also represent a cost for the healthcare systems [5]. In order to minimise pDDIs and assist clinicians with information readily available at the time of prescription, the computerised prescription support system (CPSS) INTERCheck® was developed by the IRCCS Istituto di Ricerche Mario Negri of Milan. This software provides a list of pDDIs associated to drug therapies, classifying them according to their clinical relevance: D means contraindicated (drug combinations should be avoided); C, major DDIs (drug combinations requiring close monitoring for potentially serious clinical consequences, such as severe adverse effects or lack of clinical efficacy); B, moderate (drug combinations requiring dose adjustment and/or drug concentration monitoring); A, minor (drug combinations with no known clinical relevance). INTERCheck® was already validated in the frame of clinical practice [6], confirming its effectiveness in reducing potentially severe pDDIs. However, the correlation between the clinical relevance of pDDIs as detected by this software and clinician's personal judgement was not investigated until now. We examined pDDIs in the frame of a retrospective study [7] conducted between April and October 2014 on medical records of 60 elderly patients, selected for age (65 years or older) and number of drugs administered at home (at least five), who were admitted to 4 medical wards (one geriatric, one emergency medicine and two internal medicine) of a large teaching hospital in Milan, Italy. For each patient, drugs administered at home, during the first 24 h after hospital admission and at discharge were reviewed by means of INTERCheck®, and the retrieved pDDIs collected into an internal database, excluding from the analysis repeated pDDIs stemming from medical records of the same ward. In order to define the clinicians' personal judgement, we prepared four questions to be answered for each pDDIs detected by the CPSS: 1) is the actual pDDI known? 2) is it clinically relevant? 3) if yes, why? 4) would knowledge of the pDDI at the time of prescription have changed patient management (in terms of prescribing approach or clinical monitoring)? The questionnaire was administered through a specific computerised form to clinicians, who were asked to answer pertaining to the pDDIs of
patients admitted to their wards. The revision of 60 medical records using INTERCheck® identified 961 pDDIs from 1658 drugs prescribed at home, within the first 24 h after hospital admission or at discharge. After exclusion of 513 duplicated pDDIs, 448 pDDIs were evaluated by the clinicians who filled the questionnaire and data are reported in Table 1. Overall, 51% of pDDIs (230/448) were judged clinically relevant, with a rate increasing according to the severity declared by the CPSS: 17% for A, 39% for B, 75% for C and 74% for D. Of 230 pDDIs, 67% was considered relevant for clinicians due to their potential clinical impact, 24% owing to patient complexity and/or comorbidities, and 7% because they were unknown. We found that 221 of 448 pDDIs (49%) were known to clinicians, with different percentages among the participating wards, ranging from 41% to 62%; in 23% of cases knowledge of the pDDIs as declared by the software would have changed the prescription approach. This is the first study exploring the correlation between the clinical relevance of pDDIs as detected by INTERCheck® and the clinician's personal judgement. In agreement to studies [4,6] showing that the software is an efficacious tool in order to detect and reduce potentially severe pDDIs, more than half of the electronically retrieved pDDIs were considered clinically relevant by clinicians. Ghibelli et al. [6] found that when INTERCheck® suggestions were followed by clinicians, new-onset severe pDDIs were reduced by 44%, and the patients exposed to severe pDDIs decreased by 27%. Similarly, we found that in 23% of the cases, CPSS use would have led to a different patient management, such as drug withdrawal, dose adjustment or clinical and biochemical monitoring. Even though this study found that near 50% of pDDIs were already known to clinicians, the achievement of a higher expertise in geriatric pharmacotherapy is one of the main aims for internists and geriatricians. On the other hand, because it is not realistic that all prescribers recognise each potential DDI [8], CPSS are useful tools to remind or highlight potential risks in drug therapies. It is essential that software provide clinically relevant information meant to improve the prescribing quality without waste of time. This study found an agreement between the INTERCheck® and clinicians, increasing with the severity of pDDIs. In order to improve this electronic tool so that it provides information of clinical relevance for physicians, an involvement of more prescribers in its development is necessary. In this regard, more data will be gathered by a prospective study in which INTERCheck® is going to be used as a reference CPSS in order to improve the appropriate prescribing in a hospital setting. The tool is available upon motivated request to the corresponding author of this letter. Conflict of interest None reported. Acknowledgments We wish to thank E. Bertin, C. Casiraghi, S. Damanti, M.L. Gattoni, G. Periti, M. Porzio, and R. Rossio who provided their clinical judgements by filling the questionnaires, and E. Clementi, S. Fargion, M. Marcucci,
http://dx.doi.org/10.1016/j.ejim.2015.07.004 0953-6205/© 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Antoniazzi S, et al, The value of software that provides clinically relevant information on drug interactions, Eur J Intern Med (2015), http://dx.doi.org/10.1016/j.ejim.2015.07.004
2
Letter to the Editor
Table 1 Results of physician interviews.
