Perspectives: An Opinion on Medication Risk from the United Kingdom

Richard Barker, PhD, is Director General of the Association of the British Pharmaceutical Industry. In this capacity he is also a board member of EFPIA (the European industry association) and council member of IFPMA (the International equivalent). His priorities include boosting the UK and Europe as a global leader in pharmaceutical innovation, strengthening the partnership between the industry and the health service, increasing patient engagement and access to new medicines in the UK and globally, and ensuring that the industry’s external image reflects its major contribution to health and economic prosperity.

He is a member of the NHS National Leadership Network, and a stakeholder in the TB Alliance, developing new medicines for this devastating condition, and of the UK Government’s Foresight project in infectious disease.

He is also active in the biotechnology sector, as board member of Adlyfe, developing detection technology for diseases involving protein misfolding, and of iCo Therapeutics, an early stage company developing ocular therapies. He is also a Board member of Datapharm, a company bringing online medicines information to UK prescribers and patients. His academic research was in biological magnetic resonance, at Oxford, Leeds and Munich.

Medicines and Risk

Life is about decision-making, weighing the risks and benefits. And when it comes to medication, most of us ask the same question – will the benefits justify the risks, any side-effects, any “adverse reactions” as they are called?

The making of a medication is a long journey. It begins with a process of discovery. It is first tested on experimental animals and then typically on small numbers of healthy volunteers. Then it is tested on a small group of patients and before it moves to a larger group, until thousands of patients may have received it. And each time the benefit – the efficacy, as we call it – is weighed against any side-effects that might appear. As the evidence builds up to give greater and greater levels of confidence, the drug looks more and more promising.

Finally the Food and Drug Administration (FDA) approves the medicine, but the process does not stop there. After launch, especially when there are any concerns spotted in the clinical trials, “black box” procedures require any unusual or significant reactions to be reported, so that the benefit/risk assessment can be constantly reassessed. Occasionally, but often enough to demonstrate that the process works, a drug is withdrawn, or more typically restricted in its use to minimize the risk.

Only one in 10,000 potential medicines ever reaches the patient, and only one in 20 of those that enter human trials. That’s how rigorous the process is. In what other walk of life would the odds be stacked so heavily against a new product? And what company would launch a medicine they thought would prove to be unsafe in relation to its benefits, with all the costs in financial and public relations terms that could follow?

The detective story

Think of the process this way. The industry, building on breakthroughs made in basic research, makes literally thousands of variants of promising molecular “leads”. They then try to discover, as quickly as possible, information about the benefit/risk tradeoff. It is a detective story that often lasts a decade, in the lab and in the clinic. Every test is one that each potential medicine is expected to fail – indeed the company wants anything whose risks are too high to fail early and to fail fast. Only the smallest handful of drugs will jump every hurdle and make it to market -- and even then the detective’s vigilance does not relax.

Of course, while we can all understand immediate benefits, risk is notoriously difficult for us to get into perspective. Small risks of major events loom large. Every nuclear power station evokes memories of Three Mile Island, and every plane trip the last crash that we viewed on TV.

What is the risk for me?

We sometimes hear of a medicine that it carries double the risk of something. Well, read the small print. Is it double the risk of something that happens to one person in 100,000? – then the risk is 1 in 50,000. Is that acceptable, bearing in mind the clinical benefit we receive? That is the real question.

But is it a risk of 1 in 50,000 for me?

We are learning more and more about how our unique genes and our personal metabolism affect the way our bodies react when we take a medicine – something that can only work because it interferes with our body’s biochemistry. So it is fair to ask: are there any tests that should be done to determine whether this is the right medicine for me?

In an increasing number of cases – take Herceptin for example – there is a test that guides doctors in knowing whether a particular patient will respond to the drug, in this case for breast cancer. And there are an increasing number of tests that establish if the patient’s liver can break down a medicine when it has done its work, an important indicator of whether side-effects can be expected from a build-up of medicine in the bloodstream.

The benefits

But the benefits that come with these risks are enormous. Without medication we would live in a world in where a simple infection kills; where ulcers would require stomach surgery; and HIV would be a death sentence. This world was our world, if we turn back the clock for 60 years, 30 years, or 15 years. Today we are seeing ever more sophisticated cancer treatments, a constant race to bring new drugs to battle against adaptable viruses like pandemic flu, new hope for Alzheimer’s sufferers. And, for those with epilepsy, the new drugs offer promise of a near-seizure-free life. Risks? Yes, but surely benefits well worth receiving.

Sad to say, there are no totally safe medicines, just as there are no totally safe cars, totally safe streets, or totally safe sports. Life comes with risk. What is key is for the benefits to outweigh the risks. That is all that we can ask for – and our medicines are no exception to this rule.

While medicine development is global, regulation in the UK is still local, and it is the European Agency for the Evaluation of Medical Products (EMEA) and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) that monitor this process in Europe and the UK. Each seeks to make a similar benefit/risk judgment as the FDA. However, agencies do not always come to the same conclusions. For example vigabatrin treatment used for epilepsy in the UK is not available for treatment of epilepsy in the US. Why? Different timing can result from different processes and priorities, and may not signal different criteria.

So, when we open the medicine cabinet we should do so with gratitude to all the scientists and patients on the long journey through the lab and clinic. We should look in appreciation to the rigorous testing each medicine has gone through -- not in expectation of a guarantee, but in expectation that the risks will be outweighed by lasting benefits.

Edited by Rita Watson, MPH
Reviewed by Steven C. Schachter, MD on 04/25/07