Expert Advisory Research Articles

Phase III, randomized, open-label, first-line study of gefitinib (G) versus carboplatin/paclitaxel (C/P) in selected patients (pts) with advanced non-small cell lung cancer (NSCLC) (IPASS): Evaluation of recruits in Japan

8044^ Background: The IRESSA Pan Asia Study (IPASS) demonstrated superiority of G vs C/P in 1,217 clinically selected chemonaïve pts in Asia with advanced NSCLC. PFS favored C/P initially then G, likely driven by different outcomes according to EGFR mutation (M) status. We report the planned analyses of 233 recruits in Japan (19% of overall population). Methods: From Mar 06 to Oct 07, chemonaïve, never/light ex-smokers with stage IIIB/IV NSCLC and adenocarcinoma histology were randomized to G 250 mg/day (n=114) or C (AUC 5 or 6)/P (200 mg/m2) (n=119). Primary objective was PFS in ITT population; a treatment by country interaction test (Japan vs other) was performed. Secondary endpoints were overall survival (OS), objective response rate (ORR, RECIST), QoL (FACT-L, TOI), symptom improvement (LCS subscale of FACT-L), and tolerability. Results: PFS results in pts in Japan did not significantly differ from other pts (interaction test p=0.4736). G demonstrated superior PFS compared with C/P (HR 0.69; 95% CI 0.51–0.94; p=0.0191); effect was not constant over time, favoring C/P initially then G. Preliminary OS (25% maturity; follow-up ongoing) was similar for G and C/P (HR 0.89; 95% CI 0.53–1.48). ORR for G was 41% vs 35% for C/P;odds ratio [OR] 1.34; 95% CI 0.78–2.30; p=0.2967. QoL improvement rate (TOI) was 43% for G and 28% for C/P (OR 1.92; 95% CI 1.11–3.34; p=0.0200); QoL (FACT-L 41 vs 43%; OR 0.94; 95% CI 0.56–1.60; p=0.8263) and symptom (LCS 42 vs 46%; OR 0.85; 95% CI 0.50–1.43; p=0.5340) improvement rates were similar for G and C/P. Tolerability profile was more favorable with G than C/P. There were no deaths due to ILD-type events (frequency 1.8% [G] vs 0% [C/P]). Conclusions: Efficacy and safety data for pts in Japan were generally consistent with overall population. G demonstrated improved PFS and ORR, similar OS, higher QoL (TOI) and similar symptom improvement rates, and a more favorable tolerability profile compared with C/P in chemonaïve, never/light ex-smokers with advanced NSCLC and adenocarcinoma histology. In IPASS, EGFR M status appeared to be a strong predictive biomarker for G efficacy compared with C/P. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

How do we tackle the complex field of vaccinology in the twenty-first century?

Vaccinology in the twenty-first century faces a highly complex situation given the remarkable evolutions which have recently occurred, creating a new era for immunisation policies in Europe. From a situation of vaccines targeted essentially against serious childhood diseases, we have moved to one of immunisation as a tool for preventing infectious diseases or their complications and outcomes in all age groups. At the same time, health technology assessment (HTA)—the evaluation of clinical effectiveness, cost-effectiveness and the larger impact of a health technology on patients and the health care system—has become crucial to the introduction of immunisation policies. This explains why the number of stakeholders involved in this process has grown. It now includes not only health authorities, their regulatory agencies and vaccine manufacturers, but also epidemiologists, economists, national and international advisory bodies and expert groups, scientific societies and even the general public through patient groups and/or politicians. They may have their own approaches, values and biases, but they all contribute to the implementation of immunisation policies from the long process of development all the way to registration and recommendations. With the new vaccines developed over the past decade, the number of vaccine-preventable diseases has risen from 22 to 25. But more importantly, new vaccines open new paradigms in the traditional concept of vaccinology. We are now dealing with new outcomes (prevention of disease/ medical or social consequences/impact on health care systems...) and new levels of investment owing to ever more refined biotechnologies and necessary investments in clinical development. The magnitude of recent changes requires a radical rethinking of vaccination policy-making at the country level as well as common approaches at the European Union (EU) level. Will the health care systems, and especially the EU, be able to cope with these challenges and ensure prompt accessibility of these innovative health measures to its citizens? One part of the answer inevitably entails revisiting the principles which have so far been the basis for the development and implementation of vaccination programmes. In order to begin answering the numerous questions arising as a result of the new era in vaccinology, two round tables devoted to vaccination were organised during the last two EUPHA (European Public Health Association) conferences (Montreux, Switzerland in 2006 and Helsinki in 2007). The first round table was meant to analyse the new paradigms inherent to current and future fields of vaccinology, whilst the second sought enhanced understanding of the decision-making process for introducing new vaccines in Europe. The presentations and discussions during the round tables gave rise to this special issue of the Journal of Public Health.

