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Biomedical subjects

M D Rawlins

Publications and source records attributed to M D Rawlins.

At least 19 recordsLinked to original sources
PubMed1999

Attitudinal survey of voluntary reporting of adverse drug reactions.

AIMS: Voluntary adverse drug reaction (ADR) reporting schemes have operated since the early sixties in many Western countries. It is generally recognized, however, that only a small proportion of ADRs is actually reported. The current survey was conducted to assess attitudes towards reporting of ADRs, and to study which types of ADRs are reported. METHODS: A questionnaire seeking reasons for nonreporting was sent to a random sample of 10% of medical practitioners in The Netherlands in October 1997. After 6 weeks, a reminder was sent to those who had not responded. RESULTS: One thousand four hundred and forty-two (73%) questionnaires were returned, of which 94% were complete. The percentage of GPs (51%) which had ever reported an ADR to the national reporting centre was significantly higher than the percentage of specialists (35%), who reported more often to the pharmaceutical industry (34% vs 48%). 86% of GPs, 72% of surgical specialists and 81% of medical specialists had ever diagnosed an ADR, which they had not reported. Uncertainty as to whether the reaction was caused by a drug (72%), the ADR being trivial (75%) or too well known (93%) were the most important reasons for not reporting. 18% were not aware of the need to report ADRs, 22% did not know how to report ADRs, 38% did not have enough time, 36% thought that reporting was too bureaucratic and only 26% of Dutch physicians knew which ADRs to report. A serious ADR, an unlabelled ADR, an ADR to a new drug, history of reporting of one or more ADRs, and specialty were all independently associated with reporting of 16 hypothetical ADRs. Surgical and medical specialists tended to report less often than GPs. CONCLUSIONS: There is a considerable degree of underreporting, which might partly be explained by lack of knowledge and misconceptions about spontaneous reporting of adverse drug reactions.

Adverse Drug Reaction Reporting Systems↗
PubMed1998

New active substances authorized in the United Kingdom between 1972 and 1994.

AIMS: The study was undertaken to assemble a list of all new active medicinal substances authorised in the United Kingdom between 1972 and 1994; to assess whether the pattern of introductions had changed; and to examine withdrawal rates and the reasons for withdrawal. METHODS: The identities of those new active substances whose manufacturers had obtained Product Licences between 1972 and 1994 were sought from the Medicines Control Agency's product data-base. For each substance relevant information was retrieved including the year of granting the Product Licence, its therapeutic class, whether currently authorised (and, if not, reason for withdrawal), and its nature (chemical, biological etc.). RESULTS: The Medicines Control Agency's data-base was cross-checked against two other data-bases for completeness. A total of 583 new active substances (in 579 products) were found to have been authorised over the study period. The annual rates of authorisation varied widely (9 to 40 per year). Whilst there was no evidence for any overall change in the annual rates of authorising new chemical entities, there has been a trend for increasing numbers of new products of biological origin to be authorised in recent years. Fifty-nine of the 583 new active substances have been withdrawn (1 each for quality and efficacy, 22 for safety, and 35 for commercial reasons). CONCLUSIONS: For reasons that are unclear there is marked heterogeneity in the annual rates of authorisation of new active substances. Their 10 year survival is approximately 88% with withdrawals being, predominantly, for commercial or safety reasons. This confirms the provisional nature of assessments about safety at the time when a new active substance is introduced into routine clinical practice, and emphasises the importance of pharmacovigilance.

Databases, Factual↗
PubMed1996

Panic and the pill.

Explore the source record for details and available documents.

Contraceptives, Oral↗
PubMed1996

The clinical pharmacologist in drug regulation: a European perspective.

