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This is a summary report of the American Association of Pharmaceutical Scientists, the Food and Drug Administration and the United States Pharmacopoeia cosponsored workshop on “Assuring Quality and Performance of Sustained and Controlled Release Parenterals.” Experts from the pharmaceutical industry, the regulatory authorities and academia participated in this workshop to review, discuss and debate formulation, processing and manufacture of sustained and controlled release parenterals and identify critical process parameters and their control. Areas were identified where research is needed in order to understand the performance of these drug delivery systems and to assist in the development of appropriate testing procedures. Recommendations were made for future workshops, meetings and working groups in this area.

A workshop cosponsored by the National Institute of Environmental Health Sciences and the National Institute for Occupational Safety and Health was convened in Washington, DC, on 17-18 October 2001 with the goal of developing a consensus document on the most appropriate experimental approaches and assays available to assess developmental immunotoxicity. The work group was composed of scientists from academia, the chemical and pharmaceutical industries, and federal agencies with expertise in developmental immunology, developmental toxicology, immunotoxicology, and risk evaluation. This consensus document presents an overview of the major summations made by the work group. A summary of early work in the field is provided, which includes potential immunotoxic agents, followed by brief discussions of our current understanding of developmental immunology. This report concludes with the work group's consensus of the most appropriate experimental design and tests to screen for potential developmental immunotoxic agents in experimental models, including potential limitations and data gaps.

The National Urban Air Toxics Research Center (NUATRC) hosted its first scientific workshop in 1994 that focused on possible relationships between air toxics and asthma. From that meeting came recommendations for future research including a need for more complete individual personal exposure assessments so that determinations of personal exposures to pollutants could be made. In the spring of 2001, NUATRC held a second such workshop to review progress made in this area during the intervening 7 years. Peer-reviewed articles from the workshop are published in this issue of (italic)Environmental Health Perspectives Supplements(/italic). As in 1994, academic, government, and industry scientists participated. Dave Guinnup of the Environmental Protection Agency discussed the nature of air toxics, their definition, and the basis for federal regulation. George Leikauf from the University of Cincinnati reviewed the 1994 workshop and subsequent research in this field. Current research funded by NUATRC that is addressing individual personal exposure was presented by Clifford Weisel (Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey), Patrick Kinney (Columbia University) and Candis Claiborn (Washington State University). David Corry from Baylor College of Medicine highlighted new insights into asthma pathogenesis while Stephen Redd from the Centers for Disease Control presented an overview of asthma epidemiology as well as the societal costs of the disease. Mary White (Agency for Toxic Substances and Disease Registry) discussed recent epidemiologic investigations by public health agencies into community concerns about asthma and hazardous air pollutants. David Peden (University of North Carolina) reviewed scientific studies into the links between asthma and air toxics as well as criteria air pollutants. In a session on occupational asthma, Lee Petsonk (National Institute for Occupational Safety and Health) discussed risk factors for work-related asthma, whereas Ralph Delfino (University of California, Irvine) addressed limitations of extrapolating from occupational asthma to asthma in the general population. These presentations were followed by panel discussions focusing on future research programs, both for NUATRC and similar research institutions. Recommendations for future research included improved assessments of personal exposure to air toxics as well as research focused on specific hazardous air pollutants. The latter recommendation was based on medical literature that suggests certain pollutants from the list of 188 air toxics are most likely to adversely affect respiratory health.

A two-day technical workshop was convened November 10-11, 1986, to discuss analytical approaches for determining trace amounts of cotinine in human body fluids resulting from passive exposure to environmental tobacco smoke (ETS). The workshop, jointly sponsored by the U.S. Environmental Protection Agency and Centers for Disease Control, was attended by scientists with expertise in cotinine analytical methodology and/or conduct of human monitoring studies related to ETS. The workshop format included technical presentations, separate panel discussions on chromatography and immunoassay analytical approaches, and group discussions related to the quality assurance/quality control aspects of future monitoring programs. This report presents a consensus of opinion on general issues before the workshop panel participants and also a detailed comparison of several analytical approaches being used by the various represented laboratories. The salient features of the chromatography and immunoassay analytical methods are discussed separately.

