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Biomedical subjects

I Ralph Edwards

Publications and source records attributed to I Ralph Edwards.

15 recordsLinked to original sources
PubMed2006

Extending the methods used to screen the WHO drug safety database towards analysis of complex associations and improved accuracy for rare events.

Post-marketing drug safety data sets are often massive, and entail problems with heterogeneity and selection bias. Nevertheless, quantitative methods have proven a very useful aid to help clinical experts in screening for previously unknown associations in these data sets. The WHO international drug safety database is the world's largest data set of its kind with over three million reports on suspected adverse drug reaction incidents. Since 1998, an exploratory data analysis method has been in routine use to screen for quantitative associations in this data set. This method was originally based on large sample approximations and limited to pairwise associations, but in this article we propose more accurate credibility interval estimates and extend the method to allow for the analysis of more complex quantitative associations. The accuracy of the proposed credibility intervals is evaluated through comparison to precise Monte Carlo simulations. In addition, we propose a Mantel-Haenszel-type adjustment to control for suspected confounders.

Databases, Factual↗
PubMed2006

The challenge of effectively communicating patient safety information.

Rational use of drugs and patient safety are seriously compromised by a lack of good information, education and effective communication at all stages of drug development and use. From animal trials through to dispensing, there are misconceptions and opportunities for error which current methods of drug information communication do not adequately address: they do not provide those responsible for prescribing and dispensing drugs with the data and information they need to pass on complex and often changing messages to patients and the public. The incidence of adverse reactions due to the way drugs are used; the variable impact of regulatory guidelines and warnings on prescribing behaviour; drug scares and crises suggest a great gap between the ideals of the safe use of medicines and the reality in homes, clinics and hospitals around the world. To address these challenges, the authors review the several levels at which safety information is generated and communicated, and examine how, at each stage, the content and its significance, and the method of communication can be improved.

Animals↗
PubMed2005

A bayesian recurrent neural network for unsupervised pattern recognition in large incomplete data sets.

A recurrent neural network, modified to handle highly incomplete training data is described. Unsupervised pattern recognition is demonstrated in the WHO database of adverse drug reactions. Comparison is made to a well established method, AutoClass, and the performances of both methods is investigated on simulated data. The neural network method performs comparably to AutoClass in simulated data, and better than AutoClass in real world data. With its better scaling properties, the neural network is a promising tool for unsupervised pattern recognition in huge databases of incomplete observations.

Algorithms↗
PubMed2005

The WHO World Alliance for Patient Safety: a new challenge or an old one neglected?

The WHO World Alliance on Patient Safety is a new, all encompassing project to improve medical care. Individual patients are the focus and all countries are encouraged to develop systems in which medical error, therapeutic accidents and failures are minimised. The potential for adverse events is present at all levels of healthcare and in all disciplines. One working group in the Alliance is charged with promoting and developing a 'reporting and learning' culture for adverse events in all areas of medical care. Central to current thinking for this group is a no-fault approach and to report near misses. The aim is not to provide certainty over the individual events, but rather to draw attention to possible improvements in systems that may prevent future problems. Adverse events relating to drug therapy have been reported for decades to national pharmacovigilance authorities, but this is aimed at finding problems with the drugs themselves as early as possible. The Alliance approach in the area of drug safety, by contrast, has a greater focus on safety in the systems of drug provision (including prescription and dispensing) and other systematic issues relating to safe drug provision, such as fraudulent drugs. Thus, current pharmacovigilance can be seen as representing a part of the reporting and learning envisaged by the Alliance. The two approaches are also complementary, but there are practical and philosophical areas of overlap in which difficulties may occur, such as anonymised reporting in a no-fault system and consequent impossibility for follow-up. In pharmacovigilance follow-up for more information is regarded as essential. Whether pharmacovigilance broadens into the area of patient safety or the latter involves completely new systems to do its work will be a matter for each country to consider. One thing is certain, working together both systems will improve patient care, but without cooperation more bureaucracy will take valuable health professional time with a lesser result.

Consumer Product Safety↗
PubMed2005

Standardized assessment of adverse events in rheumatology clinical trials: summary of the OMERACT 7 drug safety module update.

A presentation, demonstration, and discussion of recently developed adverse event instruments were the topics for the OMERACT 7 Drug Safety Module. The module began with a plenary introducing the needs and challenges of adverse event ascertainment. It was followed by a review of module work from previous OMERACT meetings on a prototype coding instrument (Rheumatology Common Toxicity Criteria), then a brief description of the process behind the recently developed patient self-report and investigator report adverse event instruments. These current instruments are designed for use in controlled trials although they could be used in other settings. The instruments rely primarily on patient self-reporting using a checklist, which the investigator then folds into a parallel structured but more medically sophisticated instrument. In pilot testing, this innovative dual-use system has shown reliability and acceptability, while preserving validity. A "stakeholder panel" of representatives from 8 sectors followed--patient, nurse investigator, regulator, clinician scientist, industry, OMERACT, global public health/WHO, and Cochrane Collaboration--for their perspectives on the needs, challenges, and potential ways forward for adverse event ascertainment and reporting in clinical trials. At the breakout session small focus groups participated in hands-on interactive testing of one of 3 versions of the instruments, which differ in degree of comprehensiveness. Each focus group had a participatory patient with rheumatoid arthritis. At a second plenary there was group feedback by rapporteurs and presentation of results from pilot studies of iterative testing of validity, reliability, and feasibility of the instruments. During plenary discussion a frequent suggestion for improvement was to refine the process so that event ascertainment could be done entirely using the patient instrument with minimal input from the investigator at the visit, if patient-investigator agreement was high. Most found the patient checklist attractive, particularly if the patient instrument was shown to be reliable and valid. Finally, a future research agenda was discussed.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

Assessing the impact of drug safety signals from the WHO database presented in 'SIGNAL': results from a questionnaire of National pharmacovigilance Centres.

