Wednesday, 7 January 2009

The Problem with Clinical Trials

All new medicines undergo a rigorous series of controlled studies to establish safety and efficacy before they are licensed. The need to test drug safety on a small scale before allowing it to be prescribed was underlined in the early 1960's by the well known Thalidomide Tragedy, a situation where the drug thalidomide was prescribed to pregnant women in Europe and Canada as a treatment for morning sickness. Unfortunately the drug had only been tested in animals, and nobody foresaw the severe birth defects that would be inflicted on the children of these women. In 1962 the US Food and Drug Administration (FDA) put a system in place to ensure all new drugs would be rigorously tested before coming to market.

This has resulted in the clinical trial system we have today which typically consists of three phases. Phase I begins if laboratory and animal experiments have shown convincing evidence that a new drug is effective and safe. At this stage the primary concern is drug safety and only the minimum number of patients will be treated, initially with a very low dose of the drug, increasing gradually as the trial proceeds. If the trial goes well and no patients were harmed by the drug, then it may enter phase II. In Phase II the objective is often to establish an effective treatment regime, different dose levels and frequencies are likely to be tried in order to establish how to make the drug most effective. At completion of this phase the data will be studied to determine if there is a benefit associated with use of the drug. If there is, then phaseIII will begin, often with hundreds of patients in a large scale placebo controlled study across many sites to establish beyond doubt whether the drug is truly beneficial.

The problem with this system is that it is very expensive and is a very long process, taking up to a decade or more to complete. The race to get the drug to market means companies often try to complete the first two phases as soon as possible, they see promising data from these trials and dive headfirst into PhaseIII to save as much time and money as possible. This means that detailed studies into the method of action of the drug are often overlooked, as it isn't considered worth spending the money on that until you know the drug is safe and effective, its as if nobody cares how the drug works, they just want to find out if it is effective at treating the disease. This is thought to be one large factor in why so few drugs make it through PhaseIII to market. If you don't know how the drug works, then you don't know why its failing. Within a trial the drug may work well for some patients, and have no effect on others, frequently the benefit is seen in so few patients that the drug is considered ineffective and dropped from the process. Any benefits that were seen are easily forgotten once the trial is branded a failure. There was however a potential to learn a lot from these studies, information which when used correctly could have meant the drug could have been brought to market.

The trial system is certainly protecting the public from potential dangers of new drugs, but it may also be indirectly harming them by being such an expensive and time consuming process that drugs that only seem to have a small benefit, or benefit only a small selection of patients, are never brought to market. In my next post I will explain how a surprising addition to the current system is already giving us the information we need to optimise the trial process and bring more drugs to market.

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