Could Contracts between Pharmaceutical Firms and French Veterinarians Bias Prescription Behaviour: A Principal-Agency Theory Approach in the Context of Oligopolies.

In France, veterinarians can both prescribe and deliver veterinary medicines, which is a questionable situation from the perspective of antimicrobial use (AMU) reduction to avoid antimicrobial resistance (AMR). This situation places veterinarians in direct commercial relationships with the pharmaceutical industry as purchase contracts are signed between veterinarians and pharmaceutical companies. The aim of the present work is to analyse the relationships between veterinarians and pharmaceutical firms in the oligopoly market context of French veterinary medicine to determine whether the prescription behaviour of practitioners can be biased by joint prescription and delivery. Therefore, we develop an analysis based on principal-agent theory. Contracts between pharmaceutical companies and veterinarians during the 2008-2014 period were analysed based on 382 contracts related to 47 drugs belonging to eight main pharmaceutical firms (2320 observations). The price per unit after rebate of each drug and contract was calculated. The descriptive analysis demonstrated high disparity among the contracts across pharmaceutical firms with regard to the provisions of the contracts and how they are presented. Then, linear regression was used to explain the price per unit after rebate based on the explanatory variables, which included the yearly purchase objective, year, type of drug and type of rebate. The decrease in price per unit after rebate for each extra €1000 purchase objective per drug category was established to be €0.061 per 100 kg body weight for anticoccidiosis treatments, €0.029 per 100 kg body weight for anti-inflammatories, €0.0125 per 100 kg body weight and €0.0845 per animal for antiparasitics, and €0.031 per animal for intramammary antimicrobials. Applying agency theory reveals that veterinarians can be considered agents in the case of monopolistic situations involving pharmaceutical firms; otherwise, veterinarians are considered principals (oligopolistic situations in which at least several medicines have similar indications). The present study does not provide evidence suggesting that joint prescription and delivery may introduce any potential prescription bias linked to conflicts of interest under the market conditions during the 2008-2014 period.

The economics of antimicrobial resistance in veterinary medicine: Optimizing societal benefits through mesoeconomic approaches from public and private perspectives.

Antimicrobial resistance (AMR) is a global public health threat driven by a combination of factors, including antimicrobial use (AMU) and interactions among microorganisms, people, animals and the environment. The emergence and spread of AMR in veterinary medicine (AMR-V) arising from AMU in veterinary medicine (AMU-V) can be linked to individuals' economic behaviour and institutional context. We highlight the limitations of current microeconomic approaches and propose a mesoeconomic conceptual model of AMR-V that integrates actors' strategic and routine behaviours in their context from a dynamic perspective using the concepts of externality, globality and futurity. The global solution to AMR-V management relies on a trade-off between i) the global externality assessment of AMU-V with respect to AMR-V (public perspective) and ii) farm- or value chain-level marginal abatement cost evaluation (private perspective). The improvements realized by the proposed mesoeconomic conceptual model include i) the simultaneous fight against the emergence and spread of AMR-V and ii) a local decrease in AMU-V without any loss of competitiveness for private actors due to the development of adequate production standards. A set of generic equations describing the stepwise change in the scale of analysis is finally proposed. This original contribution to the global challenge of AMR through a mesoeconomic approach bring substantial improvement for better AMU. This model can be considered a way to smoothly promote institutional change and a call for public policies that support public private partnership in the development of adequate incentives. The model requires further development prior to its application in a given value-chain or territory.

The Use of Meta-Analysis for the Measurement of Animal Disease Burden: Losses Due to Clinical Mastitis as an Example.

The literature contains an extensive panel of studies focusing on the costs of animal diseases. The losses of an agriculture holding can be influenced by many factors since farming is a complex system and diseases are closely interrelated. Meta-analysis can be used to detect effects (i.e., change in clinical mastitis losses here) across studies and to identify factors that may influence those effects. This includes the external validity of the published study results with regard to the input parameters and the internal validity of the study, particularly how other diseases related to the target disease were accounted for. Mixed-effect meta-regressions were performed to estimate the mean clinical mastitis losses per case across the literature and to elucidate to what extent clinical mastitis losses are influenced by (i) general factors, such as etiology; (ii) the types of losses that contribute to the total mastitis losses; and (iii) prices. In total, 82 observations from nine studies were included in the meta-analysis to assess mean clinical mastitis losses per case. The multivariate meta-regression showed that etiology significantly influenced the clinical mastitis loss per case. The mean loss was determined to be €224 per case for all published etiologies. In detail, mean losses equalled €457 and €101 per case of clinical mastitis due to gram-negative and gram-positive bacteria, respectively, and €428 and €74 per case of clinical mastitis due to Escherichia coli and Staphylococcus aureus, respectively. Additionally, the mean loss obtained depended on whether diagnostic costs and reduced feed intake in cases of mastitis were included in the clinical mastitis loss calculation. The monetary values of labor cost, drug cost and culling cost, as well as treatment price (all included), significantly influenced the clinical mastitis losses per case. All other tested moderators were not associated with mastitis losses, highlighting the need for more standardized economic studies, for both methods and ways results are presented, and suggesting that the mastitis losses assessed in the literature cannot be extrapolated (limited external validity). Although meta-analyses are useful to overview the burden of diseases across studies, their ability to summarize extensive literature with various economic assessments is limited. These limitations in loss assessments also suggest the need to focus on management strategies rather than on pure monetary estimations of disease costs, at least for production diseases at the farm level.

