What is a clinical trial

What is a clinical study?

What happens during a clinical trial?
Are there different types of clinical trials?
Are randomized clinical trials better than non-randomized clinical trials?
What are preclinical studies?
What are the phases of the clinical trials?

  • Phase I Studies - Is It Safe Enough To Proceed?
  • Phase II Studies - Is There Any Evidence of Beneficial Effects?
  • Phase III Studies - Is the Treatment Better?
  • Phase IV Studies - What Else?

Can I continue to take my medication if I decide to register for a clinical trial?
Is it true that I can get placebo treatment without even knowing it?
Can I opt out of a clinical trial after I have signed patient consent?

Clinical trials are medical research studies for which volunteers - both healthy and sick people - register to test treatments to prevent, detect, or cure disease.

Medical researchers are constantly suggesting and investigating new and existing treatments, diagnostic procedures, surgical interventions, or medical devices. Clinical trials are the only appropriate way to assess what is effective for patients and at what risks.

What happens during a clinical trial?

To answer a clinical question, the research team defines a clinical trial plan with all relevant details of the study. This must then be approved by the responsible authorities, an ethics committee.

The procedure depends on what type of clinical trial is being considered. Clinical studies designed to assess whether a new treatment is appropriate must confirm whether that treatment is better than what is already used - the standard treatment - without evidence of unacceptable harm to the patient. Nonetheless, every clinical trial involves a research team of doctors, nurses, and possibly health professionals who work closely with patients. In addition, statisticians and IT experts analyze the results of the study. Studies are carried out at universities, in medical centers, clinics, hospitals or even in doctor's offices.

If you are interested in registering for a clinical study, or if you have been offered to participate in such a study, a qualified member of the research team will explain the details to you and you will have the opportunity to answer any questions you may have in a face-to-face meeting (see section).

You will receive all information in writing and will need to sign and return a form if you choose to participate (this is patient consent).

If you agree to participate, the research team will review your health, give you instructions on how to participate, carefully monitor any side effects and improvements you experience during the study, and keep in touch with you after the study is complete.

Are there different types of clinical trials?

The most important difference in studies is whether it is a Intervention study or a Observational study acts.

At clinical intervention studies As the name suggests, the participants must test a certain type of treatment that “should be tested” according to strict rules clearly defined in the protocol. Randomized clinical studies are intervention studies that are considered to be the safest methods of collecting information about the effectiveness and tolerability of treatments, as they allow researchers to minimize confounding factors (bias).

However, the design of a randomized clinical trial is not always possible, sometimes for ethical reasons, but in other cases also because of the cost or long duration required or because of the question which the study is intended to answer. In addition, it would take a long time and a very large number of participants to investigate rare side effects using randomized trials.

Observational studies are the other possible way of assessing the effectiveness of treatments. Participants are monitored, sometimes followed for years to gain more knowledge about risk factors, possible effects of exposure to certain substances, lifestyles, etc. Although they can provide valuable information about everyday life, potential risk factors, or safety issues, observational studies are potentially more biased because participants are not randomly assigned to groups. For this reason, the results of observational studies should, if possible, be examined in further clinical studies.

For example, the effectiveness and safety of hormone therapy in menopause have been using for decades Observational studies examined. Groups of postmenopausal women taking treatment or not receiving treatment have been observed by research teams for years to determine the benefits (control of menopausal symptoms, prevention of cardiovascular disease, prevention of osteoporosis, prevention of uterine body cancer, etc.) and risks (occurrence of breast cancer, occurrence of heart disease, etc.).

The results always indicated a favorable one Risk-benefit ratio the treatment. Only recently (see Scientific work published on JAMA and Editorial on JAMAboth released in October 2013) showedrandomized clinical trialsIncluded in the Women's Health Initiative - and funded by the National Institutes of Health, a more complex pattern of benefits and risks.

When comparing the effectiveness of menopausal hormone therapy (estrogens plus progestins, estrogens only in women who have had hyperectomy) and the effectiveness of a placebo in a very large patient population (more than 27,000), it was found that the risks outweigh the benefits (especially in the case of estrogen plus progestins treatment), mainly because the increased risk of developing coronary artery disease, breast cancer and stroke is not related to the reduced risk of developing diabetes, improved control of postmenopausal symptoms and general well-being is outweighed.

Depending on the type of question the research team wants to answer, clinical trials can be broken down into:

Prevention studies: What are the best ways or alternatives to prevent a particular disease in healthy individuals or prevent the disease from recurring? Possible answers could be medication, vaccinations, or other lifestyles (such as diets, exercise, etc.).

Screening Program Studies: What is the best way to detect and treat certain diseases or health conditions?

Diagnostic studies: Which examinations or procedures are better suited to diagnosing and treating a particular disease or condition?

Treatment studies: Is a treatment - drug / surgery / radiation therapy / other procedure - sufficiently safe and effective in the case of a particular disease or condition? Is it better than an alternative treatment or procedure? How can the quality of life of chronically ill patients be improved?

Important: ECRAN focuses on clinical intervention studies and especially encourages volunteers to participate in independent, randomized clinical studies (see below).

Are Randomized Clinical Trials Better Than Non-Randomized Clinical Trials?

Yes. Randomized clinical trials are the gold standard of clinical trials, especially when examining the effectiveness of a treatment.

Randomization is an unbiased way of assigning study participants to one of two or more treatment groups. Without impartial treatment allocation, previous or existing diseases or differences between patients could influence study results. When only one treatment is being studied, the patients receiving it are in the “active” group while the others - receiving a dummy treatment, a placebo - are in the “control” group.

these are randomized controlled trials and patients are randomly assigned to one of the treatment control groups, as by rolling the dice.

