Unanticipated Adverse Effects Research Articles

Circulating Progenitors in Lung Injury

Circulating Progenitors in Lung Injury

Forensic Engineering Overview Of Effect Of Weather Resistive Barriers On Building Envelope Deterioration

Since Adoption And Widespread Implementation Of The Model Energy Code Promulgated By The Department Of Energy And Incorporated Into Most State Building Codes, There Has Been Widespread Experience With Deterioration Of Building Envelopes, Particularly Wood Frame Building Envelopes. Requirements For Weather Resistive Barriers (Wrbs) Have Been Added To The Major National Codes For Nearly All Applications With Multiple Significant Changes In Successive Recent Editions Of The Major Building Codes. Moisture/Water Related Problems Have Manifested In Other Types Of Construction, Including Masonry, Resultant To Recent Requirements Of Building Codes And Unanticipated Adverse Effects Caused By Lack Of Testing And Integration Between The Building Code Provisions And Energy Codes... This Paper Provides A Summary Of Actual Field Observations Of Effects Of And Performance Of Groups Of Weather Resistive Barriers (Wrbs) And Vapor Retarders Based Upon Invasive Investigation Of Building Envelopes Extending Over A Period Of 15 Years And Provides General Guidance To The Major Codes Intended To Provide A Basis For The Expert To Obtain Further Foundational Materials And Knowledge Needed In These Types Of Cases.

Take-home messages

• Post Market Environmental Monitoring (PMEM) is mandatory in all applications for deliberate release submitted under Directive 2001/18/EC and EU Regulation 1829/2003. • PMEM aims at identifying possible unanticipated adverse effects on human health or the environment which could arise directly or indirectly from GM plants. • PMEM is composed of case-specific monitoring (CSM) and general surveillance (GS). CSM is notmandatory butmaybe required to verify the environmental risk assessment while GS must be part of an application. • EFSA is responsible for assessing the scientific quality of PMEM plans submitted with each application. • EFSA has adopted guidance to applicants for developing PMEM plans (adopted December 2005). • The EFSA GMO Panel is of the opinion that GS cannot be driven by specific hypotheses (cause-effect) and should, when possible, make use of existing monitoring programmes in addition tomore focussedmonitoring systems as farm questionnaires. • Data quality, management and statistical analysis are of high importance in the design of a GS plan and comparison should be made with baseline data. • EFSA recommends early contact between applicants and Member States (selection of existing networks) and recommends harmonisation and coordination of data collection and analysis. • PMEM is a risk management measure. • The Commission and the Member States via their Competent Authorities are responsible for the PMEM and take the decisions. • The body in charge of proposing harmonisation of PMEM is the EU Monitoring Working Group. • A pragmatic PMEM for MON 810 that addresses the proposedprotectiongoals has been implemented successfully. • The 2005 monitoring report for MON 810 confirms the conclusion of safety reached in the environmental risk assessment. • The future presence of multiple events and stacks on the market will require: – some adaptation, including modularity, – a harmonised approach across the industry that has started under the EuropaBio banner.

The EFSA guidance on post market environmental monitoring of GM plants

EFSA’s role within the European regulatory framework for GMOs is to carry out scientific risk assessments or give scientific advice on GMOs. EFSA is also requested to assess the scientific quality of post market environmental monitoring (PMEM) plans submitted with each application for placing GM plants on the EU market, as requested by EU legislation. In January 2006, the EFSA GMO Panel published its opinion and guidance on PMEM. PMEM aims at identifying unanticipated adverse effects on human health or the environment which could arise directly or indirectly from GM plants. PMEM is composed of case-specific monitoring and general surveillance. Case-specific monitoring is not obligatory but may be required to verify the environmental risk assessment. A general surveillance plan is compulsory and aims at identifying unanticipated adverse effects. General surveillance is not hypothesis driven but is a general overseeing of the environment making use of existing surveillance systems in addition to developing more focused monitoring systems (e.g. farm questionnaires). Data quality, management and statistical analysis are of high importance in the design of general surveillance plans. Comparison should be made with appropriate baseline data. The EFSA GMO Panel also makes a number of recommendations for the management and conduct of PMEM by both applicants and risk managers.

General Surveillance: Roles and Responsibilities The Industry View

A General Surveillance plan to monitor for unanticipated adverse effects of genetically modified organisms (GMOs) on human health and the environment is required as part of the EU legislation for imported and cultivated GMOs.

