Comparison of the validity, perceived usefulness, and usability of I-MeDeSA and TEMAS, two tools to evaluate alert system usability.

OBJECTIVE: Two tools are currently available in the literature to evaluate the usability of medication alert systems, the instrument for evaluating human factors principles in medication-related decision support alerts (I-MeDeSA) and the tool for evaluating medication alerting systems (TEMAS). This study aimed to compare their convergent validity, perceived usability, usefulness, strengths, and weaknesses, as well as users' preferences. METHOD: To evaluate convergent validity, two experts mapped TEMAS' items against I-MeDeSA's items with respect to the usability dimensions they target. To assess perceived usability, usefulness, strengths, and weaknesses of both tools, staff with expertise in their medication alerting system were asked to use French versions of the TEMAS and I-MeDeSA. After the use of each tool, participants were asked to complete the System Usability Scale (SUS) and answer questions about the understandability and usefulness of each tool. Finally, participants were asked to name their preferred tool. Numeric scores were statistically compared. Free-text responses were analyzed using an inductive approach. RESULTS: Forty-five participants from 10 hospitals took part in the study. In terms of convergent validity, I-MeDeSA focuses more on the usability of the graphical user interface while TEMAS considers a wider range of usability principles. Both tools have a fair level of perceived usability (I-MeDeSA' SUS score = 61.85 and TEMAS' SUS score = 62.87), but results highlight that revisions are necessary to both tools to improve their usability. Participants found TEMAS more useful than I-MeDeSA (t = -3.63, p =.005) and had a clear preference for TEMAS to identify problems in formative evaluation (39 of 45; 0.867, p <.001) and to compare the usability of alert systems during the procurement process (36 of 45; 0.8, p <.001). CONCLUSIONS: The TEMAS is perceived as more useful and is preferred by participants. The I-MeDeSA seems more relevant for quick evaluations that focus on the graphical user interface. The TEMAS seems to be more suitable for in-depth usability evaluations of alert systems. Even if both tools are perceived to be equally usable, they suffer from wording, instructional, and organizational problems that hinder their use. The results of this study will be used to improve the design of I-MeDeSA and TEMAS.

Assessment of a hybrid decision support system using machine learning with artificial intelligence to safely rule out prescriptions from medication review in daily practice.

Background Medication review is time-consuming and not exhaustive in most French hospitals. We routinely use an innovative hybrid decision support system using Artificial Intelligence to prioritize medication review by scoring prescriptions by their risk of containing at least one drug related problem (DRP). Aim Our aim was to attest that the prescriptions with low risk of DRPs ruled out by the tool in everyday practice were effectively free of any DRPs with potentially severe clinical impact. Methods We conducted a randomized single-blinded study to compare the rate of pharmaceutical interventions (PI) between low and high-risk prescriptions defined by the tool's calculated score. Prescriptions were reviewed daily by a clinical pharmacist. Proportion of prescriptions with at least one severe DRP was calculated in both groups. Severe DRPs were characterized through a multidisciplinary approach. Results Four hundred and twenty (107 low score and 313 high score) prescriptions were analyzed. The percentage of prescriptions with severe DRPs was dramatically decreased in low score prescriptions (2.8% vs. 15.3% for high-risk; p = 0.0248). A significant difference was found (94% vs. 20%; p < 0.001) in the percentage of severe DRPs detected by the hybrid approach compared to a CDSS. During the study period, the hybrid tool allowed to rule out 55% of all prescriptions in our hospital.Conclusion This hybrid decision support tool has shown to be accurate to detect DRPs in daily practice. Despite some limitations, it offers the best possible solution to prioritized medication review, considering the shortage of clinical pharmacists in France and considerably improves the safety of patients' care.

Effectiveness of a 'do not interrupt' vest intervention to reduce medication errors during medication administration: a multicenter cluster randomized controlled trial.