pDDIs clinically relevant for physicians/ pDDIs detected by INTERCheck® A B C D Why the pDDI is relevant for physician? Because the pDDI was unknown Owing to patient complexity/comorbidity For severity of the clinical impact No answer pDDIs actually known to physicians pDDI that if known at prescription time would have changed patient management a
Emergency Medicine, number of pDDIs (%)
Geriatric Unit, number of pDDIs (%)
Internal Medicine 1, number of pDDIs (%)
Internal Medicine 2, number of pDDIs (%)
All wards, number of pDDIs (%)
27/68 (40)
71/135 (53)
86/103 (84)
46/142 (32)
230/448 (51)
0/1 (0) 8/44 (18) 13/17 (6) 6/6 (100)
0/3 (0) 33/82 (40) 29/39 (74) 9/11 (82)
0/6 (0) 21/91 (23) 11/21 (53) 14/24 (58)
2/12 (17) 108/275 (39) 81/108 (75) 39/53 (74)
11/27 (41) 14/27 (52) 0/27 (0) 2/27 (7) 29/68 (43) 1/39a (3)
6/71 (8) 2/71 (3) 63/71 (89) 0 (0) 70/135 (52) 16/65a (25)
0/46 (0) 12/46 (26) 31/46 (67) 3/46 (7) 58/142 (41) 6/84a (7)
17/230 (7) 54/230 (24) 154/230 (67) 5/230 (2) 221/448 (49) 52/227a (23)
2/2 (100) 46/58 (79) 28/31 (90) 10/12 (83) 0/86 (0) 26/86 (30) 60/86 (70) 0 (0) 64/103 (62) 29/39a (74)
pDDIs unknown to physicians.
D. Mari, V. Monzani, F. Peyvandi and P. Santalucia for their critical advices during the study. References [1] Nobili A, Pasina L, Tettamanti M, Lucca U, Riva E, Marzona I, et al. Potentially severe drug interactions in elderly outpatients: results of an observational study of an administrative prescription database. J Clin Pharm Ther 2009;34:377–86. [2] Becker ML, Kallewaard M, Caspers PW, Visser LE, Leufkens HG, Stricker BH. Hospitalisations and emergency department visits due to drug–drug interactions: a literature review. Pharmacoepidemiol Drug Saf 2007;16:641–51. [3] Hamilton RA, Briceland LL, Andritz MH. Frequency of hospitalization after exposure to known drug–drug interactions in a Medicaid population. Pharmacotherapy 1998;18: 1112–20. [4] Marengoni A, Pasina L, Concoreggi C, Martini G, Brognoli F, Nobili A, et al. Understanding adverse drug reactions in older adults through drug–drug interactions. Eur J Intern Med 2014;25:843–6. [5] Moura CS, Acurcio FA, Belo NO. Drug–drug interactions associated with length of stay and cost of hospitalization. J Pharm Pharm Sci 2009;12:266–72. [6] Ghibelli S, Marengoni A, Djade CD, Nobili A, Tettamanti M, Franchi C, et al. Prevention of inappropriate prescribing in hospitalized older patients using a computerized prescription support system (INTERcheck(®)). Drugs Aging 2013;30:821–8. [7] Chiarelli MT, Antoniazzi S, Lodi MC, Ladisa V, Venturini F, Pasina L, et al. Il processo di ricognizione-riconciliazione terapeutica in un campione di pazienti ricoverati: analisi retrospettiva. XXXV Congresso Nazionale SIFO: Giornale Italiano di Farmacia Clinica 2014;28:97. [8] O'Connor MN, Gallagher P, O'Mahony D. Inappropriate prescribing criteria, detection and prevention. Drugs Aging 2012;29:437–52.