The D&T Report

The D&T Report

Intensity-modulated radiotherapy for nasopharyngeal carcinoma: Clinical correlation of dose to the pharyngo-esophageal axis and dysphagia

The aim of this study was to quantify the dose delivered to the pharyngo-esophageal axis using different intensity-modulated radiation therapy (IMRT) techniques for treatment of nasopharyngeal carcinoma and to correlate this with acute swallowing toxicity. The study population consisted of 28 patients treated with IMRT between February 2002 and August 2005: 20 with whole field IMRT (WF-IMRT) and 8 with IMRT fields junctioned with an anterior neck field with central shielding (j-IMRT). Dose to the pharyngo-esophageal axis was measured using dose-volume histograms. Acute swallowing toxicity was assessed by review of dysphagia grade during treatment and enteral feeding requirements. The mean pharyngo-esophageal dose was 55.2 Gy in the WF-IMRT group and 27.2 Gy in the j-IMRT group, p < 0.001. Ninety-five percent (19/20) of the WF-IMRT group developed Grade 3 dysphagia compared with 62.5% (5/8) of the j-IMRT group, p = 0.06. Feeding tube duration was a median of 38 days for the WF-IMRT group compared with 6 days for the j-IMRT group, p = 0.04. Clinical vigilance must be maintained when introducing new technology to ensure that unanticipated adverse effects do not result. Although newer planning systems can reduce the dose to the pharyngo-esophageal axis with WF-IMRT, the j-IMRT technique is preferred at least in patients with no gross disease in the lower neck.

Issue Highlights

HomeCirculationVol. 114, No. 25Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published19 Dec 2006https://doi.org/10.1161/circ.114.25.2753Circulation. 2006;114:2753INCREASING USE OF CARDIOPULMONARY RESUSCITATION DURING OUT-OF-HOSPITAL VENTRICULAR FIBRILLATION ARREST: SURVIVAL IMPLICATIONS OF GUIDELINE CHANGES, by Rea et al.Even relatively brief interruptions of chest compressions, such as pauses required for assessment of the cardiac rhythm by an automatic external defibrillator, reduce survival in experimental models of cardiac arrest. American Heart Association guidelines for cardiopulmonary resuscitation have been revised accordingly to include a single shock, rather than stacked defibrillation shocks, followed by immediate resumption of cardiopulmonary resuscitation and delayed reassessment of cardiac rhythm. Do these changes improve patient outcomes? Rea and colleagues studied outcomes from out-of-hospital cardiac arrest before and after cardiopulmonary resuscitation protocol changes were implemented in King County, Washington. They observed an improvement in survival to hospital discharge. Recorded automatic external defibrillator data showed increased time spent with chest compressions. The findings provide support for minimizing interruptions in cardiopulmonary resuscitation. The study also illustrates how analysis of community data can provide reassurance that unanticipated adverse effects do not offset potential benefits when protocol changes supported by strong experimental evidence are applied to out-of-hospital cardiac arrest victims. See p 2760 (and editorial p 2754).ETHNIC AND GENDER DIFFERENCES IN AMBULATORY BLOOD PRESSURE TRAJECTORIES: RESULTS FROM A 15-YEAR LONGITUDINAL STUDY IN YOUTH AND YOUNG ADULTS, by Wang et al.In the United States, blacks experience a greater burden of hypertension and associated cardiovascular disease compared to whites. The reasons for these ethnic differences are incompletely understood. In this issue of Circulation, Wang and colleagues evaluated longitudinal trajectories of 24-hour ambulatory blood pressure (BP) using serial recordings obtained in black and white children over a 15-year period. The authors observed that black children had higher levels of both systolic and diastolic BP during day and night from early adolescence onwards. A striking finding was that black youth experienced a greater age-associated increase in nocturnal systolic and diastolic BP compared to whites. Black-white differences in age-associated changes in day-time BP were less striking. The authors conclude that a blunted nocturnal decline in BP that is more pronounced in adolescence may contribute to the greater burden of hypertension in blacks. If confirmed, these findings suggest the origins of adult hypertension (and ethnicity-related differences in hypertension burden) may lie in the patterns of 24-hour ambulatory BP in childhood. See p 2780.RISKS ASSOCIATED WITH STATIN THERAPY: A SYSTEMATIC OVERVIEW OF RANDOMIZED CLINICAL TRIALS, by Kashani et al.Statins, one of the most commonly prescribed drugs, reduce the risk of cardiovascular events, but there are concerns about their association with an increased risk of musculoskeletal, renal and hepatic complications. Clinical trials are the best source of unbiased information about the presence and magnitude of risk conferred by these medications. The study by Kashani et al in this issue of Circulation evaluated information about the adverse effects of statins based on 35 trials of statin monotherapy versus placebo, involving 74 102 patients. The investigators assessed the risk of myalgias, creatine kinase elevations, rhabdomyolysis, transaminase elevations, and discontinuation due to any adverse event. A caveat is that the experience in the clinical trials might underestimate risks of patients who are underrepresented in the trials, such as those who are older, have more comorbidity, or receive higher doses than specified in the trials. Nevertheless, the present study provides the best current unbiased estimates of the risks of statin therapy in the trial populations and can be used to support clinical decision making. See p 2788.Visit http://circ.ahajournals.org:Images in Cardiovascular MedicineA Quadricuspid Aortic Valve With Severe Aortic Regurgitation. See p e642. Download figureDownload PowerPointAcute Coronary Syndrome due to Intramural Hematoma. See p e644.Definitive Diagnosis of Obstructed Total Anomalous Pulmonary Venous Drainage in a Critically Ill Newborn With High-Resolution Computed Tomography. See p e646.CorrespondenceSee p e648. Previous Back to top Next FiguresReferencesRelatedDetails December 19, 2006Vol 114, Issue 25 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.114.25.2753 Originally publishedDecember 19, 2006 PDF download Advertisement