Europeanising Advisory Expertise: The Role of ‘Independent, Objective, and Transparent’ Scientific Advice in Agri-Biotech Regulation

Since various crises concerning food safety in the European Union (EU), institutional reforms have been designed to regain public confidence in regulatory decisions and their expert basis. By Europeanising advisory expertise, the European Food Safety Authority (EFSA) was also intended to help harmonise ‘science-based regulation’ and thus facilitate EU decisions. In evaluating agri-biotech products during 2003 – 05, however, the EFSA procedure extended previous expert disagreements rather than overcome them. The EFSA was designed to demonstrate that expert advice would be ‘independent, objective, and transparent’; yet tensions arose between expert experience versus independence, between transparency versus objectivity, and between harmonisation versus precaution. These conflicts have been shaped by the dominant problem diagnosis, which favours a narrow expert consensus within a specific policy view. Alternative problem diagnoses suggest that expertise should instead be pluralised, so that norms and uncertainties become more explicit. Pressure for EU reform manifests tensions between the dominant and alternative problem diagnoses.

World Trade Organization and the EC Biotech Case

The World Trade Organization is often faced with the challenge of reconciling its central objective of promoting free trade with the imperatives of avoiding adverse effects on the environment and public health. The organization has increasingly had to address this concern through its dispute settlement system and has refined several aspects of the debate through the Reformulated Gasoline, Shrimp-Turtle, Asbestos and Beef-Hormones cases. The EC Biotech case is the latest such dispute that has brought into focus the role of the World Trade Organization in protecting the environment and public health. This high-profile case has brought attention to several procedural issues pertaining to the dispute settlement system, such as the role of advisory experts and of amicus curiae briefs as well as the extended time taken in resolving these special cases, which are marked with a high level of complexity and political sensitivity. Although the panel report has retained a narrow frame of reference, the case has also drawn attention to significant substantive issues such as the definition of ‘undue delay’, the role of science and precaution and the inter-relationship between trade law and public international law. There remain, however, several questions on which the panel commented either inconclusively or not at all. In the event that the panel ruling is appealed, perhaps the Appellate Body will elaborate more fully on some of these crucial concerns that need to be addressed in order to identify a template for interaction between the objectives of free trade and the protection of environment and public health.

Expert Advice and Desertification Policy: Past Experience and Current Challenges

As the United Nations Convention to Combat Desertification (CCD) enters its implementation phase, its technical advisory bodies are endeavoring to define their purpose. Parties to the Convention have questioned the effectiveness and even the relevance of CCD science advice, recommended reforms, and estab-lished a new Group of Experts to support existing advisory processes. These efforts, however, are unlikely to bring about effective change because they overlook the mutually constitutive relationship linking natural and social order (i.e., co-production) evidenced by a century of intergovernmental cooperation on dryland degradation. Historically, knowledge about desertification has been integral to the locus of desertification governance, the definition and application of cognitive resources, and the design of policy remedies. In the CCD former sites of co-production are now sites of incongruous knowledge and policy. A comparison of past and present desertification initiatives illuminates these incompatibilities and points to ideas for fostering greater coherence in the CCD's expert advisory and implementation activities.