Alessandro Nobili Luca Pasina⁎ IRCCS—Istituto di Ricerche Farmacologiche “Mario Negri”, via Giuseppe La Masa 19, 20156 Milan, Italy ⁎ Corresponding author at: Pharmacotherapy and Appropriateness of Drugs Prescription Unit, IRCCS, Istituto di Ricerche Farmacologiche “Mario Negri”, Via Giuseppe La Masa, 19, 20156 Milano, Italy. Tel.: + 39 02 39014 579; fax: + 39 02 39001916. E-mail address: [email protected] (L. Pacina). Francesca Venturini Hospital PharmacyDepartment, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, Italy 3 July 2015 Available online xxxx
Stefania Antoniazzi1 Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital “Luigi Sacco”, Università di Milano, Via GB Grassi 74, 20157 Milan, Italy Scientific Direction, IRCCS Ca' Granda Maggiore Policlinico Hospital Foundation, via Francesco Sforza 28, 20122 Milan, Italy Maria Teresa Chiarellii1 Hospital PharmacyDepartment, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, Italy
1
Contributed equally to the work.
Please cite this article as: Antoniazzi S, et al, The value of software that provides clinically relevant information on drug interactions, Eur J Intern Med (2015), http://dx.doi.org/10.1016/j.ejim.2015.07.004
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letter to the Editor The value of software that provides clinically relevant information on drug interactions Keywords: Drug interactions Aged Polypharmacy Computerised prescription support system
Letter to the Editor Potential drug–drug interactions (pDDIs) are critical issues in the management of the elderly. The development of multiple diseases with increasing age leads to therapies based upon many concomitant drugs, a risk factor for severe pDDIs [1]. Pharmacological interactions may affect patient health by leading to adverse drug reactions and more hospitalisations [2–4], so that they also represent a cost for the healthcare systems [5]. In order to minimise pDDIs and assist clinicians with information readily available at the time of prescription, the computerised prescription support system (CPSS) INTERCheck® was developed by the IRCCS Istituto di Ricerche Mario Negri of Milan. This software provides a list of pDDIs associated to drug therapies, classifying them according to their clinical relevance: D means contraindicated (drug combinations should be avoided); C, major DDIs (drug combinations requiring close monitoring for potentially serious clinical consequences, such as severe adverse effects or lack of clinical efficacy); B, moderate (drug combinations requiring dose adjustment and/or drug concentration monitoring); A, minor (drug combinations with no known clinical relevance). INTERCheck® was already validated in the frame of clinical practice [6], confirming its effectiveness in reducing potentially severe pDDIs. However, the correlation between the clinical relevance of pDDIs as detected by this software and clinician's personal judgement was not investigated until now. We examined pDDIs in the frame of a retrospective study [7] conducted between April and October 2014 on medical records of 60 elderly patients, selected for age (65 years or older) and number of drugs administered at home (at least five), who were admitted to 4 medical wards (one geriatric, one emergency medicine and two internal medicine) of a large teaching hospital in Milan, Italy. For each patient, drugs administered at home, during the first 24 h after hospital admission and at discharge were reviewed by means of INTERCheck®, and the retrieved pDDIs collected into an internal database, excluding from the analysis repeated pDDIs stemming from medical records of the same ward. In order to define the clinicians' personal judgement, we prepared four questions to be answered for each pDDIs detected by the CPSS: 1) is the actual pDDI known? 2) is it clinically relevant? 3) if yes, why? 4) would knowledge of the pDDI at the time of prescription have changed patient management (in terms of prescribing approach or clinical monitoring)? The questionnaire was administered through a specific computerised form to clinicians, who were asked to answer pertaining to the pDDIs of
