Evaluation of a method for drug-related problems identification and classification in hospital setting: applicability and reliability.

Background Prescription evaluation by pharmacists has potential to improve pharmacotherapy management. It requires the use of robust methods to identify drug-related problems (DRP), which are important issues in pharmacotherapy. Objective To evaluate the applicability and reliability of Grupo de Investigação em Cuidados Farmacêuticos (GIGUF) method for prescription analysis, identification and classification of drug-related problems in inpatients prescriptions. Setting Department of Medical Clinic of a tertiary and teaching Brazilian hospital. Method An observational and retrospective study of identification and classification of drug-related problems. GIGUF method was used to evaluate prescriptions of hematological patients hospitalized between August and October 2015. The problems were categorized using GICUF-method classification. Three pharmacists performed inter-rater agreement analysis of the method using Kappa. Differences in prevalence of DRP was calculated by age, sex, pharmacotherapy complexity, length of stay and number of drugs. Main outcome measure (a) frequency and characteristics and (b) inter-rater agreement in identification and classification of the drug-related problems. Results A total of 211 problems were identified and 'inadequate dosing' was the most common problem. There was an association between the occurence of a drug-reklated problem and complexity of pharmacotherapy (p = 0.001) and number of drugs used (p = 0.010). The overall inter-rater agreement was moderate (k = 0.44 IC 95% 0.34-0.55) and the problem 'not suitable drug' (k = 0.55 IC 95% 0.44-0.66) had greater inter-rater agreement. Conclusion The method "Evaluation Drug Use Process" was useful for prescription analysis since it made the identification and classification of DRPs possible. The method demonstrated a moderate inter-rater agreement, and can contribute to pharmacotherapy management by hospital pharmacists.

Pharmacovigilance workflow in Europe and Italy and pharmacovigilance terminology.

The terminology used in pharmacovigilance can cause confusion, because there are similar terms that describe different phenomena (e.g. adverse reactions, adverse drug reactions, and side effects). Incorrect use of terminology can have negative effects on the reporting of adverse drug reactions and on the interpretation of these reports. To explain the most common terms used in pharmacovigilance, this article first describes the pharmacovigilance workflow process in the European Union and, as an example, in Italy. Then, the article reviews common pharmacovigilance terms.

Evaluation of different recall periods for the US National Cancer Institute's PRO-CTCAE.

AIMS: The US National Cancer Institute recently developed the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events). PRO-CTCAE is a library of questions for clinical trial participants to self-report symptomatic adverse events (e.g. nausea). The objective of this study is to inform evidence-based selection of a recall period when PRO-CTCAE is included in a trial. We evaluated differences between 1-, 2-, 3-, and 4-week recall periods, using daily reporting as the reference. METHODS: English-speaking patients with cancer receiving chemotherapy and/or radiotherapy were enrolled at four US cancer centers and affiliated community clinics. Participants completed 27 PRO-CTCAE items electronically daily for 28 days, and then weekly over 4 weeks, using 1-, 2-, 3-, and 4-week recall periods. For each recall period, mean differences, effect sizes, and intraclass correlation coefficients were calculated to evaluate agreement between the maximum of daily ratings and the corresponding ratings obtained using longer recall periods (e.g. maximum of daily scores over 7 days vs 1-week recall). Analyses were repeated using the average of daily scores within each recall period rather than the maximum of daily scores. RESULTS: A total of 127 subjects completed questionnaires (57% male; median age: 57). The median of the 27 mean differences in scores on the PRO-CTCAE 5-point response scale comparing the maximum daily versus the longer recall period (and corresponding effect size) was -0.20 (-0.20) for 1-week recall, -0.36 (-0.31) for 2-week recall, -0.45 (-0.39) for 3-week recall, and -0.47 (-0.40) for 4-week recall. The median intraclass correlation across 27 items between the maximum of daily ratings and the corresponding longer recall ratings for 1-week recall was 0.70 (range: 0.54-0.82), for 2-week recall was 0.74 (range: 0.58-0.83), for 3-week recall was 0.72 (range: 0.61-0.84), and for 4-week recall was 0.72 (range: 0.64-0.86). Similar results were observed for all analyses using the average of daily scores rather than the maximum of daily scores. CONCLUSION: A 1-week recall corresponds best to daily reporting. Although intraclass correlations remain stable over time, there are small but progressively larger differences between daily and longer recall periods at 2, 3, and 4 weeks, respectively. The preferred recall period for the PRO-CTCAE is the past 7 days, although investigators may opt for recall periods of 2, 3, or 4 weeks with an understanding that there may be some information loss.

Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

BACKGROUND: PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. METHODS: Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0-4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. RESULTS: 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55-0.90); tablet vs paper: 0.81 (0.62-0.96); IVRS vs paper: 0.78 (0.60-0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = -0.04 [-0.16-0.22]; tablet vs paper = -0.02 [-0.11-0.14]; IVRS vs paper = 0.02 [-0.07-0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/-0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported "no problems" responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. CONCLUSIONS: Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. TRIAL REGISTRATION: NCT Clinicaltrials.gov identifier: NCT02158637.

Validity and Reliability of the US National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

IMPORTANCE: To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). OBJECTIVE: To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items. DESIGN, SETTING, AND PARTICIPANTS: A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit. MAIN OUTCOMES AND MEASURES: Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30). RESULTS: A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median [range] intraclass correlation coefficient, 0.76 [0.53-.96]). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were statistically significant for 27 prespecified items (median [range] r=0.43 [0.10-.56]; all P≤.006). CONCLUSIONS AND RELEVANCE: Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials.

Trivalent Influenza Vaccine Adverse Event Analysis Based On MedDRA System Organ Classes Using VAERS Data.

We studied serious reports following influnza vaccine from VAERS database in year 2011. Our statistical analyses revealed differences of reactions among different age groups and between genders. The results may lead to additional studies to uncover factors contributing to the individual differences in susceptibility to influenza infection.

Application of drug-related problem (DRP) classification systems: a review of the literature.

BACKGROUND: For over 20 years, researchers wanting to record, discuss and compare drug-related problems (DRPs) have had the task of choosing between a multiplicity of classification systems offering a variable number of categories identified as causes of DRPs and DRPs. OBJECTIVE: To characterise studies which have reported DRPs through the use of a DRP classification system to determine types of classification systems chosen, factors influencing their choice, and methodological issues that may have affected their application. METHOD: A systematic search of MEDLINE, CINAHL, International Pharmaceutical Abstracts (Ovid), EMBASE and PubMed was performed. All English language studies reporting DRPs through the use of a classification system published between January 2000 and July 2013 were reviewed, with no limitation on the type of study. RESULTS: Of 2,774 articles screened, 268 met our inclusion criteria. We identified the use of 20 different types of DRP classification systems. Three quarters of studies modified an existing classification system or developed their own. Few studies stated reasons for choice of system. We identified issues such as variability in skills of data collectors, selective choice of patients and missing data, affecting application of classification systems and limiting quality, analysis and comparison of studies. CONCLUSION: There appeared to be no consensus on preference or structure of classification systems. Future studies should consider addressing or acknowledging the methodological issues identified. Through identification and discussion of these problems, recommendations for future studies and for practice have been made.

[Which definition and taxonomy of incident to use for a French reporting system in primary care settings?]. / Quelle définition et taxonomie utiliser pour un recueil d'événements indésirables associés aux soins primaires en France?

BACKGROUND: There is no widely accepted definition of incident for primary care doctors in France and no taxonomic classification system for epidemiological use. In preparation for a future epidemiological study on primary care incidents in France (the ESPRIT study), this work was designed to identify the definitions and taxonomic classifications used internationally along with the usual methods and results in terms of frequency in the literature. The goal was to determine a French definition and taxonomy. DESIGN: Systematic review of the literature and consensus methods. METHOD: An exhaustive search of epidemiological surveys was performed. A structured grid was used. After having identified the definitions used in the literature, a definition was chosen using the focus groups method. Taxonomies identified in the literature were classified by relationship, architecture, code number, and number of studies published. Subsequently, a consensus among experts, who independently tested these taxonomies on six incidents, was reached for choosing the most appropriate for epidemiological data collection (little information on a large number of cases). RESULTS: Twenty-four papers reporting 17 studies were selected among 139 articles. Five definitions and eight taxonomies were found. The chosen definition of incident was based on the WHO definition "A patient safety incident is an event or circumstance that could have resulted, or did result, in harm to a patient, and whose wish it is not repeated again". The test of incidents resulted in the choice of the TAPS version of the International Taxonomy of Medical Error in Primary Care for a reproducible and internationally recognized codification and the tempos method for its current use in French general practice. DISCUSSION: The definitions, taxonomies, data collection characteristics and frequency of incidents results in the international literature on incidents in primary care are key components for the preparation of an epidemiological survey on incidents in primary care.