1. The clinical pharmacologist in drug regulation has many roles to play. These include responsibilities for the premarketing assessment of a new product's efficacy and safety, for scrutiny of the summary of Product Characteristics, and for monitoring its performance after marketing. Furthermore, the clinical pharmacologist has a subsidiary responsibility in examining the results of preclinical pharmacological and toxicological studies. 2. Clinical pharmacologists in regulatory authorities have one further, and crucial, responsibility--humility. From their training and experience they will (or should) know of their own scientific limitations and of the necessity for seeking help and advice from other disciplines.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

[Reasons to report or not report side effects of drugs to the national monitoring system in the Netherlands].

OBJECTIVE: To assess the awareness of medical practitioners in the Netherlands regarding the national voluntary reporting scheme for adverse reactions to drugs, and the reasons for non-reporting. DESIGN: Questionnaire. SETTING: Netherlands Centre for Monitoring of Adverse Reactions to Drugs. METHOD: A questionnaire was sent to a random sample of 500 practitioners aged under 65 in the database of the Dutch Inspectorate for Health Care. RESULTS: Of the 500 questionnaires 265 (53%) were returned and completely filled in. Sixty-seven (25%) practitioners had reported a suspected adverse reaction on one or several occasions during their practising career; 229 (86%) would report a serious adverse reaction, 190 (72%) an unknown one, 185 (70%) an adverse reaction to a new product, and 83 (31%) a proven adverse reaction. Almost 20% said they had had difficulties reporting because they could not find the telephone number or reporting forms. Forty practitioners (15%) claimed that they were too busy to report adverse reactions. Almost all practitioners (94%) were aware of the fact that the reporting scheme serves the early detection of unknown adverse reactions.

Drug Monitoring↗
PubMed1995

The effect of gastritis on human gastric alcohol dehydrogenase activity and ethanol metabolism.

BACKGROUND: Gastric mucosal alcohol dehydrogenase (ADH) may decrease the bioavailability of ingested ethanol. Because this enzyme is found in highest concentrations in the superficial gastric mucosa, diffuse abnormalities of this tissue could lead to a decrease in the first pass metabolism of ethanol. METHODS: Thirty-three adult subjects undergoing routine upper gastrointestinal endoscopy had gastric biopsies performed for assessment of gastric histology and the measurement of gastric ADH activity. Twenty of these subjects underwent separate oral dosing and intravenous infusion of ethanol (0.15 g/kg body weight) in order to determine the first pass metabolism, and hence bioavailability, of ethanol. RESULTS: Gastric histology was normal in 10 of the biopsies, showed chronic gastritis alone in 13 and significant glandular atrophy (i.e. atrophic gastritis) in a further 10. Gastric ADH activity in specimens with normal gastric histology was significantly higher than those with chronic gastritis (P = 0.02), and was further decreased in those specimens with significant atrophy (P < 0.00001). However, no correlation was found between gastric ADH activity and the first pass metabolism of ethanol (r = 0.09, P = 0.9). CONCLUSIONS: These results suggest that although gastric ADH activity was decreased in individuals with abnormal gastric mucosa, ethanol bioavailability was not affected by gastric ADH activity. These data support the view that gastric ADH does not play a significant role in the first pass metabolism of alcohol.

Adult↗
PubMed1995

Attitudinal survey of adverse drug reaction reporting by medical practitioners in the United Kingdom.

1. Attitudes of doctors to the Committee on Safety of Medicines' (CSM) adverse drug reaction (ADR) reporting scheme were investigated in order to assess their understanding of the purposes of the scheme and to identify reasons for failing to report suspected adverse drug reactions. 2. A postal questionnaire and letter of invitation were sent to 500 doctors who were randomly selected from the 1992 Medical Directory. A reminder letter and a second copy of the questionnaire were sent to non-responders after 4 weeks. 3. 284 (57%) responded to the questionnaire. Of these, 179 (63%) stated that they had previously reported an ADR to the CSM or a pharmaceutical manufacturer. 77% of general practitioners stated that they had reported one or more ADRs compared with 55% of hospital doctors. 4. Reasons for under-reporting included lack of time, lack of report forms and the misconception that absolute confidence in the diagnosis of an adverse reaction was important in the decision to send in a report. 5. An investigation of seven commonly proposed reasons for under-reporting showed that on the whole they did not apply. 6. Most doctors knew the types of reactions that the Committee on Safety of Medicines seeks reports for but only 38% knew the precise meaning of the Committee on Safety of Medicines' black triangle symbol. There also seemed to be confusion about some of the purposes of the adverse drug reaction reporting scheme. 7. The number of reporting doctors is much higher than has previously been estimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse Drug Reaction Reporting Systems↗
PubMed1994

Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs.

