Ralf Wilhelm

Farm questionnaires for monitoring genetically modified crops: a case study using GM maize.

Monitoring is a statutory requirement for the cultivation of genetically modified (GM) crops in the European Community. Questionnaires for farmers to report on observations of effects linked with the cultivation of GM crops can form a useful part of a monitoring regime. A questionnaire for GM maize (Zea mays L.) was designed, with questions focusing on potential effects related to the GM maize grown, as well as on background information about cultivation methods and on individual field situations. In this paper we present the methodological approach of the monitoring regime, the structuring of the data, and the contents and structure of the questionnaire. The statistical requirements and background for an appropriate evaluation and interpretation of the data are described. Results of interviews made from 2001 to 2005 are also presented. It is envisaged that this approach will be developed for monitoring other cultivated GM plants and traits, and may be applicable in monitoring certain non-farmed environments.

Monitoring the commercial cultivation of Bt maize in Europe – conclusions and recommendations for future monitoring practice

Genetically modified (GM) maize expressing the insecticidal protein Cry1Ab from Bacillus thuringiensis (Bt maize) is the only GM crop planted commercially in the European Union (EU). Cultivation in accordance with Directive 2001/18/EC demands post-market environmental monitoring (PMEM) to ensure the detection and prevention of adverse effects on the environment possibly deriving from commercial cultivation. Based on a seminar organized in Berlin, Germany, in April 2008 by the EU-funded Biosafenet project, the present paper reflects on experiences and hurdles faced during the implementation of PMEM for Bt maize. It reviews and reconsiders PMEM programs of Bt maize in view of existing experiences from cultivation, current monitoring activities initiated by Member States and applicants, proposed monitoring strategies and methods as well as potential environmental impacts of cultivation. Future challenges will arise from large-scale and cumulative cultivation of various events. This will demand optimized organization structures for data collation and integration to support further decision-making and management.

A framework for stakeholder engagement during systematic reviews and maps in environmental management

People have a stake in conservation and environmental management both for their own interests and the sake of the environment itself. Environmental decision-making has changed somewhat in recent decades to account for unintentional impacts on human wellbeing. The involvement of stakeholders in environmental projects has been recognised as critical for ensuring their success and equally for the syntheses of evidence of what works, where, and for whom, providing key benefits and challenges. As a result of increased interest in systematic reviews of complex management issues, there is a need for guidance in best practices for stakeholder engagement. Here, we propose a framework for stakeholder engagement in systematic reviews/systematic maps, highlighting recommendations and advice that are critical for effective, efficient and meaningful engagement of stakeholders. The discussion herein aims to provide a toolbox of stakeholder engagement activities, whilst also recommending approaches from stakeholder engagement research that may prove to be particularly useful for systematic reviews and systematic maps.

Enhancing the interpretation of statistical P values in toxicology studies: implementation of linear mixed models (LMMs) and standardized effect sizes (SESs)

Abstract In this paper, we compare the traditional ANOVA approach to analysing data from 90-day toxicity studies with a more modern LMM approach, and we investigate the use of standardized effect sizes. The LMM approach is used to analyse weight or feed consumption data. When compared to the week-by-week ANOVA with multiple test results per week, this approach results in only one statement on differences in weight development between groups. Standardized effect sizes are calculated for the endpoints: weight, relative organ weights, haematology and clinical biochemistry. The endpoints are standardized, allowing different endpoints of the same study to be compared and providing an overall picture of group differences at a glance. Furthermore, in terms of standardized effect sizes, statistical significance and biological relevance are displayed simultaneously in a graph.

Gestaltung des Monitoring der Auswirkungen gentechnisch veränderter Pflanzen im Agrarökosystem

Zusammenfassung:Im März 2001 verabschiedeten das Europäische Parlament und der Rat die Richtlinie 2001/18/EG über die absichtliche Freisetzung gentechnisch veränderter Organismen in die Umwelt, die das Monitoring von gentechnisch veränderten Organismen, die in den Verkehr gebracht werden, vorschreibt. Seither gibt es eine rege Diskussion zu wissenschaftlichen, organisatorischen und rechtlichen Fragen ihrer Umsetzung. An der Diskussion beteiligt sich u.a. die Institutionen-übergreifende Arbeitsgruppe ,,Anbaubegleitendes Monitoring gentechnisch veränderter Pflanzen im Agrarökosystem” unter Federführung der Biologischen Bundesanstalt für Land- und Forstwirtschaft, der die Autoren angehören. Es werden Vorschläge und Gestaltungsansätze für ein Monitoring vorgestellt, die sich im Schwerpunkt auf gentechnisch veränderte Pflanzen im Agrarökosystem beziehen.Summary:In March 2001, the European Parliament passed the Directive 2001/18/EU (concerning the deliberate release of genetically modified organisms), which demands that genetically modified organisms are monitored after placing them on the market as, or in a product. The purpose is to protect the human health and the environment from possible harm coming from these organisms. Since then there is an active discussion of scientific, organisational and legal questions regarding the installation in national laws. Among others the working party ,,Anbaubegleitendes Monitoring gentechnisch veränderter Pflanzen im Agrarökosystem” guided by the Federal Biological Research Centre for Agriculture and Forestry serves as a forum attended by several public and private institutions. The authors are members of this group. In this paper suggestions about the design of a monitoring regime are presented, focussing on genetically modified plants in agroecosystems.