The workshop “Bioequivalence, Biopharmaceutics Classification System, and Beyond” was held May 21–23, 2007 in North Bethesda, MD, USA. This workshop provided an opportunity for pharmaceutical scientists to discuss the FDA guidance on the Biopharmaceutics Classification System (BCS), bioequivalence of oral products, and related FDA initiatives such as the FDA Critical Path Initiative. The objective of this Summary Workshop Report is to document the main points from this workshop. Key highlights of the workshop were (a) the described granting of over a dozen BCS-based biowaivers by the FDA for Class I drugs whose formulations exhibit rapid dissolution, (b) continued scientific support for biowaivers for Class III compounds whose formulations exhibit very rapid dissolution, (c) scientific support for a number of permeability methodologies to assess BCS permeability class, (d) utilization of BCS in pharmaceutical research and development, and (e) scientific progress in in vitro dissolution methods to predict dosage form performance.

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations.

Converging concepts were identified: enhanced knowledge of interferon-related pathways was found to be central to the understanding of immune-mediated tissue-specific destruction (TSD) of which tumor rejection is a representative facet. Although the expression of interferon-stimulated genes (ISGs) likely mediates the inflammatory process leading to tumor rejection, it is insufficient by itself and the associated mechanisms need to be identified. It is likely that adaptive immune responses play a broader role in tumor rejection than those strictly related to their antigen-specificity; likely, their primary role is to trigger an acute and tissue-specific inflammatory response at the tumor site that leads to rejection upon recruitment of additional innate and adaptive immune mechanisms.

Other candidate systemic and/or tissue-specific biomarkers were recognized that might be added to the list of known entities applicable in immunotherapy trials. The need for a systematic approach to biomarker discovery that takes advantage of powerful high-throughput technologies was recognized; it was clear from the current state of the science that immunotherapy is still in a discovery phase and only a few of the current biomarkers warrant extensive validation. It was, finally, clear that, while current technologies have almost limitless potential, inadequate study design, limited standardization and cross-validation among laboratories and suboptimal comparability of data remain major road blocks. The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions.

In July 1987, a workshop was held to evaluate the environmental health workforce. The workshop was sponsored by the Bureau of Health Professions. Health Resources and Services Administration of the Public Health Service. Participants were drawn from State and local agencies, Federal agencies, industry, and academia. Estimates of workforce needs were based on background information and informed consensus judgments of workshop participants. The final report of the workshop was published in January 1988. The authors synthesize some of the consensus judgements and review data from a position paper developed for the workshop. The supply, demand, and projected need for new academicians in environmental health on both graduate and undergraduate levels through 1992 are estimated. These estimates are based on the need for persons trained in the various environmental health subspecialties identified during the workshop. Outlined are the number and educational backgrounds of new faculty required. The types of new training programs that are required to meet the needs for environmental health specialists through 1992 are discussed.

Modified release products are complex dosage forms designed to release drug in a controlled manner to achieve desired efficacy and safety. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current industry practices and regulatory expectations for demonstrating pharmaceutical equivalence and bioequivalence of MR products, further facilitating the establishment of regulatory standards for ensuring therapeutic equivalence of these products.

Bioanalytical method validation is generally conducted using standards and quality control (QC) samples which are prepared to be as similar as possible to the study samples (incurred samples) which are to be analyzed. However, there are a variety of circumstances in which the performance of a bioanalytical method when using standards and QCs may not adequately approximate that when using incurred samples. The objective of incurred sample reproducibility (ISR) testing is to demonstrate that a bioanalytical method will produce consistent results from study samples when re-analyzed on a separate occasion. The Third American Association of Pharmaceutical Scientists (AAPS)/Food and Drug Administration (FDA) Bioanalytical Workshop and subsequent workshops have led to widespread industry adoption of the so-called “4–6–20” rule for assessing incurred sample reproducibility (i.e. at least 66.7% of the re-analyzed incurred samples must agree within ±20% of the original result), though the performance of this rule in the context of ISR testing has not yet been evaluated. This paper evaluates the performance of the 4–6–20 rule, provides general recommendations and guidance on appropriate experimental designs and sample sizes for ISR testing, discusses the impact of repeated ISR testing across multiple clinical studies, and proposes alternative acceptance criteria for ISR testing based on formal statistical methodology.