How do veterinarians influence sales of antimicrobials? A spatial-temporal analysis of the French prescribing-delivery complex in cattle.

BACKGROUND: In animal agriculture, antimicrobials (AM) are used to control infectious diseases whose incidence and severity vary across production systems, but may contribute to select AM resistant bacteria, potentially disseminating in humans. Antimicrobial resistance (AMR) represents a public threat, leading policymakers to implement measures to reduce antimicrobial use (AMU). Investigating AMU patterns at prescriber's level, beyond national AMU trends, enables evaluation of substitutions between AM classes (occurring when one product is replaced by another), or average consumption per production system. Our aim was to identify the influence veterinarians would exert on AMU by quantifying substitution between AM products prescribed and delivered in similar therapeutic indications, in cattle production. METHODS: Monthly sales data on four critically important AM in five French areas (representative of production systems) were analysed from 2008 to 2013. We calculated the animal live weight receiving a treatment course and evaluated substitutions between brand-name and generic products, and between products from different AM classes with similar indications. RESULTS: Substitutions occurred, between products of the same class (macrolides) with similar indications, between generic and brand-name products (fluoroquinolones, ceftiofur, florfenicol) and between innovative and brand-name products (marbofloxacin, ceftiofur). Innovative products reaching the market represented between 2% and 40% of the yearly sales for a given molecule, depending on the active ingredient and the area. The introduction of generic products of fluoroquinolones and ceftiofur led to a moderate adoption of the generic product at the expense of the brand-name one, unlike in human health care where the adoption reaches up to 80%. CONCLUSION: Veterinary prescription remains a strong regulating power of AMU; substitutions only occurred for products with similar indications.

Business models of the French veterinary offices in rural areas and regulation of veterinary drug delivery.

French veterinarians are authorised to both prescribe and deliver drugs. This situation of conflict of interest is sometimes denounced as a potential source of over-prescription and overuse of veterinary antimicrobials, even if no evidence is available up to now. This leads to regular calls for separating prescription from drug delivery, even if the consequences of such separation are unknown. The present work aims at describing the business model of French veterinary offices and the expected impact of separation on those offices. A dataset of 15 million observations was built with structural and accounting data collected for the period 2015-2017 from French mixed veterinary offices. Results of the baseline scenario indicate that veterinary offices' profit generated from farm animal activities is mainly driven by drug delivery (about 70%), while profit from companion animal activities is mainly driven by medical acts (i.e., consultation and advice, surgery, and laboratory analysis) and sale of accessory products (about 65%). The net margin rate is higher than 25% for all activities, except for material selling. If drug delivery or sales associated with a medical act (same day, same client, and same animal) do not require additional human resources (alternative scenario), the net margin is reduced for medical acts. For both scenarios, a high variability is observed between veterinary offices. This shows that the profit of each activity is highly driven by time spent on the activities. Our results suggest that, in the case of restrictions on drug delivery by veterinarians, their profit may dramatically decrease, especially for farm animal practitioners and those with low medical acts profitability. Further work is needed to account for the high diversity of situations faced by veterinary offices and the sensitivity of their profitability to production costs.

Exposure assessment for dioxin-like PCBs intake from organic and conventional meat integrating cooking and digestion effects.

In this paper, exposure to Polychlorinated biphenyls (PCBs) related to bovine meat consumption is assessed based on multiples sources of data, namely data collected within the national research project "SoMeat" that objectively assesses the potential risks and benefits of organic and conventional food production systems in terms of contaminants respective contents. The work focuses on dioxin like PCBs in bovine meat in France. A modular Bayesian approach is proposed including measures after production, effect of cooking, levels and frequency of consumption and effect of digestion. In each module, a model is built and prior information can be integrated through previously acquired data commonly used in food risk assessment or vague priors. The output of the global model is the exposure including both production modes (organic and conventional) for three different cooking intensities (rare, medium, and well-done), before digestion and after digestion. The main results show that organic meat is more contaminated than conventional meat in mean after production stage and after cooking although cooking reduces the contamination level. This work is a first step of refined risk assessment integrating different steps such as cooking and digestion in the context of chemical risk assessment similarly to current microbiological risk assessments.

Ab initio study of the nature and stability of the defects and multi-vacancies in TaN. Comparison with TiN.

First principles calculations have been carried out to study the native single-defects and multi-vacancies in TaN and TiN with a cubic rocksalt structure mainly used as diffusion barriers. Our results indicate that vacancies are the most stable single-defects in both compounds and that nitrogen interstitial defects in tetrahedral interstitial site are significantly more stable in TaN than in TiN. The interactions between vacancies are attractive in TaN in contrast to the case of TiN. The vacancies show a much larger tendency to cluster and to form bi- and tri- vacancies in TaN than in TiN. We suggest that the number of d electrons might explain this difference in the defect stability. These results will have impact on the use of these materials as diffusion barrier.

