Each year many UZA patients take part in clinical trials. This is done on a voluntary basis. If an appropriate trial is running on the ward where you are admitted, you will possibly be asked to take part in it. You have the complete freedom to decide whether or not you would like to take part in it. If you are participating, or in future will be participating, in clinical studies, you can approach the doctor treating you with your questions.

What is a clinical study?

The concept of a ‘clinical study’ applies to all of the investigations conducted on people in the context of scientific research.  The law speaks of ‘experiments on human subjects’.

A clinical study can be seen as a coming together of scientific questions. It may involve questionnaires that are given to participants, study of participants that may involve the administration of medicinal products, tests on healthy volunteers or on patients, etc.  Clinical studies are done in a wide variety of investigative fields in medicine.

Clinical studies are necessary so we can develop new treatments or techniques for treatments.  This is because no new medicines or new treatments are used before extensive studies have demonstrated that this new product or this new treatment is effective and safe.  The studies are however also important for preventive health care: so for example only through clinical studies can we investigate which population groups run more risk of particular conditions than others, what the impact is of nutrition, mental trauma etc. on the later development of illnesses.  In short, without clinical studies no progress would be possible in medicine. 

Clinical study in four phases

In most clinical studies a medicine is tested. That process unfolds in four phases.

Phase I study

The safety and actions of the medicine are tested on a group of healthy volunteers. The general effects are investigated (for example, absorption into the blood) and whether there are any immediate side effects.

Phase II study

The medicine is tested on a limited group of patients who have the disorder in question. The intention is to further check the safety of the medicine and to ascertain that the intended effect is achieved in the short term (for example, lowering of blood pressure).

Phase III study

The medicine is tested on a larger group of patients, so that the action and the side effects can be checked over a somewhat longer period. It is usually a comparative or controlled study. Half of the patients are given the standard treatment, or if there is no standard treatment a placebo, an inactive substance. The other half is treated with the medicine under investigation. If the medicine passes this test, it is registered with the European Medicines Agency (EMA).

Phase IV study

This phase takes place once the product is already on the market. The product is monitored further, amongst other things to detect extremely rare side effects and to study the long-term results. But, for example, also to test whether it can combat other illnesses or whether it can be prescribed to children.

Legislation regarding clinical studies

Legal basis: the experiments law

In order to protect the patients who take part in clinical studies as much as possible, European guidelines have been established.  These guidelines have been transposed into strict regulations by the Belgian legislature.  The legal basis is the law of 7 May 2004 regarding experiments on human subjects and its decree of implementation (RD) of 30 June 2004.

A number of safety mechanisms have been built in to protect patients’ interests in a clinical study. So each study must be approved by a recognised ethics committee before it starts. For research into new medicinal products the approval of the Federal Agency for Medicines and Health Products (FAGG) must moreover also be obtained.

UZA Medical Ethics Committee

The Committee for Medical Ethics, or Ethics Committee, within the UZA is a group that is composed as prescribed in the Royal Decree of 12 August 1994:  doctors, a lawyer, an ethicist, a patient counsellor, etc.  A number of scientists from the University of Antwerp also take part in this group. 

Meetings are held at regular intervals to inspect and evaluate all scientific studies that are conducted in the UZA.  Amongst other things the group examines whether the research is meaningful, checks that it does not entail too much risk for the participants, whether the information forms for the participants are sufficiently clear, and whether the patients can give their consent freely and withdraw it again.

If the committee judges that there are objections, it poses additional questions to the investigator.  At the end of its assessment the Ethics Committee gives a favourable opinion (approval) or an unfavourable opinion (rejection).  Only once the experiment has been approved by the Ethics Committee can it actually start.   So doctors certainly can’t “just start” a study. 

After a clinical study has started the Ethics Committee continues to monitor the research from a distance.  If necessary (e.g. because of unacceptable side effects of a tested medicine that become known in the course of the study) the Ethics Committee can have the study stopped prematurely.  So the Ethics Committee watches over the participants’ interests throughout the study.

How is a clinical study run?

1. Participation

In order to take part in a clinical study you must comply with certain criteria.  These criteria are described in detail in the study protocol.  Before you are allowed into a study, tests are conducted to see if you are eligible. The standard ones are a blood test, a urine test and a heart test.

