What is a clinical trial?
A clinical trial is a research study involving healthy volunteers or patients that is conducted to assess the efficacy and safety of a medicinal product. A clinical trial is one of the most important ways to assess and demonstrate the efficacy and safety of a new drug.
Clinical trials are conducted in compliance with special international guidelines for Good Clinical Practice (GCP).
Good Clinical Practice is the international standard for conducting clinical trials. In Russia, the equivalent of GCP is GOST R 52379-2005 Good Clinical Practice.
Compliance with this standard during the study publicly ensures:
· Protection of the rights of the study subjects;
· Adherence to the safety rules;
· Commitment to the do-no-harm principle;
· Integrity of the trial.
These principles have their origin in the Declaration of Helsinki of the World Medical Association (WMA).
Compliance with these principles ensures that the rights of study subjects are protected and the trial results are accurate and credible.
Clinical trials are an integral part of development of new medicinal products. Trials help find out if a new drug is effective, what side effects it has, and how harmful or life-threatening it may be to people.
Once a clinical trial is completed and its results are assessed, a pharmaceutical or biotechnology company that conducted the trial can file a marketing application to government authorities for approval of the drug. A medicinal product cannot be marketed unless it has completed the clinical research phase. Clinical trials are usually conducted in 3 phases:
· Phase I;
· Phase II;
· Phase III.
Depending on the results of the trial, the marketing application can either be approved or rejected. The drug will not be approved if it is not sufficiently effective or safe. However, even if this happens, the results of clinical trials are very important to people. They help the scientists better understand the disease and advance the search for effective and safe treatments. If the trial provides evidence of the drug’s efficacy and safety, the drug will be approved, and doctors will be able to give it to their patients.
What is a study protocol?
All clinical trials are based on a set of rules called a protocol. A protocol describes the types of people who can participate in the trial, the schedule of tests, procedures, and dosing, drug dosages, and the duration of the trial. During a clinical trial, subjects are regularly followed by the research staff to monitor their health, safety and efficacy of the treatment.
What are clinical trial stages (phases)?
Clinical trials of experimental drugs are conducted in four stages (phases).
In stage 1 (phase I) of a clinical trial, investigators study a new drug or treatment in a small group of 20 to 80 people, first, to assess its safety, establish a range of safe doses, and identify any side effects.
In stage 2 (phase II), the study drug or treatment is assigned to a larger group of 100 to 300 people to make sure that it is effective and to continue assessment of its safety.
In stage 3 (phase III), the study drug or treatment is assigned to even larger groups of 1, 000 to 3, 000 people to confirm its efficacy and safety, monitor its side effects, compare it to commonly used medications and treatments, and acquire information for safe use of the drug or treatment. Based on phase III clinical trials, a decision is made as to whether or not the study drug can be approved for marketing.
Stage 4 (phase IV) trials are conducted after the drug or treatment is approved by the Ministry of Healthcare of the Russian Federation. These trials further evaluate the study drug or treatment to collect additional information about its effects in various groups of people and identify any side effects occurring with long-term use.
There are also bioequivalence trials that are used to demonstrate the equivalence between an original drug and a generic drug. Generics are medicinal products with established bioequivalence and therapeutic interchangeability with the original product of similar composition for which a patent protection has expired. The cost of generics is significantly lower than that of the original products, while generics do not differ from the original products in efficacy or safety and are manufactured in strict compliance with applicable regulations and quality standards.
What is informed consent?
Informed consent is the process by which a patient can freely express their will (consent) to take part in a particular study. Before you give your consent, you should be informed of all aspects of the clinical trial that may affect your decision to take part in the study. A study subject must sign and date a document called an informed consent form to document their consent.
This form describes the following:
· Purpose of this clinical trial;
· Treatments to be used in the trial;
· Chances for random assignment across various treatment groups;
· Procedures you will need to complete;
· Your responsibilities as a study participant;
· Expected duration of your participation in the trial;
· Approximate number of subjects planned to be included in the trial;
· Possible risks and discomforts;
· Expected benefits;
· Other available treatments, their benefits and disadvantages;
· Compensation and treatment that may be provided if you are injured as a result of participating in the trial;
· Your right to refuse to participate or to end your participation in the trial and that your refusal will not affect your relationship with healthcare providers;
· Information that can be used to identify study subjects will remain confidential, your name will not be mentioned in any publications based on study results;
· You will be immediately informed if any new drug safety data becomes available that can affect your decision to continue in the trial;
· Names and phone numbers of contact persons who you can contact about any issues related to the trial.