BACKGROUND: The use of a 'do not interrupt' vest during medication administration rounds is recommended but there have been no controlled randomized studies to evaluate its impact on reducing administration errors. We aimed to evaluate the impact of wearing such a vest on reducing such errors. The secondary objectives were to evaluate the types and potential clinical impact of errors, the association between errors and several risk factors (such as interruptions), and nurses' experiences. METHODS: This was a multicenter, cluster, controlled, randomized study (March-July 2017) in 29 adult units (4 hospitals). Data were collected by direct observation by trained observers. All nurses from selected units were informed. A 'Do not interrupt' vest was implemented in all units of the experimental group. A poster was placed at the entrance of these units to inform patients and relatives. The main outcome was the administration error rate (number of Opportunities for Error (OE), calculated as one or more errors divided by the Total Opportunities for Error (TOE) and multiplied by 100). RESULTS: We enrolled 178 nurses and 1346 patients during 383 medication rounds in 14 units in the experimental group and 15 units in the control group. During the intervention period, the administration error rates were 7.09% (188 OE with at least one error/2653 TOE) for the experimental group and 6.23% (210 OE with at least one error/3373 TOE) for the control group (p = 0.192). Identified risk factors (patient age, nurses' experience, nurses' workload, unit exposition, and interruption) were not associated with the error rate. The main error type observed for both groups was wrong dosage-form. Most errors had no clinical impact for the patient and the interruption rates were 15.04% for the experimental group and 20.75% for the control group. CONCLUSIONS: The intervention vest had no impact on medication administration error or interruption rates. Further studies need to be performed taking into consideration the limitations of our study and other risk factors associated with other interventions, such as nurse's training and/or a barcode system. TRIAL REGISTRATION: The PERMIS study protocol (V2-1, 11/04/2017) was approved by institutional review boards and ethics committees (CPP Ile de France number 2016-A00211-50, CNIL 21/03/2017, CCTIRS 11/04/2016). It is registered at ClinicalTrials.gov (registration number: NCT03062852 , date of first registration: 23/02/2017).

A machine learning-based clinical decision support system to identify prescriptions with a high risk of medication error.

OBJECTIVE: To improve patient safety and clinical outcomes by reducing the risk of prescribing errors, we tested the accuracy of a hybrid clinical decision support system in prioritizing prescription checks. MATERIALS AND METHODS: Data from electronic health records were collated over a period of 18 months. Inferred scores at a patient level (probability of a patient's set of active orders to require a pharmacist review) were calculated using a hybrid approach (machine learning and a rule-based expert system). A clinical pharmacist analyzed randomly selected prescription orders over a 2-week period to corroborate our findings. Predicted scores were compared with the pharmacist's review using the area under the receiving-operating characteristic curve and area under the precision-recall curve. These metrics were compared with existing tools: computerized alerts generated by a clinical decision support (CDS) system and a literature-based multicriteria query prioritization technique. Data from 10 716 individual patients (133 179 prescription orders) were used to train the algorithm on the basis of 25 features in a development dataset. RESULTS: While the pharmacist analyzed 412 individual patients (3364 prescription orders) in an independent validation dataset, the areas under the receiving-operating characteristic and precision-recall curves of our digital system were 0.81 and 0.75, respectively, thus demonstrating greater accuracy than the CDS system (0.65 and 0.56, respectively) and multicriteria query techniques (0.68 and 0.56, respectively). DISCUSSION: Our innovative digital tool was notably more accurate than existing techniques (CDS system and multicriteria query) at intercepting potential prescription errors. CONCLUSIONS: By primarily targeting high-risk patients, this novel hybrid decision support system improved the accuracy and reliability of prescription checks in a hospital setting.

Complete Atrioventricular Block in an Elderly Patient Treated with Low-Dose Lacosamide.

Lacosamide, one of the last antiepileptic drugs marketed, can cause extension of PR interval. Precautions are recommended when used in elderly and with other drugs extending PR interval. Cases of severe third-degree atrioventricular block have been reported only in post-marketing case reports when used at high-doses and remain rare. We report the case of an 88-year-old woman treated with bisoprolol, who experienced a complete atrioventricular block after initiation of lacosamide for epilepsy associated with neurodegenerative disease. This dramatic event required a pacemaker implementation. Not being dose-dependent (initiation dosage used), it seemed partially explained by drug-drug interaction with bisoprolol.