Improving the use of research evidence in guideline development: 6. Determining which outcomes are important.

BackgroundThe World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the sixth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this.ObjectivesWe reviewed the literature on determining which outcomes are important for the development of guidelines.MethodsWe searched five databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct a complete systematic review ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments.Key questions and answersWe did not find a systematic review that addresses any of the following key questions and we found limited relevant research evidence.What methods should WHO use to identify important outcomes?• Methods of outcome identification should be transparent and explicit.• The consultation process should start with identification of all relevant outcomes associated with an intervention.• Those affected, including consumers, should be involved in the selection of outcomes.• A question driven approach (what is important?) is preferable to a data driven approach (what data are at hand?) to identify important outcomes.What type of outcomes should WHO consider and how should cultural diversity be taken account of in the selection of outcomes?• Desirable (benefits, less burden and savings) and undesirable effects should be considered in all guidelines.• Undesirable effects include harms (including the possibility of unanticipated adverse effects), greater burden (e.g. having to go to the doctor) and costs (including opportunity costs).• Important outcomes (e.g. mortality, morbidity, quality of life) should be preferred over surrogate, indirect outcomes (e.g. cholesterol levels, lung function) that may or may not correlate with patient important outcomes.• Ethical considerations should be part of the evaluation of important outcomes (e.g. impacts on autonomy).• If the importance of outcomes is likely to vary across cultures, stakeholders from diverse cultures should be consulted and involved in the selection of outcomes.How should the importance of outcomes be ranked?• Outcomes should be ranked by relative importance, separated into benefits and downsides.• Information from research on values and preferences should inform the ranking of outcomes whenever possible.• If the importance of outcomes is likely to vary across cultures, ranking of outcomes should be done in specific settings.• If evidence is lacking for an important outcome, this should be acknowledged, rather than ignoring the outcome.

Concepts for General Surveillance of Genetically Modified (GM) Plants: The EFSA position

The European Food Safety Authority (EFSA) is requested to assess the scientific quality of Post Market Environmental Monitoring (PMEM) plans submitted with each application for deliberate release of genetically modified (GM) plants according to part C of EU Directive 2001/18/EC and according to EU Regulation 1829/2003. PMEM aims at identifying unanticipated adverse effects on human health or the environment which could arise directly or indirectly from GM plants. PMEM is composed of case-specific monitoring and general surveillance. Case-specific monitoring is not obligatory but may be required to verify the environmental risk assessment. A general surveillance plan is compulsory and aims at identifying unanticipated adverse effects. General surveillance is not hypothesis-driven but is a general overseeing of the environment making use of existing surveillance systems in addition to developing more focused monitoring systems (e. g. farm questionnaires). Data quality, management and statistical analysis are of high importance in the design of general surveillance plans. Comparison should be made with appropriate baseline data. The EFSA GMO Panel also makes a number of recommendations for the management and conduct of PMEM by both applicants and risk managers.

