Medicines for an aging population: The EMA perspective and policies.

The European Medicines Agency adopted their Geriatric Medicines Strategy more than a decade ago. The strategy aims at elucidating the evidence basis for marketing authorization of new medicines which will be used in the older population, and at ensuring the appropriate communication of findings to the patient and healthcare provider. During the past decade new tools and data sources have emerged to support the strategy goals, and their use should be considered. Possible concrete actions are presented to improve the design of clinical trials, the data collection both pre- and post-approval, the assessment of the findings, and the communication to assist informed prescription and safe medicine taking. Implementation and prioritization of these actions should be done from the perspective of addressing the needs of patients while maximizing efficient use of resources, with the aim of integrating geriatric aspects into routine medicines development and assessment.

Inclusion of functional measures and frailty in the development and evaluation of medicines for older adults.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E7, the guidance for the conduct of clinical trials in people older than age 65 years, dates from 1994. Since then, the inclusion of older people in clinical trials has hardly improved, particularly for the oldest old age group (individuals older than age 75 years), which is the fastest growing demographic bracket in the EU. Even though most medications are taken by this group, relevant endpoints and safety outcomes for this cohort are rarely included and reported, both in clinical trials and regulatory approval documents. To improve the critical appraisal and the regulatory review of medicines taken by frail older adults, eight recommendations are presented and discussed in this Health Policy. These recommendations are brought together from different perspectives and experience of the treatment of older patients. On one side, the perspective of medical practitioners from various clinical disciplines, with their direct experience of clinical decision making; on the other, the perspective of regulators assessing the data submitted in medicine registration dossiers, their relevance to the risk-benefit balance for older patients, and the communication of the findings in the product information. Efforts to improve the participation of older people in clinical trials have been in place for more than a decade, with little success. The recommendations presented here are relevant for stakeholders, authorities, pharmaceutical companies, and researchers alike, as the implementation of these measures is not under the capacity of a single entity. Improving the inclusion of frail older adults requires awareness, focus, and action on the part of those who can effect a much needed change.

Mapping the global prevalence of bovine viral diarrhoea virus infection and its associated mitigation programmes.

The aim of this study was to collect information on the global distribution of the prevalence of bovine viral diarrhoea virus (BVDV) and respective mitigation programmes, using a questionnaire and literature review to provide as complete a picture of the worldwide BVDV situation as possible. This study collated information on 107 countries with respect to mitigation activities and 88 countries regarding BVDV infections during the observation period (1960-2017). A heterogeneous epidemiological situation for both BVDV prevalence and the presence of mitigation programmes was observed. The results of this analysis could be used to increase the visibility of the distribution of BVDV, to provide supporting data for global animal disease databases and to assist veterinary public health authorities in the decision-making processes to establish mitigation activities.

A systematic review of financial and economic assessments of bovine viral diarrhea virus (BVDV) prevention and mitigation activities worldwide.

Infection with bovine viral diarrhea virus (BVDV) results in major economic losses either directly through decreased productive performance in cattle herds or indirectly, such as through expenses for control programs. The aim of this systematic review was to review financial and/or economic assessment studies of prevention and/or mitigation activities of BVDV at national, regional and farm level worldwide. Once all predefined criteria had been met, 35 articles were included for this systematic review. Studies were analyzed with particular focus on the type of financially and/or economically-assessed prevention and/or mitigation activities. Due to the wide range of possible prevention and/or mitigation activities, these activities were grouped into five categories: i) control and/or eradication programs, ii) monitoring or surveillance, iii) prevention, iv) vaccination and v) individual culling, control and testing strategies. Additionally, the studies were analyzed according to economically-related variables such as efficiency, costs or benefits of prevention and/or mitigation activities, the applied financial and/or economic and statistical methods, the payers of prevention and/or mitigation activities, the assessed production systems, and the countries for which such evaluations are available. Financial and/or economic assessments performed in Europe were dominated by those from the United Kingdom, which assessed mostly vaccination strategies, and Norway which primarily carried out assessments in the area of control and eradication programs; whereas among non-European countries the United States carried out the majority of financial and/or economic assessments in the area of individual culling, control and testing. More than half of all studies provided an efficiency calculation of prevention and/or mitigation activities and demonstrated whether the inherent costs of implemented activities were or were not justified. The dairy sector was three times more likely to be assessed by the countries than beef production systems. In addition, the dairy sector was approximately eight times more likely to be assessed economically with respect to prevention and/or mitigation activities than calf and youngstock production systems. Furthermore, the private sector was identified as the primary payer of prevention and/or mitigation activities. This systematic review demonstrated a lack of studies relating to efficiency calculations, in particular at national and regional level, and the specific production systems. Thus, we confirmed the need for more well-designed studies in animal health economics in order to demonstrate that the implementation and inherent costs of BVDV prevention and/or mitigation activities are justified.