The National Library of the Czech Republik and the Floods of 2002

About fifty Czech libraries were inundated by floods in August 2002, more than 600,000 volumes were soaked and consequently 150,000 of them had to be frozen. A huge amount of archival material was affected and frozen as well. A strategy for their treatment has been accepted, based upon assessment of their cultural and research value. Advisory, coordination, and executive centres for paper materials damaged were established at the National Library and the State Central Archive, as well as central coordination centres at the governmental level. Effective aid came from abroad: advisory expert visits, material and financial aid, grants awarded to enable research and the testing process, books to replace those damaged by water. Financial support by the Government enabled the realization of the main goals of the Programme of repairs and preventive measures in cultural institutions. Various methods have been applied for repairing the documents affected. From the numerous potential drying technologies tested, mainly vacuum-packing and warm air drying have been applied and a great part of the material frozen has been already processed. Historical documents affected require restoration. Of protective methods, a protective boxes programme has been launched, and protective reformatting, namely micrographic technology, has been undertaken. New experience born from the process of recovery after the floods should be taken into account, either for special methods of treatment of library materials damaged, or for architectural, organizational and technical measures necessary for prevention. Heritage institutions should not underestimate disaster planning and cooperation within a common rescue system.

BSE in the UK: Why the Risk Communication Strategy Failed

The 2000 BSE Inquiry report points out that the most serious failure of the UK Government was one of risk communication. This paper argues that the government's failure to communicate the risks BSE posed to humans to a large degree can be traced back to a lack of transparency in the first risk assessment by the Southwood Working Party. This lack of transparency ensured that the working party's risk characterization and recommendations were ambiguous and thus hard to interpret. It also meant that uncertainties were not addressed in a satisfactory way. In the recommendations, the attitude to uncertainty was implicit rather than explicit. The risk communication based on the report amplified these flaws. Most importantly, it did not address the uncertainty at all. Apparently, the reason for this was fear of overreaction by the public. However, the result was counter-productive, because the risk communication did not then appear trustworthy. Later risk assessments and risk communication omitted to correct these flaws. Indeed, the fact that, following receipt of new information, advisory experts and policy makers had changed their views of the risk to humans was never clearly communicated to the public. There seemed to be little faith in the public's ability to reach a balanced judgment regarding the uncertainties. In the concluding section of the paper, this analysis is compared with the food standards agency's (FSA's) approach to BSE. The intervention of this agency was seen as one of the more important efforts to restore consumer confidence in British beef. And the agency certainly appears to be committed to openness and to addressing scientific uncertainty. However, using the risk of BSE in sheep as a case study, the paper shows that transparency – i.e., the clear presentation of factual and normative claims and assumptions underlying advice, and openness about the reasoning based on these claims and assumptions – is less than fully achieved in the FSA's work.

Knowledge modeling and the creation of El-Tech: a performance support and training system for electronic technicians

Abstract This paper contains a description of a unique approach to the creation of an expert system to provide performance support and training for electronics technicians. The starting point for development of the system was the creation of a semantically rich knowledge model comprised of Concept Maps and other digital media. The knowledge model was used to create the inference part of the system, and then retained to furnish explanation of the inference component's behaviors, and as content for training. The paper starts with a survey of relevant approaches to knowledge elicitation and modeling for performance support, and a review of other systems that have been created to assist with electronics troubleshooting. Following this, El-Tech (Electronic Technician), an expert advisory and training system that was created as part of a joint research effort with the Chief of Naval Education and Training, Pensacola, FL, is described.

Humanitarian and commercial deal in one

The inventors of vitamin A-enriched rice (Golden Rice), Ingo Protrykus (Swiss Federal Institute of Technology, Zurich, Switzerland) and Peter Beyer (University of Freiburg, Germany), have reached an agreement with Greenovation (Freiburg, Germany) and Zeneca (London, UK), and are working with agencies throughout the world to enable the delivery of this technology free-of-charge for humanitarian purposes in the developing world. Local farmers will each be allowed to earn an annual $10 000 without paying royalties. Zeneca has contributed to the European Union carotenoid research project since 1996 and will explore commercial opportunities for sales of Golden Rice in the growing health food market. Golden Rice contains the anti-oxidant β-carotene – anti-oxidants have been shown to play a role in the fight against cancer and coronary disease. At the same time, Zeneca will provide regulatory, advisory and research expertise to assist in making Golden Rice available in developing countries (http://www.zenecaagproducts.com/newinfo/newsrelease/archive/goldenrice.htm;www.greenovation.com).

UK: precautionary commercialization?

