How Do Hospital Pharmacists Approach Substitution of Nanomedicines? Insights from a Qualitative Pilot Study and a Quantitative Market Research Analysis in Five European Countries

We conducted research to assess hospital pharmacists’ familiarity with/interpretation of data requirements for the different regulatory approval frameworks and the impact of this on their approach to substitution in the formulary. The online questionnaire included a small molecule (acetylsalicylic acid—follow-ons approved via the generic pathway), two biologic drugs (insulin glargine and etanercept—follow-ons approved via the biosimilar pathway), a non-biologic complex drug (NBCD; glatiramer acetate—follow-ons approved via the hybrid pathway) and a nanomedicine, ferric carboxymaltose (no follow-ons approved as yet). The study was conducted in two phases: an initial qualitative pilot study with 30 participants, followed by a quantitative stage involving 201 pharmacists from five European countries. Most expected negligible safety/efficacy differences between reference and follow-on products. Head-to-head clinical data showing therapeutic equivalence as a prerequisite for reference product/follow-on substitution was perceived to be needed most for biologics (47%), followed by NBCDs (44%)/nanomedicines (39%) and small molecules (23%). Overall, 28% did not know the data requirements for follow-on approval via the hybrid pathway; 16% were familiar with this pathway, compared with 50% and 55% for the generic and biosimilar pathways, respectively. Overall, 19% of respondents thought the European Medicines Agency (EMA) was responsible for defining the substitutability of follow-ons. Education is required to increase hospital pharmacist’s knowledge of regulatory approval frameworks and their relevance to substitution practices

A multiple stakeholder multicriteria decision analysis in diabetic macular edema management: the MULTIDEX‑EMD study

Background The clinical and economic management of retinal diseases has become more complex following the introduction of new intravitreal treatments. Multicriteria decision analysis (MCDA) ofers the potential to overcome the challenges associated with traditional decision-making tools. Objectives A MCDA to determine the most relevant criteria to decision-making in the management of diabetic macular edema (DME) based on the perspectives of multiple stakeholders in Spain was developed. This MCDA was termed the MULTIDEX-EMD study. Methods Nineteen stakeholders (7 physicians, 4 pharmacists, 5 health authorities and health management experts, 1 psychologist, and 2 patient representatives) participated in this three-phase project. In phase A, an advisory board defned all of the criteria that could infuence DME treatment decision-making. These criteria were then screened using a discrete choice experiment (DCE) (phase B). Next, a multinomial logit model was ftted by applying the backward elimination algorithm (relevant criteria: p value<0.05). Finally, the results were discussed in a deliberative process (phase C). Results Thirty-one criteria were initially defned (phase A) and grouped into 5 categories: efcacy/efectiveness, safety, organizational and economic impact, patient-reported outcomes, and other therapeutic features. The DCE results (phase B) showed that 10 criteria were relevant to the decision-making process for a 50- to 65-year-old DME patient: mean change in best corrected visual acuity (p value<0.001), percentage of patients with an improvement of ≥15 letters (p value<0.001), efect duration per administration (p value=0.008), retinal detachment (p value<0.001), endophthalmitis (p value=0.012), myocardial infarction (p value<0.001), intravitreal hemorrhage (p value=0.021), annual treatment cost per patient (p value=0.001), health-related quality of life (HRQoL) (p value=0.004), and disability level (p value=0.021). Conclusions From a multi-stakeholder perspective, the selection of an appropriate treatment for DME patients should guarantee patient safety and maximize the visual acuity improvement and treatment efect duration. It should also contribute to system sustainability by being afordable, it should have a positive impact on HRQoL, and it should prevent disability

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Pasado y futuro de la infección por VIH. Un documento basado en la opinión de expertos

[EN] HIV infection is now almost 40 years old. In this time, along with the catastrophe and tragedy that it has entailed, it has also represented the capacity of modern society to take on a challenge of this magnitude and to transform an almost uniformly lethal disease into a chronic illness, compatible with a practically normal personal and relationship life. This anniversary seemed an ideal moment to pause and reflect on the future of HIV infection, the challenges that remain to be addressed and the prospects for the immediate future. This reflection has to go beyond merely technical approaches, by specialized professionals, to also address social and ethical aspects. For this reason, the Health Sciences Foundation convened a group of experts in different aspects of this disease to discuss a series of questions that seemed pertinent to all those present. Each question was presented by one of the participants and discussed by the group. The document we offer is the result of this reflection.[ES] La infección por VIH cumple ahora casi 40 años de existencia. En este tiempo, junto a la catástrofe y la tragedia que ha supuesto, ha representado también la capacidad de la sociedad moderna de asumir un reto de esta magnitud y de transformar, gracias al tratamiento antirretroviral, una enfermedad mayoritariamente letal en una enfermedad crónica, compatible con una vida personal y de relación prácticamente normales. Este aniversario parecía un momento idóneo para pararse a reflexionar sobre el futuro de la infección VIH, los retos que todavía quedan por abordar y las perspectivas para el inmediato futuro. Esa reflexión tiene que ir más allá de planteamientos meramente técnicos, de profesionales especializados, para abordar aspectos sociales y éticos. Por este motivo, la Fundación de Ciencias de la Salud convocó a un grupo de expertos en distintos aspectos de esta infección para discutir una serie de preguntas que parecieron pertinentes a todos los convocados. Cada pregunta era expuesta por uno de los participantes y discutida por el grupo. El documento que ofrecemos es el resultado de esa reflexión.For transparency purposes, we would like to inform you that GSK has contributed to the funding of this publicationPeer reviewe

Urinary tract infections and post-operative fever in percutaneous nephrolithotomy

Purpose: To review the incidence of UTIs, post-operative fever, and risk factors for post-operative fever in PCNL patients. Materials and methods: Between 2007 and 2009, consecutive PCNL patients were enrolled from 96 centers participating in the PCNL Global Study. Only data from patients with pre-operative urine samples and who received antibiotic prophylaxis were included. Pre-operative bladder urine culture and post-operative fever (>38.5°C) were assessed. Relationship between various patient and operative factors and occurrence of post-operative fever was assessed using logistic regression analyses. Results: Eight hundred and sixty-five (16.2%) patients had a positive urine culture; Escherichia coli was the most common micro-organism found in urine of the 350 patients (6.5%). Of the patients with negative pre-operative urine cultures, 8.8% developed a fever post-PCNL, in contrast to 18.2% of patients with positive urine cultures. Fever developed more often among the patients whose urine cultures consisted of Gram-negative micro-organisms (19.4-23.8%) versus those with Gram-positive micro-organisms (9.7-14.5%). Multivariate analysis indicated that a positive urine culture (odds ratio [OR] = 2.12, CI [1.69-2.65]), staghorn calculus (OR = 1.59, CI [1.28-1.96]), pre-operative nephrostomy (OR = 1.61, CI [1.19-2.17]), lower patient age (OR for each year of 0.99, CI [0.99-1.00]), and diabetes (OR = 1.38, CI [1.05-1.81]) all increased the risk of post-operative fever. Limitations include the use of fever as a predictor of systemic infection. Conclusions: Approximately 10% of PCNL-treated patients developed fever in the post-operative period despite receiving antibiotic prophylaxis. Risk of post-operative fever increased in the presence of a positive urine bacterial culture, diabetes, staghorn calculi, and a pre-operative nephrostomy. © 2012 The Author(s)