State of the art in benefit-risk analysis: medicines.

Benefit-risk assessment in medicine has been a valuable tool in the regulation of medicines since the 1960s. Benefit-risk assessment takes place in multiple stages during a medicine's life-cycle and can be conducted in a variety of ways, using methods ranging from qualitative to quantitative. Each benefit-risk assessment method is subject to its own specific strengths and limitations. Despite its widespread and long-time use, benefit-risk assessment in medicine is subject to debate and suffers from a number of limitations and is currently still under development. This state of the art review paper will discuss the various aspects and approaches to benefit-risk assessment in medicine in a chronological pathway. The review will discuss all types of benefit-risk assessment a medicinal product will undergo during its lifecycle, from Phase I clinical trials to post-marketing surveillance and health technology assessment for inclusion in public formularies. The benefit-risk profile of a drug is dynamic and differs for different indications and patient groups. In the end of this review we conclude benefit-risk analysis in medicine is a developed practice that is subject to continuous improvement and modernisation. Improvement not only in methodology, but also in cooperation between organizations can improve benefit-risk assessment.

State of the art in benefit-risk analysis: consumer perception.

Benefit and risk perception with respect to food consumption, have been a part of human daily life from beginning of time. In today's society the food chain is long with many different types of actors and low degree of transparency. Making informed food choices where knowledge of benefits and risks is part of the decision making process are therefore complicated for consumers. Thus, to understand how consumers perceive benefits and risks of foods, their importance in relation to quality evaluations are aspects that need to be addressed. The objective of this paper is to discuss state of the art in understanding consumer perceptions of benefits and risks of foods in order to improve understanding of consumer behaviour in the food domain. Risks may be associated with both acute and long term consequences, some of which may have serious effects. Perceived risks are connected to morbidity and mortality along two dimensions relating to unknown risk, and to which extent the risk is dreaded by the consumer. Unfamiliar, uncertain, unknown, uncontrollable, and severe consequences are some factors associated with risk perception. Novel food processing techniques, for instance, score high on several of these parameters and are consequently regarded with suspicion and perceived as risky by consumers. On a daily basis, benefits of foods and food consumption are more important in most consumers' minds than risks. Benefits are often associated with food's ability to assuage hunger, and to provide pleasure through eating and socialising. In addition, two main categories of benefits that are important for acceptance of product innovations are health and environmental benefits. Benefit and risk perception of foods seem to be inversely correlated, so when something is perceived as being highly beneficial, it is correspondingly perceived as having low risk. However, slightly different paths are used in the formation of these perceptions; benefit perception is based on heuristics and experience, while risk perception is to a larger extent the result of cognitive information processing. Consumers are particularly conservative when it comes to perception and acceptance of foods compared to other products. Benefit-risk evaluations tend to be skewed towards acceptance of all that is traditional and well-known (benefits), and rejection or suspicion towards anything that is novel or highly processed (risks) regardless of actual risk. Knowledge of how consumers perceive benefits and risks of foods, may contribute to understanding benefit-risk perception in other areas related to personal, societal or environmental perspectives.

State of the art in benefit-risk analysis: economics and marketing-finance.

All market participants (e.g., investors, producers, consumers) accept a certain level of risk as necessary to achieve certain benefits. There are many types of risk including price, production, financial, institutional, and individual human risks. All these risks should be effectively managed in order to derive the utmost of benefits and avoid disruption and/or catastrophic economic consequences for the food industry. The identification, analysis, determination, and understanding of the benefit-risk trade-offs of market participants in the food markets may help policy makers, financial analysts and marketers to make well-informed and effective corporate investment strategies in order to deal with highly uncertain and risky situations. In this paper, we discuss the role that benefits and risks play in the formation of the decision-making process of market-participants, who are engaged in the upstream and downstream stages of the food supply chain. In addition, we review the most common approaches (expected utility model and psychometrics) for measuring benefit-risk trade-offs in the economics and marketing-finance literature, and different factors that may affect the economic behaviour in the light of benefit-risk analyses. Building on the findings of our review, we introduce a conceptual framework to study the benefit-risk behaviour of market participants. Specifically, we suggest the decoupling of benefits and risks into the separate components of utilitarian benefits, hedonic benefits, and risk attitude and risk perception, respectively. Predicting and explaining how market participants in the food industry form their overall attitude in light of benefit-risk trade-offs may be critical for policy-makers and managers who need to understand the drivers of the economic behaviour of market participants with respect to production, marketing and consumption of food products.