patients admitted to their wards. The revision of 60 medical records using INTERCheck® identified 961 pDDIs from 1658 drugs prescribed at home, within the first 24 h after hospital admission or at discharge. After exclusion of 513 duplicated pDDIs, 448 pDDIs were evaluated by the clinicians who filled the questionnaire and data are reported in Table 1. Overall, 51% of pDDIs (230/448) were judged clinically relevant, with a rate increasing according to the severity declared by the CPSS: 17% for A, 39% for B, 75% for C and 74% for D. Of 230 pDDIs, 67% was considered relevant for clinicians due to their potential clinical impact, 24% owing to patient complexity and/or comorbidities, and 7% because they were unknown. We found that 221 of 448 pDDIs (49%) were known to clinicians, with different percentages among the participating wards, ranging from 41% to 62%; in 23% of cases knowledge of the pDDIs as declared by the software would have changed the prescription approach. This is the first study exploring the correlation between the clinical relevance of pDDIs as detected by INTERCheck® and the clinician's personal judgement. In agreement to studies [4,6] showing that the software is an efficacious tool in order to detect and reduce potentially severe pDDIs, more than half of the electronically retrieved pDDIs were considered clinically relevant by clinicians. Ghibelli et al. [6] found that when INTERCheck® suggestions were followed by clinicians, new-onset severe pDDIs were reduced by 44%, and the patients exposed to severe pDDIs decreased by 27%. Similarly, we found that in 23% of the cases, CPSS use would have led to a different patient management, such as drug withdrawal, dose adjustment or clinical and biochemical monitoring. Even though this study found that near 50% of pDDIs were already known to clinicians, the achievement of a higher expertise in geriatric pharmacotherapy is one of the main aims for internists and geriatricians. On the other hand, because it is not realistic that all prescribers recognise each potential DDI [8], CPSS are useful tools to remind or highlight potential risks in drug therapies. It is essential that software provide clinically relevant information meant to improve the prescribing quality without waste of time. This study found an agreement between the INTERCheck® and clinicians, increasing with the severity of pDDIs. In order to improve this electronic tool so that it provides information of clinical relevance for physicians, an involvement of more prescribers in its development is necessary. In this regard, more data will be gathered by a prospective study in which INTERCheck® is going to be used as a reference CPSS in order to improve the appropriate prescribing in a hospital setting. The tool is available upon motivated request to the corresponding author of this letter. Conflict of interest None reported. Acknowledgments We wish to thank E. Bertin, C. Casiraghi, S. Damanti, M.L. Gattoni, G. Periti, M. Porzio, and R. Rossio who provided their clinical judgements by filling the questionnaires, and E. Clementi, S. Fargion, M. Marcucci,
http://dx.doi.org/10.1016/j.ejim.2015.07.004 0953-6205/© 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Antoniazzi S, et al, The value of software that provides clinically relevant information on drug interactions, Eur J Intern Med (2015), http://dx.doi.org/10.1016/j.ejim.2015.07.004
2
Letter to the Editor
Table 1 Results of physician interviews.
pDDIs clinically relevant for physicians/ pDDIs detected by INTERCheck® A B C D Why the pDDI is relevant for physician? Because the pDDI was unknown Owing to patient complexity/comorbidity For severity of the clinical impact No answer pDDIs actually known to physicians pDDI that if known at prescription time would have changed patient management a
Emergency Medicine, number of pDDIs (%)
Geriatric Unit, number of pDDIs (%)
Internal Medicine 1, number of pDDIs (%)
Internal Medicine 2, number of pDDIs (%)
All wards, number of pDDIs (%)
27/68 (40)
71/135 (53)
86/103 (84)
46/142 (32)
230/448 (51)
0/1 (0) 8/44 (18) 13/17 (6) 6/6 (100)
0/3 (0) 33/82 (40) 29/39 (74) 9/11 (82)
0/6 (0) 21/91 (23) 11/21 (53) 14/24 (58)
2/12 (17) 108/275 (39) 81/108 (75) 39/53 (74)
11/27 (41) 14/27 (52) 0/27 (0) 2/27 (7) 29/68 (43) 1/39a (3)
6/71 (8) 2/71 (3) 63/71 (89) 0 (0) 70/135 (52) 16/65a (25)
0/46 (0) 12/46 (26) 31/46 (67) 3/46 (7) 58/142 (41) 6/84a (7)
17/230 (7) 54/230 (24) 154/230 (67) 5/230 (2) 221/448 (49) 52/227a (23)
2/2 (100) 46/58 (79) 28/31 (90) 10/12 (83) 0/86 (0) 26/86 (30) 60/86 (70) 0 (0) 64/103 (62) 29/39a (74)
pDDIs unknown to physicians.
