Suitability of Preference Methods Across the Medical Product Lifecycle: A Multicriteria Decision Analysis.

OBJECTIVES: This study aimed to understand the importance of criteria describing methods (eg, duration, costs, validity, and outcomes) according to decision makers for each decision point in the medical product lifecycle (MPLC) and to determine the suitability of a discrete choice experiment, swing weighting, probabilistic threshold technique, and best-worst scale cases 1 and 2 at each decision point in the MPLC. METHODS: Applying multicriteria decision analysis, an online survey was sent to MPLC decision makers (ie, industry, regulatory, and health technology assessment representatives). They ranked and weighted 19 methods criteria from an existing performance matrix about their respective decisions across the MPLC. All criteria were given a relative weight based on the ranking and rating in the survey after which an overall suitability score was calculated for each preference elicitation method per decision point. Sensitivity analyses were conducted to reflect uncertainty in the performance matrix. RESULTS: Fifty-nine industry, 29 regulatory, and 5 health technology assessment representatives completed the surveys. Overall, "estimating trade-offs between treatment characteristics" and "estimating weights for treatment characteristics" were highly important criteria throughout all MPLC decision points, whereas other criteria were most important only for specific MPLC stages. Swing weighting and probabilistic threshold technique received significantly higher suitability scores across decision points than other methods. Sensitivity analyses showed substantial impact of uncertainty in the performance matrix. CONCLUSION: Although discrete choice experiment is the most applied preference elicitation method, other methods should also be considered to address the needs of decision makers. Development of evidence-based guidance documents for designing, conducting, and analyzing such methods could enhance their use.

Effectiveness of risk minimisation measures for valproate: A cross-sectional survey among physicians in Europe.

PURPOSE: This study evaluated the effectiveness of risk minimisation measures (RMMs) implemented following the 2014 referral for valproate in Europe. METHODS: Cross-sectional survey was conducted over 2-month period in 2016 among physicians who prescribed valproate in France, Germany, the United Kingdom, Spain and Sweden. The web-based questionnaire included five endpoints to evaluate physicians' knowledge on (a) prescribing valproate only for epilepsy and bipolar disorder in women if other treatments were ineffective or not tolerated; (b) ensuring supervision by experienced physicians while treating these conditions; (c) considering alternative treatments for women planning pregnancy, regular review of treatment needs and re-assessing the benefit-risk balance in women and girls reaching puberty; (d) informing patients about the risks of taking valproate during pregnancy and (e) advising women on effective contraception during their treatment. RESULTS: Among 1153 physicians, 95.5% responded prescribing valproate for epilepsy and bipolar disorder in women only if other treatments are ineffective/not tolerated; 66.5% supervised while treatment; 76.6% considered alternative treatments for women planning pregnancy; 92.1% informed patients about the risks of taking valproate during pregnancy and 94.4% advised patients on the use of effective contraception during its treatment. Overall, 25.8% physicians recalled receiving both educational material (EM) and Dear Healthcare Professional Communication (DHPC). All endpoint rates were higher for physicians who acknowledged receipt of both DHPC and EM compared to physicians who did not receive them. CONCLUSIONS: Although results varied across geography and physician speciality, majority of physicians had good knowledge about the indication and safety aspects of prescribing and using valproate.

Pre/post effectiveness evaluation of updated additional risk minimisation measures for an orphan disease: Myozyme (alglucosidase alfa) Safety Information Packet.

BACKGROUND: The alglucosidase alfa (Myozyme®) Safety Information Packet ("previous SIP") was updated to improve readability and content ("updated SIP"). We compared the previous and updated SIPs. METHODS: A two-wave pre-post multicountry survey was conducted among health care professionals (HCPs) who prescribed or monitored patients on alglucosidase alfa in the largest European Union ("EU5") countries and Poland. Wave (W) 2 started 15 months after completion of W1 and the implementation of the updated SIP. Changes between the waves were analysed. RESULTS: Forty-six HCPs (34 physicians/12 nurses) participated in W1 and 52 in W2 (42 physicians/10 nurses); 22 participated in both waves. Nonsignificant differences were observed between waves 1 and 2 for awareness (75.6% in W1 and 82.4% in W2) and receipt (77.7% in W1 and 74.5% in W2) of the SIP, reading (88.6% in W1 and 89.5% in W2) and usage (88.2% in W1 and 89.5% in W2) among receivers of the SIP, or the overall knowledge about immunological testing (61.1% in W1 vs 55.1% in W2). Frequency of performance of immunological testing was significantly higher in W2 than in W1 (50.3% vs 34.4%; P = .024) with a tendency for increases in the appropriate performance of all types of testing in W2. CONCLUSIONS: Both versions of the SIP showed relatively high awareness, receipt, reading, and usage, with an overall trend for most measures to improve numerically in W2. The updated SIP did not require further changes.