Identification of variables influencing pharmaceutical interventions to improve medication review efficiency.

Background Clinical pharmacists' involvement has improved patients' care, by suggesting therapeutic optimizations. However, budget restrictions require a prioritization of these activities to focus resources on patients more at risk of medication errors. Objective The aim of our study was to identify variables influencing the formulation of pharmaceutical to improve medication review efficiency. Setting This study was conducted in medical wards of a 643-acute beds hospital in Paris, France. Methods All hospital medical prescriptions of all patients admitted within four medical wards (cardiology, rheumatology, neurology, vascular medicine) were analyzed. The study was conducted in each ward for 2 weeks, during 4 weeks. For each patient, variables prospectively collected were: age, gender, weight, emergency admission, number of high-alert medications and of total drugs prescribed, care unit, serum creatinine. Number of pharmaceutical interventions (PIs) and their type were reported. Main outcome measures Variables influencing the number of pharmaceutical interventions during medication review were identified using simple and multiple linear regressions. Results A total of 2328 drug prescriptions (303 patients, mean age 70.6 years-old) were analyzed. Mean number of hospital drug prescriptions was 7.9. A total of 318 PIs were formulated. Most frequent PIs were drug omission (n = 88, 27.7%), overdosing (n = 69, 21.7%), and underdosing (n = 51, 16.0%). Among variables studied, age, serum creatinine level, number of high-alert medications prescribed and total number of drugs prescribed were significantly associated with the formulation of pharmaceutical interventions (adjusted R2 = 0.34). Conclusions This study identified variables (age, serum creatinine level, number of high-alert medication, number of prescribed drugs) that may help institutions/pharmacists target their reviews towards patients most likely to require pharmacist interventions.

Efficacy of next treatment received after nivolumab progression in patients with advanced nonsmall cell lung cancer.

Nivolumab for the treatment of advanced nonsmall cell lung cancer (NSCLC) evaluated in phase III trials showed 50% progression at first evaluation, but better overall survival (OS), suggesting regained efficacy of treatments given thereafter. We aimed to evaluate the efficacy of nivolumab and of next treatment received after nivolumab progression in patients with advanced NSCLC. Our multicentre retrospective study included all patients receiving nivolumab between January and December 2015. The primary end-point was progression-free survival (PFS) of treatment given after nivolumab. The 303 patients had the following characteristics: median age 63 years, 69% males, 92% smokers, 67% performance status 0-1 and 61% adenocarcinoma. Nivolumab was given as second-line treatment in 40% of patients. With 13.7 months of median follow-up, nivolumab PFS and OS were 2.6 and 11.3 months, respectively. At the cut-off analysis 18% were controlled under nivolumab, 14% were deceased and 5% were lost to follow-up under nivolumab. Among the 191 (63%) patients eligible for post-nivolumab (PN) treatment, 115 (38%) received further treatment and were characterised by better performance status (p=0.028) and by receiving more injections of nivolumab (p=0.001). Global PN-OS and PN-PFS were 5.2 and 2.8 months, respectively. Drugs most frequently used after nivolumab were gemcitabine (23%), docetaxel (22%) and erlotinib (16%), with median PFS of 2.8, 2.7 and 2.0 months, respectively. Nivolumab produced similar efficacy as in phase III trials, although patients received nivolumab later and had worse performance status. 38% received treatment after nivolumab progression with efficacy comparable to historical second-line trials.

The effect of partial patients' adherence to antihypertensive drugs: scope for pharmacists' role in hypertension care.

In many individuals, blood pressure varies between clinic visits conducted days, weeks, or months apart. This visit-to-visit variability (VVV) of blood pressure has been recently related with an increased risk of coronary heart disease, stroke, and mortality, independently of mean blood pressure. As for other chronical diseases, patients' adherence to hypertensive therapies remains low and partial adherence to antihypertensive treatment may constitute a source of VVV, as suggested by recent studies. This data should lead to a new clinical approach for hypertension care, based on patients' real adherence to treatment. Therapeutic strategies should include patients' adherence. In this context, the role of community pharmacists for patients' follow-up of hypertension should be reinforced, as they represent efficient and easily accessible health professionals.