The Adverse Drug Event Collaborative: a joint venture to measure medication-related patient harm.

AIM: To measure the extent of patient harm caused by medications (rate of Adverse Drug Events) in three DHBs, using a standardised trigger tool method. METHODS: Counties Manukau, Capital and Coast and Canterbury DHBs decided to work collaboratively to implement the ADE Trigger Tool (TT). Definitions of ADE were agreed on and triggers refined. A random sample of closed charts (from March 2010 to February 2011) was obtained excluding patients who were admitted for <48 hours, children under the age of 18 and psychiatric admissions. In each DHB trained reviewers scanned these in a structured way to identify any of the 19 triggers. If triggers were identified, a more detailed, though time-limited review of the chart was done to determine whether an ADE had occurred. The severity of patient harm was categorised using the National Coordinating Council for Medication Error Reporting and Prevention Index. No attempt was made to determine preventability of harm and ADEs from acts of omission were excluded. RESULTS: The ADE TT was applied to 1210 charts and 353 ADE were identified, with an average rate of 28.9/100 admissions and 38/1,000 bed days. 94.5% of the ADE identified were in the lower severity scales with temporary harm, however in 5 patients it was considered that the ADE contributed to their death, 9 required an intervention to sustain life and 4 suffered permanent harm. The most commonly implicated drugs were morphine and other opioids, anticoagulants, antibiotics, Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and diuretics. Patients who suffered an ADE were more likely to be female, older with more complex medical illnesses, and have a longer length of stay. CONCLUSION: The rate of medication-related harm identified by the ADE TT is considerably higher than that identified through traditional voluntary reporting mechanisms. The ADE TT provides a standardised measure of harm over time that can be used to determine trends and the effect of medication safety improvement programmes. This study not only shows the problem of medication-related patient harm, but it also shows the utility of informal collaboratives as a mechanism for change.

Text mining for the Vaccine Adverse Event Reporting System: medical text classification using informative feature selection.

OBJECTIVE: The US Vaccine Adverse Event Reporting System (VAERS) collects spontaneous reports of adverse events following vaccination. Medical officers review the reports and often apply standardized case definitions, such as those developed by the Brighton Collaboration. Our objective was to demonstrate a multi-level text mining approach for automated text classification of VAERS reports that could potentially reduce human workload. DESIGN: We selected 6034 VAERS reports for H1N1 vaccine that were classified by medical officers as potentially positive (N(pos)=237) or negative for anaphylaxis. We created a categorized corpus of text files that included the class label and the symptom text field of each report. A validation set of 1100 labeled text files was also used. Text mining techniques were applied to extract three feature sets for important keywords, low- and high-level patterns. A rule-based classifier processed the high-level feature representation, while several machine learning classifiers were trained for the remaining two feature representations. MEASUREMENTS: Classifiers' performance was evaluated by macro-averaging recall, precision, and F-measure, and Friedman's test; misclassification error rate analysis was also performed. RESULTS: Rule-based classifier, boosted trees, and weighted support vector machines performed well in terms of macro-recall, however at the expense of a higher mean misclassification error rate. The rule-based classifier performed very well in terms of average sensitivity and specificity (79.05% and 94.80%, respectively). CONCLUSION: Our validated results showed the possibility of developing effective medical text classifiers for VAERS reports by combining text mining with informative feature selection; this strategy has the potential to reduce reviewer workload considerably.

Prescribed drugs and violence: a case/noncase study in the French PharmacoVigilance Database.

