This article was taken from the August 2012 issue of Wired magazine. Be the first to read Wired's articles in print before they're posted online, and get your hands on loads of additional content by subscribing online.
It seems paradoxical that, as medical scientists make huge advances in discovering the mechanisms of common diseases, fewer and fewer innovative drugs are reaching the market. Indeed, the pharmaceutical industry worldwide is in difficulty -- it is becoming harder and harder to make new drugs.
But there is one major exception to this trend. New drugs for cancer continue to be developed, often remarkably quickly.
In 2002, researchers at the Wellcome Trust Sanger Institute found that the gene BRAF was mutated in the majority of patients with the skin cancer malignant melanoma. In 2011 a new drug, vemurafenib, targeted to mutations in BRAF, was licensed for therapy. Why is cancer therapy different when it comes to speedy approval of drugs?
We all want our drugs to be safe -- and so an essential part of the pathway to the development of a new drug is approval by a regulator. In the US it's the Food and Drug Administration, in the UK the Medicines and Healthcare products Regulatory Agency and the European Medicines Agency. No one doubts the need for good regulation to ensure drug safety. However, there are increasing worries that regulation is driving up the costs of drug development and driving down productivity. If this is preventing effective drugs from reaching the market and also driving up to unaffordable levels the price of the drugs that do make it, it is very bad news.
The problem is that the incentive system for regulators is weighted too much towards an extremely cautious position. The cause is asymmetry: a regulator can get sacked for allowing something harmful to happen. But a regulator cannot get sacked for preventing something from happening that might have caused good. So, if there appears to be any risk from allowing something to happen, it's much easier and safer to stop it. Of course, this is a caricature, but it contains a germ of truth.
The job of the medicines regulator is to balance the risks from the disease with the benefits and possible side-effects of the therapy. So why are we doing better for cancer therapy? It is because of an obvious balance between benefits and risks. Untreated cancer is frequently lethal. The risk-benefit ratio for new treatments is easy to understand.
The principle of treating cancer is to kill the abnormally dividing cells. Many drugs achieve this in a relatively unselective way, killing any cell that is dividing.
Everyone has accepted that cancer therapy is often associated with unpleasant side effects, from vomiting to failure of the bone marrow, even fatality. But if the alternative is death, then patients, doctors and drug regulators are prepared to take the risk.
But what if the disease is not lethal? The balance of risks and benefits may differ for the patient, the doctor and the regulator.
When a vaccine against rotavirus, which causes infantile diarrhoea, was developed in the US in the 90s, it was found very probably to cause a form of bowel obstruction called intussusception in a tiny minority of children.
Because rotavirus infection is nasty, but not life-threatening in rich countries, US regulators rejected it. Yet this decision meant the vaccine was then not developed for use in countries such as India, Pakistan and Bangladesh, where rotavirus kills, and the jab had the potential to save many thousands of lives.
Vaccines must be safe, but the risk-benefit equation for a vaccine in the US is <span class="s3">different from the risk-benefit in south Asia.
Asymmetry in regulation goes beyond medicine. We will have the best regulators if they are held to account for both permissive and preventative decisions. Regulation must balance risks and benefits. This cannot be achieved if regulators are held accountable only if things go wrong.
The example of medicine shows that, sometimes, more harm can flow by denying those who would benefit from a new medicine than from exposing them to proportionate side effects. Common sense, proportionality and judgment are the skills we must seek in those we choose to regulate our lives.
Sir Mark Walport FRS FMedSci is director of the Wellcome Trust
This article was originally published by WIRED UK
