The Pharmaceutical Journal Vol 267 No 7172 643-649
3 November 2001

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Letters to the Editor

Drug safety

New drugs must be prescribed judiciously

From Mr A. R. Cox, MRPharmS and Mr J. L. Underhill, MRPharmS

Bill Fullagar, president of the Association of the British Pharmaceutical Industry and president of Novartis UK, noted that only 16 per cent of the money spent by the National Health Service goes on new medicines (launched within the past five years) and that the United Kingdom has the highest rate of generic prescribing in Europe. He asked, "Why does Britain pride itself on using medicines that (by definition) are at least 20 years old, rather than enjoying the benefit of major advances in medical science?" and compared uptake of new drugs to that of new computing technology (PJ, 20 October, p539).

In answer to this question, we would suggest that there are good reasons why we should be proud of this situation and our so-called "therapeutic conservatism". Two main points are clear about newly licensed drugs.

First, the safety profile of new drugs is at best provisional, as clinical trials cannot define uncommon, yet important, adverse drug reactions. If n patients are treated, and none suffers a specified adverse drug event, then we can be 95 per cent sure that the true incidence of that adverse effect is between 0/n and 3/n.¹ Generally, licensing decisions are based on trials involving an average of 1,500 patients,² so a serious reaction that affects as many as 1 in 500 patients may not be detectable from such a limited body of evidence. In addition, only occasionally will more than 100 trial patients have received a new drug for more than a year.²

An analysis of five drugs withdrawn in one year in the United States (fenfluramine, dexfenfluramine, terfenadine, mibefradil, and bromfenac) showed that 19.8 million patients (nearly 10 per cent of the US population) had been exposed to these five drugs before their withdrawal.³ High prescribing rates of new drugs may expose large populations to drugs with potentially serious side effects before pharmacovigilance systems have the chance to detect new safety issues.

Second, although the European Medicines Evaluation Agency and Medicines Control Agency assess the safety, efficacy and quality of a drug, comparative data on efficacy are often limited and cost-effectiveness is not considered. Trials tend to exclude people with co-existing diseases or who are taking other medicines, as well as the young, elderly people and women. They do not, therefore, produce evidence which is generalisable to the population at large. The body of this evidence may also suffer from positive publication bias and studies are often sponsored by the manufacturers of the products being studied rather than by independent researchers.

Given that the first principle of medicine is primum non nocere (first do no harm), there is a balance to be found between the overzealous use of new and largely unproven drugs and ensuring patients receive the best possible care. Certain individuals may well benefit from receiving newer drugs, but these should only be prescribed where other interventions are inappropriate or have failed to produce a benefit over a reasonable length of time.

The development of new drugs is undoubtedly important for other reasons, such as to maintain the profitability of the pharmaceutical industry and, therefore, the UK's balance of payments, but these agents must be prescribed judiciously. Rather than cajoling prescribers to prescribe the next new drug to enter the market, we consider that it is far more important to ensure patients are allowed to make the best use of established drugs, which have better described safety profiles and ensuring "patient involvement in medicine taking". We would also remind health professionals of the importance of reporting any adverse reactions to new drugs (identified in the British National Formulary by a black triangle) through the yellow card scheme.

Anthony Cox
Sutton Coldfield, West Midlands

Jonathan Underhill
Knutsford, Cheshire

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