Introduction to Clinical Trials

All new drugs need to be vigorously tested to ensure they are safe and effective before they are licensed for use. Testing is conducted in the laboratory and in the clinic. Drugs are tested in the laboratory to ensure they are pharmacologically safe for human use. They are then tested in the clinic by administration to humans in clinical trials. The data collected during laboratory testing and clinical trials are compiled by the pharmaceutical company into a product license application. This application is submitted to the regulatory authority in each individual country to obtain a license to allow the pharmaceutical company to market and sell the drug.

There are 3 phases of clinical trials, as described below;

Phase I clinical trials are the first studies in humans. These trials are conducted with small numbers of patients or healthy volunteers (usually male). They are used to investigate the most effective dose of the drug in humans and to determine what side effects are most likely to occur.

Phase II clinical trials investigate the safety and efficacy of the drug in larger numbers of patients (100s) with a focus on the effectiveness of the treatment at different doses and its safety in the target patient population. Usually when phase II is completed the pharmaceutical company will decide whether the safety and efficacy of the drug in the target patient population warrants further development. The drug will only be taken into phase III development if there is a very good chance of the drug meeting the strict safety and efficacy guidelines stipulated by the regulatory authorities.

Phase III clinical trials involve large numbers of patients (1000s), usually on a global scale, and are used to compare the efficacy and safety of the new drug with either the standard existing treatment or placebo (dummy treatment). These studies are usually randomized and blinded so that the patients (and the doctor in the case of double-blind clinical trials) do not know which treatment they are receiving to avoid a biased interpretation of the results. Data obtained from phase III clinical trials are used to demonstrate the benefits of the new treatment over existing treatment or placebo.

Who conducts clinical trials and where do they take place?

Clinical trials involve a number of different organisations. Often, clinical trials are designed, planned and sponsored by a pharmaceutical company or a public health agency. These organisations may subcontract the implementation, monitoring and reporting of clinical trials to a contract research organisation (CRO). The design, monitoring, analysis and reporting of clinical trials require specialised scientific expertise contributed by the staff employed by the pharmaceutical company, the health agency or the CRO.

Clinical trials are conducted in hospital departments, GP surgeries or specialist phase I units, depending on the phase of the trial and the patient population under investigation. There will be a team of doctors, scientists, nurses and other medical and healthcare professionals running the clinical trial, which will be led by a doctor with a number of years research experience (the principal investigator).

Before a trial can start, it is reviewed by the regulatory body of the country where the trial is taking place to ensure strict regulatory guidelines are being followed in the design and planned conduct of the trial. It is then reviewed by an Ethics Committee (or Ethical Review Board) to ensure that the patient’s rights are protected and the highest standards of clinical practice will be observed to ensure the safety of the patient or volunteer.

Deciding to participate in a clinical trial

When deciding whether to take part in a clinical trial, you should be clear about the purpose of the clinical trial and what is expected of you. You need to consider the following fully before you enroll in a clinical trial;

• You will be cared for by doctors and nurses with detailed knowledge about the latest treatments for your condition.
• You will be monitored very closely during the trial and may benefit from additional testing that would not normally be carried out in routine clinical practice.
• You will be given the opportunity to be one of the first patients to benefit from the new treatment under investigation; if you are not responding well to current therapies, participation in a clinical trial may give you access to a treatment that will work better for you.

However, you may experience unexpected side effects to the new treatment and/or it may not be an effective treatment for you. The new drug may prove to be less effective than current available treatments.

Close monitoring of the trial may result in more frequent hospital visits and more testing than would occur if you were not on the clinical trial. This could be disruptive to your life.

You should discuss any concerns or issues you have regarding your health and care during the clinical trial with your doctor before enrolling. It is very important to be fully informed about the purpose of the clinical trial, potential benefits and side effects of taking the new treatment and what is expected of you in terms of hospital visits and tests during the clinical trial.

Phase III clinical trials usually compare a new treatment with either current treatment or a placebo or dummy treatment. It is important to remember that in these clinical trials treatments are randomly allocated and usually neither you nor your doctor will know which treatment you are on until the end of the trial. You or your doctor will not be able to choose which treatment you receive.

At the end of the trial, if you were receiving the least effective treatment you might be given the opportunity to switch to the more effective treatment; your doctor will discuss this with you.

For participation in a clinical trial you will always be asked to sign a consent form to indicate your agreement to take part and that you are fully informed about the treatment under investigation and what is expected of you during the trial. You have the right to withdraw from a clinical trial at any time, and you do not have to give an explanation. Your care at the hospital or clinic will not be affected in any way and you will be offered current, existing treatment for you condition.

All information collected during a clinical trial, including your personal details and case notes, will be kept strictly confidential. The organisation responsible for analysing and reporting the results of the trial will identify your test results and details by a number and your initials only.