Envelopes have been flopping through the letterboxes of doctors all over the country bearing news about the drug Atomoxetine, which is prescribable for young people and adults with Attention Deficit Hyperactivity Disorder (ADHD).
Atomoxetine was launched in Britain in July last year, after being used in the US since 2002 with a total world exposure of 2.3 million patients. However, says the letter - jointly sent by the drugs company Lilly and the government's Committee for the Safety of Medicines (CSM) - serious liver problems have been found with Atomoxetine, although this has been rare. Forty-one accounts of liver disorders have been reported among users, which have, in two cases, resulted in acute hepatitis.
This sounds very alarming. But the reality is that doctors get warning letters like this all the time . All drugs have side effects. Most of the time, prescribing a course of medication is a hope that the benefits are going to outweigh the harms. Particular problems arise when the hazards of using medication are unpredictable. Even a very large clinical trial would have been unlikely to detect the rare liver problem with Atomoxetine. Lilly says that when it used the drug on more than 6,000 patients as part of a clinical trial, there was no evidence of liver injury.
So how was the problem picked up? The answer is bright yellow. The doctor's bible - at least mine - is the BNF, or British National Formulary. This thick tome contains a full list of all available medicines, the indications for medication, known side effects, drug interactions and doses, and it is my most used and favourite bedside companion.
At the back of the book is a small sheaf of tear-out Yellow Cards, which are designed to be used to alert the CSM to possible drug reactions. This is especially important where new drugs are being used, and doctors have always been encouraged to report any "adverse reaction" in these circumstances.
The BNF lists new drugs with black triangles beside their names, reminding us to fill out a card, even if we are uncertain that a patient's adverse reaction is anything to do with the drug. Caution rules. In the case of Atomoxetine, the CSM says that 67 reports of suspected drug reactions were made in Britain, with three reports of liver problems.
The Yellow Card scheme was launched in Britain in 1964 after the birth defects caused by thalidomide made it obvious that following up problems after a drug had been licensed was extremely important. Since then, 400,000 reports have been filed to the CSM, a unit of the Department of Health that receives and analyses the results. Initially, only doctors could file the reports, but nurses, pharmacists, coroners, dentists, radiographers and optometrists have all been encouraged to sign and post the cards. And after a review of the scheme last year, patients and carers are now invited to report suspected adverse reactions under a pilot project launched last month at www.yellowcard.gov.uk. Not only can you file a report online, but you can also see what other people have filed. This gives a good idea about trends occurring in the use of a particular medicine, even though these are reports about yet-unproven suspicions.
Is this enough? There is yet another balance to strike. Many trials, done over a long time, may result in lots of knowledge about a drug's safety - but extended tests can deprive some people who would have benefited from the drug. Too short a period spent testing a drug in too few people will be inadequate to instil confidence in patients and doctors, or to show up rare side effects. And for rare diseases, it is much harder to gather large numbers of patients to do big trials. But there are rarely wonder drugs we really cannot wait for.
After Vioxx - the drug that was recently withdrawn over fears about adverse cardiac reactions - the Department of Health is looking at introducing a fourth clinical stage to trials of drugs before they are licensed. Currently, drugs go through three phases: laboratory-based; small-scale and then larger groups of patients; then wider use, and the Yellow Card scheme to monitor. The proposed fourth stage would involve a limited licence to use the drug in a closely monitored larger group of patients before it was given a full licence. Maybe this is the way forward, but whatever drugs we use, there will always be the possibility of side effects. More important, we'll need to learn how to manage our own risks, and what risks we want to take. This can mean not just taking account of the risk of taking a medicine, but of not taking it.
