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Biomedical subjects

W H Inman

Publications and source records attributed to W H Inman.

At least 19 recordsLinked to original sources
PubMed1996

Testing for adverse reactions using prescription event monitoring.

The Drug Safety Research Unit's current methods of investigating adverse drug reactions using prescription event monitoring are discussed. The statistical properties of estimators of rates of occurrence of events in post-marketing surveillance using prescription event monitoring are considered, and a simple model is proposed based on an exponential distribution of time to first occurrence of the event. It is shown that current methodology closely relates to the use of maximum likelihood estimation under this assumption and the distributions of the estimators are shown to be approximately normal, which allows simple confidence intervals and tests to be developed. Two recent applications are considered and corresponding simulations are presented to verify the approximate properties of the test statistics, based on ratios of rates over time and between drugs. Sources of bias in the rates and rate ratios are considered, including under-reporting in later months. A rule-of-thumb, developed from many years experience, is shown to be generally conservative, except when these under-reporting biases are large.

Adverse Drug Reaction Reporting Systems↗
PubMed1996

ACE-inhibitor-induced cough, an adverse drug reaction unrecognised for several years: studies in prescription-event monitoring.

OBJECTIVE. This study examines cough recorded in Prescription-Event Monitoring (PEM) of four ACE-inhibitors. Particular attention was paid to the study of enalapril because the drug was monitored before the causal relationship between cough and ACE-inhibitors had been widely accepted. RESULTS. Several factors which had obscured the causal relationship in the individual cases were found to be also an obstacle in PEM. For example, cough was a common and non-serious event and was under-reported in the PEM study of enalapril and the rate was not strikingly different from that recorded for other drugs. Cough induced by ACE-inhibitors has several characteristics which reduce the chance of a recognisable "signal'. The original questionnaires returned from doctors in the PEM study of enalapril have been reexamined. The observation that the rate of cough diminished after enalapril had been stopped rather than increased after starting, provided the best evidence of causality, because this was not affected by many biases such as the publicity that had occurred prior to doctors participating in PEM completed later reports.

Adult↗
PubMed1995

Vasodilation-related adverse events in diltiazem and dihydropyridine calcium antagonists studied by prescription-event monitoring.

The incidence of vasodilation-related events (flushing, headache, dizziness and oedema) was determined in a total of 37,670 patients treated with diltiazem, nicardipine, isradipine or amlodipine and studied by Prescription-Event Monitoring between 1984 and 1991. Event rates are expressed as the percentage of patients who experienced these events during the six months after the first prescription. The rates for all these events with the newer vasoselective dihydropyridines (nicardipine, isradipine and amlodipine) were higher than those with diltiazem. Among the three dihydropyridines, there were large individual differences in the rates. With nicardipine, the frequency of each of the four vasodilation-related events were similar to one another (approximately 3%). With isradipine, the rates were also similar to one another but all were approximately twice those measured in the nicardipine study (approximately 6%). These differences may have been due to confounding factors such as the publicity about adverse drug reactions, the indication for use by individual patients or the doses actually being used at the time the event occurred. With amlodipine, in contrast, the rate for oedema was two to four times larger than the rates for flushing, headache or dizziness.

Adult↗
PubMed1994

Terminology in prescription-event monitoring.

The terminology used in prescription-event monitoring for postmarketing surveillance is described. It has been developed by the Drug Safety Research Unit while processing records of 500,000 events associated with the use of new chemical entities by 460,000 patients in England since 1981. Currently, the events are arranged in 24 classes which include 108 high-level terms and 1197 low-level terms. Low-level terms are used to code individual events reported by general practitioners, usually without an opinion about any possible causal relationship with a particular drug. Some low-level terms are lumped together as one high-level term when the event rates are estimated.

Drug Prescriptions↗
PubMed1994

Prescription-event monitoring of 10,401 patients treated with fluvoxamine.

Prescription-event monitoring (PEM) is one of two national systems of drug safety monitoring practised in Britain. The objective of this PEM study was to assess the safety of fluvoxamine and to monitor the occurrence of untoward and other events during treatment. A total of 10,401 patients treated with the drug in general practices throughout England were studied and data were analysed in the Drug Safety Research Unit, Southampton. The main outcome measures were the overall incidence of events per 1000 patients; the incidence during the first month of treatment; the mean incidence for months 2-6 of treatment; and the ratio of these rates as a signal that an event could be drug related. The most commonly reported category of events was neuropsychiatric while the most commonly reported individual events were nausea and vomiting. Fluvoxamine was shown to be a safe drug and no unexpected or previously undetected drug-related events were encountered. There was a relatively high incidence of gastro-intestinal symptoms, but other adverse reactions often encountered during treatment with tricyclic antidepressants were not frequently reported.

Adolescent↗
PubMed1991

Prescription-event monitoring of 10,895 patients treated with alprazolam.

'Prescription-event monitoring' (PEM) is one of two national systems of post-marketing surveillance in operation in Britain. It identified 22,065 patients who had received NHS prescriptions for alprazolam, and data available on 10,895 of these were analysed. The main reasons for treatment with alprazolam were anxiety and depression. The patients provided 3360 patient-years of treatment and 7540 patient-years of follow-up. No serious events clearly associated with treatment were recorded. The main events reported during treatment, albeit infrequently, were drowsiness and depression, although depression is more likely to be due to the disorder being treated than to the drug. Some of the other alleged unwanted effects of alprazolam in published reports were not encountered. Since PEM is unable to determine the dependence potential of alprazolam, further evaluation of this problem is called for.

