Clinical trials - the importance to science

Written by: 
Jacky Law, medical writer

What are clinical trials?

Clinical trials are research studies that aim to find new, safer or more effective medical interventions. This could be a drug, a procedure such as surgery, or a method for preventing disease such as screening. The idea is to ensure all interventions:

  • Have benefits that outweigh the risks
  • Are effective in bringing about the desired result
  • Are an improvement on the existing standard treatment or, in the case of a new intervention, are better than doing nothing
  • Can be administered at the optimum frequency and, in the case of drugs, in the optimum doses and/or combinations with other drugs.

Why do we need them?

Clinical trials enable people to appreciate the risks and benefits of medical interventions. There are several kinds of clinical trials depending on what is being researched. They could be:

  • Prevention trials: to find better ways to prevent disease
  • Screening trials: to ascertain the best way to detect diseases
  • Treatment trials: to test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy
  • Quality-of-life trials: to explore ways to improve the quality of life for people with a chronicA disease of long duration generally involving slow changes. disease.

How do clinical trials work?

Clinical trials are highly controlled experiments that aim to compare like with like. As such, they are organised into at least two arms, one of which is composed of patients who are given the intervention in question and another of similar patients who act as a control for the experiment. Patients on this latter arm are given a mock intervention, known as a placebo, that looks and feels like the one being tested.

The purpose of the control is to show what happens in the absence of the intervention.

Another important aspect when comparing like with like is to eliminate any bias that may arise from either the doctor or the patient knowing an intervention has been administered. For this reason, clinical trials are usually:

  • Randomised: People taking part in a trial are randomly assigned to one of the various arms of the study.
  • Blind or double-blind: If a study is blind, the people on the trial don’t know what arm they are on and therefore what intervention they receive, if any. If it is double-blind, the researchers also don’t know.
  • Placebo-controlled: By assigning patients at random to the placebo-controlled arm of the trial, researchers can demonstrate what happens in the absence of any intervention.

Who oversees trials?

The cornerstone document regarding ethical conduct in human experimentation is the Declaration of Helsinki, a fundamental principle of which that the welfare of the individual takes precedence over the interests of science and society. Although not binding in international law, it draws its authority from the extent to which it has been codified into national and international legislation and is morally binding on doctors.

All clinical trials must also be approved by the regulatory authority of the country in which they are conducted. This normally comes via an ethics committee, which is primarily concerned with approving the study plan (protocol), ensuring the people taking part are informed about what the trial involves, and that it conforms to internationally recognised Good Clinical Practice (GCP).

What is informed consent?

It is a legal requirement in all countries that patients must give informed consent before taking part in a clinical trial. Patients should expect to be given a document outlining:

  • The purpose of the trial and how it has been planned
  • An explanation of how the research affects the patient
  • How long it will last
  • The procedures involved (extra tests or hospital visits, for example)
  • The risks, benefits and alternative treatments
  • People to contact if something is unclear
  • Clarification that participation is voluntary, confidentiality is respected and that patients retain the right to withdraw at any time without prejudicing future medical care.

The principle of competency applies, which means people must be able to clearly understand what is involved. If they are a child or incapacitated in some way, a legal representative must give consent on their behalf.

How do I assess whether a clinical trial is safe?

All trial plans are subject to independent scientific review before they are scrutinised by an ethics committee (see above). Researchers must tell the ethics committee if they observe unexpected side-effects.

Most drug trials also have an independent data monitoring committee that can look at the interim results and recommend a trial is stopped if unexpected side-effects are observed or, if it is so successful, it is deemed unethical to deprive treatment to those on the control arm.

How much testing has been done before patients join a trial?

Where a new drug is concerned, patients are normally recruited onto a trial at Phase III, after a series of safety checks has been passed. These are:

  • Pre-clinical trials: Various doses of a potential drug are tested on animals and/or in the laboratory to get an idea if it works, its toxicity, how it is metabolised and how long it takes to be eliminated from the body.  
  • Phase I trials: The drug is then tested in various doses in healthy volunteers to assess how it is tolerated and how fast it passes through the body. In terminal conditions, such as cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body., actual patients may be used. In general, Phase I studies are safe but there is always some risk with new classes of drug as was seen with the now infamous trials on TGN 1412, a monoclonal antibodyOne of a group of special proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. (MAB), that resulted in a severe and unexpected immune reaction.
  • Phase II trials: These look at how well the drug actually performs against agreed endpoints to show efficacy in various doses while continuing safety observations.

Do trial patients get better treatment?

Patients tend to get better treatment on a trial because their doctors are obliged to follow the protocal. This can mean more thorough investigations, monitoring and following-up of any problems.

In some conditions, such as cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body., where the drug costs are prohibitive in several countries, patients may also have a better chance of being on a new drug, albeit an experimental one.

The disadvantage of being on a trial is that patients don’t know if they are on the active drug or not. Moreover, when the trial ends, there is no guarantee they can stay on the drug.

What happens at the end of a trial?

The data amassed is analysed and submitted to the regulatory authority of the country concerned in the hope of getting approval for the intervention.