Antimicrobial drug use on Austrian dairy farms with special consideration of the use of "highest priority critically important antimicrobials".

The use of antibiotics in livestock production is coming under growing criticism. Beside overall antimicrobial use, specific substances listed by the WHO as "highest priority critically important antimicrobials" (HPCIAs)--these include fluoroquinolones, macrolides, 3rd and 4th generation cephalosporins, as well as glycopeptides--have been placed under specific restrictions and should only be applied in particular cases according to strict indication criteria. In this study, the consumption of antimicrobial substances on Austrian dairy farms was evaluated quantitatively. The data covered 8,027 prescription records on the use of antibiotics on 465 dairy farms. Eleven veterinary practices provided data from between four to 27 months during the period from 2008 to 2010 and the total consumption of antimicrobials was estimated. The amount of active substance(s) in grams used per livestock unit (g/LU) per year and the number of product-related daily doses used per livestock unit (n PrDD(LU)/LU) per year were determined as units of measurement. These parameters were estimated by applying Monte Carlo simulation techniques, respecting variances in annual working days of the veterinary practices as well as variances in the proportion of non-treated populations. Total antimicrobial consumption in the population-at-risk was determined to be 2.59 g/LU and 1.30 PrDD(LU)/LU per year. HPCIAs were used at a proportion of 24.6% (0.31 PrDD(LU)/LU) of the total consumption of antimicrobials for systemic and intramammary use. Of these, 3rd and 4th generation cephalosporins were most frequently administered, particularly for the treatment of mastitis and foot diseases. The total consumption of antimicrobials in Austrian dairy cattle production is negligible compared to their use in pig and poultry production systems. However, the use of HPCIAs, especially 3rd and 4th generation cephalosporins, should be minimised further.

The use of the "highest priority critically important antimicrobials" in 75 Austrian pig farms--evaluation of on-farm drug application data.

The World Health Organization lists antimicrobial substances which are essential for the treatment of specific infections in humans as "highest priority critically important antimicrobials" (HPCIAs): macrolides, fluoroquinolones, 3rd and 4th generation cephalosporins as well as glycopeptid antibacterials. The use of these substances in livestock husbandry should be restricted in order to minimise the risk of antimicrobial resistance. To date, there is little knowledge about the amounts of HPCIAs used in animal husbandry and the different animal species and diagnoses these antimicrobials are prescribed for. In a retrospective study, drug application data recorded from 2008 until 2011 from 75 conventional pig farms were evaluated. Data were assessed directly by the farmer at farm-level. The annual antimicrobial consumption was expressed in "weight of active substance(s) in [mg]" and "number of Daily Doses". Results were referred to the animal biomass, evaluated per pig age class (piglets, weaners, fattening pigs < 60 kg biomass; fattening pigs > 60 kg biomass, sows, boars) and broken down to some variables such as the substance class and the therapy indication. The focus was especially laid on the HPCIAs. The total usage of the HPCIAs in the study population was on average 3.0 mg/ kg/year; 1.1 UDD(kg)/kg/year; 0.2 ADD(kg)/kg/year and 0.6 PrDD(kg)/kg/year. This represents about 9%, 22%, 12% and 22% of total antimicrobial consumption, respectively, depending on the unit of measurement. Fattening farms showed the highest consumption of the named substances. The main part of the HPCIAs (nADD(kg)/year) was applied to weaners, piglets and fattening pigs < 60 kg. They played an important role in the therapies of piglets (approximately 40% of the total antimicrobial consumption in piglets). Macrolides played the major role within the HPCIAs and were mainly used for digestive tract diseases. A not negligible portion of macrolides was prescribed for metaphylactic and prophylactic measures.