[Translation and adaptation of a tool prescribing errors related to computerized physician order entry coding to the French hospital background]. / Traduction et adaptation au contexte hospitalier français d'un outil de codification des erreurs de prescription liées aux logiciels.

Prescribing errors related to computerized physician order entry are current and may have serious consequences for patients. They can be detected by pharmacists during prescriptions analysis and lead to pharmacist's interventions. In France, few monocentric studies have studied Pharmacist Interventions triggered by prescribing errors identified as System-Related Errors (PISREs) in French hospitals. However, their respective analysis method prevent any comparison between computerized physician order entry systems in order to identify the safest and rule out the most dangerous. A computerized physician prescribing error related to the software is characterized by its causes, consequences and mechanism of occurrence. US researchers have developed and validated a tool to classify and illustrate these three characteristics. The objectives of this article are to present this tool, to propose a French adaptation and to describe the perspectives analyze and understand prescription errors related to computerized physician order entry based on data of Act-IP©. The adaptation was performed using PISREs extracted from the Act-IP© observatory of the French Society of Clinical Pharmacy. Each item of the codification is illustrated with an example of PI. We are considering a training plan in order to allow wide use of this tool. Once adopted this tool, the next step will be to organize a prospective multicenter study including as many computerized prescription order entry systems as possible. The aim of this study will be identifying the safest systems. Consequently, it will then be possible to have arguments to qualify the most dangerous and thus propose their withdrawal from the market.

Immunogenicity of Rituximab biosimilar GP2013 in chronic inflammatory rheumatic disorders in daily clinical practice.

OBJECTIVE: To study in daily practice the risk of immunogenicity of patients treated with the biosimilar rituximab (RTX) GP2013 used for chronic inflammatory rheumatic disorders. METHODS: A prospective monocentric routine care study was carried out between September 2018 and May 2021, including consecutive patients treated with the biosimilar RTX GP2013. Biosamples were taken before each infusion to quantify anti-RTX antibodies (ADAbs) and serum RTX trough levels by ELISA (Lisa Tracker Duo Rituximab, LTR005, Theradiag). RESULTS: 168 GP2013-treated patients were included (129 who switched from originator RTX and 39 originator RTX naïve). The analysis of 602 samples identified 15 patients (8%) with positive ADAbs including 6 and 9 with transient and persistent ADAbs, respectively. The switch from originator RTX to GP2013 did not increase the risk of immunogenicity, with an incidence rate of 0.8 for 100 patient years. The frequency of persistent ADAs was higher in non-RA patients (5/56, 9% vs. 4/112, 3.5%). Patients with positive persistent ADAbs were more frequently non-caucasian (7/9, 78%, vs. 56/159, 35%, p<0.01) and all had detectable circulating B cells (vs. 40% in ADAb-negative patients, P<0.001). ADAb positivity was not associated with disease activity or RTX discontinuation but patients with ADAb titers >100 ng/mL experienced reduced treatment efficacy or severe infusion-related reaction. CONCLUSION: Within the study duration, the immunogenicity of GP2013 is a rare event affecting the pharmacodynamics of RTX. Although development of ADAbs had no impact on treatment discontinuation, possible harmful consequences may be observed in patients with high antibody levels.

Impact of a clinical pharmacist in a multidisciplinary consultation on the switch to a biosimilar for inflammatory rheumatic diseases.

OBJECTIVE: Despite several studies proving the efficacy and safety of biosimilars compared with original drugs, switching to a biosimilar remains challenging when the decision is at the discretion of physicians with mandatory consent from patients. Educating patients about biosimilars seems important to increase the prescription rate of biosimilars. This study aimed to evaluate the impact of a clinical pharmacist consultation on the switch to and retention rate of a biosimilar for patients with inflammatory rheumatic diseases. METHODS: This retrospective study compared 2 groups of adult patients receiving (intervention) or not (control) a consultation with a pharmacist right before the rheumatologist consultation. The primary outcome was the frequency of patients who switched to a biosimilar at the end of the rheumatologist visit. RESULTS: We analysed 141 patients (50% women, 50±15years old, on original adalimumab (62%) or etanercept (38%)) who had never used biosimilars: 85 in the intervention group and 56 in the control group. The switch rate to a biosimilar significantly differed between the groups: 69.4% versus 41.1% in the intervention group versus the control group respectively (P<0.01). After a 1-year follow-up period, 72.5% versus 81.3% of patients who switched were still on biosimilar in the intervention versus control group respectively. CONCLUSIONS: This study highlights the positive impact of a pharmacist consultation before the physician's one on switching to a biosimilar, but more studies are needed to assess the impact of this pharmacist consultation on preventing the nocebo effect and therefore on improving the retention rate of biosimilars.

