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). 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 they have 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.
Each phase has its specific purposes and the potential for benefits, risks and harms may vary with each phase.
Clinical trials can also look at other aspects of care, such as improving the quality of life for people with chronic illnesses
People participate in clinical trials for a variety of reasons. Healthy volunteers say they participate to help others and to contribute to moving science forward. Participants with an illness or disease also participate to help others, but also to possibly receive the newest treatment and to have the additional care and attention from the clinical trial staff.
Clinical trials offer hope for many people and an opportunity to help researchers find better treatments for others in the future.
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:
- results in-patient hospitalization,
- results in prolonged hospitalization,
- results in persistent/significant disability/incapacity,
- causes congenital anomaly/birth defect,
- threatens the life of a person,
- causes death of a child of the participant who was exposed to the study medication or medical device during pregnancy, causes death
The benefits and risk of participating in a trial vary depending on the type and purpose of a trial. Possible advantages and disadvantages of trial participation are outlined below:
Possible advantages: 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 may gain access during and after the clinical trial to new treatments that are not yet available to the general population
- You may obtain medical care free of charge
- You will be closely monitored for possible adverse events
- You are contributing to medical research that may result in the advancement of medicine and healthcare in general thereby helping other fellow human beings
- Participating in clinical trials is not a source of primary or additional income. However almost all sponsors reimburse persons that participate in trials for all reasonable expenses related to participating in the trial, including travel expenses, food, medical care and compensation for provable and insured adverse events that are related to the trial.
Possible disadvantages: There may be serious adverse events (SAEs) that are related to the medications used or procedures that are done in the trial; however study participants are intensively monitored so that SAEs may be detected early and managed appropriately. There is also insurance cover for some SAEs, so that participants may be compensated accordingly.
The medicines, vaccines, medical devices or treatment options used in the trial may not be effective for your disease; there are, however, safety procedures in place so that those participants who do not benefit from the trial medical management options may be switched to alternative effective treatment immediately or at the end of the trial.
The trial guidelines may require some adjustment of one or more aspects of your life, such as:
- You may need to set aside time for trial related activities like visiting the trial site
- You may not use certain medications including traditional medications without the approval of your trial doctor
- Your personal private or social life may be affected, e.g. sexual activity, reproductive functioning, consumption of alcohol, tobacco or other drugs of abuse, etc.
- You may have to consult your usual healthcare provider for all your other illnesses that are not related to the trial, but still you have to inform your provider that you are part of a trial and that certain medications or treatment options may not be compatible with your trial protocol
- Your employer, medical aid, personal insurance and/or Commissioner for Compensation for Occupational Injuries may not pay for claims that are related to events due to your participation in clinical trials; it is therefore extremely important that you verify that the sponsor of the trial has an appropriate comprehensive insurance cover for you.
You should ensure that you discuss your participation in a clinical trial with your health care provider (ie doctor), your family and all those who may be affected before joining the trial.
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 device which is being subjected to a clinical trial.
- Department of Health – National
- South African Ethics Application System
- Medical Research Council of South Africa
- Medicines Control Council of South Africa
- South African Aids Vaccine Initiative
- The World Health Organisation
- Clinical Trials.gov – an American register equivalent to SANRR
- National Research Registry – an English register equivalent to SANRR
- Guidelines for Good Practice in the Conduct of Clinical Trials in Human Participants in South Africa
- Guidelines on ethics for medical research: HIV Preventive Vaccine Research
- Guidelines on ethics for medical research – General Principles
- Law audit applicable to child participation in research and clinical trials
Any person making a decision to participate or who 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 are unconstitutional, unethical and unscientific.
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 trial out of his/her own free will.
As a potential research participant or participant in a clinical trial, you must know that:
- Your informed consent is a necessary requirement for ethical and scientific research. This means that your right, dignity and well-being as a research participant must be protected, respected and promoted at all times before, during and after the research study ;
- You have the right to be provided with all the necessary information before you make any decision to participate;
- Information must be given in a simple and clear style via the use of your home language (mother tongue). This is done to ensure that you understand and are able ask questions;
- Your decision to participate must be free of coercion, undue influence or incentives. You will not be penalised if you refuse to participate;
- Your informed consent must be both written and verbal;
- Your informed consent must be given, in writing, for access to your medical records for trial related activities and audits, ethics committee review and regulatory inspection;
- You are free to withdraw from participating in a clinical trial at any time;
- If you withdraw from the clinical trial, this will not affect the standard of care you receive.
As a potential participant or participant you have the right to be informed on :
- What the purpose of the clinical trial is;
- Trial treatments and possibility of random assignment to each treatment;
- Methods and procedures to be followed or used during the trial ;
- Alternatives apart from participating in research;
- Potential or real harms and risks involved in participating;
- Expected benefits to you as a participant and/or other persons in the trial;
- Extent to which confidentiality and privacy will be maintained;
- Available insurance in event of injury or damage caused whilst participating in a trial;
- Who the contact person is in the event of a trial related injury incentives given for participation. Any differences across sites in incentives must be explained;
- The availability of treatment beyond the duration of the clinical trial;
- Who the sponsor is and any potential conflict of interests;
- Proof of ethics committee approval.
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 Medicines Control Council (MCC) is a statutory body 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.
For more information on the MCC refer to http://www.mccza.com