Program to Manage New and Expensive Drugs in Pediatrics: Profile of a New Drug Policy and a 12-Month Descriptive Study.

BACKGROUND: With growing financial pressure and the range of new and expensive drugs, hospital administrators, clinicians, and pharmacy directors are facing tough decisions on how to manage drug budgets. At a Canadian mother-child hospital, a policy for new and expensive drugs was developed, with the goal of managing their use and costs. OBJECTIVES: To describe the development and implementation of a policy for new and expensive drugs in a mother-child teaching hospital and to describe the profile of requests for these therapies over a 12-month period. METHODS: A brainstorming session was conducted with members of the pharmacy and therapeutics committee to define the criteria for new and expensive drugs at the study hospital and a new process to evaluate requests for these drugs. Over the 12-month period following implementation of the policy, all requests for new and expensive drugs were evaluated through collection and analysis of relevant data. RESULTS: The new drug policy was launched on October 1, 2014. Over the following 12-month period, a total of 58 requests for new and expensive drugs were discussed, but only 47 request forms were completed and signed by a physician and a clinical pharmacist. CONCLUSIONS: New and expensive drugs represent a challenge for clinicians and hospital stakeholders. This study illustrates the implementation of a new policy for these drugs in a mother-child teaching hospital over a 12-month period.

CONTEXTE: Les budgets de plus en plus serrés et la gamme de médicaments nouveaux ou coûteux placent les administrateurs, les cliniciens et les directeurs de pharmacie des hôpitaux devant des décisions difficiles en ce qui touche la gestion des dépenses en médicaments. On a mis au point, dans un hôpital canadien mère-enfant, une politique concernant les médicaments nouveaux ou coûteux avec pour objectif de gérer leur utilisation et leurs coûts. OBJECTIFS: Décrire l'élaboration et la mise en place d'une politique sur les médicaments nouveaux ou coûteux dans un hôpital universitaire mère-enfant et décrire le profil des demandes pour ces pharmacothérapies sur une période de 12 mois. MÉTHODES: Les membres du comité de pharmacologie ont procédé à une séance de remue-méninges dans le but de définir les critères pour les médicaments nouveaux ou coûteux dans l'hôpital à l'étude et un nouveau processus servant à évaluer les demandes pour ces médicaments. Au cours des 12 mois suivant la mise en place de la politique, toutes les demandes pour des médicaments nouveaux ou coûteux ont été évaluées à l'aide d'une cueillette et d'une analyse de données pertinentes. RÉSULTATS: La nouvelle politique sur les médicaments a été lancée le 1er octobre 2014. Au cours des 12 mois suivants, un total de 58 demandes pour des médicaments nouveaux ou coûteux ont été analysées, mais seulement 47 formulaires de demande ont été remplis et signés par un médecin et un pharmacien clinicien. CONCLUSIONS: Les médicaments nouveaux ou coûteux représentent un défi pour les cliniciens et les parties prenantes des hôpitaux. La présente étude décrit la mise en place d'une nouvelle politique pour ces médicaments dans un hôpital universitaire mère-enfant sur une période de 12 mois.

Retrospective Analysis of Emerging Drugs Use in a Quebec Women's and Children's University Hospital and Perspectives for Safe and Optimal Drug Use.