Characteristics of pharmacist's interventions triggered by prescribing errors related to computerised physician order entry in French hospitals: a cross-sectional observational study.

OBJECTIVES: Computerised physician order entry (CPOE) systems facilitate the review of medication orders by pharmacists. Reports have emerged that show conception flaws or the misuse of CPOE systems generate prescribing errors. We aimed to characterise pharmacist interventions (PIs) triggered by prescribing errors identified as system-related errors (PISREs) in French hospitals. DESIGN: This was a cross-sectional observational study based on PIs prospectively documented in the Act-IP observatory database from January 2014 to December 2018. SETTING: PISREs from 319 French computerised healthcare facilities were analysed. PARTICIPANTS: Among the 319 French hospitals, 232 (72.7%) performed SRE interventions, involving 652 (51%) pharmacists. RESULTS: Among the 331 678 PIs recorded, 27 058 were qualified as due to SREs (8.2%). The main drug-related problems associated with PISREs were supratherapeutic (27.5%) and subtherapeutic dosage (17.2%), non-conformity with guidelines/contraindications (22.4%) and improper administration (17.9%). The PI prescriber acceptation rate was 78.9% for SREs vs 67.6% for other types of errors. The PISRE ratio was estimated relative to the total number of PIs. Concerning the certification status of CPOE systems, the PISRE ratio was 9.4% for non-certified systems vs 5.5% for certified systems (p<0.001). The PISRE ratio for senior pharmacists was 9.2% and that for pharmacy residents 5.4% (p<0.001). Concerning prescriptions made by graduate prescribers and those made by residents, the PISRE ratio was 8.4% and 7.8%, respectively (p<0.001). CONCLUSION: Computer-related prescribing errors are common. The PI acceptance rate by prescribers was higher than that observed for PIs that were not CPOE related. This suggests that physicians consider the potential clinical consequences of SREs for patients to be more frequently serious than interventions unrelated to CPOE. CPOE medication review requires continual pharmacist diligence to catch these errors. The significantly lower PISRE ratio for certified software should prompt patient safety agencies to undertake studies to identify the safest software and discard software that is potentially dangerous.

CLEO: a multidimensional tool to assess clinical, economic and organisational impacts of pharmacists' interventions.

OBJECTIVES: Clinical pharmacists' interventions (PIs) are an important element in ensuring good pharmaceutical care. We aimed to develop and validate a comprehensive multidimensional tool for assessing the potential impact of PIs for daily practice of medication review. METHODS: Experts of the French Society of Clinical Pharmacy (SFPC) developed the CLinical, Economic and Organisational (CLEO) tool, consisting of three independent dimensions concerning clinical, economic and organisational impact. They were asked to analyse 30 scenarios of PIs, and re-rated 10 PIs with a washout of 1 month (internal validation). Then, seven external experts not involved in the development of the tool rated 60 scenarios collected when using the CLEO in daily practice. Inter- and intra-rater reliabilities were determined by calculation of the intra-class correlation (ICCA,1). Users' satisfaction and acceptability of the tool were assessed on a 7-level Likert scale with a 17-item questionnaire. RESULTS: For internal reliability, the inter-rater reliability for the CLEO tool was good for clinical dimensions (ICCA,1=0.693), excellent for economic dimensions (ICCA,1=0.815) and fair for organisational dimensions (ICCA,1=0.421); and the intra-rater reliability was good for clinical dimensions (ICCA,1=0.822), excellent for economic dimensions (ICCA,1=0.918) and good for organisational dimensions (ICCA,1=0.738). For external reliability, the inter-rater reliability was good for clinical dimensions (ICCA,1=0.649), excellent for economic dimensions (ICCA,1=0.814) and fair for organisational dimensions (ICCA,1=0.500). CLEO was viewed as relevant (mean±SD 4.93±1.27), acceptable (4.81±1.78), practicable (5.56±1.45) and precise (5.38±1.47). CONCLUSIONS: CLEO is a comprehensive tool assessing clinical, economic and organisational impacts of PIs which has been developed, validated and was reliable and feasible for use in routine clinical practice.

Impact of a pharmacist-led programme on biologics knowledge and adherence in patients with spondyloarthritis.

