Clinical Research

What is clinical research?

Clinical Research fuels the knowledge for better treatment. Medical therapies must be evidence-based, which means that they require scientific proof. When doing research, it needs to be proved that the product is safe, and it works for patients.

From basic research to patient oriented research, the different phases of clinical research are the following:

1. Basic science – This stage must define how the theory works.
2. Translational research – Researchers must confirm if the theory can be studied in people.
3. Toxicology studies in animals – The last pre-clinical stage conducted in animals defines if the treatment is safe and what the potential effects would be in people.
4. First in Man & Phase I Clinical Trials: A phase 1 trial tends to find out if the therapy is safe, if it works in people and what their effects are. It can take more than 1 year to run this phase with 20 to 80 people involved.
5. Phase II: If the first phase is successful, phase II is started on a bigger group of people (100-300) and it can take approximately 1-3 years to run. Phase 2 trials aim to find the best dosage.
6. Phase III – If the second phase is also successful, comes phase III with an even bigger group of subjects (1,000-3,000) in the next 2-3 years. It collects information on effectiveness, possible risks and safety. Phase 3 trials can be run at various sites in different countries.
7. Phase IV – The last stage is phase IV, which happens after marketing authorization and aims to seek how well the treatment works in real-world settings.

All medical treatments have been tested on people before they obtain a marketing authorisation. Without study participants, there is no progress in medical treatment.

Within 1 year after the end of a trial, study outcome and a summary for laypersons is posted on the public clinical trials database website: https://www.clinicaltrialsregister.eu/

What is a clinical trial?

Clinical trials are about testing and learning, meanwhile the everyday regular care is using the treatments. Clinical trials pose a dual responsibility. Meanwhile clinical trials are focusing on testing (treatment, dosage – regimen, performing measurements) and learnings (from collected data), regular care uses the defined treatment.

When participating in a clinical study:

• You receive the most recent medical care
• More tests are performed, but you are also more medically monitored compared to normal medical practice
• Costs of tests and investigated therapy are not for you to pay
• Your medical data are kept confidential
• You can stop your participation at any timepoint without any reprisal
• You can contribute to the development of better treatment for the disease

We differentiate commercial or initiated and non-commercial or investigator-initiated clinical trials. Commercial or initiated clinical trials are managed and financed by a company for commercial purposes (i.e. collect data for market authorisation of the tested therapy. Non-commercial or investigator-initiated trials are initiated, managed, financed by a non-commercial organisation without commercial purposes.

Ethical rules of clinical research

The ethical rules are different for regular medical care and for clinical research.

Your medical doctor provides regular medical care and he/she is bound to the Hippocrates oath, meanwhile the rules for clinical research are regulated by the ‘Good Clinical Practice (GCP)’.

The good clinical practice guideline E6(R2) is developed by the International Council of Harmonisation. The Declaration for Helsinki (DOH), developed by the World Medical Association, is also an international guideline on ethical principles for medical research involving human subjects. Adherence to both GCP and DOG is mandatory by the European and national legislation.

Good clinical practice ensures that participants are protected, studies are based on sound science (study data have quality and are reliable) and that study procedures are undertaken and documented. At the same time, if it is not followed, participants may be at risk, the collected study data are unreliable (have no value) and the study could be rejected by regulatory authorities.

Each clinical study must be described in a “study protocol” which includes the rationale, objectives, treatment details and endpoints of the study. The study protocol is to be followed, except for protocol deviations implemented to avoid urgent medical emergencies. It also includes design, key parameters, procedures, assessments, statistical considerations and practical organisation.

Each “study protocol” must be approved by an ethics committee before the study can start.

Trial design

When a clinical trial seeks to develop a new treatment, different therapy groups are compared to each other. One group is receiving experimental treatment, while the other (control) group is on an existing standard treatment or a placebo. During the control period – according to the hypothesis – any difference between different therapy groups is caused by the tested drug and not by chance or other factors (placebo-effect).

