DECEMBER 2002
This booklet contains information of general nature about clinical trials. Specific information about the clinical trial that you intend participating in or you are being recruited to participate in must be provided by and obtained from the trial investigators.
The booklet was produced with the assistance and contributions of experts and members from various committees including the Ministerial Committee on Health Research Ethics. Contributions were also made by officials of the Department of Health in particular Health Systems Research, Research Coordination and Epidemiology and Medicines Administration.
The booklet used various sources including:
A clinical trial is a research study or investigation intended to test safety (not harmful or dangerous to human health ), quality (ingredients are of good quality ), effectiveness (working to diagnose, treat, prevent or cure a disease condition) and efficacy (better/ best when compared with other treatment or medicine for a similar condition) of new and/or existing or old medicines, medical devices and/or treatment options, using human participants.
The word “medicine’ includes medicines that are used to treat diseases (therapeutic medicines), to prevent diseases (prophylactic medicines, e.g. vaccines), and medicines that are used in special investigations (diagnostic medicines, e.g. medicines used during special X ray examinations to map out kidneys).
Phases/Steps followed in conducting clinical trials
New medicines or devices are studied in great detail (extensively) over a long period, in the laboratory and in various animals to establish its initial safety and effectiveness. Trials or testing of medicines and/or devices in people only takes place after it has been tested thoroughly in the laboratory on animal studies. The testing of investigational (new) drugs, vaccines and medical devices in humans usually follows a process that can be broken up into four phases or steps. These are described below:
Phase 1: During this first phase a new drug, vaccine or medical device is tested in a small group of usually healthy persons for the very first time. In the Phase I clinical trials the aims are to determine the general safety, the correct dosage and possible negative or undesirable effects of the new drug, vaccine or medical device.
Phase II: In Phase II clinical trials the new drug, vaccine or medical device is tested in a larger group( several hundred healthy people). At this stage people with the disease for which the new drug, vaccine or medical device is developed are also given the opportunity to participate in testing it. The purpose of phase II is to further test the safety and effectiveness of the new drug, vaccine or medical device.
Phase III: During this phase, the new drug, vaccine or medical device is tested in a larger group (several hundred to few thousand ) of people who suffer from the disease/illness for which the new drug, vaccine or medical device is intended. The effectiveness and possible undesirable effects are evaluated in more dept during this phase. The new drug, vaccine or medical device is compared to old registered (licensed) drugs, vaccines or medical devices, or alternative treatment options.
Phase IV: Clinical trials in this phase are done after the new drug, vaccine or medical device has been registered and licensed for sale by the Medicines Control Council (MCC). During phase IV the drug, vaccine or medical device is tested in several thousand people to :-define its safety, effectiveness, long-term undesirable effects, test the new drug, vaccine or medical device in certain high risk sectors of the population like children, the elderly, people with liver and kidney diseases, and find new uses (indications) of the new drug, vaccine or medical device.
Each phase has its specific purposes and the potential for benefits, risks and harms may vary with each phase.
All participants in clinical trials are closely monitored and assessed for possible side effects or adverse events (AEs) during all phases of the trials. AEs are any unfavourable and unintended signs, symptoms or diseases that are caused or can be linked to the medicine/treatment being studied. Most adverse events are not serious. An adverse event is considered serious or severe if it :-
Experimental drug is a new or newly discovered drug (medicine) that is still being developed.
Marketed drug is a medicine that is already registered with the local regulatory authority (MCC) for use for specific diseases. This medicine has gone beyond the developmental stage and its quality, safety and effectiveness are already known. Marketed drugs are also referred to as licensed drugs or registered drugs.
Investigational product refers to a medicine/s, vaccine/s or medical device/s whose quality, safety and/or efficacy are being tested in a specific clinical trial. There may be more than one investigational product in a clinical trial. Investigational products may be registered or unregistered medicines, vaccines or medical devices. Other terms used are: study drug, study medicine, trial drug/medicine, and trial product.
A sponsor is an individual, company, institution or organisation which takes responsibility for the initiation, management, and financing of a clinical trial. Sponsors are usually manufacturers of pharmaceutical products, government, research institutions, World Health Organization (WHO), foreign governments, etc.
An investigator is a suitably qualified professional person who has the responsibility to design, conduct, analyse and/or report on a specific clinical trial. Investigators usually work as a team. A leader of a team of investigators is called a Principal Investigator (PI). The PI is accountable to the sponsor and regulatory authority. An investigator may be a medical doctor, dentist, nurse, statistician, medical scientist, pharmacist, mental health professional, or a member of the paramedical professions, etc.