BACKGROUND: Only few medicines are licensed for children. The use of emerging drugs (unmarketed drug, off-label drug with poorly documented use, and/or costly drugs) might represent an essential alternative for pediatric patients. OBJECTIVES: The objective of the study was to assess emerging drug uses rate and profile in our women's and children's centre to support the implementation of an appropriate policy. METHODS: We identified retrospectively emerging drugs used between 2013-01-01 and 2014-02-28, using computerized pharmacist software extraction of drugs used. Conventional oncologic drugs were excluded. Retrospective analysis of medical charts for patients who received an emerging drug and literature review for each drug were performed to determine efficacy and safety endpoints. Median delays between first intention and final decision to use the drug and between final decision and first administration were calculated. Proportion of patients who experienced a positive evolution under treatment or a side effect possibly related to the drug was calculated. RESULTS: A total of 26 emerging drugs were identified (89 patients, 99 uses). Median treatment duration was 66 days [1-1435]. Median delay between first evocation and final decision to use the drug was 2 days [0-333] and 0 day [0-404] between final decision and first administration. 52/99 (53%) of patients experienced a positive evolution under treatment and 26/99 (26%) experienced a side effect possibly related to emerging drug use. CONCLUSIONS: This study allowed us to describe emerging drug uses in a women and children tertiary hospital. It led to the implementation of a local emerging drug use policy ensuring optimal and safe use of these drugs. There is a significant number of emerging drugs used in pediatric which shows positive improvement in 56% of patients.

Strategies for reduction in the duration of intravenous drug use: Interest of drug tracers as quality indicators to improve intravenous to oral switch.

RATIONALE, AIMS, AND OBJECTIVES: Intravenous (IV) to oral (PO) drug switch is a challenge for tertiary care institutions for several reasons: catheter-related infections, patient's pain and discomfort or higher costs, and overuse of IV drugs considered as an irrational use of medicines. The objective was to evaluate yearly acetaminophen and proton-pump inhibiters' (PPIs) IV/PO ratios from 2011 to 2015 and to determine their correlation with all drugs IV/PO ratios and their relevance as drug tracers. A secondary objective was to estimate costs savings associated with a IV to PO switch improvement. METHODS: Data on IV and PO consumptions and impact on costs were presented to physicians yearly, followed by the development of a computerized tool and pharmaceutical validation of prescriptions. Intravenous and PO drug consumptions were extracted yearly for all drugs, acetaminophen, and PPIs from 2011-01-01 to 2015-12-31. Acetaminophen and PPIs' IV/PO ratios were compared to IV/PO consumptions for all drugs. Costs savings associated with this switch were calculated yearly by multiplying the difference in average cost per dose by the total number of doses delivered (fixed purchase prices, euros) for both routes. RESULTS: All drugs IV/PO ratio decreased every year to achieve a 16.3% reduction between 2011 and 2015. Acetaminophen and PPIs also decreased respectively by 35.5% and 16.5%. Same tendency of decrease of ratios year by year was noted for all drugs, PPIs, and acetaminophen. Savings for both acetaminophen and PPIs IV/PO switch were over 98 000€ for 5 years. CONCLUSIONS: This study demonstrated that acetaminophen IV/PO ratio, easily produced in routine, was a relevant tracer to follow IV/PO switch improvement as it was correlated with all drugs IV/PO ratio. Direct cost savings associated with IV/PO switch improvements were consequent and illustrate well the impact of our approach on the efficiency of therapeutics' management.

Intravenous Immunoglobulin Therapy in Pediatric Narcolepsy: A Nonrandomized, Open-Label, Controlled, Longitudinal Observational Study.