OBJECTIVES: In spondyloarthritis (SpA), improving patients' knowledge on their biologics is a key factor to enhance adherence. The information given to the patient has to ensure the acquisition of safety skills regarding their treatment. The aims of this trial were to evaluate the impact of a pharmacist's educational interview on knowledge and adherence to biologics in these patients. METHODS: Consecutive adult patients with well-controlled axial SpA, stable on biologics were enrolled in a randomised, controlled, single-centre, open-label, 6-month trial. A pharmacist's educational interview provided information on biologics management at baseline in the intervention group and at month 6 in the control group. The changes in a weighted knowledge score concerning the management of biologics and the change in the Medication Possession Ratio (MPR) at month-6 were primary outcomes. The changes in disease activity (BASDAI) and patients' satisfaction regarding the pharmacists' interview were secondary outcomes. RESULTS: Patients' characteristics at baseline were comparable among the 89 included patients (46 in the intervention group, 43 in the control group). The patient's knowledge score concerning biologics management improved at a greater magnitude in the educational group (+11.0±11.5 vs. +3.0 ±10.6 in the intervention versus the control group, respectively, p<0.0001). There was also a trend in a better adherence (+2.2±13.9 vs. -0.6±18.9 in the intervention versus the control group, respectively, p=0.691). The disease activity remained stable in both groups. CONCLUSIONS: This study is strongly in favour of the benefit of a pharmacist's educational interview in the management of patients with axial SpA.

Effects of successive switches to different biosimilars infliximab on immunogenicity in chronic inflammatory diseases in daily clinical practice.

OBJECTIVE: To evaluatre the risk of immunogenicity in patients with chronic inflammatory diseases who experienced successive non-medical swiches to different biosimilars infliximab. PATIENTS AND METHODS: Observational study over a 3-year observation period assessing the risk of immunogenicity in i) patients in maintenance therapy with innovator infliximab who were successively switched to CT-P13, then to SB2 (cohort-1) and ii) biologic-naive patients initiated with CT-P13 before being switched to SB2 (cohort-2). A propotion meta-analysis was also performed, integrating our results to 16 additional studies. RESULTS: Cohort-1 included 265 patients who switched to CT-P13, and 140 patients were subsequently switched to SB2. Among the 235 anti-drug antibody (ADA)-free patients at baseline, 20 patients (8.5%) developed ADA over the 3-year observation period (rate of 3 for 100 patient years). Cohort-2 included 44 patients, of whom 29 subsequently switched to SB2. A total of 11 patients (25%) developed ADA within 3 years (rate of 14 for 100 patients years). We found no influence of the number of biosimilars infliximab received on ADA deveopment in both cohorts. The risk of treatment discontinuation was significantly higher in patients with positive ADA in both cohorts. The meta-analysis including our data exposed an incidence of immunogenicity of 4.7% (95% CI 3.5-6.1%) after the switch from innovator infliximab to biosimilar infliximab and 21.1% (95% CI 13.1-30.3%) in patients initiating biosimilar infliximab. CONCLUSION: Immunogenicity was not favored by successive non-medical switches to biosimilars infliximab in our study, but was associated with treatment discontinuation.

Systematic switch from innovator infliximab to biosimilar infliximab in inflammatory chronic diseases in daily clinical practice: The experience of Cochin University Hospital, Paris, France.

OBJECTIVE: To investigate effectiveness of systematic switching treatment from innovator infliximab to biosimilar infliximab, and its associated factors. METHODS: In this prospective observational study, all adult patients receiving maintenance therapy with innovator infliximab in Cochin University Hospital were systematically switched to biosimilar infliximab. Effectiveness was assessed by the retention rate of biosimilar infliximab at the time of the third infusion. Sensitivity analyses for effectiveness included changes of disease activity parameters and infliximab trough levels between baseline and the last visit as well as the occurrence of adverse events leading to drug discontinuation. Factors associated with biosimilar infliximab discontinuation at the last visit were explored. RESULTS: A total of 260 patients fulfilled the inclusion criteria, including 31 rheumatoid arthritis (RA), 131 axial spondyloarthritis (axSpA) and 64 inflammatory bowel diseases. The retention rate was 85% (221/260 patients) at the time of the third biosimilar infusion. Between baseline and the last visit (mean follow-up of 34 weeks), 59 patients (23%) discontinued biosimilar infliximab, mainly due to experienced inefficacy (n = 47, 80%). No clinical or biological factors were associated with biosimilar discontinuation. No serious adverse events occurred. No change in objective disease activity parameters or infliximab trough levels was detected. However, a significant increase of BASDAI (2.94 ± 2.20 vs. 3.18 ± 2.21, P = 0.046, before vs. after switch, respectively) was observed in patients with axSpA. Innovator infliximab was re-established in 47/59 patients (80%). CONCLUSION: No changes in drug trough levels or objective parameters were observed after the systematic switch to biosimilar infliximab in a real clinical practice setting. Only changes in patient-reported outcomes were observed, suggesting attribution effects rather than pharmacological differences.