If you are considering taking part in a study, the research staff should give you an informed consent form containing details of the trial. If Russian is not your native language, you can ask for a consent document in your native language. Before you agree to take part in a clinical trial, you should ask any questions you may have about the trial and informed consent form (in writing or orally).
You can also take the consent form with you to discuss it with your family, relatives, and friends. Discussing your informed choice will help you feel more comfortable and confident with the decision you make. If you decide to take part in the clinical trial, make sure that you have a signed and dated copy of the informed consent form and that you can review it at any time.
Please, remember that an informed consent is more than just a signed document. It is not just your signature. It is a process that continues throughout the trial.
You should feel free to ask the investigators any questions before, during, and after the trial.
Who can take part in a clinical trial?
All clinical trials have rules describing who can participate. These rules are based on factors such as age, type of disease, medical history, and current health. Before you participate, you need to qualify for the study. Some trials seek subjects with diseases or certain conditions while others need healthy volunteers. Healthy volunteers take part in phase I clinical trials, vaccine testing, and disease prevention studies conducted in adults and children.
Factors that allow you to participate in a trial are called “inclusion criteria”, while those that prevent you from taking part are called “exclusion criteria”. It is important to note that inclusion and exclusion criteria are not used to refuse people personally. Instead, these criteria are used to identify suitable participants and ensure their safety. The criteria help investigators answer the questions planned in the trial.
Who orders (sponsors) a clinical trial?
Clinical trials can be ordered (sponsored) by the government, Ministry of Healthcare, medical institutions, research organisations, pharmaceutical companies, or individual investigators. Trials can be conducted in hospitals, policlinics, medical institutes, or clinics.
What happens during a clinical trial?
The clinical trial process depends on the type of the trial that you are participating in. The research team includes doctors, nurses, and social workers. At the beginning of the trial, they check your health, give you special instructions, and then carefully monitor you during the trial, and contact you after you complete the study.
Some clinical trials involve more tests and examinations than you would normally have for your disease or condition. Regardless of the type of the trial, you will work with a research team. Your participation will be the most successful if you follow the protocol carefully and cooperate with the research staff. Explanations of some terms below will help you understand what happens in a trial.
What is a placebo?
A placebo is an inactive substance (tablet, solution, or powder) with no therapeutic effect. In clinical trials, experimental treatments are often compared to a placebo to assess the treatment efficacy. You should be aware of the probability of random assignment of study subjects to treatment groups.
What is a control group?
A control group is a standard used to evaluate experimental observations. Many clinical trials have a group of subjects receiving an experimental drug or treatment and a control group that gets a standard treatment or placebo.
What is a blinded or masked trial?
A blinded or masked trial is a research in which the participants (subjects) do not know whether they have been assigned to the experimental or control group.
What is a double blind or double masked study?
A double blind or double masked trial is a research in which neither the participants (subjects) nor the study staff know who is receiving the experimental treatment and who is receiving a standard treatment or placebo. These studies are conducted so that the subjects’ or doctors’ expectations about the experimental drug have no influence on the treatment outcome.
What is a side effect and an adverse drug reaction?
A side effect is any unwanted effect of the drug or treatment. Adverse or side effects can include headache, nausea, weakness, skin irritation, or other medical problems. Experimental treatments should be evaluated for both immediate and long-term side effects.
What are the benefits and hazards (risks) of participation in a clinical trial?
There are both benefits and risks associated with participation in a clinical trial. By participating in a clinical trial, you may be able:
· To take an active part in your own health care;
· To get access to new treatments that are not available to other people;
· To receive professional medical care at leading medical institutions and from leading medical experts; you will also get access to additional diagnostic technologies and assessments;
· To help other patients.
Clinical trials have the following hazards (risks):
· There may be side effects from using medications;
· The treatment may be ineffective for you;
· The trial programme (protocol) may take up a lot of your time (study site visits, treatment);
· Dosing regimens can be more complicated than they would be with standard medical care.