Comparison of text processing methods in social media-based signal detection.

PURPOSE: Adverse event (AE) identification in social media (SM) can be performed using various types of natural language processing (NLP) and machine learning (ML). These methods can be categorized by complexity and precision level. Co-occurrence-based ML methods are rather basic, as they identify simultaneous appearance of drugs and clinical events in a single post. In contrast, statistical learning methods involve more complex NLP and identify drugs, events, and associations between them. We aimed to compare the ability of co-occurrence and NLP to identify AEs and signals of disproportionate reporting (SDR) in patient-generated SM. We also examined the performance of lift in SM-based signal detection (SD). METHODS: Our examination was performed in a corpus of SM posts crawled from open online patient forums and communities, using the spontaneously reported VigiBase data as reference data set. RESULTS: We found that co-occurrence and NLP produce AEs, which are 57% and 93% consistent with VigiBase AEs, respectively. Among the SDRs identified both in SM and in VigiBase, up to 55.3% were identified earlier in co-occurrence, and up to 32.1% were identified earlier in NLP-processed SM. Using lift in SM SD provided performance similar to frequentist methods, both in co-occurrence and in NLP-processed AEs. CONCLUSION: Our results indicate that using SM as a data source complementary to traditional pharmacovigilance sources should be considered further. Various levels of SM processing may be considered, depending on the preferred policies and tolerance for false-positive to false-negative balance in routine pharmacovigilance processes.

Web-Based Signal Detection Using Medical Forums Data in France: Comparative Analysis.

BACKGROUND: While traditional signal detection methods in pharmacovigilance are based on spontaneous reports, the use of social media is emerging. The potential strength of Web-based data relies on their volume and real-time availability, allowing early detection of signals of disproportionate reporting (SDRs). OBJECTIVE: This study aimed (1) to assess the consistency of SDRs detected from patients' medical forums in France compared with those detected from the traditional reporting systems and (2) to assess the ability of SDRs in identifying earlier than the traditional reporting systems. METHODS: Messages posted on patients' forums between 2005 and 2015 were used. We retained 8 disproportionality definitions. Comparison of SDRs from the forums with SDRs detected in VigiBase was done by describing the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, receiver operating characteristics curve, and the area under the curve (AUC). The time difference in months between the detection dates of SDRs from the forums and VigiBase was provided. RESULTS: The comparison analysis showed that the sensitivity ranged from 29% to 50.6%, the specificity from 86.1% to 95.5%, the PPV from 51.2% to 75.4%, the NPV from 68.5% to 91.6%, and the accuracy from 68% to 87.7%. The AUC reached 0.85 when using the metric empirical Bayes geometric mean. Up to 38% (12/32) of the SDRs were detected earlier in the forums than that in VigiBase. CONCLUSIONS: The specificity, PPV, and NPV were high. The overall performance was good, showing that data from medical forums may be a valuable source for signal detection. In total, up to 38% (12/32) of the SDRs could have been detected earlier, thus, ensuring the increased safety of patients. Further enhancements are needed to investigate the reliability and validation of patients' medical forums worldwide, the extension of this analysis to all possible drugs or at least to a wider selection of drugs, as well as to further assess performance against established signals.

The IMI PROTECT project: purpose, organizational structure, and procedures.

The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) initiative was a collaborative European project that sought to address limitations of current methods in the field of pharmacoepidemiology and pharmacovigilance. Initiated in 2009 and ending in 2015, PROTECT was part of the Innovative Medicines Initiative, a joint undertaking by the European Union and pharmaceutical industry. Thirty-five partners including academics, regulators, small and medium enterprises, and European Federation of Pharmaceuticals Industries and Associations companies contributed to PROTECT. Two work packages within PROTECT implemented research examining the extent to which differences in the study design, methodology, and choice of data source can contribute to producing discrepant results from observational studies on drug safety. To evaluate the effect of these differences, the project applied different designs and analytic methodology for six drug-adverse event pairs across several electronic healthcare databases and registries. This papers introduces the organizational structure and procedures of PROTECT, including how drug-adverse event and data sources were selected, study design and analyses documents were developed, and results managed centrally.