Integrated Approaches to General Surveillance

General Surveillance has been established to observe unanticipated adverse effects and to then trigger action in response to these observations. The first response will be to determine levels of harm and causes of the adverse effect. A possible cause of such an effect could be that farmers are cultivating combinations or sequences of GM crops in a manner that was not expected. However, in order to determine this, appropriate data would need to be collated and analysed across farms, regions and years in order to try to correlate impacts with specific combinations or sequences of events.

Evaluation of transgenic hybrid corn (VIP3A) in broiler chickens

A 49-d feeding study evaluated whether standard broiler diets prepared with Syngenta Seeds VIP3A transgenic derived corn grain had any unanticipated adverse effects on male or female broiler chickens as compared with diets prepared with nontransgenic (isoline) control corn grain. Two commercial lots of grain grown in North Carolina during the 1999 (NC 1999) and 2000 (NC 2000) seasons were included for reference purposes.Broiler growth was excellent with males reaching 3466 g and females reaching 2882 g at 49 d of age. Final BW of the VIP3A, isoline, and NC 1999 corn groups were within 21.1 g, whereas the NC 2000 group was 42.4 g lower than the lowest of this group. There was no overall corn source effect on adjusted feed conversion ratio (FCR) or mortality to 49 d of age. Carcass analysis demonstrated no differences in percentage yield due to corn source among males and females other than percentage wings in females. Comprehensive clinical chemical analyses of blood taken from representative birds at 49 d of age showed no differences due to corn sources.The transgenic VIP3A hybrid diets numerically supported the most rapid broiler chicken growth, the second lowest mortality rate and best FCR, without practical differences in carcass yield. The few differences found in this study were not unique to a given corn source but instead appeared to be distributed equally across the diet groups evaluated in the study. Although it was not clear whether small differences in performance were attributable to the transgenic corn per se or were due to possible slight differences in overall composition of the formulated diets, it was clear that the transgenic corn had no deleterious effects on broiler performance and carcass yield in this study.

Effectiveness and Safety of the PEGT/PBT Copolymer Scaffold as Dermal Substitute in Scar Reconstruction Wounds (Feasibility Trial).

Skin defects left after excision of hypertrophic scars were treated with a dermal substitute and split-thickness skin grafts transplanted after vascularisation of the substitute. The used substitute was a synthetic porous scaffold made from the biodegradable copolymer polyethyleneglycol-terephtalate and polybuthylene-terephtalate. The study was designed to assess the rate of granulation tissue formation, graft take, and after 3 and 12 months the quality of life (pain, comfort of treatment, cosmetic or functional nuisance), scar formation and wound contraction. In addition, scaffold biodegradation and scar tissue formation were evaluated histologically.Seven patients with different causes of burn injury were enrolled, of which 5 completed the study. In the first 4 patients the time between scaffold application and split-thickness skin overgrafting was in between 17 and 24 days. The time point of overgrafting was significantly reduced to 10-12 days by meshing of the dermal scaffold as evidenced in the last 3 patients. Histological evaluation at 3 months revealed normal generation of dermal tissue, however, the collagen bundles were parallel organized like in scar tissue. In the deeper layers of the neodermis, fragments of the dermal substitute were present, causing a mild inflammatory response. One year post-treatment, some fragments of the copolymer were still observed. The extent of wound contraction after successful overgrafting ranged from 30% to 57% after 1 year. All 5 patients showed an improvement in the total Vancouver Scar Score compared to the value before scar removal being similar to what can be expected when treated with split-thickness skin grafts alone. No unanticipated adverse effects due to application of the substitute were observed.We conclude that although this synthetic dermal substitute can be safely used in humans, the presence of 3D dermal template in a full-thickness skin defect will not automatically improve the skin tissue regeneration process or inhibit wound contraction.

Can nutrient supplements modify brain function?