AIM: Our aim was to identify prescribed drugs associated with violent behaviours using the French PharmacoVigilance Database (FPVD). METHODS: All reports of adverse drug reactions (ADR) recorded in the FPVD between 1 January 1985 and 31 July 2008 and including the terms aggressiveness or violence were selected. We compared proportion of exposure to different drugs between cases (reports with violence) and noncases (other reports in the database). RESULTS: Among 537 cases, 56 were included (48 men, mean age 46 years). Misuse was observed in ten cases (18%). In 25 cases (44.6%), a previous psychiatric history was documented. Main drugs involved were nervous system (63.6%) followed by respiratory (7.8%), alimentary tract and metabolism (7.8%), dermatological (5.2%) and anti-infective (5.2%) agents. Case/noncase analysis found an association with dopaminergic agonists (pergolide, pramipexole, bromocriptine, piribedil), benzodiazepines (alprazolam, bromazepam) and serotoninergic antidepressants (taken as a whole), but not antipsychotics or antiepileptics. Association was also found with varenicline, isotretinoin, interferon alpha-2b, rimonabant, benfluorex, topiramate and antiviral drugs (ribavirin, efavirenz). CONCLUSION: Dopaminergic agonists, benzodiazepines and serotoninergic antidepressants are the main pharmacological classes able to induce aggressive behaviour. This study also emphasises the putative role of other drugs less known to be involved in such ADR.

Effects of e-mails containing ADR information and a current case report on ADR reporting rate and quality of reports.

BACKGROUND: Spontaneous reporting of adverse drug reactions (ADRs) is one approach to increasing our knowledge on the risks of drugs in clinical practice. Under-reporting is a shortcoming of this system. OBJECTIVES: To evaluate if repeated e-mails with attachments on ADR information can affect (1) the reporting of ADRs and (2) the quality of the ADR reports. METHODS: All 117 heads of primary health care units in the region of Västra Götaland in Sweden were randomly allocated (1:1) to an intervention group or a control group. The intervention consisted of e-mails with attachments sent out to each of the 117 heads in January, May and September 2007. These e-mails included (1) the heading "Every ADR report is important", (2) a current case report of an ADR and (3) instructions on how to report. The number of reports from each primary health care unit run by the same head was registered, as was the quality of the report. The quality was defined as high if the ADR was (1) serious, (2) unexpected or (3) related to the use of new drugs and not labeled as common in the summary of product characteristics. All other reports were regarded as low-quality reports. RESULTS: The total number of reports increased from 89 in 2006 to 111 in 2007 (P = 0.037). No difference in the number of reports between intervention (n = 56) and control (n = 55) units could be detected. The proportion of high-quality reports before and after the intervention was 36 and 48%, respectively (intervention, P = 0.11) and 40 and 36%, respectively (control, P = 0.55). CONCLUSIONS: No apparent effect of repeated ADR e-mails on the reporting of ADRs could be detected, although an increase in the reporting rate in general was noted.

Comparing 4 classification systems for drug-related problems: processes and functions.

BACKGROUND: Counseling patients on drug-related problems (DRPs) is a new enterprise for pharmacists. Accordingly, a variety of classification systems have been created to document DRPs. This aroused our interest in finding out how classification systems differ. OBJECTIVE: The objective is to explore and describe the characteristics of 4 classification systems for DRPs to understand their similarities and differences with regard to processes and functions. METHODS: Four established classification systems were selected; they were Strand, Granada-II, Pharmaceutical Care Network Europe v5.0, and Apoteket. To gain experience of the use of the systems, an existing database containing documented problems that were identified during patient counseling at community pharmacies was used. The entries in the database were classified using the 4 selected classification systems, one at a time. In the following analysis, focus was set on what issues were classified and how they were classified in each system. Based on similarities and differences, 8 themes were identified and characteristics of the 4 systems were listed according to these themes. Characteristics of each system were thoroughly scrutinized and interpreted. RESULTS: The processes of selecting classification categories were different in all 4 systems, and as a result the contents of categories in systems were different. The systems had different characteristics and a decisive characteristic was whether the patients were involved in the classification of problems or not. Because of the different characteristics the systems had different functions. CONCLUSIONS: To understand the usefulness of a classification system, both structure of categories and work process must be considered. The studied systems had different functions that revealed different aims embedded in the systems. To develop the counseling role of pharmacists, a limited number of classification systems would be beneficial. To get there, common aims and common systems must be developed.

Care ideologies reflected in 4 conceptions of pharmaceutical care.