If the patients in the active group and in the control group do not know which group they are in - and therefore ignore the treatment they are taking (the active / new or the dummy standard treatment?) - the study is called "simply blind". Even if the medical professionals administering the treatment do not know who is taking what, the study is referred to as "double blind" designated.

The blinding prevents patients and researchers from being influenced in observing positive and negative effects of the treatment. In fact, if you knew you were in the placebo group, you would probably ignore any good or bad effects, while for example you would report more perceived effects to the research team if you were in the active group.

What are preclinical studies?

These studies, also known as laboratory tests, are the first steps you need to take

when developing a new drug before testing it in humans. Preclinical studies include cell studies and animal experiments.

Developing new treatments is often a very long process that typically takes years: laboratory and animal studies are often required before researchers can work with volunteers in a clinical trial. Few new treatments reach this point and even fewer go through the various phases (LINK) of clinical trials.

What are the phases of the clinical trials?

The process in clinical trials is very strict and usually involves 4 different phases when researchers test a new drug. Each stage has a different purpose, helping the research team answer different questions about the treatment, and pointing out different risks and benefits for you.

Clinical trial registries provide information on the active phases of any clinical trial that you are considering participating in.

As noted (in the introductory box), the process described below is more typical of a new drug development, but in terms of doses, placebo, etc, it also applies to all other types of intervention ... if relevant.

Phase I Studies - Is It Safe To Proceed?

At this stage low up to therapeutic doses of a new one are used Experimental treatment is used in a small group of people (20-80) to assess their safety and identify side effects.

Phase 1 studies are trying to find the highest dose of the new treatment that can be given without serious side effects. These studies can also help identify the best way to administer a new treatment.

If you are in a phase 1 study, you will initially be given a low dose of treatment and then closely observed. You may have to spend the night in the hospital. If you experience minor side effects, some other patients may be given higher doses. This procedure is repeated until the researchers find a dose that is most likely to be effective with an acceptable level of side effects.

Important: This phase does not allow the identification of rare side effects as only a small number of patients are involved. It is the potentially riskiest phase for the participants.

Phase II Studies - Is There Any Evidence of Beneficial Effects?

In this phase, the new treatment is given to a larger group of people (100-300) to investigate its hoped-for positive effects and to further evaluate its safety. Researchers look for clues that the treatment is working - this depends on the goals of the treatment and the type of disease being studied, such as lowering blood pressure with a new antihypertensive treatment - and continue to monitor patients carefully for possible side effects.

If you are in a phase II study, you will be given the same dose of treatment as any other volunteer - the dose determined in phase I studies - and no placebo or dummy treatment will be used. This phase is more likely to provide evidence of the hoped-for benefits than phase I studies. Less common side effects are more likely to occur as the number of participants increases.

Phase III Studies - Is the Treatment Better?

If a new treatment “passes” Phase II, it will eventually be tested on a larger group of people (usually 1000-3000), usually in multiple research centers. At this point, efficacy and safety are not enough, the new treatment must prove to be better than the standard treatment; H. it must offer more benefits or fewer risks to patients than the treatment already in use.

If you are in a Phase III study, you are likely to be randomized to one of two or more treatment groups. You will not be told what treatment you will be receiving (blinding).

If the results of the study are positive and the research team collects evidence of efficacy in two different phase 3 studies, the researchers can apply for a marketing authorization with the relevant authority. In the EU this is the European Medicines Agency, but there are also national agencies in every member state.

Important: It is unethical to give a placebo if another beneficial treatment is already known or in use.

Phase IV Studies - What Else?

Rare and potentially serious side effects of a new treatment - but also the benefits in ordinary clinical practice - can be difficult to see even after the new treatment has been used on thousands of patients. Because of this, researchers often continue to collect information about benefits, risks, and optimal uses after a drug has been approved for sale and made available to the public.

If you are in a Phase IV trial, it will be very similar to treatment outside of a clinical trial in that the treatment has already been approved and the risks you face are much lower than in other phases.

Important: You do not need to register for Phase IV trials to receive treatment.

Can I continue to take my medication if I decide to register for a clinical trial?

Depending on the protocol (i.e. the study design, the type of patients who can volunteer, the questions the study aims to answer, etc.) you may be asked to reduce your previous medication for a period of time or, if possible, to stop it altogether.

Important: Always ask your doctor what risks you are taking in stopping your medication or reducing the dose.

Is it true that I can get placebo treatment without even knowing it?

If you participate in a randomized clinical trial, you will be randomly assigned to either the active group - i.e. H. the group of patients taking the new treatment - or the control group - d. H. the other participants who receive standard treatment or dummy treatment if no other treatment is available.

Also, if it is a blind study, you will not be told which group you are in. If the study is double-blind, not even the research team knows how the participants are divided into the two groups.

Why? The researchers want to make sure that no one is influenced when reporting or observing side effects and improvements.

Can I opt out of a clinical trial after I have signed patient consent?

The patient consent that you have signed is not a contract and is in no way binding on you. Therefore, you have the right to withdraw from a clinical trial at any time without having to provide an explanation to the research team. However, communicating potential problems to the research team can help and may even solve the problem.

Important: If you decide to withdraw from a clinical trial, be sure to ask the research team or your doctor whether it is safe to interrupt the experimental treatment. If necessary, you can gradually reduce the dose or use other procedures.