Over the past 40 y, several lines of investigation have shown that the chemistry and function of both the developing and the mature brain are influenced by diet. Examples are the effect of folate deficiency on neural tube development during early gestation, the influence of essential fatty acid deficiency during gestation and postnatal life on the development of visual function in infants, and the effects of tryptophan or tyrosine intake (alone or as a constituent of dietary protein) on the production of the brain neurotransmitters derived from them (serotonin and the catecholamines, respectively). Sometimes the functional effects are clear and the underlying biochemical mechanisms are not (as with folate and essential fatty acids); in other cases (such as the amino acids tyrosine and tryptophan), the biochemical effects are well understood, whereas the effect on brain function is not. Despite the incomplete knowledge base on the effects of such nutrients, investigators, physicians, and regulatory bodies have promoted the use of these nutrients in the treatment of disease. Typically, these nutrients have been given in doses above those believed to be required for normal health; after they have been given in pure form, unanticipated adverse effects have occasionally occurred. If this pharmacologic practice is to continue, it is important from a public safety standpoint that each nutrient be examined for potential toxicities so that appropriate purity standards can be developed and the risks weighed against the benefits when considering their use.

Impact of Integrated Pest Management on Academia in Entomology in the United States

Events leading to integrated pest management (IPM) have been addressed in depth (e.g., Bottrell 1979, Flint and Van den Bosch 1981, Metcalf and Luckmann 1994), allowing a truncated treatment here by way of introduction. World War II (1939-1945) mobilized the intellectual and industrial efforts of scientists and engineers to devise solutions to a wide range of problems. Breakthroughs in chemistry and engineering proved especially important to agriculture by developing and delivering chemicals to protect human-valued resources. DDT and 2-4-D were the harbingers of a wave of pesticides that appeared to herald the end of pest problems and the need for specialized scientists to study them. The success of these pesticides lasted about a generation before spectacular failures chronicled problems of pesticide resistance and pollution for the general public. Familiar milestones in this journey are the seminal papers on integrated control (Stern et al. 1959, Geier and Clark 1961), Silent Spring by Carson (1962), the Mrak Commission Report (USDHEW 1969), the NAS Report (Anonymous 1969), and the establishment of the Environmental Protection Agency by Executive Order in 1972. IPM emerged to resolve these pesticide problems, and significant funding for the development and delivery of these IPM programs through research and Extension began with programs such as the Huffaker project in 1972 (P.L. Adkisson, personal communication). Entomologists were at the forefront of developing IPM because insecticides lost efficacy and public confidence due to resistance and pollution before fungicides and herbicides encountered similar difficulties. This was leadership born of desperation with a failed chemical control paradigm compounded by unanticipated adverse effects on

Cortical connections of the primary somatosensory cortex and cortical taste area in rats

The EU legislation requests post-market environmental monitoring (PMEM) of a genetically modified (GM) organism even if its pre-market risk assessment indicated negligible risks. It has been claimed that the monitoring of the only currently commercially cultivated GM plant in the EU, Bt MON810 maize, has not revealed any adverse effects. However, the implementation of its PMEM has been criticised repeatedly by the European Food Safety Authority (EFSA).Although EFSA agreed with the monitoring plan consisting of four tools, as proposed by the company which markets MON810, in practice PMEM has relied on famers’ questionnaires, a farmers’ complaint system, and a literature survey. The fourth approach, environmental surveillance networks, has not been utilised yet. Furthermore, PMEM requires that farmers plant a refuge of non-Bt maize in order to sustain the efficiency of the plant in combating the targeted pest.This paper aims to contribute to improved PMEM by means of a critical evaluation of its implementation in the Czech Republic based on interviews and a questionnaire survey of farmers who cultivated MON810. The results indicate that a quarter of the farmers who were surveyed did not comply with the refuge requirement. Moreover, farmers often lacked the knowledge, time, and motivation to observe and report the potential impacts of Bt maize on biodiversity, which is supposed to be monitored by the PMEM farmers’ questionnaire.The findings of this study compound the previous criticism and suggest that the current practice of PMEM limits its aim of detecting unanticipated adverse effects of MON810 maize cultivation on human and animal health and the environment. The PMEM plan should be revised before the approval process of the application for the renewal of the authorisation for MON810 cultivation in the EU continues.

Disease Management: New Wine in New Bottles?