Multi-centre, multi-database studies with common protocols: lessons learnt from the IMI PROTECT project.

PURPOSE: To assess the impact of a variety of methodological parameters on the association between six drug classes and five key adverse events in multiple databases. METHODS: The selection of Drug-Adverse Event pairs was based on public health impact, regulatory relevance, and the possibility to study a broad range of methodological issues. Common protocols and data analytical specifications were jointly developed and independently and blindly executed in different databases in Europe with replications in the same and different databases. RESULTS: The association between antibiotics and acute liver injury, benzodiazepines and hip fracture, antidepressants and hip fracture, inhaled long-acting beta2-agonists and acute myocardial infarction was consistent in direction across multiple designs, databases and methods to control for confounding. Some variation in magnitude of the associations was observed depending on design, exposure and outcome definitions, but none of the differences were statistically significant. The association between anti-epileptics and suicidality was inconsistent across the UK CPRD, Danish National registries and the French PGRx system. Calcium channel blockers were not associated with the risk of cancer in the UK CPRD, and this was consistent across different classes of calcium channel blockers, cumulative durations of use up to >10 years and different types of cancer. CONCLUSIONS: A network for observational drug effect studies allowing the execution of common protocols in multiple databases was created. Increased consistency of findings across multiple designs and databases in different countries will increase confidence in findings from observational drug research and benefit/risk assessment of medicines.

The risk of acute liver injury associated with the use of antibiotics--evaluating robustness of results in the pharmacoepidemiological research on outcomes of therapeutics by a European consortium (PROTECT) project.

PURPOSE: To examine the robustness of findings of case-control studies on the association between acute liver injury (ALI) and antibiotic use in the following different situations: (i) Replication of a protocol in different databases, with different data types, as well as replication in the same database, but performed by a different research team. (ii) Varying algorithms to identify cases, with and without manual case validation. (iii) Different exposure windows for time at risk. METHODS: Five case-control studies in four different databases were performed with a common study protocol as starting point to harmonize study outcome definitions, exposure definitions and statistical analyses. RESULTS: All five studies showed an increased risk of ALI associated with antibiotic use ranging from OR 2.6 (95% CI 1.3-5.4) to 7.7 (95% CI 2.0-29.3). Comparable trends could be observed in the five studies: (i) without manual validation the use of the narrowest definition for ALI showed higher risk estimates, (ii) narrow and broad algorithm definitions followed by manual validation of cases resulted in similar risk estimates, and (iii) the use of a larger window (30 days vs 14 days) to define time at risk led to a decrease in risk estimates. CONCLUSIONS: Reproduction of a study using a predefined protocol in different database settings is feasible, although assumptions had to be made and amendments in the protocol were inevitable. Despite differences, the strength of association was comparable between the studies. In addition, the impact of varying outcome definitions and time windows showed similar trends within the data sources.

Treatment preferences for preventive interventions for rheumatoid arthritis: protocol of a mixed methods case study for the Innovative Medicines Initiative PREFER project.

INTRODUCTION: Amidst growing consensus that stakeholder decision-making during drug development should be informed by an understanding of patient preferences, the Innovative Medicines Initiative project 'Patient Preferences in Benefit-Risk Assessments during the Drug Life Cycle' (PREFER) is developing evidence-based recommendations about how and when patient preferences should be integrated into the drug life cycle. This protocol describes a PREFER clinical case study which compares two preference elicitation methodologies across several populations and provides information about benefit-risk trade-offs by those at risk of rheumatoid arthritis (RA) for preventive interventions. METHODS AND ANALYSIS: This mixed methods study will be conducted in three countries (UK, Germany, Romania) to assess preferences of (1) first-degree relatives (FDRs) of patients with RA and (2) members of the public. Focus groups using nominal group techniques (UK) and ranking surveys (Germany and Romania) will identify and rank key treatment attributes. Focus group transcripts will be analysed thematically using the framework method and average rank orders calculated. These results will inform the treatment attributes to be assessed in a survey including a discrete choice experiment (DCE) and a probabilistic threshold technique (PTT). The survey will also include measures of sociodemographic variables, health literacy, numeracy, illness perceptions and beliefs about medicines. The survey will be administered to (1) 400 FDRs of patients with RA (UK); (2) 100 FDRs of patients with RA (Germany); and (3) 1000 members of the public in each of UK, Germany and Romania. Logit-based approaches will be used to analyse the DCE and imputation and interval regression for the PTT. ETHICS AND DISSEMINATION: This study has been approved by the London-Hampstead Research Ethics Committee (19/LO/0407) and the Ethics Committee of the Friedrich-Alexander-Universität Erlangen-Nürnberg (92_17 B). The protocol has been approved by the PREFER expert review board. The results will be disseminated widely and will inform the PREFER recommendations.

Structured benefit-risk evaluation for medicinal products: review of quantitative benefit-risk assessment findings in the literature.

A favorable benefit-risk profile remains an essential requirement for marketing authorization of medicinal drugs and devices. Furthermore, prior subjective, implicit and inconsistent ad hoc benefit-risk assessment methods have rightly evolved towards more systematic, explicit or "structured" approaches. Contemporary structured benefit-risk evaluation aims at providing an objective assessment of the benefit-risk profile of medicinal products and a higher transparency for decision making purposes. The use of a descriptive framework should be the preferred starting point for a structured benefit-risk assessment. In support of more precise assessments, quantitative and semi-quantitative methodologies have been developed and utilized to complement descriptive or qualitative frameworks in order to facilitate the structured evaluation of the benefit-risk profile of medicinal products. In addition, quantitative structured benefit-risk analysis allows integration of patient preference data. Collecting patient perspectives throughout the medical product development process has become increasingly important and key to the regulatory decision-making process. Both industry and regulatory authorities increasingly rely on descriptive structured benefit-risk evaluation and frameworks in drug, vaccine and device evaluation and comparison. Although varied qualitative methods are more commonplace, quantitative approaches have recently been emphasized. However, it is unclear how frequently these quantitative frameworks have been used by pharmaceutical companies to support submission dossiers for drug approvals or to respond to the health authorities' requests. The objective of this study has been to identify and review, for the first time, currently available, published, structured, quantitative benefit-risk evaluations which may have informed health care professionals and/or payor as well as contributed to decision making purposes in the regulatory setting for drug, vaccine and/or device approval. PLAIN LANGUAGE SUMMARY: Quantitative evaluation of the benefit-risk balance for medicinal products The review of the benefits and the risks associated with a medicinal product is called benefit-risk assessment. One of the conditions for a medicinal product to receive marketing authorization is to demonstrate a positive benefit-risk balance in which the benefits outweigh the risks. In order to enhance the transparency and consistency in the assessment of benefit-risk balance, frameworks and quantitative methods have been developed for decision making purposes and regulatory approvals of medicinal products. This article considers published quantitative benefit-risk evaluations which may have informed health care professionals and/or payor as well as contributed to decision making purposes in the regulatory setting for drug, vaccine and/or device approval.

Remission in the outpatient care of schizophrenia: 3-year results from the Schizophrenia Outpatients Health Outcomes (SOHO) study in France.

OBJECTIVE: To analyse the contribution of socio-demographics, clinical profile and psychotropic treatment on remission in patients with schizophrenia. METHODS: Among 933 French outpatients recruited in the European observational Schizophrenia Outpatient Health Outcomes study (SOHO), 563 were followed-up for 3 years, had at most one missing visit, and were included in the analysis. Symptomatic remission was defined as a score of 3 (mild severity) or less on the Clinical Global Impression-Schizophrenia (CGI) overall, positive, negative and cognitive symptom scales, maintained for at least 6 months and without hospitalization. A logistic regression model was used to analyse the factors associated with time in remission. RESULTS: 60.6% of patients achieved remission during the 3-year follow-up. Patients never treated before inclusion in the study (OR=2.3) and those having paid employment (OR=1.4) were more likely to achieve remission. Higher baseline clinical severity was associated with a significantly lower likelihood of achieving remission: CGI overall (OR=0.67), CGI positive (OR=0.85) and CGI negative (OR=0.74). Compared with olanzapine, other atypicals (OR=0.71) and conventional antipsychotics (OR=0.69) were associated with a lower probability of achieving remission. CONCLUSIONS: Remission can be achieved in a high proportion of patients. Factors such as being previously untreated, having paid employment and taking olanzapine are predictors of remission.

Assessing the Risk for Peripheral Neuropathy in Patients Treated With Dronedarone Compared With That in Other Antiarrhythmics.

PURPOSE: There are few data on the risk for peripheral neuropathy associated with dronedarone, a newer antiarrhythmic medicine. The objective of this study was to assess whether dronedarone is potentially associated with an increased risk for peripheral neuropathy compared with other antiarrhythmics, including amiodarone, sotalol, flecainide, and propafenone. METHODS: The MarketScan database was used for identifying patients who were at least 18 years of age, had atrial fibrillation or flutter, and had not been diagnosed with peripheral neuropathy in the 180-day period prior to or on the date of the first prescription of an antiarrhythmic between July 20, 2009, and December 31, 2011. Peripheral neuropathy that occurred during the treatment period for a study drug was ascertained using ICD-9-CM diagnostic codes. For each antiarrhythmic, the incidence rate of peripheral neuropathy was calculated. The adjusted hazard ratio (aHR) for peripheral neuropathy for dronedarone compared with another antiarrhythmic was obtained, with control for age, sex, diabetes mellitus status, and the presence of other comorbidities. FINDINGS: The study population included 106,933 patients treated with dronedarone (n = 12,989), amiodarone (n = 45,173), sotalol (n = 22,036), flecainide (n = 14,244), or propafenone (n = 12,491). The incidence rates (per 1000 person-years) of peripheral neuropathy were 1.33 for dronedarone, 2.38 for amiodarone, 1.20 for sotalol, 1.08 for flecainide, and 1.97 for propafenone. The aHRs for peripheral neuropathy for dronedarone relative to other drugs ranged from 0.53 (95% CI, 0.21-1.34) compared with propafenone, to 0.94 (95% CI, 0.38-2.30) compared with sotalol. A new-user analysis showed similar results. IMPLICATIONS: The risks for peripheral neuropathy were not significantly different between dronedarone and other antiarrhythmics.

Assessment of the Utility of Social Media for Broad-Ranging Statistical Signal Detection in Pharmacovigilance: Results from the WEB-RADR Project.

INTRODUCTION AND OBJECTIVE: Social media has been proposed as a possibly useful data source for pharmacovigilance signal detection. This study primarily aimed to evaluate the performance of established statistical signal detection algorithms in Twitter/Facebook for a broad range of drugs and adverse events. METHODS: Performance was assessed using a reference set by Harpaz et al., consisting of 62 US Food and Drug Administration labelling changes, and an internal WEB-RADR reference set consisting of 200 validated safety signals. In total, 75 drugs were studied. Twitter/Facebook posts were retrieved for the period March 2012 to March 2015, and drugs/events were extracted from the posts. We retrieved 4.3 million and 2.0 million posts for the WEB-RADR and Harpaz drugs, respectively. Individual case reports were extracted from VigiBase for the same period. Disproportionality algorithms based on the Information Component or the Proportional Reporting Ratio and crude post/report counting were applied in Twitter/Facebook and VigiBase. Receiver operating characteristic curves were generated, and the relative timing of alerting was analysed. RESULTS: Across all algorithms, the area under the receiver operating characteristic curve for Twitter/Facebook varied between 0.47 and 0.53 for the WEB-RADR reference set and between 0.48 and 0.53 for the Harpaz reference set. For VigiBase, the ranges were 0.64-0.69 and 0.55-0.67, respectively. In Twitter/Facebook, at best, 31 (16%) and four (6%) positive controls were detected prior to their index dates in the WEB-RADR and Harpaz references, respectively. In VigiBase, the corresponding numbers were 66 (33%) and 17 (27%). CONCLUSIONS: Our results clearly suggest that broad-ranging statistical signal detection in Twitter and Facebook, using currently available methods for adverse event recognition, performs poorly and cannot be recommended at the expense of other pharmacovigilance activities.

[Evaluation of a screening programme for diabetic retinopathy (DODIA study)]. / Dépistage de la rétinopathie diabétique par des photographies do fond d'oeil. Evaluation d'un programme en médecine libérale (étude DODIA).

CONTEXT: In France, 43% to 63% of diabetics have an annual fundoscopy. Do the new screening tools, coupled with teletransmission of the images, allow for satisfying ophthalmological screening? It is an important matter given the foreseeable reduction in the number of French ophthalmologists in the forthcoming years. OBJECTIVES: To measure the quality of screening for diabetic retinopathy (DR), in the framework of a network, by the provision of a retinograph by numeric camera (with teletransmission of the images and centralised interpretation), in a screening centre located in town. METHOD: The study evaluated the quality of screening obtained in two comparable groups of general practitioners, one using the retinograph and the other using the classical method of screening by ophthalmologist. The screening was targeted at diabetics who had not had a fundoscopy in the preceding year, nor had known DR or a treating ophthalmologist (for the retinography group only). RESULTS: 667 patients were sampled in the retinography group (456 included) and 707 in the control group (426 included) between 1/04/02 and 1/11/02; 417 patients were followed until the end of the study in the 2 groups. A screening examination was considered effective if it was performed within the six months following its request, and by the presence of a report in the file of the general practitioner. The percentage of patients thus screened was 74% in the retinography group and 71,5% in the other group (not significant). 16% of diabetics in the retinography group had DR compared with 10% of patients in the control group. The analysis of the level of satisfaction of patients tended to show a preference for the system of screening by fundal photography. CONCLUSION: In the framework of a healthcare network, the availability of a retinograph by numeric camera, with the interpretation of photos by teletransmission of the images, obtained a high level of quality of screening for diabetic retinopathy that was at least as good as that obtained by a healthcare network using the classical ophthalmological screening method.

Validation of New Signal Detection Methods for Web Query Log Data Compared to Signal Detection Algorithms Used With FAERS.

INTRODUCTION: Post-marketing drug surveillance is largely based on signals found in spontaneous reports from patients and healthcare providers. Rare adverse drug reactions and adverse events (AEs) that may develop after long-term exposure to a drug or from drug interactions may be missed. The US FDA and others have proposed that web-based data could be mined as a resource to detect latent signals associated with adverse drug reactions. METHODS: Recently, a web-based search query method called a query log reaction score (QLRS) was developed to detect whether AEs associated with certain drugs could be found from search engine query data. In this study, we compare the performance of two other algorithms, the proportional query ratio (PQR) and the proportional query rate ratio (Q-PRR) against that of two reference signal-detection algorithms (SDAs) commonly used with the FDA AE Reporting System (FAERS) database. RESULTS: In summary, the web query methods have moderate sensitivity (80%) in detecting signals in web query data compared with reference SDAs in FAERS when the web query data are filtered, but the query metrics generate many false-positives and have low specificity compared with reference SDAs in FAERS. CONCLUSION: Future research is needed to find better refinements of query data and/or the metrics to improve the specificity of these web query log algorithms.

Patient satisfaction with psychotropic drugs: sensitivity to change and relationship to clinical status, quality-of-life, compliance and effectiveness of treatment. Results from a nation-wide 6-month prospective study.

OBJECTIVE: To see if patient satisfaction with psychotropics (PSP) could be used as a patient-oriented outcome variable in the evaluation of PSP drugs in clinical epidemiological studies, relationships between PSP, clinical status, QoL, compliance and the type of antipsychotic were analyzed. Elements of validation of PSP were also assessed. METHOD: In a 6-month prospective study, 933 schizophrenic outpatients with initiation or change to their antipsychotic treatment were enrolled. Psychiatrists completed five CGI-SCH scales (positive, negative, cognitive, depressive and global), hospitalization, compliance, and prescription variables. Patients completed PSP, EuroQoL scales, sexual function and compliance variables. RESULTS: A satisfactory structural equation model was obtained showing significant relationships PSP/compliance (coef.=0.16), QoL/PSP (coef.=0.37), clinical status/QoL (coef.=0.61), clinical status/compliance (coef.=0.09). Patients receiving olanzapine were more satisfied than patients receiving other atypicals (coef.=012) and had better clinical status than patients treated with typicals (coef.=0.08). Evolution of PSP was related to clinical status, QoL, and continuation of treatment (all P<001). Sensitivity to change of PSP was moderate (effect size=0.2). CONCLUSION: PSP produced consistent results in relation to validated outcome variables. However, a single-item measure was not sufficiently sensitive to change. Multi-item questionnaires evaluating different dimensions are needed.

Management and relief of pain in an emergency department from the adult patients' perspective.

To estimate the prevalence of pain in adult patients attending an emergency department (ED) and to identify risk markers for insufficient pain relief, a cross-sectional survey was conducted for 16 days, 24 hours each day, in the ED of a Paris university hospital. A structured questionnaire was used to collect characteristics of pain and its management from patients. Pain intensity was evaluated both on arrival and before discharge using two scales (a numerical descriptor scale or a verbal pain intensity scale). On arrival, 78% of the patients complained of pain; among them, 54% complained of intense pain and 47% suffered procedural pain. Insufficient pain relief was assessed in 289 (77%) patients. We identified the following risk markers for insufficient pain relief: moderate or low pain intensity, no intervention in the ED before the medical examination, and no use of medication before arrival.

Pain prevalence in a French teaching hospital.

To measure the prevalence and intensity of pain in hospitalized patients and to assess the quality of pain management, an exhaustive cross-sectional study was conducted in every department in a university hospital. Patients hospitalized for 24 hours or more completed an anonymous self-report questionnaire. Among the 1,475 inpatients, 998 completed the questionnaire. During the 24-hour period prior to our survey, 55% experienced pain. On 100 mm pain intensity measures, the median maximum pain experienced in the 24 preceding hours was 60 mm and the median pain intensity at the time of the survey was 30 mm. Although pain measured at the time of survey disappeared in only 16% of patients, 79% were satisfied with pain management. Despite a high satisfaction level, the prevalence and intensity of pain were very high. This study provided baseline data on pain in a French hospital and led to the implementation of a program for improving pain management.

Assessment of dronedarone utilization using US claims databases.

BACKGROUND: A dronedarone utilization study using US MarketScan and InVision Data Mart databases was conducted to estimate the prevalence of the following: (1) dronedarone use in contraindicated patients with worsening heart failure (HF) or hospitalization for HF within 1 month before dronedarone prescription; (2) concomitant prescribing of contraindicated drugs; and (3) recommended creatinine testing after dronedarone initiation among dronedarone users. METHODS: In this retrospective cohort study, data in the MarketScan database between July 20, 2009, and December 31, 2011, and in the InVision Data Mart database between July 20, 2009, and March 31, 2012, were analyzed. The study population included patients who received ≥1 dronedarone prescription during the study period. The following variables were reported: worsening of or hospitalization for HF, concomitant prescribing of potent cytochrome P450 CYP 3A4 inhibitors or QT-prolonging drugs, and creatinine testing. RESULTS: There were 31,408 and 7025 dronedarone users identified in the MarketScan and InVision Data Mart databases, respectively. Approximately 86% to 90% of patients had a diagnosis of atrial fibrillation in each database. In the MarketScan database, 40% were women and 54% were aged ≥65 years. In the InVision Data Mart database, 31% were women and 32% were aged ≥65 years. The corresponding prevalence of worsening or hospitalization for HF was 6.4% (95% CI, 6.2-6.7) and 4.7% (95% CI, 4.2-5.2) in each database, respectively. The corresponding estimates of concomitant prescribing of potent cytochrome P450 CYP 3A4 inhibitors and QT-prolonging drugs within 30 days before initiation or refilling of dronedarone were 2.0% (95% CI, 1.8-2.1) and 10.0% (95% CI, 9.7-10.4), respectively, in the MarketScan database, and 2.3% (95% CI, 2.0-2.7) and 11.2% (95% CI, 10.5-12.0) in the InVision Data Mart database. More than 50% of patients in each database had serum creatinine tests conducted after dronedarone initiation. CONCLUSIONS: The results of the present analysis based on a long-term follow-up (nearly 3 years) were consistent with the previous findings that dronedarone has mostly been used appropriately in compliance with US prescribing in the target populations.

A prospective observational study of treatment practice patterns in acute coronary syndrome patients undergoing percutaneous coronary intervention in Europe.

BACKGROUND: The AntiPlatelet Therapy Observational Registry (APTOR) was a prospective observational study of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in France, Spain, and the UK. AIMS: To evaluate patterns of ACS healthcare use, focusing on APTOR results from France. METHODS: Consecutive presenting ACS patients requiring PCI were recruited between January and August 2007. Treatments and outcomes were recorded from the qualifying ACS event to 12 months follow-up. RESULTS: In France, qualifying diagnosis was unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI) in 255(53%) patients and ST-segment elevation myocardial infarction (STEMI) in 228(47%)patients. Ninety-six percent underwent PCI with stent implantation. Drug eluting stents were used less frequently in France(22%) than Spain (54%) or the UK (42%). In France, antiplatelets were more frequently received in the ambulance (21%); a 200-299mg aspirin-loading dose was most frequently received (50%) and more than a third of patients received a clopidogrel-loading dose of over 300mg (34%). At 12 months in France, 86% were still receiving aspirin, 75% clopidogrel, and 73% combination treatment. CONCLUSION: There was considerable country-variation in ACS management. These results provide a benchmark of physician practice to compare with guidelines.