Tried and tested method that ain’t broke but needs fixing

Clinical trials are the best method we have for assessing medicines and treatments. So why is clinical-trial activity in Ireland and Europe in decline?

Patient participation is required at levels substantially above where they are today in clinical trials in Ireland. Photograph:Getty Images

Patient participation is required at levels substantially above where they are today in clinical trials in Ireland. Photograph:Getty Images

Thu, May 16, 2013, 02:00

What have cider, elixir of vitriol, vinegar, seawater, citrus fruits and spicy barley water got in common? They were the “treatments” given to six pairs of sailors suffering from scurvy aboard HMS Salisbury in 1747 by Royal Navy physician, James Lind.

Scurvy is a condition characterised by bleeding gums, stiff joints and slow wound-healing. The sailors given the citrus fruits recovered demonstrably more than any other pair, a result we now know was attributable to Vitamin C.

This experiment, carried out almost 300 years ago, is commonly viewed as the first “clinical trial”. May 20th is World Clinical Trials Day, a celebration of this experimental tool, arguably one of the most important means to improving health.

In simple terms, the purpose of a clinical trial is to prove a medicine works and is safe for humans. Prior to the advent of proper clinical trials, many drugs were introduced to the market that did not meet these requirements.

The thousands of children born with limb defects due to thalidomide, which was prescribed to pregnant women with morning sickness, dramatically attest to this. More recently, poorly interpreted clinical-trials data contributed to the MMR scare in the late 1990s, led by Andrew Wakefield. The spike in measles cases observed recently in the UK, arising from reduced immunisation rates, illustrates clearly the consequence of this.

It’s regrettable that certain forms of “medicines” escape the rigour of proper scientific and clinical validation. The so-called cures of many homeopathic remedies are most likely attributable to the placebo effect, a phenomenon observed in a patient following a particular treatment that arises from the patient’s expectations concerning the treatment, rather than from the treatment itself. A properly designed clinical trial can eliminate such biases when testing the claims of a particular therapy and accurately gauge whether it is effective or not.

Positive outcomes
On the plus side, and thankfully the clinical-trials story is mostly a positive one, many medicines have been approved by the relevant regulatory bodies. These have been assessed and proven safe and effective by this most pivotal of scientific tools.

Pause a moment and look at this list, which samples just a few medicines that have been vetted by the clinical trial: the contraceptive pill, vaccines, cholesterol-lowering drugs. It is probable that the life of someone close to you, perhaps even your life, has been improved or saved by a treatment approved for use following clinical trial.

The randomised, controlled trial, the most modern form of clinical trial, was recently voted in a top 20 of great British innovations, along with illustrious companions such as the world wide web and Turing’s virtual machine.

Unfortunately, clinical trials activity in Ireland, as in much of Europe, is declining. There is much debate on this topic but in my view the cause is essentially this: the burden of proof to demonstrate a medicine’s safety and effectiveness has, rightly, become very high but the systems to support meeting that burden are struggling to cope. Such systems include legislation, regulation, research-led clinical care and patient participation.

There are considerable developments afoot in many of these areas including imminent changes to our clinical trials legislation. Driven from Brussels, it will effectively create a common market for approval of treatments, operating to a single, high standard across Europe.

Other changes in our clinical research infrastructure, such as the networking of our clinical-research centres, should complement the legislative changes to help meet the requirements to prove a medicine’s safety and effectiveness in an efficient manner.

However, these alone will not deliver a well-functioning clinical-trials system in Ireland. Patient participation is required at levels substantially above where they are today. Whilst legislation, research infrastructure and so on are matters of resource allocation and commitment to implementation, patient participation is a more challenging, cultural matter.

At the individual level, there are significant advantages to participating in clinical trials, such as early access to new medicines. However, the real benefit is not at the level of the individual but at the level of society. The cumulative effect of patients participating in clinical studies and trials is to generate new medical knowledge that can be put into practice in preventing, diagnosing and treating disease.

In many ways, participating in a clinical trial is much like donating blood. Both are matters of civic responsibility and a high donor/participation rate is an indicator of a society investing in itself.

For those of us responsible for the clinical-trials system, it is critical we build it and deliver it with the patient at the centre, on a firm foundation of trust. On Monday, when we celebrate World Clinical Trials Day, let us recognise that we have come far but we have some way to go.

Dr Graham Love is chief executive of Molecular Medicine Ireland