Cost pressures are driving the reorganization of the health care delivery system in the United States, causing health care delivery organizations to become larger and more diversified. These new health care delivery entities are arriving at the same time as a new approach to clinical care: commercial population-based medicine. This approach is sharing an increasing amount of space with the traditional physician-patient-based approach and offers strategies for managing a population's risk, demand, diseases, and outcomes. Although commercial population-based medicine strategies such as disease management may use many of the same tools as traditional public health approaches, they focus on the relatively short-term health needs of defined populations because of the underlying economic incentives facing payers. Population-based-medicine promises better use of resources and a systems approach to health care delivery, but it also presents the pitfalls of subversion by the needs of commercial companies, unanticipated adverse effects, and wide application without adequate preparation.

Randomized clinical trials: Alternatives to conventional randomization

The randomized allocation format remains an exceedingly powerful tool for clinical research. Because humans are the subjects in clinical research, this area of scientific study must operate within the limits dictated by such basic principles as individual autonomy, justice, and beneficence. As randomized studies have become more common in clinical research, it has become apparent that there is often need for modification of the basic randomized format or for alternatives. The most widespread modification is the use of sequential analyses to monitor the progress of a trial and ensure early identification of either unanticipated adverse effects or more pronounced differences than expected. Although this modification does not affect the basic randomized allocation format, it does provide a protection that is lacking in the conventional trial and should be utilized whenever feasible. Modifications that do affect the basic structure of the randomized trial include adaptive allocation and pre-randomization. The former is attractive and useful but limited to studies in which results from early enrollees are known before late enrollees are allocated. The greater the linkage between preceding subject results and subsequent assignments, the greater is the protection afforded by such a format. Pre-randomization, more universally applicable than adaptive allocation, suffers from pronounced cross-over potential and has been criticized on ethical grounds, a combination of weaknesses that raises questions of whether pre-randomization truly offers advantages to conventional randomized formats. True alternatives to the randomized format include the self-controlled study and the historical control design. Both possess significant ethical advantages over the simple randomized study. Unfortunately, both are at some methodological disadvantage when the same comparison is made. The self-controlled study is limited to the study of conditions sufficiently stable or recurrent that they permit two or more treatment courses in a single patient. In emergency medicine and critical care, this description fits only a small proportion of the illness spectrum. This design is underutilized in clinical research focused on less severe problems of the type seen in ambulatory and primary-care settings. Such problems can be suitable topics for research by emergency medicine specialists. Historical control studies are eminently applicable in the emergency and critical-care setting. Indeed, in such clinical venues, many of the major weaknesses of the historical control design may be mitigated because the delivery of care is more standardized and there may be less difficulty in determining the comparability of subject populations. The historical control design must be used carefully and interpreted cautiously, but it can validly be applied to the study of emergency medical problems. In all cases, the best strategy for clinical research is a strategy that has been chosen after consideration of the unique requirements and demands of the research situation.

Psychotropic Drug Effects Contributing to Psychiatric Hospitalization of Children

Over an 11-month period on a Children's Psychiatric Unit 5% of 60 first admissions for hospitalization were apparently associated with adverse effects of psychotropic medication. Forty (66%) of the first admissions had used, prior to hospitalization, a wide variety of drugs including stimulants, major and minor tranquilizers, anticonvulsants, antidepressants and over-the-counter drugs containing antihistamines and analgesics. It is suggested that inappropriate and injudicious use of psychotropic medications may be associated with unanticipated adverse behavioral effects, which can result in deterioration of a child's functioning to the point of necessitating psychiatric hospitalization. Early identification of these unwanted psychotropic effects has diagnostic, prognostic, economic, and legal implications.

First FDA Medical Device Regulations Will Affect Development of Many Experimental Contraceptives

New Food and Drug Administration regulations designed to protect human subjects involved in clinical testing of experimental devices require obtaining consent from each experimental subject after he or she is informed of possible risks, and reporting of any unanticipated adverse effects to the FDA within 20 days. Responsibility for adhering to the standards is divided between the manufacturer, who is forbidden to make a profit from clinical trials, the clinical investigator, and the Institutional Review Board. Implants intended to remain in the body 30 days or more are specifically included as significant risk devices, and this ruling will affect research on many devices designed to be implanted in the fallopian tubes and vas deferens and on IUDs not containing physiologically active components. Many contraceptive devices besides implants are affected, as are all instruments and most reagents used in prenatal diagnostic testing. The manufacturer is required to file a final report on the investigation to the FDA within 6 months of completion of tests. Once the FDA has ruled on whether a new device may be marketed, the agency has the authority to release a detailed summary of the clinical trials.