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I R Edwards

Publications and source records attributed to I R Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1997

Reasons for reporting adverse drug reactions--some thoughts based on an international review.

A pilot study was made to explore positive reasons for physicians and pharmacists taking time to report adverse reactions, rather than reasons for failing to report which has been studied by many authors. The 34 national drug monitoring centres participating in the international programme at the time of the study were asked by letter from the WHO Collaborating Centre for International Drug Monitoring, Uppsala to investigate the reasons why adverse reactions were reported. National Centres were asked to write to 20 consecutive reporters, sending each a copy of their own report, asking why they had chosen to report that particular reaction, and asking for more general comment. Twelve countries responded with information about the habits and views of the reporters of 177 cases. Since this was an explorative pilot study the letter to reporters deliberately had only an open question about reason for reporting. Categories were developed by the WHO Centre from the responses given. Reasons for reporting fell into a total of 14 categories with the great majority in the top six: motivation to contribute to medical knowledge, reaction previously unknown to reporter, reaction to new drug, all significant reactions reported, known association between drug and reaction, and severity of reaction.

Journal Article↗
PubMed1997

Withdrawal reactions with selective serotonin re-uptake inhibitors as reported to the WHO system.

OBJECTIVE: The present study was performed both to investigate whether there might be a difference between the selective serotonin re-uptake inhibitors, (SSRIs) with regard to the incidence of withdrawal reactions, and to describe the associated symptoms. From the WHO database, therefore, all case reports from the year of introduction for each of the SSRIs, fluoxetine, paroxetine and sertraline, were retrieved. Sales figures were obtained from Intercontinental Medical Statistics International. The reporting rates were calculated as the number of reports per million defined daily doses (DDDs) sold per year. RESULTS: The reporting rate of withdrawal reactions for paroxetine was found to be higher than that for sertraline and fluoxetine in each of the countries selected for detailed analyses (US, UK and Australia), as well as for all 16 countries combined. Moreover, using the WHO system of organ classification, the ratio of central nervous system to psychiatric withdrawal symptoms was 1.9 and 2.1 for paroxetine and sertraline, respectively, whereas that for fluoxetine was 0.48, indicating a possible qualitative difference between the SSRIs with respect to the nature of the withdrawal syndrome.

1-Naphthylamine↗
PubMed1997

How does cystitis affect a comparative risk profile of tiaprofenic acid with other non-steroidal antiinflammatory drugs? An international study based on spontaneous reports and drug usage data. ADR Signals Analysis Project (ASAP) Team.

Series of well-documented case reports strongly suggest a causal association between tiaprofenic acid and a form of aseptic cystitis, which can cause serious and long-term morbidity if the drug is not withdrawn promptly. These findings are supported in the Australian and UK spontaneous reporting data-bases. Using sales data as the denominator, a comparison of NSAIDs in the WHO drug monitoring data-base indicates that the reaction is specific to tiaprofenic acid and cannot be accounted for by changes in reporting patterns in certain countries or years. Delayed recognition is an important feature of this reaction and possible reasons for this are discussed. Comparison of the risk profiles of seven NSAIDs indicated that tiaprofenic acid had the poorest risk profile, compared with NSAIDs of similar efficacy, when cystitis reports were included. The results suggest that combining spontaneous reports, classified according to severity, with sales data may enhance the ability of drug monitoring data-bases to contribute to risk benefit appraisals.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Principles of signal detection in pharmacovigilance.

Adverse drug effects are manifold and heterogenous. Many situations may hamper the signalling (i.e. the detection of early warning signs) of adverse effects and new signals often differ from previous experiences. Signals have qualitative and quantitative aspects. Different categories of adverse effects need different methods for detection. Current pharmacovigilance is predominantly based on spontaneous reporting and is mainly helpful in detecting type B effects (those effects that are often allergic or idiosyncratic reactions, characteristically occurring in only a minority of patients and usually unrelated to dosage and that are serious, unexpected and unpredictable) and unusual type A effects (those effects that are related to the pharmacological effects of the drug and are dosage-related). Examples of other sources of signals are prescription event monitoring, large automated data resources on morbidity and drug use (including record linkage), case-control surveillance and follow-up studies. Type C effects (those effects related to an increased frequency of 'spontaneous' disease) are difficult to study, however, and continue to pose a pharmacoepidemiological challenge. Seven basic considerations can be identified that determine the evidence contained in a signal: quantitative strength of the association, consistency of the data, exposure response relationship, biological plausibility, experimental findings, possible analogies and the nature and quality of the data. A proposal is made for a standard signal management procedure at pharmacovigilance centres, including the following steps: signal delineation, literature search, preliminary inventory of data, collection of additional information, consultation with the World Health Organization Centre for International Drug Monitoring and the relevant drug companies, aggregated data assessment and a report in writing. A better understanding of the conditions and mechanisms involved in the detection of adverse drug effects may further improve strategies for pharmacovigilance.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

The challenge of effectively communicating risk-benefit information.

Although the techniques involved in drug safety monitoring (pharmacovigilance) have dramatically improved in recent years, communication of these issues to health professionals and the public lags far behind. Several measures need to be taken in order to address this discrepancy. A climate of greater openness concerning the basis of merit assessments must be created. We need to develop merit-assessment formulations that are more accurate and helpful when treating individual patients in clinical situations. All of the involved groups must be educated about the nature of drugs and drug therapy, and the possibilities and limitations of such therapy. More effective techniques and systems have to be developed in order to stimulate higher rates of high quality spontaneous reporting of adverse effects. More conscientious and purposeful attention to the theory and practice of communications, in order to ensure the effective delivery of optimal benefits to patients, clinicians and society at large, would also be advantageous. We must ensure that where issues of public health and confidence in the medical profession are at stake, we employ the very best communications practices.