Tools for Assessing Potential Significance of Pharmacist Interventions: A Systematic Review.

INTRODUCTION: Assessing the significance of pharmacist interventions (PIs) is essential to demonstrate the added value of pharmacists. Methods and tools for assessing the potential significance of PIs are diverse and their properties are questionable. OBJECTIVES: We aimed to systematically review the tools available to assess the potential significance of PIs. METHODS: We conducted a systematic search for English- or French-language publications from 1986 to 2013 in PubMed, PsycINFO, PASCAL, and CINAHL. Studies were screened by two independent reviewers based on inclusion/exclusion criteria and were abstracted for content, structure of tools, and validation process. RESULTS: Of 873 citations screened, 82 distinct tools were identified from 133 studies. While clinical aspects were often defined quite clearly, terminology regarding humanistic, economic, and process-related aspects of PIs was omitted, incomplete, or ambiguous in most tools. The probabilities of consequences of PIs/drug-related problems were evaluated in 20/82 tools. Few tools simultaneously measured economic, clinical, humanistic, and process-related variables. Structure of the tools varied from an implicit, mono-dimensional tool to an explicit, multi-dimensional algorithm. Validation processes were diverse in terms of quantification and number of raters, rating method, and psychometric parameters. Of 133 identified studies, there was limited evidence of validity (8/133, 6.0%), inter-rater reliability (49/133, 36.8%), and intra-rater reliability (2/133, 1.5%). CONCLUSIONS: The majority of tools focused primarily on assessing clinical aspects and failed to detect comprehensive impacts. The heterogeneity of tools and assessment processes hindered our ability to synthesize the results of evaluations. Limited results for their validity and reliability cast doubt on the credibility of this methodology for justification of the value of PIs. Recommendations for development of tools with optimal theoretical, pragmatic, and psychometric properties are proposed.

Assessment of clinical pharmacists' interventions in French hospitals: results of a multicenter study.

BACKGROUND: The development of clinical pharmacy activities in most European countries is underway; however, data on these activities are still poorly reported. Multicenter studies are necessary to standardize and demonstrate the value of clinical pharmacy activities in these countries. OBJECTIVE: To document clinical pharmacists' daily routine interventions (PIs) to identify trends of intervention, drugs, and situations most frequently associated with drug-related problems (DRPs) and to estimate physicians' acceptance of PI. METHODS: A prospective study of PIs was conducted in 6 French hospitals. The sample consisted of 300 randomized PIs per hospital, recorded during the medication order validation process when a DRP was identified. We recorded patients' demographic characteristics, drugs involved, wards, DRP description, pharmacists' recommendations, and whether or not the recommendations were accepted by the physicians. RESULTS: A total of 38,626 medication orders were analyzed by 28 clinical pharmacists, leading to 1800 PIs (4.66 PIs per 100 medication orders). Of the 1800 PIs, 25.9% targeted psychotropic drugs, 15.9% targeted antithrombotic drugs, 15.5% targeted digestive and metabolic drugs, and 15.0% targeted cardiovascular drugs. The most commonly identified DRPs were nonconformity to guidelines or contraindication (21.3%), followed by improper administration (20.6%), supratherapeutic dose (19.2%), and drug interaction (12.6%). Nearly half (42.2%) of the pharmacists' recommendations were related to drug choice (drug switch 22.2%, drug discontinuation 16.3%, addition of a new drug 3.7%) followed by dose adjustment (23.8%), optimization of administration (21.9%; change of administration route 10.3%, administration modalities 11.6%), and need for drug monitoring (12.2%). The rate of physicians' acceptance was 73.4% (15.3% refusals, 11.3% not assessable). CONCLUSIONS: In French hospitals, pharmacists contribute to preventing DRPs during medication order validation. This study suggests that a few types of drugs and errors constitute a substantial proportion of PIs. Knowledge of the most frequent DRPs could significantly increase the efficiency of clinical PIs.

[Factors to consider in managing drug interactions in clinical practice]. / Facteurs à prendre en considération pour la gestion des interactions médicamenteuses en pratique clinique.

The huge number of drug interactions makes it impossible to memorize them all. Detecting them and preventing adverse effects requires the use of reference works or databases. There are numerous discordances between the so-called "reference" books and databases. Nonexistent and unconfirmed interactions are published. The wording of the "drug interactions" section of the summary of product characteristics (SCP) sometimes sheds very little light on the risks involved. The delay by AFSSAPS in updating its drug interaction thesaurus may present problems in clinical practice. It is essential to know the limitations of the computerized systems for detecting and reporting drug interactions.