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of peptic ulcer complications, but it is not clear whether some drugs are more likely than others to cause such complications. We compared previous use of NSAIDs in 1144 patients aged 60 and older admitted to hospitals in five large cities with peptic ulcer bleeding and in 1126 hospital controls and 989 community controls matched for age and sex. Peptic ulcer bleeding was strongly associated with use of non-aspirin NSAIDs of any type during the 3 months before admission (411 cases, 351 controls; odds ratio 4.5 [95% CI 3.6 to 5.6]). The odds ratios for peptic ulcer bleeding were lowest for ibuprofen (2.0 [1.4-2.8]) and diclofenac (4.2 [2.6-6.8]), and intermediate for indomethacin, naproxen, and piroxicam (11.3 [6.3-20.3], 9.1 [5.5-15.1], and 13.7 [7.1-26.3]). Azapropazone and ketoprofen carried the highest risks (31.5 [10.3-96.9] and 23.7 [7.6-74.2]). Risks also increased with drug dose (low dose 2.5 [1.7-3.8], intermediate 4.5 [3.3-6.0], and high 8.6 [5.8-12.6]) for all drugs combined. Appropriate clinical strategies could prevent many episodes of peptic ulcer bleeding: NSAIDs should be used only in patients who do not respond to other analgesics; the lowest possible doses should be used; and the least toxic NSAIDs should be selected.

Aged↗
PubMed1994

Flumecinol for the treatment of pruritus associated with primary biliary cirrhosis.

OBJECTIVE: To determine whether flumecinol (3-trifluoromethyl-alpha-ethylbenzhydrol, Zixoryn) is effective in ameliorating pruritus of cholestasis, particularly in primary bilary cirrhosis. METHODS AND RESULTS: 50 patients (46 with primary biliary cirrhosis, PBC) took oral flumecinol 600 mg or identical placebo once weekly for 3 weeks. Patients assessed pruritus by scoring a daily 100 mm visual analogue scale (VAS; 0 = no itch, 100 = severe, continuous, day and night intolerable itch). Quality of life was similarly measured. Patients scored the VAS daily for a 7-day baseline and for a further 21 days. Subjectively, pruritus improved in 13 of 24 on flumecinol and 10 of 26 on placebo (chi 2 = 1.24, P = 0.27). Median difference in fall in VAS pruritus score between baseline week (mean score for each individual used) and the last week was 8.0 [95% confidence interval (CI) -2.1 to 20.8] and for VAS quality of life was 5.0 (95% Cl 0.4 to 13.0) both in favour of flumecinol over placebo. Later, 19 patients (all PBC) were randomised to flumecinol 300 mg or placebo daily for 3 weeks. Subjectively, pruritus improved in 7 of 10 on flumecinol and 1 of 9 on placebo (Fisher's exact test, P = 0.02). Median difference in fall in VAS pruritus score was 19.8 mm (95% CI 3.3 to 40.7 mm) in favour of flumecinol over placebo and for quality of life was 3.5 mm (95% Cl -5.9 to 24.9 mm). Flumecinol did not significantly affect liver function tests, antipyrine clearance or serum total bile acids, and was not associated with any significant side-effects. CONCLUSION: Flumecinol was safe at the above doses and short term treatment with 300 mg daily, significantly ameliorated pruritus in primary biliary cirrhosis.