State of the art in benefit-risk analysis: introduction.

Risk-taking is normal in everyday life if there are associated (perceived) benefits. Benefit-Risk Analysis (BRA) compares the risk of a situation to its related benefits and addresses the acceptability of the risk. Over the past years BRA in relation to food and food ingredients has gained attention. Food, and even the same food ingredient, may confer both beneficial and adverse effects. Measures directed at food safety may lead to suboptimal or insufficient levels of ingredients from a benefit perspective. In BRA, benefits and risks of food (ingredients) are assessed in one go and may conditionally be expressed into one currency. This allows the comparison of adverse and beneficial effects to be qualitative and quantitative. A BRA should help policy-makers to make more informed and balanced benefit-risk management decisions. Not allowing food benefits to occur in order to guarantee food safety is a risk management decision much the same as accepting some risk in order to achieve more benefits. BRA in food and nutrition is making progress, but difficulties remain. The field may benefit from looking across its borders to learn from other research areas. The BEPRARIBEAN project (Best Practices for Risk-Benefit Analysis: experience from out of food into food; http://en.opasnet.org/w/Bepraribean) aims to do so, by working together with Medicines, Food Microbiology, Environmental Health, Economics & Marketing-Finance and Consumer Perception. All perspectives are reviewed and subsequently integrated to identify opportunities for further development of BRA for food and food ingredients. Interesting issues that emerge are the varying degrees of risk that are deemed acceptable within the areas and the trend towards more open and participatory BRA processes. A set of 6 'state of the art' papers covering the above areas and a paper integrating the separate (re)views are published in this volume.

State of the art in benefit-risk analysis: food microbiology.

Over the past years benefit-risk analysis (BRA) in relation to foods and food ingredients has gained much attention; in Europe and worldwide. BRA relating to food microbiology is however a relatively new field of research. Microbiological risk assessment is well defined but assessment of microbial benefits and the weighing of benefits and risk has not been systematically addressed. In this paper the state of the art in benefit-risk analysis in food microbiology is presented, with a brief overview of microbiological food safety practices. The quality and safety of foods is commonly best preserved by delaying the growth of spoilage bacteria and contamination by bacterial pathogens. However, microorganisms in food can be both harmful and beneficial. Many microorganisms are integral to various food production processes e.g. the production of beer, wine and various dairy products. Moreover, the use of some microorganisms in the production of fermented foods are often claimed to have beneficial effects on food nutrition and consumer health. Furthermore, food safety interventions leading to reduced public exposure to foodborne pathogens can be regarded as benefits. The BRA approach integrates an independent assessment of both risks and benefits and weighs the two using a common currency. Recently, a number of initiatives have been launched in the field of food and nutrition to address the formulation of the benefit-risk assessment approach. BRA has recently been advocated by EFSA for the public health management of food and food ingredients; as beneficial and adverse chemicals can often be found within the same foods and even the same ingredients. These recent developments in the scoping of BRA could be very relevant for food microbiological issues. BRA could become a valuable methodology to support evaluations and decision making regarding microbiological food safety and public health, supplementing other presently available policy making and administrative tools for microbiological food safety management.

State of the art in benefit-risk analysis: food and nutrition.

Benefit-risk assessment in food and nutrition is relatively new. It weighs the beneficial and adverse effects that a food (component) may have, in order to facilitate more informed management decisions regarding public health issues. It is rooted in the recognition that good food and nutrition can improve health and that some risk may be acceptable if benefit is expected to outweigh it. This paper presents an overview of current concepts and practices in benefit-risk analysis for food and nutrition. It aims to facilitate scientists and policy makers in performing, interpreting and evaluating benefit-risk assessments. Historically, the assessments of risks and benefits have been separate processes. Risk assessment is mainly addressed by toxicology, as demanded by regulation. It traditionally assumes that a maximum safe dose can be determined from experimental studies (usually in animals) and that applying appropriate uncertainty factors then defines the 'safe' intake for human populations. There is a minor role for other research traditions in risk assessment, such as epidemiology, which quantifies associations between determinants and health effects in humans. These effects can be both adverse and beneficial. Benefit assessment is newly developing in regulatory terms, but has been the subject of research for a long time within nutrition and epidemiology. The exact scope is yet to be defined. Reductions in risk can be termed benefits, but also states rising above 'the average health' are explored as benefits. In nutrition, current interest is in 'optimal' intake; from a population perspective, but also from a more individualised perspective. In current approaches to combine benefit and risk assessment, benefit assessment mirrors the traditional risk assessment paradigm of hazard identification, hazard characterization, exposure assessment and risk characterization. Benefit-risk comparison can be qualitative and quantitative. In a quantitative comparison, benefits and risks are expressed in a common currency, for which the input may be deterministic or (increasingly more) probabilistic. A tiered approach is advocated, as this allows for transparency, an early stop in the analysis and interim interaction with the decision-maker. A general problem in the disciplines underlying benefit-risk assessment is that good dose-response data, i.e. at relevant intake levels and suitable for the target population, are scarce. It is concluded that, provided it is clearly explained, benefit-risk assessment is a valuable approach to systematically show current knowledge and its gaps and to transparently provide the best possible science-based answer to complicated questions with a large potential impact on public health.