Some frequently occurring criteria are:

• age
• medical and mental history of the participants
• pregnant women are usually excluded
• participants may not take part in another clinical study at the same time

2. Signing the informed consent

Participation in a clinical study is always done on a voluntary basis.  In order to be able to take a well-informed decision about taking part, you must be informed, amongst other things, about the purpose of the study, which steps will be gone through and what the possible side effects or risks might be: you must as a participant know in advance what to expect.  Therefore a great deal of importance is attached to informing the participants thoroughly.  This is called informed consent.

• You are given an information document by the doctor or investigator presenting all the useful information about the study. 
• You will be asked to sign an ‘informed consent form’.  This is a form in which you confirm that you have been sufficiently informed, and in which you give your consent in writing to participation in the clinical study. 
• By signing the informed consent form you declare that you agree to participate in the study.  You can also withdraw that consent again at any time, without having to provide an explanation.
  You can always approach the investigator, the doctor or the study nurse with all your questions.

Rights and obligations of participants

Right of voluntary participation  

A clinical study is always performed on a voluntary basis. As a patient you are always free to participate and you are never pushed in a particular direction.  If your doctor asks you to take part in a study you may simply refuse.

Right to be informed

Before consenting to collaborate, participants must always be completely informed about the purpose of the study, the duration, the side effects, the steps they have to go through, etc. Even after you have given your consent, you can request additional information from the investigator, the doctor or the study nurse at any time during the study.

Right of withdrawal

You can revoke your decision to participate at any time during the study and withdraw from the study. If you had to take special medicines for the investigation it may be necessary to taper off the treatment, or to have another check-up appointment.  This is purely in the interests of your own health.

Confidentiality of the data  

All information collected during the study is treated in strict confidence.  In later publications of the study results no information will be made public from which the identity of the participants could be derived.

Duties

In addition to rights, you as a patient also have some responsibilities if you participate in a clinical study. You must follow the proposed treatment schedule, get yourself to the hospital on time as requested, allow blood to be taken, etc., take the prescribed medicinal products faithfully, etc. If you do not comply with the stated conditions you can also be made to leave the study.

Liability and insurance

In the Experiments Act of 7 May 2004 the legislation requires the sponsor (this is the body taking the initiative) of a clinical study to have no-fault liability for any harm that a participant encounters and which is directly or indirectly connected with the study. 

This means that if you as a participant suffer harm, you only have to demonstrate that the injury is connected with the study.  You do not have to show any fault of the doctor or investigator in addition to that. 

The sponsor of a study is obliged to take out insurance for this risk.  Depending on the nature of the study this falls under the general liability insurance that each doctor takes out in the context of his practice, or a specific insurance policy taken out especially for the study.  The ethics committee checks that the insurance to which the sponsor refers is sufficiently attuned to the nature and the possible risks of the study.  

Compassionate use and medical need

Sometimes a medicine that is not yet available can, out of compassion, nevertheless be made available to one or more patients. 

The patients concerned:

• are suffering from a chronic disease
• have a disease that severely undermines their health or is considered life-threatening
• cannot be treated with an available medicine in a satisfactory manner. (‘compassionate use’)

In addition to the use of as yet unauthorised new medicinal products in particular cases, rules have also been laid down for the use of an authorised medicine for an indication other than that for which it has been registered (‘medical need’).  Included in this category are patients who are suffering from a chronic disease, a disease that seriously undermines the health or a life-threatening disease, which cannot be treated in a satisfactory manner with a medicine authorised for the treatment of that disorder. 

In both cases a medicine (without authorisation or with authorisation but only for other indications) is used for therapeutic reasons for the treatment of seriously ill patients. These are not clinical studies so the legislation for experiments on human subjects does not apply.  Other rules apply here to protect the patient:

• The patients involved must be suffering from a chronic disease, a disease that severely undermines the health or a life-threatening disease, that cannot be treated in a satisfactory way with a mainstream medicine;
• The intention to use an unlicensed agent or a medicine licensed for another indication must be submitted to the ethics committee.

Useful links

• Federal Authority for Public Health: www.health.belgium.be
• Federal Agency for Medicines and Health Products:  www.fagg-afmps.be Pharma.be: www.pharma.be
• European Committee:  http://ec.Europe.eu/research/health
• European Forum for Good Clinical Practice:  www.efgcp.be
• Office of Human Subjects Research:  http://ohsr.od.nih.gov
• Association of Clinical Research Professionals:  www.acrpnet.org
• U.S. Food and Drug Administration:  www.fda.gov/MedicalDevices/ScienceandResearch