Placebo refers to a treatment known to be without effect; usually used to compare against a potential effective medicine, or vaccine, or medical devise which is being subjected to a clinical trial.
The Medicines Control Council (MCC) is a local institution that regulates the performance of clinical trials and registration of medicines and medical devices for use in specific diseases. The MCC is responsible to ensure that all clinical trials of both non- registered medicines and new indications of registered medicines comply with the necessary requirements for safety, quality and efficacy.
Applications for clinical trials and for registration of medicines and medical devices are reviewed by an MCC expert committee, which considers amongst other issues the scientific, medical and ethical issues of the applications. Reports on the progress of the study are sent to the MCC on a regular basis . Proof of safety, quality and efficacy must be submitted when applying to the MCC for approval and registration of a medicine for use in South Africa.
THE SPONSOR AND INVESTIGATORS ARE JOINTLY RESPONSIBLE TO REPORT SERIOUS ADVERSE EVENTS WITHIN 24 HOURS TO THE APPROPRIATE BODIES INCLUDING THE MEDICINES CONTROL COUNCIL AND ETHICS COMMITTEES
Any person making a decision to participate or is already participating as a research participant (subject) in a clinical trial has the right to informed consent. The Constitution of the Republic of South Africa Act 108 of 1996: Section 12 (2) says “Everyone has the right to bodily and psychological integrity which includes the right – (c) not to be subjected to medical or scientific experiments without their informed consent’.
CLINICAL TRIALS DONE WITHOUT PROPER INFORMED CONSENT OF PARTICIPANTS OR PERSONS ACTING ON THEIR BEHALF IS UNCONSTITUTIONAL, UNETHICAL AND UNSCIENTIFIC.
What is informed consent?
Informed consent is an ongoing process in which a (prospective) participant is informed about the facts of a specific clinical trial so that he/she can decide whether or not to participate or continue to participate in a specific clinical trial.
Informed consent involves signing a written consent form, which forms the basis of the person’s willingness to participate in a trial. The informed consent form is not a contract, but it is signed to ensure that a person takes part in a trials out of his/her own free will.
As potential research participant or participant in a clinical trial, you must know that: -
Necessary Information For Informed Consent
As a potential participant or participant you have the right to be informed on :-
All people who are able to give informed consent or on whose behalf a valid informed consent is obtained, can participate in clinical trials. Participants include the whole of people from unborn children, children , adults to the older persons, males or females, the very healthy to the critically ill.
You may participate indirectly or passively in a clinical trial by giving your consent for the use of medical information contained in your previous or current medical records that are held by your healthcare provider (e.g doctor)..
Guidelines exist by which the suitability of a person to participate in a specific clinical trial is determined. Inclusion criteria are those guidelines which determines who should be included in a trial. Exclusion criteria are those guidelines which determines who should not be included in a specific trial.
Inclusion and exclusion criteria are extremely important, are designed to protect the trial participants and to ensure that the objectives of the trial are achieved without unnecessary complications.
The South African Clinical Trials Guidelines require that protocols and other essential documents for proposed clinical trials must undergo an independent ethical review by an accredited ethics committee complying with standards set by the National Health Research Ethics Council. Ethical review aims to ensure the protection of potential research participants. Only trials that have been approved by accredited ethics committees can be done in South Africa.
When reviewing proposals for clinical trials ethics committees consider the following :-
The South African Clinical Trials Guidelines require ethics committees to give special consideration to certain groups of people including children; adolescents; pregnant women; prisoners; disabled persons; mentally ill persons; vulnerable communities; terminally ill persons; older persons; minorities and employees, to ensure that their rights are protected and respected.
Clinical trials are done with the sole aim of testing medicines, medical devices and treatments that will ultimately be made available for human health. By participating in trials:-
You should therefore ensure that you discuss your participation in a clinical trial with your family and all those who may be affected before joining the trial.
Members of the Ministerial Committee on Health Research Ethics as appointed in June 2000:
Prof SR Benatar (Chair),Prof LE Mazwai (Deputy Chair), Ms D Biyela, Ms R Prinlsoo, Dr LE Makubalo, Prof H Rees, Ms P Matsoso, Dr XGM Kanta (alternate member), Dr P Mahlathi, Prof YK Seedat, Prof TJ Mariba, Prof D du Toit, Ms M Dioke, Prof S Clow, Dr W Bannenberg, Dr S Cooper, Ms K Nevhutalu, Prof O BW Greeff, Prof C IJsselmuiden, Dr M Hlongwane & Prof L London
c/o Health Systems Research, Research Coordination and Epidemiology
Department of Health
Private Bag X828
Pretoria
0001
Phone: 012-312-0995
Fax: 012-328-9381
Email: hsrrce@health.gov.za