Adult↗
PubMed1990

Prescription-event monitoring: methodology and recent progress.

Event monitoring was first suggested 25 years ago as a way of detecting adverse reactions to drugs. Prescription-event monitoring (PEM), which has been developed by the Drug Safety Research Unit, is the first large-scale systematic post-marketing surveillance method to use event monitoring in the U.K. PEM identifies patients, who have been prescribed a particular drug, and their doctors from photocopies of National Health Service prescriptions which are processed centrally in England. A personalized follow-up questionnaire ("green form") is mailed to each patient's general practitioner, usually on the first anniversary of the initial prescription, asking for information about the patient, especially any "events" that he or she may have experienced since beginning treatment with the drug. The methodology of PEM is presented, together with examples of analyses that can be performed using results from recent studies. The problems and benefits of PEM are discussed.

Drug Prescriptions↗
PubMed1988

Postmarketing surveillance of enalapril. I: Results of prescription-event monitoring.

To identify and measure the incidence of adverse effects of the angiotensin converting enzyme inhibitor enalapril 13,713 patients were studied for one year by prescription-event monitoring. Precise information about the duration of treatment was available for 12,543 patients. The frequency of many events was calculated, including dizziness (483 patients; 3.9%), persistent dry cough (360; 2.9%), headache (310; 2.5%) hypotension (218; 1.7%), and syncope (155; 1.2%). Less common reactions included angioedema, urticaria, and muscle cramps. Altogether 1098 (8%) patients died and the notes of 913 of them (83%) were obtained for detailed scrutiny. With the exception of a few patients with renal failure who deteriorated during treatment (reported on separately), no death was attributed to enalapril. Enalapril was considered to be effective, even in patients with advanced cardiac failure. These results for enalapril are reassuring and provide further evidence of the value of prescription-event monitoring.

Adolescent↗
PubMed1988

Postmarketing surveillance of enalapril. II: Investigation of the potential role of enalapril in deaths with renal failure.

The possibility that enalapril might damage renal function was investigated in 1098 deaths recorded in a prescription-event monitoring study. Case notes for 913 patients were examined. In seventy five there was a rise in the urea or creatinine concentration of 50% or more above pretreatment values. Enalapril appeared to have contributed to a decline in renal function and subsequent death in 10 of these patients. Several characteristics were identified among these patients, including old age, the use of high dose or potassium sparing diuretics, and pre-existing renal disease. Adding a non-steroidal anti-inflammatory drug was also associated with a deterioration in patients with previously stable renal function. No death was encountered of a patient with uncomplicated hypertension. Enalapril infrequently contributed to a substantial decline in renal function in certain vulnerable patients, especially those receiving other drugs known to be capable of adversely affecting renal function. Awareness of the characteristics of these patients and of their concomitant treatment may serve to reduce the risk.

Acute Kidney Injury↗
PubMed1988

Clinical profile of angioedema associated with angiotensin converting-enzyme inhibition.

Based on data from three studies with complete recording of adverse events in about 12,000 patients each, we determined that angioedema in association with the angiotensin converting-enzyme inhibitor enalapril maleate occurred during the first week of therapy at the rate of one case per 3000 patients per week. Thereafter, the incidence was 14-fold lower, without evidence of a temporal trend in incidence beyond the first week of therapy. The cumulative incidence was one case per 1000 patients treated (0.1%). An additional 138 case reports consistent with the diagnosis of angioedema were obtained from our overall controlled and marketed experience using enalapril in more than 1.2 million patients. These reports were examined to further characterize the reaction. The cases generally were mild, and they resolved on discontinuation of drug therapy. Seven patients experienced angioedema or urticaria in association with both enalapril and captopril, a structurally different angiotensin converting-enzyme inhibitor. This further suggested that the side effect is mechanism based. If angioedema is suspected, therapy with any angiotensin converting-enzyme inhibitor should be interrupted promptly, respiratory distress should be treated appropriately, and subsequent therapy should be initiated with an agent from an alternative class of medication.

Angioedema↗
PubMed1988

Blood disorders and suicide in patients taking mianserin or amitriptyline.

26,781 patients who had been prescribed mianserin and 42,082 prescribed amitriptyline were followed up by means of a questionnaire addressed to their general practitioners. No patient had aplastic anaemia, agranulocytosis, or leucopenia severe enough to endanger life, and in only 2 patients in each group was a causal association likely. If either drug dose cause leucopenia, the incidence is likely to be in the range of 1 in 10,000 to 1 in 100,000 patients. Among patients who were reported to have attempted suicide, 56 of 246 survivors of amitriptyline overdoses required intensive care, compared with none of 92 patients who overdosed with mianserin. 4 patients who overdosed with amitriptyline alone died, compared with none of the patients who overdosed with mianserin alone. Both drugs are associated with a low risk of blood disorders, but mianserin is appreciably safer than amitriptyline because of its low toxicity in overdosage.

Amitriptyline↗