Lincolnshire Clinical Research Facility

About trials (definitions)

Clinical trials

According to the Good Clinical Practice (GCP) guidelines, a clinical trial implies any systematic study in human subjects, whether patients or non-patient volunteers, in order to discover or verify the effects of and/or to identify any adverse reaction to the investigational products or interventions, and/or to study (in the case of drugs) their absorption, distribution, metabolism, and excretion in order to ascertain the efficacy and safety of the products (GCP 1991).

Phases of clinical trials

A clinical trial can usually be categorised as falling into one of four stages or "phases". Each phase is designed to determine specific information about the potential new treatment such as its risks, safety and effectiveness compared with standard therapy. The hope is that the new therapy will be an improvement over the previous standard therapy. However, the definition of the phases is essentially arbitrary. It is also important to remember that the phases overlap. Phase I studies may still be ongoing when Phase II has started, for example. This may depend on how strictly Phase I is defined (Giovanna and Hayes 2001).

Phase I trials

Clinical studies in Phase I are the first experiments carried out in humans. Healthy volunteers are usually studied in these trials, but this may not be appropriate to all therapies, for example, cytotoxic agents. The primary objective of these studies is to gather safety data, but they are also concerned with defining a dose that might be effective, and with investigating the absorption, pharmacokinetics, metabolism and excretion of the drug (i.e. the pharmacokinetic/pharmacodynamic profile).

Phase II trials

In Phase II the drug is administered to the trial subjects with the target disease, and it is these trials that may be defined as ‘therapeutic pilot studies’. The aim of Phase II is essentially to demonstrate the pharmacological activity and to assess short-term safety in subjects suffering from the target indication.

Studies in this phase will involve small numbers of subjects, and the information collected about each subject during the course of the trial and its follow-up will be very detailed. Phase II studies allow a determination of appropriate dose regimens and dose/response relationships.

Throughout Phase II the clinical development programme will identify milestones or targets; at these points key decisions will be made, for example, whether or not to continue the programme into Phase III or whether there is a need for a modification or tighter definition of the Phase III programme.

Phase III trials

Phase III trials compare a new drug or therapy with a standard therapy in a randomised and controlled manner in order to determine proof of effectiveness. Phase III trials require a large number of patients to measure the statistical validity of the results because patient age, sex, race, and other unknown factors could affect the results. To obtain an adequate number of patients, several physicians (investigators) from different institutions typically participate in phase III clinical trials.

During Phase III the use of drug should be as close as possible to its ultimate clinical use, which is likely to be very different from the intense monitoring of the Phase II trial.

Phase IV trials

Phase IV studies are those performed after approval of a drug for a product licence. They are sometimes carried out to answer questions specific to one particular market, or to enable physicians to gain experience of a new drug under controlled conditions. They tend to be carried out in very large numbers of subjects and much less data is collected for each subject than in Phase II and Phase III. Nevertheless, Phase IV studies can be vital to establish a large comparative safety database for a drug. The most widely used type of Phase IV study is post-marketing surveillance (PMS).

Randomised Clinical Trials

A randomised clinical trial (RCT) is a trial where a treatment (or intervention) is compared with another active reference treatment, placebo treatment, or no treatment. The fact that patients should be randomly assigned is not intuitively appealing either to the layman or to the medical profession. Randomised clinical trials encompass a number of ethical and practical problems. However, from non-randomised studies it is very difficult to obtain valid and reliable assessments of treatment efficacy and adverse effects (Pocock, 1990). Therefore, the randomised clinical trial is today the accepted method for evaluating therapies and interventions.

Blind trials

A blind trial is a trial where the people taking part do not know which treatment they are getting. They could be receiving the new treatment, standard treatment or a placebo, depending on the design of the trial. All patients will receive identical injections or tablets so they cannot tell.

Double blind trials

A double blind trial is a trial where neither the researchers nor the patients know what they are getting. The computer gives each patient a code number. And the code numbers are then allocated to the treatment groups. The treatment arrives with the code number on it. Neither the patient, nor the doctor knows whether it is the new treatment or not.

The list of patients and their code numbers is kept secret until the end of the trial. In an emergency the researchers would be able to find out which trial group a patient was in, but generally no one knows until the trial has finished.

Clinical Research Organisations (CRO)

A Clinical Research Organisation is an organisation, which facilitates, co-ordinates, and performs clinical trials, mostly RCTs. A CRO may be built up as an in-house organisation in the drug and device industry or may exist as an organisation outside the industry. In the latter case, these organisations may be divided into profit organisations or Contract Research Organisations (CROs) or non-profit organisations. These non-profit organisations - facilitating, co-ordinating, and performing clinical trials - are mostly called Clinical Trials Units (CTUs) in UK, and Clinical Research Centres (CRCs) or Clinical Research Organisations in the USA.