Clinical trials are research projects in which patients can voluntarily participate. They are part of the many years lasting process of development of new medicinal products, which may end up with a drug registration and its use in common practice. The path of each drug starts in laboratories, then animal tests continue, and after long research the medicinal products that have proven to be sufficiently safe and effective start to be tested in clinical trials involving patients or healthy volunteers. All clinical trials are approved by the EU or national regulatory authority – In Czech republic by The State Institute for Drug Control and relevant ethics committees.

In order to subject the drug a clinical evaluation, it must undergo a thorough testing under laboratory conditions. In reality it happens the way that out of every 50,000 new molecules developed in laboratories, only 5 potential drugs get to the clinical trials stage. Only 1 of them stands and gets to the patients. Others, during the extensive clinical trial, do not show sufficient efficacy, suitability or safety, etc. In these cases, the research is terminated.

Each drug must undergo a Phase I - III of clinical evaluation prior to its introduction into standard medical practice. Phase I : If you are in a Phase I of a clinical trial, it means that it usually concerns the first time administration of the drug under research to humans. These trials are attended by only a small number of healthy volunteers around the world (approximately 15-30). At this stage, it is determined whether the new treatment is safe and how it affects individual organs of the body. The dose which is tolerated by the body, and does not cause significant side effects, is measured. In rare cases, the drug subjected to research is administered not only to healthy volunteers, but also eg to oncology patients. Phase II: The substance is first administered to a small number of patients with a target disease. The therapeutic effects on the human organism are verified, adequate dosing is sought, additional data on the effect of the potential drug are collected, eg for what type of tumour it is suitable. This phase of evaluation is attended by a maximum of hundreds of patients. Phase III : This concerns already large clinical trials involving up to thousands of patients in different hospitals around the world. The main goal of Phase III trials is to find out whether the new treatment is better or at least as good as the one used as standard. These are mostly randomized (randomly allocated), or eventually placebo-controlled trials. Phase IV: It is a so-called Post-Authorization Trial. Clinical trials continue even after approval, the drug registration. Their goal is to gain further new knowledge of the side effects of the drug.

Clinical trials are carried out by healthcare professionals, ie doctors, nurses and other healthcare personnel. Studies are performed in reputable health care workplaces around the world, in the Czech Republic it happens especially at universities and regional hospitals or specialized workplaces, such as the Masaryk Memorial Cancer Institute.

The object of evaluation may be either a healthy volunteer, or a patient. A volunteer may become the person to whom the doctor addresses and offers them a participation in the trial. A volunteer or a patient may be included in the trial only after meeting all the criteria set out in the protocol relating to their disease and general health condition and after following the completion of prescribed initial examinations. Their consent to participate in a clinical trial is confirmed by their signature of the so-called Informed Consent, however the patient can change their mind at any time and terminate their participation without any further consequences. Participation in the study is free of charge.

All information on the conducted trial is thoroughly inspected and analysed. If the drug does not prove sufficient efficacy and safety, the trial is discontinued. The tools to secure safety are as follows: • compliance with the protocol of the trial • ensuring the Signature of the Informed Consent and advising the patient • control by ethics committees • inspection by the State Institute for Drug Control, eventually by other authorities • compulsory insurance of participants in clinical trials • observing the principles of Good Clinical Practice Clinical trials at a specific workplace are also watched by so-called monitors that are send to regular inspection visits by the sponsor of the trial to ensure that each clinical trial is conducted exactly in accordance with the rules. You can find all information concerning security also in the Informed Consent.

Possible benefits: • access to new treatment before it is generally available • assistance to the future or other patients through participation in a new treatment research Possible risks: • not all side effects of the treatment under investigation are known, they may be less or more relevant compared to standard treatment • it is a clinical research project and it may prove that the treatment is not better or even as good as the standard treatment

Clinical trials take place around all the world, including many Czech workplaces. The database of all ongoing clinical trials is available from the State Institute for Drug Control, and you can also find there a workplace where the clinical trials are taking place. You can, of course, ask directly your physician a targeted question about the possibility of being enrolled in a clinical trial. Where to find more information: • http://www.sukl.cz/ • http://www.linkos.cz/slovnicek/klinicka-studie/ • http://www.cancer.gov/clinicaltrials (english) • http://www.clinicaltrials.com/ • https://www.clinicaltrialsregister.eu/ (engllish) • https://www.mou.cz/klinicke-studie

Clinical trials are conducted for various diagnoses and at various stages of diseases. So as the treatment could be promising and effective, it is necessary to proceed exactly in accordance with the clinical trial protocol. Od course, patients or their close people may ask on their own about the possibility to take part in clinical trials. The fact whether a patient may be enrolled in a clinical trial is assessed by a doctor who knows the protocol of the clinical trial while being well acquainted with the patient's illness.