State of the art in benefit-risk analysis: environmental health.

Environmental health assessment covers a broad area: virtually all systematic analysis to support decision making on issues relevant to environment and health. Consequently, various different approaches have been developed and applied for different needs within the broad field. In this paper we explore the plurality of approaches and attempt to reveal the state-of-the-art in environmental health assessment by characterizing and explicating the similarities and differences between them. A diverse, yet concise, set of approaches to environmental health assessment is analyzed in terms of nine attributes: purpose, problem owner, question, answer, process, use, interaction, performance and establishment. The conclusions of the analysis underline the multitude and complexity of issues in environmental health assessment as well as the variety of perspectives taken to address them. In response to the challenges, a tendency towards developing and applying more inclusive, pragmatic and integrative approaches can be identified. The most interesting aspects of environmental health assessment are found among these emerging approaches: (a) increasing engagement between assessment and management as well as stakeholders, (b) strive for framing assessments according to specific practical policy needs, (c) integration of multiple benefits and risks, as well as (d) explicit incorporation of both scientific facts and value statements in assessment. However, such approaches are yet to become established, and many contemporary mainstream environmental health assessment practices can still be characterized as relatively traditional risk assessment.

Looking beyond borders: integrating best practices in benefit-risk analysis into the field of food and nutrition.

An integrated benefit-risk analysis aims to give guidance in decision situations where benefits do not clearly prevail over risks, and explicit weighing of benefits and risks is thus indicated. The BEPRARIBEAN project aims to advance benefit-risk analysis in the area of food and nutrition by learning from other fields. This paper constitutes the final stage of the project, in which commonalities and differences in benefit-risk analysis are identified between the Food and Nutrition field and other fields, namely Medicines, Food Microbiology, Environmental Health, Economics and Marketing-Finance, and Consumer Perception. From this, ways forward are characterized for benefit-risk analysis in Food and Nutrition. Integrated benefit-risk analysis in Food and Nutrition may advance in the following ways: Increased engagement and communication between assessors, managers, and stakeholders; more pragmatic problem-oriented framing of assessment; accepting some risk; pre- and post-market analysis; explicit communication of the assessment purpose, input and output; more human (dose-response) data and more efficient use of human data; segmenting populations based on physiology; explicit consideration of value judgments in assessment; integration of multiple benefits and risks from multiple domains; explicit recognition of the impact of consumer beliefs, opinions, views, perceptions, and attitudes on behaviour; and segmenting populations based on behaviour; the opportunities proposed here do not provide ultimate solutions; rather, they define a collection of issues to be taken account of in developing methods, tools, practices and policies, as well as refining the regulatory context, for benefit-risk analysis in Food and Nutrition and other fields. Thus, these opportunities will now need to be explored further and incorporated into benefit-risk practice and policy. If accepted, incorporation of these opportunities will also involve a paradigm shift in Food and Nutrition benefit-risk analysis towards conceiving the analysis as a process of creating shared knowledge among all stakeholders.

Characteristics of injured skiers in Norway. A case-control study.

A case-control study investigating the characteristics of injured versus uninjured skiers was carried out. The study comprised patients (n = 67) who had received medical treatment for ski injuries at a hospital in Norway in 1993, and controls (n = 227) taken from the same population but who had not sustained any ski injuries. The results showed that the hospital cases skied more often, were more confident in their skiing ability, had a higher education but that the younger members of this group tended to be less safety conscious compared with the corresponding controls. A reduction in the risk of ski injury might be possible if younger persons could be encouraged to adopt the same level of safety behaviour as older persons.

Occurrence and trends in ski injuries in Norway.