D. Mari, V. Monzani, F. Peyvandi and P. Santalucia for their critical advices during the study. References [1] Nobili A, Pasina L, Tettamanti M, Lucca U, Riva E, Marzona I, et al. Potentially severe drug interactions in elderly outpatients: results of an observational study of an administrative prescription database. J Clin Pharm Ther 2009;34:377–86. [2] Becker ML, Kallewaard M, Caspers PW, Visser LE, Leufkens HG, Stricker BH. Hospitalisations and emergency department visits due to drug–drug interactions: a literature review. Pharmacoepidemiol Drug Saf 2007;16:641–51. [3] Hamilton RA, Briceland LL, Andritz MH. Frequency of hospitalization after exposure to known drug–drug interactions in a Medicaid population. Pharmacotherapy 1998;18: 1112–20. [4] Marengoni A, Pasina L, Concoreggi C, Martini G, Brognoli F, Nobili A, et al. Understanding adverse drug reactions in older adults through drug–drug interactions. Eur J Intern Med 2014;25:843–6. [5] Moura CS, Acurcio FA, Belo NO. Drug–drug interactions associated with length of stay and cost of hospitalization. J Pharm Pharm Sci 2009;12:266–72. [6] Ghibelli S, Marengoni A, Djade CD, Nobili A, Tettamanti M, Franchi C, et al. Prevention of inappropriate prescribing in hospitalized older patients using a computerized prescription support system (INTERcheck(®)). Drugs Aging 2013;30:821–8. [7] Chiarelli MT, Antoniazzi S, Lodi MC, Ladisa V, Venturini F, Pasina L, et al. Il processo di ricognizione-riconciliazione terapeutica in un campione di pazienti ricoverati: analisi retrospettiva. XXXV Congresso Nazionale SIFO: Giornale Italiano di Farmacia Clinica 2014;28:97. [8] O'Connor MN, Gallagher P, O'Mahony D. Inappropriate prescribing criteria, detection and prevention. Drugs Aging 2012;29:437–52.
Alessandro Nobili Luca Pasina⁎ IRCCS—Istituto di Ricerche Farmacologiche “Mario Negri”, via Giuseppe La Masa 19, 20156 Milan, Italy ⁎ Corresponding author at: Pharmacotherapy and Appropriateness of Drugs Prescription Unit, IRCCS, Istituto di Ricerche Farmacologiche “Mario Negri”, Via Giuseppe La Masa, 19, 20156 Milano, Italy. Tel.: + 39 02 39014 579; fax: + 39 02 39001916. E-mail address: [email protected] (L. Pacina). Francesca Venturini Hospital PharmacyDepartment, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, Italy 3 July 2015 Available online xxxx
Stefania Antoniazzi1 Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital “Luigi Sacco”, Università di Milano, Via GB Grassi 74, 20157 Milan, Italy Scientific Direction, IRCCS Ca' Granda Maggiore Policlinico Hospital Foundation, via Francesco Sforza 28, 20122 Milan, Italy Maria Teresa Chiarellii1 Hospital PharmacyDepartment, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, Italy
1
Contributed equally to the work.
Please cite this article as: Antoniazzi S, et al, The value of software that provides clinically relevant information on drug interactions, Eur J Intern Med (2015), http://dx.doi.org/10.1016/j.ejim.2015.07.004