This report outlines the content of a one-day workshop on Generic Medicines that was held at KIST Medical College, Lalitpur, Nepal on 13th December 2010, which was attended by 32 delegates from different institutions in Nepal, including pharmacists, pharmacologists and medical doctors. Right medicine, right patient, right dose, right frequency and duration, right information and right monitoring are conditions to be fulfilled for the rational use of medicine (RUM). The World Health Organization (WHO) defines generic medicine as ‘a pharmaceutical product, usually intended to be interchangeable with the innovator product, marketed after the expiry of patent or other exclusivity rights’. Economic factors, supportive legislation and regulation, public and professional acceptance and quality assurance are key enabling factors promoting use of generics. Increased patent protection for medicines and removing process patents is a key feature of new trade agreements and newer medicines for diseases like HIV/AIDS, tuberculosis and infectious diseases are likely to be more expensive. The Medicine and Therapeutics Committee (MTC) can play a key role in promoting generic medicine use in institutions.

Nepal being among the Least Developed Countries (LDCs) need not provide patent protection for medicines until 31st December 2015. Only a few ‘true’ generics are available in Nepal and there is huge cost variation in the price of different branded generics. Clinicians have concerns about the quality of medicines in general, substitution of poor quality brands by pharmacists and about therapeutic substitution. Generics have to meet the same regulatory requirements and be bioequivalent to reference preparations assuring their quality.

In this report we present the findings from a nanotoxicology workshop held 6–7 April 2006 at the Woodrow Wilson International Center for Scholars in Washington, DC. Over 2 days, 26 scientists from government, academia, industry, and nonprofit organizations addressed two specific questions: what information is needed to understand the human health impact of engineered nanoparticles and how is this information best obtained? To assess hazards of nanoparticles in the near-term, most participants noted the need to use existing in vivo toxicologic tests because of their greater familiarity and interpretability. For all types of toxicology tests, the best measures of nanoparticle dose need to be determined. Most participants agreed that a standard set of nanoparticles should be validated by laboratories worldwide and made available for benchmarking tests of other newly created nanoparticles. The group concluded that a battery of tests should be developed to uncover particularly hazardous properties. Given the large number of diverse materials, most participants favored a tiered approach. Over the long term, research aimed at developing a mechanistic understanding of the numerous characteristics that influence nanoparticle toxicity was deemed essential. Predicting the potential toxicity of emerging nanoparticles will require hypothesis-driven research that elucidates how physicochemical parameters influence toxic effects on biological systems. Research needs should be determined in the context of the current availability of testing methods for nanoscale particles. Finally, the group identified general policy and strategic opportunities to accelerate the development and implementation of testing protocols and ensure that the information generated is translated effectively for all stakeholders.

Bioanalytical methods used to support the drug development process are validated to ensure that they function in the manner in which they are intended. “Incurred” or study samples can vary in their composition when compared with the standards and quality control samples used to validate the method and analyze these samples. During the 3rd American Association of Pharmaceutical Scientists(AAPS)/Food and Drug Administration(FDA) Bioanalytical Workshop, it was suggested that the reproducibility in the analysis of incurred samples be evaluated in addition to the usual prestudy validation activities performed. This manuscript provides recommendations concerning the number and types of samples that should be analyzed in such an evaluation, as well as the manner in which the resultant data should be analyzed. Suggestions as to follow-up activities and data reporting are also discussed. This approach is at best a beginning and is offered as a platform for future discussion, comments, and revision.

The European Medicines Agency (EMEA) workshop on biosimilar monoclonal antibodies (mAbs), held July 2, 2009 at the EMEA headquarters in London, was a harbinger with potentially far-reaching implications for all groups interested in antibody therapeutics development. These groups include not only regulators and the innovator and generic biopharmaceutical industries, but also physicians, patients and payers. The objective of the workshop was to discuss and assess the feasibility of the development and authorization of mAbs using EMEA's biosimilar regulatory pathways. The workshop sequentially focused on questions relevant to three areas: (1) chemistry, manufacturing and controls (CMC), (2) non-clinical issues and (3) clinical issues, including outcome measures. Proceedings of the workshop are presented in Part 1 of this report, and discussed within the context of the legal, regulatory and business environments of the European Union, Asia and the United States in Parts 2, 3 and 4, respectively.

This is the report of the first workshop “Validation of Toxicogenomics-Based Test Systems” held 11–12 December 2003 in Ispra, Italy. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and organized jointly by ECVAM, the U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). The primary aim of the workshop was for participants to discuss and define principles applicable to the validation of toxicogenomics platforms as well as validation of specific toxicologic test methods that incorporate toxicogenomics technologies. The workshop was viewed as an opportunity for initiating a dialogue between technologic experts, regulators, and the principal validation bodies and for identifying those factors to which the validation process would be applicable. It was felt that to do so now, as the technology is evolving and associated challenges are identified, would be a basis for the future validation of the technology when it reaches the appropriate stage. Because of the complexity of the issue, different aspects of the validation of toxicogenomics-based test methods were covered. The three focus areas include a) biologic validation of toxicogenomics-based test methods for regulatory decision making, b) technical and bioinformatics aspects related to validation, and c) validation issues as they relate to regulatory acceptance and use of toxicogenomics-based test methods. In this report we summarize the discussions and describe in detail the recommendations for future direction and priorities.

Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible for these diseases has initiated genetic diagnostics in many countries around the world, including the Middle East, Europe, USA, Japan and Australia. However, diverse testing methods and reporting practices are employed and there is a clear need for consensus guidelines for HRF genetic testing.

Draft guidelines were prepared based on current practice deduced from previous HRF external quality assurance schemes and data from the literature. The draft document was disseminated through the European Molecular Genetics Quality Network for broader consultation and amendment. A workshop was held in Bruges (Belgium) on 18 and 19 September 2011 to ratify the draft and obtain a final consensus document. An agreed set of best practice guidelines was proposed for genetic diagnostic testing of HRFs, for reporting the genetic results and for defining their clinical significance.

The Consensus Workshop on Formaldehyde consisted of bringing together scientists from academia, government, industry and public interest groups to address some important toxicological questions concerning the health effects of formaldehyde. The participants in the workshop, the Executive Panel which coordinated the meeting, and the questions posed, all were chosen through a broadly based nomination process in order to achieve as comprehensive a consensus as possible. The subcommittees considered the toxicological problems associated with formaldehyde in the areas of exposure, epidemiology, carcinogenicity/histology/genotoxicity, immunology/sensitization/irritation, structure activity/biochemistry/metabolism, reproduction/teratology, behavior/neurotoxicity/psychology and risk estimation. Some questions considered included the possible human carcinogenicity of formaldehyde, as well as other human health effects, and the interpretation of pathology induced by formaldehyde. These reports, plus introductory material on the procedures used in setting up the Consensus Workshop are presented here. Additionally, there is included a listing of the data base that was made available to the panel chairmen prior to the meeting and was readily accessible to the participants during their deliberations in the meeting. This data base, since it was computerized, was also capable of being searched for important terms. These materials were supplemented by information brought by the panelists. The workshop has defined the consensus concerning a number of major points in formaldehyde toxicology and has identified a number of major deficits in understanding which are important guides to future research.

Abrupt and rapid ecosystem shifts (where major reorganizations of food-web and community structures occur), commonly termed regime shifts, are changes between contrasting and persisting states of ecosystem structure and function. These shifts have been increasingly reported for exploited marine ecosystems around the world from the North Pacific to the North Atlantic. Understanding the drivers and mechanisms leading to marine ecosystem shifts is crucial in developing adaptive management strategies to achieve sustainable exploitation of marine ecosystems. An international workshop on a comparative approach to analysing these marine ecosystem shifts was held at Hamburg University, Institute for Hydrobiology and Fisheries Science, Germany on 1–3 November 2010. Twenty-seven scientists from 14 countries attended the meeting, representing specialists from seven marine regions, including the Baltic Sea, the North Sea, the Barents Sea, the Black Sea, the Mediterranean Sea, the Bay of Biscay and the Scotian Shelf off the Canadian East coast. The goal of the workshop was to conduct the first large-scale comparison of marine ecosystem regime shifts across multiple regional areas, in order to support the development of ecosystem-based management strategies.

ABSTRACT

OBJECTIVE

To determine if participation in a procedural skills workshop during family practice residency affects future use of these skills in postgraduate clinical practice.

DESIGN

Survey involving self-assessment of procedural skills experience and competence.

SETTING

British Columbia.

PARTICIPANTS

Former University of British Columbia family practice residents who trained in Vancouver, BC, including residents who participated in a procedural skills workshop in 2001 or 2003 and residents graduating in 2000 and 2002 who did not participate in the procedural skills workshop.

MAIN OUTCOME MEASURES

Self-assessed experience and competence in the 6 office-based procedural skills that were taught during the procedural skills workshops in 2001 and 2003.

RESULTS

Participation in a procedural skills workshop had no positive effect on future use of these skills in clinical practice. Participation in the workshop was associated with less reported experience (P = .091) in injection of lateral epicondylitis. As with previous Canadian studies, more women than men reported experience and competence in gynecologic procedures. More women than men reported experience (P = .001) and competence (P = .004) in intrauterine device insertion and experience (P = .091) in endometrial aspiration biopsy. More men than women reported competence (P = .052) in injection of trochanteric bursae. A third year of emergency training was correlated with an increase in reported experience (P = .021) in shoulder injection.

