June 7, 2007
What is a clinical trial?
When you develop a drug, you must carry out a range of tests before putting it on the market. The first phase involves preclinical trials in which the active substances are tested, eitherin vivo (on rats, mice and other animals) or in vitro (on cultures), to study their properties and effectiveness and determine whether they are toxic.
If the preclinical trials are positive, you move to the next phase, in which the active substance is tested on humans. Clinical trials require four phases. Phase I is carried out on healthy volunteers to determine the maximum tolerable dose. Phase II is conducted on ill subjects to study whether the substance is “active enough” and determine the optimum dose. In Phase III, the new treatment is compared to a benchmark or placebo and the substance is tested on a larger number of patients (300-500). Phase IV involves studying the drug’s long-term effects on the general population (several thousand people) in what is referred to as “pharmacovigilance.”
Manufacturers use Phase III results to seek approval from drug regulatory authorities, which may then issue market authorization. The French regulatory agency is the Agence française de sécurité sanitaire des produits de santé (AFSSAP, the French Health Product Safety Agency). The drug then moves into the manufacturing phase, which must meet international standards known as Best Manufacturing Processes (BMP).
What ethical rules must be applied in these trials?
Each institution carrying out clinical trials is responsible for establishing its procedures, referred to as “best clinical practices.” That said, ethical guidelines do exist that provide a specific framework; specifically, the Helsinki Declaration, which was adopted in 1964 and revised several times since then. It presents the ethical principles that doctors and practitioners are to follow when conducting medical research on human subjects. They are the basis for establishing research protocols.
When an institution wants to set up clinical trials, it establishes a protocol that must be submitted to the ethics committee of the country where the research will take place. It may also submit its protocol to an independent ethical committee. That’s what Epicentre does when we want to conduct research, for example. We submit all our research protocols to an independent European ethics committee, which also issues its opinion.
In concrete terms, what are the primary rules that must be followed?
The first is to submit the research protocol to an ethics committee. The others involve the signed document referred to as “informed consent” (which includes patient information and the agreement to participate), insurance for patients and practitioners conducting the study and creation of an independent tolerance data monitoring committee, particularly if the substance tested is potentially toxic. Finally, at the urging of the large scientific journals, since 2004 clinical trials are now registered by various independent organizations describing the nature of the experiments underway to ensure that the public is informed of the tests.
What information must be given to patients?
To obtain informed consent from patients, the institution conducting the test must provide them an explanation of the study to be conducted, including information on its goal, how it will be carried out and over what period of time. The potential subject must also be informed of the risks and benefits of the treatment being tested. Last, patients must be informed that they will not be penalized if they choose not to participate.
What happens if the treatment being tested is toxic?
In that case, a Data Safety Security Board is set up. This is an independent tolerance data monitoring committee with access to all necessary information throughout the course of the study. It may interrupt a drug if the trial puts patients in danger.
Do clinical trials carried out in Africa follow the same rules as those in wealthy countries?
The same rules apply. In our research center in Mbarara, Uganda, we follow exactly the same procedures. We are currently conducting trials with pregnant women infected by malaria to study the effectiveness of two antimalarial drugs, Coartem and quinine. The goal of this study is to determine which of the two treatments is most effective and least harmful. Malaria is a potentially fatal disease. Pregnant woman are particularly vulnerable and at greater risk of death from malaria, so particularly strict rules must be followed. It is critical to conduct clinical trials in Africa on diseases that affect poor countries. Research that complies with ethical rules can be conducted and such studies must be developed.
© 2013 Doctors Without Borders/Médecins Sans Frontières (MSF)