As genetically modified (GM) products approach the market stage, the UK government and agro-food industry have faced a suspicious or hostile public. Since 1998 many retail chains have undertaken to exclude any GM-derived ingredients from their own-brand lines. This commercial blockage has intensified pressures for greater precaution, even for a moratorium on cultivating GM crops. Political protest has led to strategies for precautionary commercialization. Government and industry have cooperated to plan a ‘managed development’ of GM crops. Across the agricultural supply chain, industry has devised voluntary guidelines to ensure segregation of GM crops and to limit the spread of GM herbicide-tolerance. In particular UK regulators seek to test the risk that broad-spectrum herbicide sprays could damage wildlife habitats; they have broadened the advisory expertise accordingly. These measures open up the precautionary content to further debate, at both national and EU levels. Market-stage precautions establish a means to test claims that GM crops are environmentally-friendly products. By translating public concerns into broader risk-assessment criteria, the UK procedure involves critics in potentially influencing standards of scientific evidence and environmental harm. This social process has become a prerequisite for legitimizing commercial use.

RISK MANAGEMENT AND EXPERTISE: UK: Strategies for Precautionary Commercialization of GM Crops

As genetically modified (GM) products approach the market stage, the UK government and agro-food industry have faced a suspicious or hostile public. Since 1998 many retail chains have undertaken to exclude any GM-derived ingredients from their own-brand lines. This commercial blockage has intensified pressures for greater precaution, even for a moratorium on cultivating GM crops. Political protest has led to strategies for precautionary commercialization. Government and industry have cooperated to plan a “managed development” of GM crops. Across the agricultural supply chain, industry has devised voluntary guidelines to ensure segregation of GM crops and to limit the spread of GM herbicide-tolerance. In particular UK regulators seek to test the risk that broad-spectrum herbicide sprays could damage wildlife habitats; they have broadened the advisory expertise accordingly. These measures open up the precautionary content to further debate, at both national and EU levels. Market-stage precautions establish a means to test claims that GM crops are environmentally-friendly products. By translating public concerns into broader risk-assessment criteria, the UK procedure involves critics in potentially influencing standards of scientific evidence and environmental harm. This social process has become a prerequisite for legitimizing commercial use.

Advisory Expert System for Nonlinear Seismic Analysis/Design of Coupled Walls

Nonlinear analysis techniques are rapidly being developed and have been recognized as indispensable tools in the research community. However, their use in the structural design office requires especially skilled structural engineers. Consequently, they are not generally accepted as production analysis/design tools. This paper describes an expert system for the inelastic dynamic analysis and design of coupled shear walls subjected to earthquake forces. The system has been implemented using Quintec-Prolog, Quintec-Flex, and FORTRAN 77, and runs on a SUN SPARCstation. Using this prototype, a novice structural engineer is guided and assisted on the nonlinear dynamic analysis and design of coupled shear walls based on theoretical, mathematical formulation and design experience.

A structured approach to conflict prediction in information systems strategy implementation

Organizational power and politics are the central issues of this paper. By developing a model of organizational power it is possible to determine whether an organizational change initiative is likely to be politically feasible. The formal model described has been derived largely from research reported in the social sciences. The modelling process involved using formal methods, in logic and entity relationship analysis, to discover an effective and consistent means of representing key organizational power concepts. The result is an advisory expert system called MP/L1 that can be employed by change agents to predict likely sources of potential resistance to major change initiatives and to suggest tactics that might be effective in combating anticipated resistance. Industrial experience with MP/L1 to date indicates that it has significant potential as a change management tool within the IS strategy-implementation domain. © 1998 John Wiley & Sons, Ltd.

A structured approach to conflict prediction in information systems strategy implementation

Organizational power and politics are the central issues of this paper. By developing a model of organizational power it is possible to determine whether an organizational change initiative is likely to be politically feasible. The formal model described has been derived largely from research reported in the social sciences. The modelling process involved using formal methods, in logic and entity relationship analysis, to discover an effective and consistent means of representing key organizational power concepts. The result is an advisory expert system called MP/L1 that can be employed by change agents to predict likely sources of potential resistance to major change initiatives and to suggest tactics that might be effective in combating anticipated resistance. Industrial experience with MP/L1 to date indicates that it has significant potential as a change management tool within the IS strategy-implementation domain. © 1998 John Wiley & Sons, Ltd.