STUDY OBJECTIVES: Previous case reports of intravenous immunoglobulins (IVIg) in pediatric narcolepsy have shown contradictory results. METHODS: This was a nonrandomized, open-label, controlled, longitudinal observational study of IVIg use in pediatric narcolepsy with retrospective data collection from medical files obtained from a single pediatric national reference center for the treatment of narcolepsy in France. Of 56 consecutively referred patients with narcolepsy, 24 received IVIg (3 infusions administered at 1-mo intervals) in addition to standard care (psychostimulants and/or anticataplectic agents), and 32 continued on standard care alone (controls). RESULTS: For two patients in each group, medical files were unavailable. Of the 22 IVIg patients, all had cerebrospinal fluid (CSF) hypocretin ≤ 110 pg/mL and were HLA-DQB1*06:02 positive. Of the 30 control patients, 29 were HLA-DQB1*06:02 positive and of those with available CSF measurements, all 12 had hypocretin ≤ 110 pg/mL. Compared with control patients, IVIg patients had shorter disease duration, shorter latency to sleep onset, and more had received H1N1 vaccination. Mean (standard deviation) follow-up length was 2.4 (1.1) y in the IVIg group and 3.9 (1.7) y in controls. In multivariate-adjusted linear mixed-effects analyses of change from baseline in Ullanlinna Narcolepsy Scale (UNS) scores, high baseline UNS, but not IVIg treatment, was associated with a reduction in narcolepsy symptoms. On time-to-event analysis, among patients with high baseline UNS scores, control patients achieved a UNS score < 14 (indicating remission) less rapidly than IVIg patients (adjusted hazard ratio 0.18; 95% confidence interval: 95% confidence interval: 0.03, 0.95; p = 0.043). Shorter or longer disease duration did not influence treatment response in any analysis. CONCLUSIONS: Overall, narcolepsy symptoms were not significantly reduced by IVIg. However, in patients with high baseline symptoms, a subset of IVIg-treated patients achieved remission more rapidly than control patients. COMMENTARY: A commentary on this article appears in this issue on page 363.

Can a two-hour lecture by a pharmacist improve the quality of prescriptions in a pediatric hospital? A retrospective cohort study.

BACKGROUND: A high rate of prescription errors exists in pediatric teaching hospitals, especially during initial training. OBJECTIVES: To determine the effectiveness of a two-hour lecture by a pharmacist on rates of prescription errors and quality of prescriptions. METHODS: A two-hour lecture led by a pharmacist was provided to 11 junior pediatric residents (PGY-1) as part of a one-month immersion program. A control group included 15 residents without the intervention. We reviewed charts to analyze the first 50 prescriptions of each resident. RESULTS: Data were collected from 1300 prescriptions involving 451 patients, 550 in the intervention group and 750 in the control group. The rate of prescription errors in the intervention group was 9.6% compared to 11.3% in the control group (p=0.32), affecting 106 patients. Statistically significant differences between both groups were prescriptions with unwritten doses (p=0.01) and errors involving overdosing (p=0.04). We identified many errors as well as issues surrounding quality of prescriptions. CONCLUSION: We found a 10.6% prescription error rate. This two-hour lecture seems insufficient to reduce prescription errors among junior pediatric residents. This study highlights the most frequent types of errors and prescription quality issues that should be targeted by future educational interventions.

Unlicensed and off-label drug use in paediatrics in a mother-child tertiary care hospital.

OBJECTIVE: To assess unlicensed and off-label drug use in a tertiary care paediatric hospital in Canada on a single day. METHODS: A cross-sectional study in a tertiary care paediatric hospital was conducted on one randomly selected day. Active prescriptions for children <18 years of age were analyzed. Unlicensed drug use was defined as the use of nonmarketed drugs in Canada or marketed drugs with pharmacy compounding. Off-label drug use was defined as the use of marketed drugs in Canada for an unapproved age group, indication, dosing, frequency and/or route of administration. Off-label drug uses associated with strong scientific support were analyzed using the Pediatric Dosage Handbook, 14th edition and Micromedex(®) Solutions. Number and proportion of unlicensed and off-label drug uses, and off-label drug uses associated with strong scientific support were measured. RESULTS: A total of 2145 drug prescriptions were extracted on March 5, 2014, for inclusion in the present study. The unlicensed drug use rate was 8.3% (57 unlicensed drug products; 75 nonmarketed drug prescriptions and 103 pharmacy compounding prescriptions) and the off-label drug use rate was 38.2% (161 substances; 819 prescriptions). Reasons for off-label drug use included unapproved age group (n=436 [53.2%]), dosing (n=226 [27.6%]), frequency (n=206 [25.2%]), indication (n=45 [5.5%]) and administration route (n=46 [5.6%]). Of the off-label drug prescriptions, 39.3% (n=322) were associated with strong scientific support. CONCLUSIONS: On a randomly selected day, 8.3% of prescriptions were unlicensed and 38.2% were off-label for children hospitalized at the authors' institution. Of off-label prescriptions, only 39.3% were associated with strong scientific support.