Randomisation and blinding are different from regular medical practice when the physician decides which treatment for which patient is to be used, because they reduce bias and generate reproducible results. In a trial, comparing standard product with a new product, the best way to avoid bias is that both new and control product, as well as both the patients and the investigator are blinded.

Trials are only designed for the “right” subjects, therefore different inclusion & exclusion criteria exist regarding age, gender, race, type & stage of disease, subject’s previous treatment history, presence or absence of other medical conditions. All of the existing criteria must be fulfilled to allow someone to participate in a clinical trial and no exceptions are permitted. This ensures patients’ safety during the study, provides data (justification) of appropriateness of subjects and makes sure that the study reaches its objectives (primary endpoints).

Rights of trial participants

The rights, safety and well-being of each participating study subject must be protected.

The investigator and his staff must inform potential study participants about the study according to the level of understanding of the study participants.

Participants of a clinical study have the right to be fully informed by conversation and in writing before participation. They must understand the following:

• Reasonably expected risks and benefits
• Study schedule
• The chance they have to receive the tested product or a comparator/placebo
• Tests or procedures before and during the study
• Their responsibilities during the trial
• Responsibilities of the study staff
• Alternative treatments
• Their rights as a volunteer (withdrawal)
• Who they can contact if they have problems or questions?

The study participants have the right to be “fully informed” and decide “freely. They understand what it means to be in the study. They have read the written information. They have time to process the information and they can make and express freely their personal decision.

If it is not written, it did not happen! Make sure to sign the informed consent form before the start of study procedures and study therapy!

 Each participant subject has to be informed and they must consent freely by signing an informed consent form. No unduly influence can be exerted to start and/or continue participation.

Each participant has the right to be compensated for injuries caused by the study therapy.

Informed consent

Informed consent means that a study participant should be able to explain the study to his/her brother/sister. It also means that study participant is free to follow the advice of the investigator, but only after receiving all the information first.

Informed consent also means that subjects sign the form after having ample time to read the written information, but always before the first study procedure.

In case someone is too sick or unable to sign the informed consent form, a legally authorised representative can sign on the behalf of the study participant.

Always anticipate signing the informed consent with conversation and time to read written information. You have the right to ask medical questions to a medically qualified person and you also have the right to consult your partner, family or another doctor beforehand. If you agree, you need to write your name, signature and date personally on the consent form. Someone can only do that on your behalf, if you are incapable of providing consent personally, or in case of being a minor.

Before consent don’t forget to:

• Get information from your physician, patient organization, the internet
• Ask questions to understand information, and if you want, consult with family and/or other doctor
• Accept that participation is not possible if you do not have the correct in- and exclusion criteria
• Personally sign & date the informed consent form to confirm your agreement to participate in the study if you have the correct criteria

During consent don’t forget to:

• Visit the hospital according to scheduled appointments
• Take study treatments exactly as explained by the investigator’s team
• Return all unused treatments
• Inform the investigator about any adverse event
• Inform the investigator about any dosage mistakes, if this happened

Frequently Asked Questions (FAQ) about Clinical Research in MS

Ongoing research and how to get involved

Investigators all around the world are working hard to find a cure and better treatments against MS. Hundreds of clinical trials are conducted across Europe at the moment, with the objective of discovering new treatments for MS, improving treatments for MS or ultimately finding a cure for MS.

Thanks to the European Clinical Trial Regulation 536/2014 (67) and its transparency directive in the clinical trials, an EU database contains all relevant information with regard to clinical trials. The EU database is be publicly accessible and data is presented in an easily searchable format, including summaries in plain English, as well as linking to data from other clinical trials which used the same investigational medicinal product.

The search engine of the EU Clinical Trials Register allows users to search by European identification Number, Medical Condition, Medicinal Product, Country, Age, Trial Status/Phase, Gender, Date Range, Sponsor etc. in its advanced search field.

To find ongoing clinical trials in the EU database for Multiple Sclerosis please click on the button below: