Preparation of a fully-liquid hexavalent vaccine can be completed in half the time necessary to prepare a non-fully liquid vaccine. The simplicity of the fully-liquid hexavalent vaccine preparation helps optimise reduction of immunisation errors.

Purpose The ENCePP Code of Conduct provides a framework for scientifically independent and transparent pharmacoepidemiological research. Despite becoming a landmark reference, practical implementation of key provisions was still limited. The fourth revision defines scientific independence and clarifies uncertainties on the applicability to postauthorisation safety studies requested by regulators. To separate the influence of the funder from the investigator's scientific responsibility, the Code now requires that the lead investigator is not employed by the funding institution. Method To assess how the revised Code fits the ecosystem of noninterventional pharmacoepidemiology research in Europe, we first mapped key recommendations of the revised Code against ISPE Good Pharmacoepidemiology Practices and the ADVANCE Code of Conduct. We surveyed stakeholders to understand perceptions on its value and practical applicability. Representatives from the different stakeholders' groups described their experience and expectations. Results Unmet needs in pharmacoepidemiological research are fulfilled by providing unique guidance on roles and responsibilities to support scientific independence. The principles of scientific independence and transparency are well understood and reinforce trust in study results; however, around 70% of survey respondents still found some provisions difficult to apply. Representatives from stakeholders' groups found the new version promising, although limitations still exist. Conclusion By clarifying definitions and roles, the latest revision of the Code sets a new standard in the relationship between investigators and funders to support scientific independence of pharmacoepidemiological research. Disseminating and training on the provisions of the Code would help stakeholders to better understand its advantages and promote its adoption in noninterventional research.

Background and aims Simplified vaccine preparation steps would save time and reduce the potential of mishandlings. The aim of the study was to assess vaccine preparation time with fully liquid hexavalent vaccine (DTaP-IPV-HB-PRP-T, Sanofi Pasteur MSD, Lyon, France) versus hexavalent vaccine that needs reconstitution (DTPa-HBV-IPV/Hib, GlaxoSmithKline Biologicals, Rixensart, Belgium). Methods 96 Health Care Professionals (HCPs) participated in a randomised, cross-over, open-label, Time and Motion study in Belgium (2014). HCPs prepared each vaccine (time recorded using video equipment) in a cross-over manner with a wash-out period of 3–5 min. An independent nurse assessed preparation mishandlings by systematic review of the videos. HCPs satisfaction and preference were evaluated by a self-administered questionnaire. Results Average preparation time was 36 seconds for DTaP-IPV-HB-PRP-T versus 70.5 seconds for DTPa-HBV-IPV/Hib (p ≤ 0.001). Extrapolated yearly time savings was estimated to 664 days/year (based on 520 000 hexavalent vaccines administered per year in Belgium). On 192 preparations, 57 mishandlings occurred: 47 in the DTPa-HBV-IPV/Hib group (including one missing reconstitution of Hib component), 10 in the DTaP-IPV-HB-PRP-T group. 71.9% of HCPs were very or somewhat satisfied with ease of handling of both vaccines; 66.7% and 67.7% were very or somewhat satisfied with speed of preparation in DTaP-IPV-HB-PRP-T and DTPa-HBV-IPV/Hib groups, respectively. Almost all HCPs (97.6%) stated they would prefer the use of DTaP-IPV-HB-PRP-T vaccine in their daily practice. Conclusions Fully liquid DTaP-IPV-HB-PRP-T vaccine offers significant time gains for vaccine preparation. It has the potential to reduce mishandlings and could therefore be very useful in daily practice.

caused by the bounded scale. Various analytical approaches have recently been proposed for use in cross-sectional studies, however, less attention is paid to longitudinal designs. We examined the use of beta regression models to analyze HRQL data over time using two empirical examples. METHODS: The HRQL measures employed in our empirical examples were the generic SF-6D and the disease-specific Stroke Impact Scale (SIS). Data came from the German KORA cohort study and from a clinical setting, respectively. We fitted mixed and marginal beta models and explain the conceptual difference between these two model classes, namely the population-averaged and the subject-specific perspective. We compared overall fit and predictive accuracy of the models to the commonly used linear mixed model (LMM). RESULTS: The SF-6D data were highly skewed to the left and the SIS data exhibited a pronounced ceiling effect. In both examples, the beta distribution fitted the data better than the normal distribution. Beta regression accounted for the fact that predicted values must fall into the bounded support of the scales and overall fit measures suggested that the mixed beta model was superior to the LMM (AIC: Ϫ2723 vs. Ϫ2441 and Ϫ904.1 vs. Ϫ376.4). However, mixed beta regression underestimated the mean at the upper part of the distribution. Adjusted group mean scores from the marginal beta model were nearly identical to those derived from the LMM. CONCLUSIONS: Longitudinal beta regression models are potential candidates to analyze HRQL over time since they account for the specific characteristics such data typically have. However, our results show that in practice, estimates may only differ slightly from those of commonly used methods.

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Functioning can be defined as the ability to perform daily activities, and to maintain interpersonal relationships and work capacity/productivity. Major Depressive Disorder (MDD) is associated with substantial impairment in functioning. The study examined associations between various measures of functioning (patient assessment) and MDD symptoms (clinician assessment). A major challenge was to ensure MDD patient compliance with regular self-assessments and retention in a long-term study.Objectives: The purpose of the Direct to Patient Contact (DPC) approach was to maximize patient compliance to Patient Reported Outcomes (PRO) data collection and retention in a study conducted in real life settings over a two-year follow-up period. MethOds: This was an international, multicentric, observational, prospective longitudinal cohort study involving 1,500 MDD patients followed-up for two years in five European countries. Patients were recruited by General Practitioners or psychiatrists and data collected using a hybrid method: clinical data by physicians and PRO data self-assessment by patients. DPC actions included PRO questionnaire shipments to patients at five time points, followed by phone reminder contacts for non-returned questionnaires. Results: 1,450 patients were included in the study, 97.8% of whom agreed to be contacted directly by DPC staff. Overall, 71.7% of patients were reached by phone and 75.6% of PRO questionnaires were returned; the questionnaire completion rate reached 95.3%. 79.6% of patients remained until study end, 0.1% died, 3.5% voluntarily withdrew from the study and 16.7% were withdrawn for other reasons. There were no patients lost to follow up. cOnclusiOns: This study demonstrates that the use of DPC in a MDD population, likely to be study non-compliant/unresponsive, produced excellent long-term response rates. It minimized voluntary patient drop-outs and lost to follow up rates, and ensured an enhanced data collection of self-assessed PROs, thus improved reliability of study outcomes.

nel during standard-of-care visits. Although this is the traditional approach, it has several practical shortcomings: infrequent or irregular standard-of-care visits; patients switching health care providers; transient nature of some safety events; treatment at non-study sites, and the lack of care-seeking for the safety events. An alternative study design that overcomes several of these shortcomings includes direct-to-patient contact (DPC) and follow-up. Objectives: The purpose of this study is to describe patients' short and long term management patterns including the detection and verification of events of interest by contacting patients' event treating physician (ETP). MethOds: This is multinational multicenter observational prospective longitudinal cohort study involving 10,600 patients in Europe and South America. Patients were enrolled at hospital and followed up by telephone by a specialized DPC unit at 6 weeks then quarterly up to 2 years after hospital discharge. Data collected include clinical outcomes, safety events of interest, economic burden and quality of life. Results: A total of 88,276 phone calls to patients were performed, achieving a reachable rate of 88.5% and an interview successful rate of 84.6%. 87.2% of the initial sample completed the 2-year follow-up period: 5.7% of the sample died, 6.0% voluntarily withdrew and 0.9% was withdrawn to participate to a clinical trial. Only 19 patients were never reached (0.2%). In total, 2144 events of interest were detected and a medical verification from ETPs was obtained in 72.3% of the case. cOnclusiOns: This study demonstrates that DPC along with a proactive pharmacovigilance system achieved very high response rates from both patients and ETPs. It represents an effective alternative methodology to collect patients data, including safety data, in real life settings.

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