BACKGROUND: Different ways to practice pharmaceutical care have been developed. One expression of this fact is the existence of many different classification systems to document drug-related problems (DRPs). Evidence suggests that classification systems have different characteristics and that these characteristics reflect different conceptions of pharmaceutical care. To increase the understanding of conceptions of pharmaceutical care, underlying values and beliefs (ideologies) can be explored. OBJECTIVE: To explore various conceptions of pharmaceutical care to identify the care ideologies on which these conceptions are based. METHODS: Representatives of 4 selected conceptions of pharmaceutical care were interviewed in face-to-face meetings. During the interviews, 4 basic questions were asked. Three were focused on pharmaceutical care and 1 on DRPs. Interview transcripts were analyzed by an inductive method inspired by grounded theory. The conceptions studied were Strand, Granada-II, PCNE v5.0, and Apoteket. RESULTS: In Strand, patients are given a more active role in the pharmaceutical care process, as compared to Granada-II, PCNE v5.0, and Apoteket. Pharmacists in all the conceptions of pharmaceutical care assume they have special knowledge that patients benefit from. However, they use their knowledge in different ways in the various pharmaceutical care conceptions. In Strand, individual goals of drug therapy are established together with the patient, whereas in Granada-II, PCNE, and Apoteket goals are not explicitly discussed. The identified differences correspond to different care ideologies. CONCLUSIONS: The pharmaceutical care conceptions are based on different care ideologies. The ideology is expressed in how therapy goals are set and patient needs defined. Strand is based on a patient-centered ideology; patient therapy goals and needs are defined by the patient together with the practitioners. Granada-II, PCNE, and Apoteket are based on an evidence-based medicine approach; patient therapy goals and needs are defined by the practitioners, based on available scientific knowledge.

Drug-related problems: evaluation of a classification system in the daily practice of a Swiss University Hospital.

AIM: To evaluate the Pharmaceutical Care Network Europe (PCNE) classification system as a tool for documenting the impact of a hospital clinical pharmacology service. SETTING: Two medical wards comprising totally 85 beds in a university hospital. MAIN OUTCOME MEASURE: Number of events classified with the PCNE-system, their acceptance by the medical staff and cost implications. METHODS: Clinical pharmacy review of pharmacotherapy on ward rounds and from case notes were documented, and identified drug-related problems (DRPs) were classified using the PCNE system version 5.00. RESULTS: During 70 observation days 216 interventions were registered of which 213 (98.6%) could be classified: 128 (60.1%) were detected by reviewing the case notes, 33 (15.5%) on ward rounds, 32 (15.0%) by direct reporting to the clinical pharmacist (CP), and 20 (9.4%) on non-formulary prescriptions. Of 148 suggested interventions by the CP 123 (83.0%) were approved by the responsible physician, 12 ADR reports (8.1%) were submitted to the local pharmacovigilance centre and 31 (20.9%) specific information given without further need for action. An evaluation of the DRPs showed that direct drug costs of 2,058 within the study period or 10,731 per year could be avoided. CONCLUSION: We consider the PCNE system to be a practical tool in the hospital setting, which demonstrates the values of a clinical pharmacy service in terms of identifying and reducing DRPs and also has the potential to reduce prescribing costs.

[Classification of drug-related problems]. / Klassifisering av legemiddelrelaterte problemer.

BACKGROUND: Drug-related problems are prevalent and cause considerable patient morbidity and in some cases death, as well as increased health care expenditures. A classification system may contribute to identify such problems, and further to resolve and prevent them. MATERIAL AND METHODS: A draft classification was circulated to a panel of physicians and pharmacists and comments were requested. Consensus was achieved after two subsequent hearing rounds where the structure, content and relevance of the draft were discussed. By means of mini cases the classification was validated concerning various professionals' understanding and interpretation of the problem categories. RESULTS: The classification has a hierarchical structure with 6 main categories (drug choice, dosing, adverse reaction, interaction, wrong use and other) and 12 subcategories. The system is relevant for hospitals, general practices, nursing homes and pharmacies. Validation of the system revealed that a majority would assign identical categories to 9/10 cases. INTERPRETATION: We propose a validated Norwegian classification system for drug-related problems. The systems may facilitate better and more systematic documentation and communication on such problems.