Can systematic reviews inform GMo risk assessment and risk management

Systematic reviews represent powerful tools to identify, collect, synthesize, and evaluate primary research data on specific research questions in a highly standardized and reproducible manner. They enable the defensible synthesis of outcomes by increasing precision and minimizing bias whilst ensuring transparency of the methods used. This makes them especially valuable to inform evidence-based risk analysis and decision making in various topics and research disciplines. Although seen as a “gold standard” for synthesizing primary research data, systematic reviews are not without limitations as they are often cost, labor and time intensive and the utility of synthesis outcomes depends upon the availability of sufficient and robust primary research data. In this paper, we (1) consider the added value systematic reviews could provide when synthesizing primary research data on genetically modified organisms (GMO) and (2) critically assess the adequacy and feasibility of systematic review for collating and analyzing data on potential impacts of GMOs in order to better inform specific steps within GMO risk assessment and risk management. The regulatory framework of the EU is used as an example, although the issues we discuss are likely to be more widely applicable.

Variability of control data and relevance of observed group differences in five oral toxicity studies with genetically modified maize MON810 in rats.

The data of four 90-day feeding trials and a 1-year feeding trial with the genetically modified (GM) maize MON810 in Wistar Han RCC rats performed in the frame of EU–funded project GRACE were analysed. Firstly, the data obtained from the groups having been fed the non–GM maize diets were combined to establish a historical control data set for Wistar Han RCC rats at the animal housing facility (Slovak Medical University, Bratislava, Slovakia). The variability of all parameters is described, and the reference values and ranges have been derived. Secondly, the consistency of statistically significant differences found in the five studies was analysed. In order to do so, the body weight development, organ weight, haematology and clinical biochemistry data were compared between the studies. Based on the historical control data, equivalence ranges for these parameters were defined, and the values measured in the GM maize–fed groups were compared with these equivalence ranges. Thirdly, the (statistical) power of these feeding studies with whole food/feed was assessed and detectable toxicologically relevant group differences were derived. Linear mixed models (LMM) were applied, and standardized effect sizes (SES) were calculated in order to compare different parameters as well as to provide an overall picture of group and study differences at a glance. The comparison of the five feeding trials showed a clear study effect in the control data. It also showed inconsistency both in the frequency of statistically significant differences and in the difference values between control and test groups.

European-wide GMO-monitoring data management and analysis

Abstract:Since GMO monitoring is an European challenge, data from different observation systems and different cultivation areas must be managed and analysed in a centralised way. Well-founded statistics that powerfully can analyse monitoring data for possible adverse effects of GMO cultivation needs precise definitions of monitoring characters and quantifications of such effects. Whereas today the fundamental concept for GMO monitoring seems to be clear (identification of protection goals, derivation of monitoring characters, analysis of these characters for adverse effects) the kind of gathering data, especially the use of existing networks, and therefore the amount of monitoring characters and their handling is still controversial.Of course GMO monitoring should take place where GMOs are cultivated. Therefore the network of monitoring locations is settled by cultivation areas. As a basic tool for GMO monitoring farm questionnaires have been established. Data gathered on monitoring characters for protection goals in the agro ecosystem build the fundamental database for the analyses on possible adverse effects. Additional information on characters which may be not provided by this tool can be gathered by existing environmental observation networks which were established to act as continuous and comprehensive reporting systems and therefore to survey and analyse environmental data.Considering the data management and analysis, each observation system has its own, but similar structure: monitoring characters are surveyed and analysed for trends or significant differences. While the data from farm questionnaires are clearly analysed for a GMO effect, the existing networks report on trends in general – where the causes for unusual or adverse trends – may even be unknown.A practical GMO monitoring therefore should use these systems by checking the reports on unusual trends for their possible connection to GMO cultivation. This can only be done by linking their data to the data gathered from cultivation sites, and therefore to the basic monitoring database – i. e. the data being surveyed by farm questionnaires.The data management systems and possible intersection points of farm questionnaires and other existing networks will be presented. A proposal for the organisation of a European-wide monitoring will be given.

Inclusive development and prioritization of review questions in a highly controversial field of regulatory science

How to best assess potential health, environmental and other impacts of genetically modified organisms (GMOs) and how to interpret the resulting evidence base have been long-standing controversial issues in the EU. As a response, transparency and inclusiveness became a major focus of regulatory science activities in the GMO impact area. Nevertheless, nearly three decades of controversies resulted in a heavily polarized policy environment, calling for further efforts. Against this backdrop the EU funded project GRACE explored the value of evidence synthesis approaches for GMO impact assessment and developed an evidence synthesis framework with a strong emphasis on openness, stakeholder engagement, transparency, and responsiveness to tackle regulatory science challenges. This framework was tested and implemented in the course of 14 systematic reviews or maps conducted on selected review questions spanning potential health, environmental, and socioeconomic impacts of GMOs. An inclusive development and prioritisation of review questions is of key importance in evidence synthesis as it helps to provide a better link between stakeholder demands and concerns and policy relevant outcomes. This paper, therefore, places a particular focus on the stakeholder involvement strategy developed and experiences gathered during this particular step in the course of the GRACE project. Based on this experience, possible lessons for future engagement exercises in highly controversial fields of regulatory science are discussed.

Proposed criteria for the evaluation of the scientific quality of mandatory rat and mouse feeding trials with whole food/feed derived from genetically modified plants

In recent years, animal feeding trials conducted with whole food/feed have been a focal issue in the controversy on the safety assessment of genetically modified (GM) plants and derived food/feed. Within the scientific community and among stakeholders, quite different views have been expressed on how these studies should be conducted, analysed and interpreted, what they might add in terms of information relevant to safety and whether 90-day rodent feeding trials should be mandatory. Despite the fact that the Commission Implementing Regulation (EU) No. 503/2013 (specifying the requirements for the risk assessment of GM food/feed) requests mandatory 90-day feeding trials for GM plants with single transformation events, the controversy continues. This is due to the fact that in 2016 the European Commission will have to review this particular provision in the legislation (ibid, Article 12), and because of questions raised by long-term feeding studies with GM maize.