[Pharmacists' interventions before and after prescription computerization in an internal medicine department]. / Interventions pharmaceutiques avant et après informatisation de la prescription dans un service de médecine interne.

OBJECTIVE: To compare and analyze the number and types of pharmacist interventions when prescriptions were handwritten (period 1) or entered on 2 different computerized physician order entry systems (CPOE): Phedra (period 2) and Actipidos (period 3). METHODS: This study took place over 54 weeks (18 weeks for each period) in a 46-bed internal medicine department. Pharmacist interventions were categorized as either simple substitution to an available drug or "complex" interventions such as changing dosage (D), changing drug (M), stopping or substituting in cases of contraindication or overdosing (CO), new medication (N) and identifying errors due to CPOE (C). RESULTS: The study analyzed 12420 prescriptions that led to 1420 interventions. There were 720 substitutions and 98 interventions in period 1, 40 and 238 in period 2, and 97 and 227 in period 3. The percentage of interventions by types for each of the three periods, respectively were D: 52, 37 and 34%; M: 21, 22 and 35%; CO: 16, 12 and 16%; N: 11, 5 and 2%; and C: 0, 24 and 13%. The errors due to CPOE were mainly wrong dosage units and duplicate orders. DISCUSSION: Introduction of CPOE drastically reduced the number of simple substitutions and significantly increased the complex interventions. CPOE introduced new risks of serious errors. CONCLUSION: In our study, CPOE did not prevent medication errors and led to new types of errors. The presence and intervention of clinical pharmacists remained necessary.

Validation of an instrument for the documentation of clinical pharmacists' interventions.

OBJECTIVE: To validate an instrument for documentation of clinical pharmacy interventions in French speaking hospitals in France and outside of France. METHOD: A panel of 12 French speaking clinical pharmacists (six from France; six from French speaking countries) was asked to analyse a set of 60 pharmacist's interventions on drug prescription. They used a form including (1) the identification of the drug related problems (DRPs) (10 items), (2) the pharmacist's intervention (7 items). We assessed the level of agreement between the 12 pharmacists on the test DRPs and on the interventions. MAIN OUTCOME MEASURES: Kappa coefficient of concordance was used to assess the level of agreement between experts for DRPs and interventions. We also assessed the userfriendliness of the instrument using Likert scales. RESULTS: The level of concordance observed in the validation was 0.76 for DRPs and 0.89 for the type of intervention. Eleven experts out of 12 were "very satisfied" or "satisfied" and one "not satisfied" with the tool. Ten out of the 12 experts were ready to use it in daily practise. CONCLUSION: The present instrument proposed by the French Society of Clinical Pharmacy (SFPC) is the first coding system for pharmacist's interventions with a French interface. The validation process using a standard statistical methodology helps support the external validity of our tool. The level of concordance between users can be considered as satisfactory, allowing the use of the tool in daily clinical pharmacy practise. To enhance the diffusion of the instrument and of the general process of routine documentation of interventions, a spreadsheet is provided on the French Society of Clinical Pharmacy website.

Intravenous to oral conversion of fluoroquinolones: knowledge versus clinical practice patterns.

STUDY OBJECTIVES: To assess the knowledge of prescribers regarding intravenous to oral conversions of fluoroquinolones, the frequency and time until conversion, and to compare prescriber knowledge with the data collected concerning the reasons stated for continuation of intravenous fluoroquinolones. DESIGN: Prospective chart review and questionnaire. SETTING: Large teaching hospital in Paris, France. PATIENTS: Fifty-one males and females. INTERVENTION: Data were collected on in-patients receiving intravenous fluoroquinolone for at least three days and hospitalized in one of six in-patient units. Patients receiving intravenous fluoroquinolone for less than three days were excluded. A questionnaire to assess the awareness of a potential conversion was distributed to those practitioners who had patients reviewed during the data-collection phase. MAIN RESULTS: The questionnaire revealed the ten most common reasons for continuing intravenous administration for more than three days. However, the physicians agreed that most patients should be converted as soon as possible. Practice patterns differed, with only 17 of 51 patients actually converted to oral therapy. CONCLUSION: In theory, the clinicians were aware of when to perform the conversion. However, in practice, the frequency of conversion was lower than optimum. Changes in clinical practice are needed to decrease the costs of intravenous therapy, without jeopardizing quality of care.