OBJECTIF: Évaluer l'emploi des médicaments non brevetés et utilisés dans une indication non autorisée en une seule journée dans un hôpital pédiatrique de soins tertiaires du Canada. MÉTHODOLOGIE: Des chercheurs ont réalisé une étude transversale dans un hôpital pédiatrique de soins tertiaires au cours d'une journée sélectionnée au hasard. Ils ont analysé les prescriptions actives des enfants de moins de 18 ans. Les médicaments non brevetés désignaient les médicaments non commercialisés au Canada ou commercialisés, mais préparés en pharmacie. Les médicaments utilisés dans une indication non autorisée (MUINA) désignaient les médicaments commercialisés au Canada utilisés dans un groupe d'âge, une indication, une dose, une fréquence ou une voie d'administration non approuvé. Les chercheurs ont analysé les MUINA associés à un solide appui scientifique au moyen du Pediatric Dosage Handbook, 14th edition et de Micromedex® Solutions. Ils ont calculé le nombre et la proportion de médicaments non brevetés et de MUINA prescrits, ainsi que celui des MUINA liés à un solide appui scientifique. RÉSULTATS: Le 5 mars 2014, les chercheurs ont extrait 2 145 prescriptions de médicaments qu'ils ont incluses dans la présente étude. Le taux d'utilisation de médicaments non brevetés s'élevait à 8,3 % (57 produits non brevetés, 75 médicaments non commercialisés et 103 préparations pharmaceutiques) et celui de MUINA, à 38,2 % (161 substances; 819 prescriptions). Les raisons pour lesquelles les prescriptions étaient considérées comme des MUINA étaient un groupe d'âge (n=436 [53,2 %]), une dose (n=226 [27,6 %]), une fréquence (n=206 [25,2 %]), une indication (n=45 [5,5 %]) ou une voie d'administration (n=46 [5,6 %]) non approuvé. Parmi les MUINA, 39,3 % (n=322) étaient liés à un solide appui scientifique. CONCLUSIONS: Au cours d'une journée sélectionnée au hasard, 8,3 % des prescriptions n'étaient pas brevetées et 38,2 % étaient utilisées dans une indication non autorisée chez les enfants hospitalisés dans l'établissement des auteurs. Parmi les MUINA, seulement 39,3 % étaient liés à un solide appui scientifique.

Unlicensed and Off-Label Drug Use in Children Before and After Pediatric Governmental Initiatives.

OBJECTIVES: Governmental agencies (US Food and Drug Administration and European Medicines Agency) implemented initiatives to improve pediatric clinical research, starting in 1997 and 2007, respectively. The aim of this review was to quantify the unlicensed and off-label drug uses in children before and after these implementations. METHODS: Literature review of unlicensed and off-label drug uses was performed on PubMed and Google-Scholar from 1985 to 2014. Relevant titles/abstracts were reviewed, and articles were included if evaluating unlicensed/off-label drug uses, with a clear description of health care setting and studied population. Included articles were divided into 3 groups: studies conducted in United States (before/after 2007), in Europe (before/after 2007), and in other countries. RESULTS: Of the 48 articles reviewed, 27 were included. Before implementation of pediatric initiatives, global unlicensed drug use rate in Europe was found to be 0.2% to 36% for inpatients and 0.3% to 16.6% for outpatients. After implementation, it marginally decreased to 11.4% and 1.26% to 6.7%, respectively. Concerning off-label drug use rates, it was found to be 18% to 66% for inpatients and 10.5% to 37.5% for outpatients before the implementation. After implementation, it decreased marginally to 33.2% to 46.5% and to 3.3% to 13.5%, respectively. In other countries, unlicensed and off-label drug use rates were found to be, respectively, 8% to 27.3% and 11% to 47%. CONCLUSIONS: Governmental initiatives to improve clinical research conducted in children seem to have had a marginal effect to decrease the unlicensed and off-label drug uses prevalence in Europe.