M. D. Rawlins

National Institute for Clinical Excellence and its value judgments.

NICE has to make both scientific and social value judgments when appraising health technologies and developing clinical guidelines for the NHS. Here, its chair and previous vice chair explain the rationale behind the decisions

Prophylactic aspirin and risk of peptic ulcer bleeding

Abstract Objective: To determine the risks of hospitalisation for bleeding peptic ulcer with the current prophylactic aspirin regimens of 300 mg daily or less. Design: A case-control study with hospital and community controls. Setting: Hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth. Subjects: 1121 patients with gastric or duodenal ulcer bleeding matched with hospital and community controls. Results: 144 (12.8%) cases had been regular users of aspirin (taken at least five days a week for at least the previous month) compared with 101 (9.0%) hospital and 77 (7.8%) community controls. Odds ratios were raised for all doses of aspirin taken, whether compared with hospital or community controls (compared with combined controls: 75 mg, 2.3 (95% confidence interval 1.2 to 4.4); 150 mg, 3.2 (1.7 to 6.5); 300 mg, 3.9 (2.5 to 6.3)). Results were not explained by confounding influences of age, sex, prior ulcer history or dyspepsia, or concurrent non-aspirin non-steroidal anti-inflammatory drug use. Risks seemed particularly high in patients who took non-aspirin non-steroidal anti-inflammatory drugs concurrently. Conclusion: No conventionally used prophylactic aspirin regimen seems free of the risk of peptic ulcer complications. Key messages Key messages This finding applies to doses in common use of 75, 150, and 300 mg daily Despite these results, overall benefits of treatment are likely considerably to outweigh possible risks

A prescription for better prescribing

Many medical students are unprepared for skilled prescribing

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.

Human liver and plasma aspirin esterase

The plasma, in addition to the liver, is a major site of hydrolysis of aspirin. Human plasma and liver aspirin esterase activities in samples from a group of patients varied over a two fold range and there was a significant correlation between individual plasma and liver activities. Human liver aspirin esterase was present in the cytosolic and microsomal fractions. Cytosolic and microsomal enzymes had different activities and apparent affinities for aspirin.

Variability in Response to Drugs

Variability in the response to drugs is due to three principal components—the disease, the responsiveness of tissues, and the concentration of the drug at its site of action (as reflected by its plasma concentration). The relative contributions of these components will differ not only for different drugs but also for different effects of the same drug. Rational drug therapy depends on knowledge of all three factors.

European network for the case-population surveillance of rare diseases (Euronet). A prospective feasibility study

AbstractObjective: Euronet, a case-population surveillance scheme, aims to estimate the risk of certain rare conditions which are commonly iatrogenic, by comparing drug use amongst non-selective cases with overall drug use in the general population. Methods: The method is based on three provisos: (1) all incident cases (irrespective of suspected aetiology) should be ascertained and studied; (2) a full drug history should be obtained from cases by direct interview; and (3) drug-use data for the products of interest should be available for this population from which cases are chosen. The feasibility of this problem-oriented approach for the identification of new signals of adverse drug reactions and for risk estimation will be tested in relation to agranulocytosis, Stevens-Johnson syndrome and toxic epidermal necrolysis in four defined areas in Europe, totalling 19 × 106 inhabitants, with these latest two outcomes being studied in only three regions. The design, methods and main limitations of this case–population surveillance approach are described.

The UK's NHS and pharma: need for more clinical pharmacologists

through the science of pharmacology. The spotlight should particularly be thrown on to medical students (whose prescribing education has languished in recent years through a declining complement of consultant clinical pharmacologists) and general practitioners (who are the major prescribers of medicines).We have previously proposed a “prescription for prescribing”,

7-Ethoxyresorufin deethylase (EROD) in human liver —The effect of alcoholic liver disease

SummaryWe have investigated the effect of alcoholic liver disease (ALD) on the metabolism of 7-ethoxycoumarin 0-deethylase in human liver microsomes. EROD activity was significantly reduced in tissue from ALD patients who smoked, compared to smoking controls. A similar trend was seen in non-smokers. These results have implications for the metabolism of environmental carcinogens.