INTRODUCTION: A major task for the Uppsala Monitoring Centre (UMC) is to detect early signals of suspected adverse drug reactions (ADRs) in the WHO Database. The database currently contains over 2.8 million spontaneously reported ADR case reports continuously collected by National Pharmacovigilance Centres in countries participating in the WHO Programme for International Drug Monitoring. The database is scanned every quarter and drug-ADR combinations are filtered out using different selection criteria intended to catch potential international drug safety signals at an early stage. Summary case data are reviewed by experts on the UMC's review panel and the signals are presented to the Programme members in the restricted circulation document entitled 'SIGNAL'. OBJECTIVE: The aim of the study was to investigate: (i). how the signals presented in 'SIGNAL' are used; (ii). if they reach the right target group; (iii). if they are of interest and relevance to the recipients; (iv). if they are timely and; (v). if they make any difference. We were also interested in knowing the view of member countries regarding the definition of what a signal is. METHODS: A questionnaire was sent out to 71 countries participating in the WHO Programme. The recipients were asked to state what actions were taken for 26 different signal headings included in three issues of 'SIGNAL' sent out during 2001 and to rate how useful they considered these topics to be. RESULTS: Responses were received from 45 countries (63%). The Centres' average ratings of relevance, importance and usefulness on a scale 1-10 of the selected 26 signals were all above the expected average rating 5.5. The content of 'SIGNAL' in general was seen as always or often useful in 63.5% of the respondents. In 2001, 17 countries took actions on at least one signal. Actions were rarely taken without considering the signal from the UMC. All responding centres agreed on the WHO definition of a signal, but there were differences in the interpretation of what constitutes a signal. CONCLUSION: The 'SIGNAL' publication is timely, plays an important role and has a direct impact on drug safety issues handled by members of the WHO Programme for International Drug Monitoring.

Adverse Drug Reaction Reporting Systems↗
PubMed2002

A data mining approach for signal detection and analysis.

The WHO database contains over 2.5 million case reports, analysis of this data set is performed with the intention of signal detection. This paper presents an overview of the quantitative method used to highlight dependencies in this data set. The method Bayesian confidence propagation neural network (BCPNN) is used to highlight dependencies in the data set. The method uses Bayesian statistics implemented in a neural network architecture to analyse all reported drug adverse reaction combinations. This method is now in routine use for drug adverse reaction signal detection. Also this approach has been extended to highlight drug group effects and look for higher order dependencies in the WHO data. Quantitatively unexpectedly strong relationships in the data are highlighted relative to general reporting of suspected adverse effects; these associations are then clinically assessed.

Adverse Drug Reaction Reporting Systems↗
PubMed2002

Signal selection and follow-up in pharmacovigilance.

The detection of unknown and unexpected connections between drug exposure and adverse events is one of the major challenges of pharmacovigilance. For the identification of possible connections in large databases, automated statistical systems have been introduced with promising results. From the large numbers of associations so produced, the human mind has to identify signals that are likely to be important, in need of further assessment and follow-up and that may require regulatory action. Such decisions are based on a variety of clinical, epidemiological, pharmacological and regulatory criteria. Likewise, there are a number of criteria that underlie the subsequent evaluation of such signals. A good understanding of the logic underlying these processes fosters rational pharmacovigilance and efficient drug regulation. In the future a combination of quantitative and qualitative criteria may be incorporated in automated signal detection.

Adverse Drug Reaction Reporting Systems↗
PubMed2002

Labelling and 'Dear Doctor' letters: are they noncommittal?

Over the past few years, a number of drugs have been withdrawn for safety reasons, either by drug approval authorities, or by the manufacturer. A recent example is the withdrawal of cerivastatin in connection with rhabdomyolysis. Several other drugs have also been taken off the market as a security measure, not because the nature of the risk involved was unknown but because the risk had proved apparently uncontainable. It seems that the inclusion of a warning or contraindication in the Summary of Product Characteristics (SPC) or sending a 'Dear Doctor' letter is insufficient to ensure compliant prescription behaviour. There appears to be a discrepancy between the careful use of evidence underpinning the SPC content and formal warnings and changes to the SPC and the effect they have on the prescription and dispensing of the drugs involved. This results in undue loss or damage for both the manufacturer and the patient. There are no easy solutions to tackle this problem; the ineffectiveness of labelling and 'Dear Doctor' letters has ramifications for the whole regulatory/ industrial/educational complex. We discuss briefly four possible strategies for improving the current situation, with the emphasis on the place the prescriber has in this process. The first strategy is education-based. Clinicians need to know about the comparative merits of the effectiveness and risk of drugs, as well as how they work pharmacologically, toxicologically, and what interactions they have with each other. The second strategy involves improving the information available for clinicians. Frequently, physicians do not consult the SPC for verification, leaving aside whether they have taken notice of the contents of the official SPC in the first place. It is recommended that the accessibility of SPCs is enhanced for doctors and pharmacists, drawing attention specifically to any changes. There needs to be a single body of information that covers every drug. The third strategy involves communication. There is much to be done in this area both in terms of follow-up and understanding of health professional's behaviour and how to empower best practise. The final strategy involves professional freedom. It goes without saying that doctors who issue off-label prescriptions may need to justify their actions. Deviating from the SPC should always be a considered decision and health professionals need to be aware of the additional responsibilities associated with such a decision. The dispensing pharmacist can play an important role in the implementation of warnings and contraindications.

Contraindications↗