Status report on education in the economics of animal health: results from a European survey.

Education on the use of economics applied to animal health (EAH) has been offered since the 1980s. However, it has never been institutionalized within veterinary curricula, and there is no systematic information on current teaching and education activities in Europe. Nevertheless, the need for economic skills in animal health has never been greater. Economics can add value to disease impact assessments; improve understanding of people's incentives to participate in animal health measures; and help refine resource allocation for public animal health budgets. The use of economics should improve animal health decision making. An online questionnaire was conducted in European countries to assess current and future needs and expectations of people using EAH. The main conclusion from the survey is that education in economics appears to be offered inconsistently in Europe, and information about the availability of training opportunities in this field is scarce. There is a lack of harmonization of EAH education and significant gaps exist in the veterinary curricula of many countries. Depending on whether respondents belonged to educational institutions, public bodies, or private organizations, they expressed concerns regarding the limited education on decision making and impact assessment for animal diseases or on the use of economics for general management. Both public and private organizations recognized the increasing importance of EAH in the future. This should motivate the development of teaching methods and materials that aim at developing the understanding of animal health problems for the benefit of students and professional veterinarians.

Herd-level and territorial-level factors influencing average herd somatic cell count in France in 2005 and 2006.

Mastitis is a multifactorial disease and the most costly dairy production issue. In spite of extensive literature on udder-health risk factors, effects of metabolic diseases, farmers' competencies and livestock farming system on somatic cells count (SCC) are sparsely described. Herd-level or territorial-level factors affecting monthly composite milk weighted mean cow SCC (CMSCC) were analysed with a linear mixed effect model. The average CMSCC was 266,000 cells/ml. Half of the herds had CMSCC >300,000 cells/ml for 2-6 months a year, and 15% of herds for more than 7 months a year. CMSCC was positively associated with the number of cows, having a beef or fattening herd in addition to the dairy herd, the monthly average days in milk, the yearly age at first calving, the yearly proportion of purchased cows and the yearly culling rate. Moreover, a positive association is reported between CMSCC and the monthly proportion of cows probably with subacute ruminal acidosis (fat percentage minus protein percentage ≤0·30%, for Holstein) and negative energy balance (protein to fat ratio ≤0·66, for Holstein), the yearly average calving interval, having at least one dead cow and the mean monthly temperature. The association was negative for a predominant breed other than Holstein, the monthly milk production, the yearly dry-off period length, the monthly first calving cow proportion, having an autumn calving peak, being a Good Breeding Practices member, the monthly number of days with rain, the altitude and the territorial cattle density. CMSCC varied widely among the 11 dairy production areas. In conclusion, this study showed the average CMSCC for the French dairy cows, compared with international results. Moreover, it quantified the contribution of several factors to CMSCC, in particular metabolic diseases and the farm environment.

Consumers' willingness to pay for beef direct sales. A regional comparison across the Pyrenees.

Willingness to pay (WTP) for direct market of beef is investigated in two Spanish and two French regions located on both sides of the Pyrenees. Given the novelty of this distribution system, especially in Spain, a contingent valuation approach is undertaken, and a double-bounded model is estimated. Different patterns of awareness, use and WTP are found across regions. Likewise, the profile of current and potential users of direct sale chains is investigated. Experience in the different stages involved from choice to final consumption of beef, intensity of varied beef consumption, familiarity with direct market of food in general, and beef in particular, are some of the relevant factors to explain WTP and the probability of getting engaged into a direct distribution system of beef.

The motivations and practice-area interests of first-year French veterinary students (2005-2008).

Concerns about new trends in the veterinary profession in several industrialized countries have received significant attention recently. We conducted an online survey among first-year veterinary students enrolled between 2005 and 2008 in France's four National Veterinary Schools (Ecoles Nationales Vétérinaires [ENV]) to inquire into what determined future graduates' practice-area interests and how they built a concept of their future work. A total of 1,080 students-or 70% of first-year students-responded to the survey. These students were predominantly of middle and higher social classes and most of them lived in urban areas. About 96% of the respondents had made the ENV their first choice when taking the entrance examination. In total, 39.7% declared "vocation" as the leading factor influencing their career choice. Together, the three leading practice types (wild animals, pets, and mixed) contemplated by students after graduating amount to 64.7% of the points awarded. Practice types that are not directly related to animal health were disregarded in this analysis. The results convey both how early and how firmly the choice of the veterinary career is made. They highlight the preponderance of the image of the veterinarian as an "animal doctor," the gap between the respective proportions of practice areas in the current employment pattern of veterinarians, and the aspirations of students upon admission to the ENV. A longitudinal study after one year is needed to test whether or not these career choices change during the five years of the ENV program under the influence of teaching and extramural studies.