Administration, Oral↗
PubMed1994

The efficacy of locally applied morphine in post-operative pain after bilateral third molar surgery.

1. Recent evidence has hinted at a peripheral site of action of morphine analgesic efficacy. 2. Previous studies by the same authors have developed a model for testing local analgesic efficacy by placing drugs into tooth sockets after third molar surgery. 3. The present studies test the hypothesis of local morphine activity at two dosage concentrations, 100 ng ml-1 and 100 micrograms ml-1 after third molar surgery. 4. No significant analgesic efficacy was found at either dose when compared with placebo.

Administration, Oral↗
PubMed1993

Are systemic levels of non steroidal anti inflammatory drugs relevant to acute upper gastrointestinal haemorrhage?

It is uncertain as to the extent which gastrointestinal (GI) haemorrhage related to NSAIDs is due to a local, topical effect or to an action related to systemic absorption. We hypothesised that, should systemic drug concentrations be of importance, plasma levels of NSAIDs might be higher in patients who had developed GI haemorrhage, from controls who had not. Ten patients with GI haemorrhage, who had ingested piroxicam (and no other NSAID), within the preceding 64 h, at the same dosage and on no new medication for the past 14 days, had blood taken at presentation for measurement of piroxicam concentrations. Plasma piroxicam concentrations were measured in 19 community dwelling controls, matched for age +/- 8 years, gender, daily piroxicam dosage, and time from last dose as their respective index case. All had been taking piroxicam for at least 3 months, and none had experienced GI adverse effects. Median plasma piroxicam concentrations in patients at 8.27 micrograms/l, was higher than in controls at 5.06 micrograms/l. These results suggest that a systemic component, at least with piroxicam, may play a significant (though not necessarily exclusive) role in causing major gastrointestinal haemorrhage.

Acute Disease↗
PubMed1993

United Kingdom Product Licence applications involving new active substances, 1987-1989: their fate after appeals.

1. The overall fate of Product Licence applications for new active substances considered by the Committee on the Safety of Medicines between 1987 and 1989 is described. 2. Fifty-one applications were the subject of appelate procedures and 44 (86%) were successful. In 19 (43%) of the latter, applicants sought either decreased dosage regimens, substantially reduced indications, or (once) topical rather than systemic treatment. 3. Overall 57% of Product Licence applications considered between 1987 and 1989 either do not reach the market (23%) or only with substantial restrictions on dosage or indications (34%). Drug regulation, in the United Kingdom, thus plays a significant role in promoting public health rather than merely delaying the entry of new products to the market. 4. The number of volunteers and patients exposed to new active substances at the time of marketing varied widely within and between therapeutic classes. The median number of patients (1528) available for the assessment of safety underlies the importance of postmarketing safety surveillance.

Drug Approval↗
PubMed1992

Review of company postmarketing surveillance studies.

OBJECTIVES: To review postmarketing surveillance studies sponsored by the pharmaceutical industry since the introduction of voluntary guidelines in 1987 and to evaluate their contribution to monitoring drug safety. DESIGN: Retrospective analysis of the information submitted to the Medicines Control Agency on postmarketing surveillance studies. SETTING: United Kingdom. MAIN OUTCOME MEASURES: Study designs, projected and actual sample sizes, provision of interim and final reports, number of suspected serious adverse reactions reported, identification of new drug safety hazards. RESULTS: 31 studies had been conducted under the guidelines, of which 27 were prospective and four retrospective. Nine studies had at least one comparator group, the remainder were uncontrolled. The median projected sample size for the studies was 5600 patients. Only five studies had achieved at least 75% of the projected sample size. 11 studies had been abandoned, predominantly because of difficulties in recruitment, and 15 were ongoing. One study had identified an important new safety hazard. CONCLUSIONS: Company postmarketing surveillance studies have made only a limited contribution to the assessment of drug safety, principally because of weak study designs and difficulties in recruitment. The guidelines require modification to take this experience into account.

Drug Industry↗