INVEX: Investment Advisory Expert System

Abstract: Capital investment is a very important business decision, because it is largely irreversible and usually long‐term. We believe that the use of expert systems as a decision aid for interactive investment decision‐making offers several advantages to an unassisted human decision‐maker, or even to the human/conventional‐DSS combination. For example, the expert system could capture valuable information about so called ‘hard data’, and about the attitude towards some drastic changes in the environment, that are not easy to include in any quantitative method. However, if one expert can play a very important role in the decision‐making process, perhaps different experts can be even more valuable, bringing different approaches and somewhat different sets of information to a decision‐making situation. Our multiparadigm blackboard framework, called BEST (Blackboard‐based Expert Systems Toolkit), allows its user to combine knowledge coming from different experts, and to use different methods/paradigms to capture that knowledge, according to the type of partial problem at hand where each knowledge source is a single paradigm program. In investment decision‐making, judgmental investment ranking and selection from expert economists, embedded in a rule‐based knowledge source, might be combined with decisions from operational research methods (embedded in a knowledge source that fully respects multicriteria optimization paradigm) and from risk analysis method (embedded in a conventional, procedural knowledge source). When the decisions being combined come from different types of knowledge sources, redundancy is likely to be reduced and the combined decision is likely to be more objective.

ES ∗: An expert systems development planner using a constraint and rule-based approach

Numerous expert systems (ES) applications have been developed in the field, yet at this time no systematic, computerized tool for ES development planning exists. In this article, we present an ES development planner that adopts the constraint and rule satisfaction problems framework. We represent knowledge concerning ES development planning with objects, constraints, and rules under multiple objectives. We also present a unified reasoning process to obtain a consistent ES development plan, which has the following features: (1) supporting user interaction to reflect user intention about the problem situation and to resolve conflicts between objectives; (2) concurrent reasoning with multiple starting points to enhance the search efficiency; and (3) integrated reasoning encompassing the backward chaining popularly used in the rule-based systems and constraint propagation methods developed for constraint satisfaction problems. A prototype system ES ∗ is developed using the tool UNIK and LISP language on a SUN 4 SPARC workstation, and an application on tax advisory expert system development planning is illustrated.

Characterizing advisory interactions between statisticians and entomologists

An advisory expert system needs to model the expert's problem-solving behaviour as well as the interaction between advisor and client. An empirical study is reported that investigates advisory-client interactions in the field of insect sampling plan design. A form of discourse analysis was used to ascertain the roles of the participants and to develop a model of the functions performed during advice giving. The study used simulated interactions. Analysis of the interactions showed that the advisor controlled the relationship. The interaction can be characterized by a three-part model: information collecting, advice giving and closing. In three quarters of the interactions the advisor cycled between the information collecting and advice-giving episodes. This interchanging among episodes indicates a refinement of the advice as the statistician collects more information.

Development of an advisory expert system for elastic mechanism design

The design and analysis of high-speed mechanisms is a complex, iterative process requiring a high level of expertise and engineering intuition. Efficient finite element analysis, analysis validation, and preliminary synthesis techniques are the bottlenecks in the process. All these phases of the design process are thus prime candidates for automation. In order to help automate such complex systems, a prototype advisory expert system for finite element analysis and optimal design of flexible mechanisms was developed. The development of this system and the related backgroud are presented in this paper.

Advisory expert system for flexible pavement design

The adoption of an expert system approach to flexible pavement design could be especially useful, because of the complexity of the design algorithm involving numerous possible combinations of pavement material types and traffic data, and the heavy reliance on empirical correlations, which can vary from one region or state to another. This paper describes the development of an advisory expert system for flexible pavement design that attempts to mimic the design process of pavement engineering specialists. The highly interactive microcomputer expert system was developed, using an expert system shell.

A Modular Knowledge Base for the Follow-Up of Clinical Protocols

From the knowledge engineering point of view, the observation of patients subjected to clinical protocols of therapy constitutes a domain characterized by the existence of strongly structured knowledge. We have approached the problem from the perspective of a homogeneous and modular knowledge representation theory, based on the concept of Generalized Magnitude. This concept arises from identifying and collecting all possible facts of a domain established a priori, and being inspired by the concept of physical magnitudes. The Generalized Magnitudes scheme includes temporal extensions necessary to solve a medical problem for which exists a therapy and a follow-up plan with temporal specifications, and also facilitates the creation of advisory expert systems.