CONCLUSION

Participation in a procedural skills workshop during family practice residency did not produce a significant increase in the performance of these skills on the part of participants once they were in clinical practice. The benefit of a skills workshop might be lost when there is no opportunity to practise and perfect these skills. Sex bias in the case of some procedures might represent a needs-based acquisition of skills on the part of practising physicians. Short procedural skills workshops might be better suited to graduated physicians with more clinical experience.

Background

Brief alcohol interventions (BAI) reduce alcohol use and related problems in primary care patients with hazardous drinking behavior. The effectiveness of teaching BAI on the performance of primary care residents has not been fully evaluated.

Methods

A cluster randomized controlled trial was conducted with 26 primary care residents who were randomized to either an 8-hour, interactive BAI training workshop (intervention) or a lipid management workshop (control). During the 6-month period after training (i.e., from October 1, 2003 to March 30, 2004), 506 hazardous drinkers were identified in primary care, 260 of whom were included in the study. Patients were interviewed immediately and then 3 months after meeting with each resident to evaluate their perceptions of the BAI experience and to document drinking patterns.

Results

Patients reported that BAI trained residents: conducted more components of BAI than did controls (2.4 vs 1.5, p = .001); were more likely to explain safe drinking limits (27% vs 10%, p = .001) and provide feedback on patients’ alcohol use (33% vs 21%, p = .03); and more often sought patient opinions on drinking limits (19% vs 6%, p = .02). No between-group differences were observed in patient drinking patterns or in use of 9 of the 12 BAI components.

Conclusions

The BAI-trained residents did not put a majority of BAI components into practice, thus it is difficult to evaluate the influence of BAI on the reduction of alcohol use among hazardous drinkers.

The workshop “Pharmacogenetics in Individualized Medicine: Methods, Regulatory, and Clinical Applications” was held November 15–16, 2008 in Atlanta, Georgia, USA. This workshop provided an opportunity for pharmaceutical scientists, clinical practitioners, clinical laboratory scientists, and FDA to discuss methods, regulatory, and the application of pharmacogenetics in clinical practice and drug discovery. Key highlights of the workshop were: (a) the use of genetic information in individualized medicine has significant potential in advancing drug development and human health by optimizing drug response, drug efficacy, and preventing adverse drug reactions; (b) various barriers exist preventing the advance of the individualized medicine in the society, industry, and clinical practice; and (c) the barriers may be overcome by integrated approaches; the education of researchers, clinical practitioners, and patients and fostering interactive communication among stakeholders. By targeting the AAPS audience, this workshop was one step among many steps that AAPS–FIP is intending to take towards removing the barriers to widespread uptake of pharmacogenetics in drug discovery and clinical practice.

This is a report on the 3-day workshop “The Neuroscience of Responsibility” that was held in the Philosophy Department at Delft University of Technology in The Netherlands during February 11th–13th, 2010. The workshop had 25 participants from The Netherlands, Germany, Italy, UK, USA, Canada and Australia, with expertise in philosophy, neuroscience, psychology, psychiatry and law. Its aim was to identify current trends in neurolaw research related specifically to the topic of responsibility, and to foster international collaborative research on this topic. The workshop agenda was constructed by the participants at the start of each day by surveying the topics of greatest interest and relevance to participants. In what follows, we summarize (1) the questions which participants identified as most important for future research in this field, (2) the most prominent themes that emerged from the discussions, and (3) the two main international collaborative research project plans that came out of this meeting.

We implemented a “how to study” workshop for small groups of students (6–12) for N = 93 consenting students, randomly assigned from a large introductory biology class. The goal of this workshop was to teach students self-regulating techniques with visualization-based exercises as a foundation for learning and critical thinking in two areas: information processing and self-testing. During the workshop, students worked individually or in groups and received immediate feedback on their progress. Here, we describe two individual workshop exercises, report their immediate results, describe students’ reactions (based on the workshop instructors’ experience and student feedback), and report student performance on workshop-related questions on the final exam. Students rated the workshop activities highly and performed significantly better on workshop-related final exam questions than the control groups. This was the case for both lower- and higher-order thinking questions. Student achievement (i.e., grade point average) was significantly correlated with overall final exam performance but not with workshop outcomes. This long-term (10 wk) retention of a self-testing effect across question levels and student achievement is a promising endorsement for future large-scale implementation and further evaluation of this “how to study” workshop as a study support for introductory biology (and other science) students.