Drug Labeling↗
PubMed1997

Causal or casual? The role of causality assessment in pharmacovigilance.

As with any other study method, 'spontaneous reporting' in pharmacovigilance is a process of data acquisition, assessment, presentation and interpretation. The provision of information (i.e. of interpreted data) concerning previously unknown, or otherwise important adverse drug reactions is a major goal. The assessment of case reports in spontaneous reporting takes place in 2 steps: first the assessment of each case individually, and secondly the interpretation of the aggregated data. The latter step is only completed for a minority of case reports, such as when actions or measures are deemed necessary. Uncertainty in case reports regarding the involvement of the suspected drugs is an inherent drawback of spontaneous reporting. Standardised case-causality assessment has become a routine at pharmacovigilance centres around the world. It aims at a decrease in ambiguity of the data and plays a role in data exchange and the prevention of erroneous conclusions. A variety of systems for standardised causality assessment have been developed, ranging from short questionnaires to comprehensive algorithms. Since none of the available assessment systems has been validated (i.e. shown to consistently and reproducibly produce a fair approximation of the truth), causality assessment has only limited scientific value. Causality assessment neither eliminates nor quantifies uncertainty but, at best, categorises it in a semiquantitative way. Routine causality assessment is usually part of the first step in case assessment, and is based on a general system that is intended for all reactions and all drugs. During the subsequent phase of aggregated assessment, causality assessment is likely to be repeated and the use of a specific aetiological-diagnostic system may be more appropriate. It may be recommended to restrict case-causality assessment to selected case reports that are likely to play an active role in pharmacovigilance and to use specific systems, adapted to the reaction or problem involved. It is an inherent limitation of spontaneous reporting that, with the exception of rare proof-positive case reports, conclusive evidence cannot usually be produced. Standardised causality assessment has not really changed this situation. As a rule, confirmation of the connection between a drug and an adverse reaction requires further analytical or experimental study.

Adverse Drug Reaction Reporting Systems↗
PubMed1996

Omeprazole and visual disorders: seeing alternatives.

In the WHO data base, visual disorders reported spontaneously with omeprazole, ranitidine and cimetidine, are very rare in the context of the widespread use of these drugs. There is a maximum reporting rate of severe visual impairment possibly ascribed to i.v. omeprazole of 0.94 reports per million treatment days in one year and in one country, Germany. This gives the worst quantitative case scenario for omeprazole by a single route of administration, to be compared with the worldwide reporting rate of all severe visual disorders by all routes of administration--0.008 reports per million treatment days. Moreover, the reported visual abnormalities have a varied pathophysiological aetiology and their number increased in Germany after the first signal was raised in that country. Thus, apart from a direct causal relationship, solicited reporting artifact is one alternate plausible explanation for the apparent excess of cases of visual disturbance to omeprazole compared with cimetidine and ranitidine. That reporting rates of clinical events on newly marketed drugs are generally higher than with older drugs is a second factor for higher reporting rates with omeprazole. Vasculitis has been suggested as an aetiological factor, but the even lower reporting rate of this reaction makes this an unlikely hypothesis without any other supporting evidence. The authors are unaware of any drug that has caused a vasculities solely affecting the eye. Information on the prevalence of relevant visual disorders in the community would have been of considerable help in interpreting this signal, and a case control study of visual events in relationship to severe illness would be of public health interest, since no data seems to exist concerning this.

Journal Article↗
PubMed1993

Drug safety monitoring: an international perspective.

The issue of drug safety must always be considered from the patient's perspective. Efforts in drug safety monitoring must seek to improve care and give prescribers and their patients with the best possible information to make a risk-benefit judgement. The concept of a 'signal' of an adverse reaction to a drug needs to be clearly understood, and the nature of the process to determine which signals become established 'adverse reactions' is important. Good clinical and pharmaco-epidemiological studies and insight are needed for the investigation of a signal. International cooperation utilising the WHO Programme for International Drug Monitoring and other organisations helps with the discovery, evaluation and dissemination of information on drug issues, but in the end it is the alert clinician who is both likely to spot new unexpected drug problems and have the individual patient knowledge to use drugs to their maximum benefit and minimal harm.

Drug Evaluation↗
PubMed1992

Reporting side-effects.

Explore the source record for details and available documents.

Adverse Drug Reaction Reporting Systems↗
PubMed1992

Pharmacokinetics of pirmenol in young and elderly subjects.

The steady state pharmacokinetics of pirmenol was compared in twelve healthy young (aged 18 to 45 y) and 11 elderly subjects (over 65 y) subjects given pirmenol HCl 100 mg every 12 h for a total of 14 doses. In addition, the single-dose pharmacokinetics of pirmenol was determined following a 100 mg oral dose in the young subject group for comparison with the results of repeated administration. In the young subjects, the mean single-dose and steady-state CLR of pirmenol were similar; however, Ae was 29% higher and CL/f was 22% lower at steady state than after the single dose. Steady-state (fourteenth dose) Cmin, Cmax, tmax, lambda z, Ae, CL/f, CLR and V values were similar in the young and elderly subjects. Based on pharmacokinetic considerations, the dosage of pirmenol is unlikely to differ in young and elderly subjects.

Adult↗