OBJECTIVES: To provide an overview of ski injuries in Norway and to describe the changes between 1990 and 1996. METHODS: All ski injuries (7966) treated at four hospitals providing health care to a defined population of about 11% of the Norwegian population were registered prospectively from 1990 to 1996. For this study, 6462 injuries sustained in cross country skiing, downhill skiing, telemark skiing, and snowboarding were selected for further analysis. RESULTS: The relative distribution of ski injuries by type of skiing changed significantly from 1990 to 1996 (p<0.001). Injuries from snowboarding showed the highest relative increase, and those sustained during downhill skiing showed a decline. The proportion of fractures in all types of skiing increased during the study period (p=0.001). The proportion of injuries to knee/lower leg decreased and the proportion to the forearm/wrist/hand increased during the study period (p=0.03). The mean age of the injured skiers differed significantly among the different types of skiing activity (p<0.001): cross country skiers were the oldest followed by telemark skiers, downhill skiers, and snowboarders. CONCLUSIONS: Ski injury surveillance results in early detection of changes in temporal injury trends, allowing timely adjustment of injury prevention strategies. Injuries from snowboarding are on the increase in Norway, warranting more effective injury prevention measures.

Safety measures taken by Norwegian mothers.

OBJECTIVES: To identify predictors of the adoption of safety measures by mothers of 2 year old children. SETTING: 26 municipalities in the county of Sogn and Fjordane, and four municipalities in the county of Møre and Romsdal in Norway. METHODS: Data was collected by questionnaires mailed to all mothers of 2 year olds in the 30 municipalities (response rate 70.7%, n = 1233). Information was obtained on socioeconomic variables, the child's injury history, adoption of safety measures, and variables describing mother's health related beliefs (parent health locus of control) and the value of health (health value). RESULTS: Income, municipality of residence, age of the mother, and marital status were significantly associated with the reported adoption of safety measures. High income and older, married mothers were positively associated with the adoption of safety measures. CONCLUSIONS: The significant effect of income on the adoption of safety measures, underlined by the fact that safety measures were less often adopted by young single mothers, may indicate that the implementation of structural measures such as loan schemes and subsidies, are necessary to increase the adoption of child safety measures. The lack of association between education and social cognitive beliefs, respectively, and the adoption of safety measures, offer less optimism for traditional health education initiatives.

[Risk of injuries among older drivers]. / Personskaderisiko for eldre bilførere.

In a population of 307,486 persons living in four Norwegian cities a total of 2,189 road traffic injuries requiring treatment in hospitals or casualty wards occurred in 1990. 4.4% of the injured were between 65-74 years of age, and 2.9% were older than 75. The incidence of injuries from road traffic accidents was greatest among the youngest group (18-24 years), and decreased with increasing age. We also analyzed the traffic accident risk per million kilometers driven. The driver's risk of injury was highest for adolescents (18-24 years), and decreased with increasing age (up to 75 years). The youngest driver runs the greatest risk of injury in traffic. Drivers in the 65-75 age group have a lower risk of injury per kilometers driven, in this group the incidence of traffic accidents is lower than the average for all drivers. The injury statistics provide no indication that older drivers should be required to renew their license more frequently.

Opposite effect of cold on energetic efficiency in normal and obese Wistar rats with hypothalamic lesions.

Reduced thermogenesis in brown adipose tissue (BAT) may contribute to increased energetic efficiency and obesity in rats with ventromedial hypothalamic (VMH) lesions. Thermogenic activity of BAT is a function of the environmental temperature. If a relationship exists, it follows that the increased energetic efficiency of VMH-lesioned rats likewise should be governed by temperature. We have therefore investigated the energy balance of normal and VMH-lesioned rats housed at 30 degrees C and 10 degrees C. Experiments at differing feeding levels allowed calculation of maintenance energy requirements and the net energetic efficiencies of each group. VMH-lesioned rats at thermoneutrality (30 degrees C) accumulated more body fat at all feeding levels than did normal rats. Maintenance energy requirement was reduced, but the net energetic efficiency did not differ significantly from normal. The reduced maintenance energy requirement of lesioned rats persisted at 10 degrees C. Net energetic efficiency decreased in normal rats acclimated to cold but increased in the lesioned group. The difference was significant (P less than 0.05). The cold-induced increase in interscapular brown adipose tissue (IBAT) oxidative capacity of VMH-lesioned rats was only half that of normal rats. Differences in BAT thermogenesis may be the basis for the differing temperature effects on net energetic efficiency.