This report summarizes the proceedings of the 6th and 7th workshops of the Genomic Standards Consortium (GSC), held back-to-back in 2008. GSC 6 focused on furthering the activities of GSC working groups, GSC 7 focused on outreach to the wider community. GSC 6 was held October 10-14, 2008 at the European Bioinformatics Institute, Cambridge, United Kingdom and included a two-day workshop focused on the refinement of the Genomic Contextual Data Markup Language (GCDML). GSC 7 was held as the opening day of the International Congress on Metagenomics 2008 in San Diego California. Major achievements of these combined meetings included an agreement from the International Nucleotide Sequence Database Consortium (INSDC) to create a “MIGS” keyword for capturing ”Minimum Information about a Genome Sequence” compliant information within INSDC (DDBJ/EMBL /Genbank) records, launch of GCDML 1.0, MIGS compliance of the first set of “Genomic Encyclopedia of Bacteria and Archaea” project genomes, approval of a proposal to extend MIGS to 16S rRNA sequences within a “Minimum Information about an Environmental Sequence”, finalization of plans for the GSC eJournal, “Standards in Genomic Sciences” (SIGS), and the formation of a GSC Board. Subsequently, the GSC has been awarded a Research Co-ordination Network (RCN4GSC) grant from the National Science Foundation, held the first SIGS workshop and launched the journal. The GSC will also be hosting outreach workshops at both ISMB 2009 and PSB 2010 focused on “Metagenomics, Metadata and MetaAnalysis” (M3). Further information about the GSC and its range of activities can be found at http://gensc.org, including videos of all the presentations at GSC 7.

A 2-day workshop on “Physiologically Based Pharmacokinetics (PBPK) in Drug Development and Regulatory Science” came to a successful conclusion on May 30, 2002, in Washington, DC. More than 120 international participants from the environmental and predominantly pharmaceutical industries, Food and Drug Administration (FDA), and universities attended this workshop, organized by the Center for Drug Development Science, Georgetown University, Washington, DC. The first of its kind specifically devoted to the subject, this intensive workshop, comprising 7 plenary presentations and 10 breakout sessions addressed 2 major objectives: (1) to “define demonstrated and potential contributions of PBPK in drug development and regulatory science,” and (2) to “assess current PBPK methodologies with the identification of their limitations and outstanding issues.” This report summarizes the presentations and recommendations that emerged from the workshop, while providing key references, software, and PBPK data sources in the appendices. The first day was initially devoted to presentations setting the stage and providing demonstrated applications to date. This was followed by breakout sessions that considered further opportunities and limitations, and which extended into Day 2 to deal with developments in methodologies and tools. Although the primary emphasis was on pharmacokinetics, consideration was also given to its integration specifically with mechanism-based pharmacodynamics.

BACKGROUND

Recent advances in our understanding of the causes of infertility and of assisted reproductive technology (ART) have led to the development of complex diagnostic tools, prognostic models and treatment options. The Third Evian Annual Reproduction (EVAR) Workshop Meeting was held on 26–27 April 2008 to evaluate evidence supporting current approaches to the diagnosis and management of infertility and to identify areas for future research efforts.

METHODS

Specialist reproductive medicine clinicians and scientists delivered presentations based on published literature and ongoing research on patient work-up, ovarian stimulation and embryo quality assessment during ART. This report is based on the expert presentations and subsequent group discussions and was supplemented with publications from literature searches and the authors' knowledge.

RESULTS

It was agreed that single embryo transfer (SET) should be used with increasing frequency in cycles of ART. Continued improvements in cryopreservation techniques, which improve pregnancy rates using supernumerary frozen embryos, are expected to augment the global uptake of SET. Adaptation and personalization of fertility therapy may help to optimize efficacy and safety outcomes for individual patients. Prognostic modelling and personalized management strategies based on individual patient characteristics may prove to represent real progress towards improved treatment. However, at present, there is limited good-quality evidence to support the use of these individualized approaches.

CONCLUSIONS

Greater quality control and standardization of clinical and laboratory evaluations are required to optimize ART practices and improve individual patient outcomes. Well-designed, good-quality studies are required to drive improvements to the diagnosis and management of ART processes.