Clinical trials at RTC

The RTC is responsible for the conceptual design of clinical trials and supports the Clinic and Policlinic for Cardiac Surgery of Rostock to implement the trials.
A multicentric Phase III study with stem cells initiated by the Clinic and Policlinic for Cardiac Surgery of Rostock will start soon. It is based on the preceding successful Phase I/IIA and Phase IIB studies of intramyocardiac stem cell therapy after myocardial infarction and will meet all standards according to the GCP guidance (Good Clinical Practice).
The Institut for Medical Informatics and Biometry of Rostock will assist the RTC-team with complex statistical and epidemiological issues during the preparation phase. Before starting a study it is neccessary to know the defined number of patients to obtain stastistically significant results concerning efficacy and safety. Among other factors, this number depends on the clinical end-point and the patients´ population.

All details of a clinical study are documented in a clinical trial protocol containing design, goals, choice of patients, treatment methods, individual tests, issues of safety and ethics and many more. Results of individual tests and distinctive features during treatment have to be documented in a so-called Case Record Form (CRF) by authorized physicians. All this has to be done according to strict rules (GCP). Compliance with these rules principally needs to be approvable during external evaluation.

A considerable improvement and simplification of that time-consuming documentation system provides the electronic documentation and security system Trial-Doc for the docmentation of data from clinical studies. This system was developed in a joint research project by the research group of the RTC together with D-Trust, a branch of “Bundesdruckerei GmbH” in Berlin, the company Advanced Therapies Partners GmbH from Rostock and all other project partners.
This documentation and security system is tailored for studies on regenerative medicine and complies with the requirements of European and American approbation authorities.
TrialDoc will be used for the first time during the planned Phase III study and will also be used for future projects at RTC and beyond.

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Background information: Good Clinical Practice

Before medical products can be placed on the market, except for some special cases, they have been required to undergo an authorisation procedure. In Germany, this authorisation is granted by the Federal Institute for Drugs and Medical Devices (BfArM) and the Paul-Ehrlich-Institut (PEI), respectively, and in Europe by the  European Agency for the Evaluation of Medicinal Products (EMEA) Only after all proofs of the pharmaceutical quality, efficacy, and safety by non-clinical (laboratory/animal experiments) and clinical (probands/patients) studies have been provided according to the authorisation standards, market-authorisation for the medical product will be granted.

The German Medicines Act (AMG) provides clear guidance for the protection of hum ans during clinical trial. A clinical trial is each examination of a patient which is dedicated to the assessment of the clinical or pharmaceutical effects of drugs in order to prove its safety and/or efficacy. Each clinical trial must be performed in compliance with the regulations of “Good Clinical Practise”(GCP). The GCP-regulations define all tasks, areas of responsibility, and procedures for the planning, authorisation, application, and surveyance of trials, as well as their documentation and corresponding reporting.

The GCP-regulations can be found here.
The German Medicines Act can be found here.

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 Background Information: Procedure of Clinical Trials

Before each clinical trial an application for approval has to be directed to the corresponding federal authority. This application must comply with a number of requirements both regarding its content as well as its form. These include a detailed trial plan, a description of the drug with detailed information e.g. regarding its quality, production, production license, and data security. In addition to the required aproval by the federal authority – or the Paul-Ehrlich-Institute (PEI) for the case of products related to regenerative medicine – an evaluation is required from the ethics comission which also has to comply with a number of requirements.

Only after all approvals have been received and after all preparations have been completed, the trial may start.All patients involved in the trial will certainly be informed beforehand, will be given sufficient time for consideration whether they want to join or not, and are required to confirm their willingness for participation in written form. In addition, all participants is entitled to quit his/her participation at any time.
The procedure of any clinical trial has to be in accordance with the approved trial plan has to comply with all GCP-regulations. Documentation of all trial results has to be performed pseudonymizely and has to be identical with the patient’s records. After completion of the study the data will be statistically analyzed and documented in a report which is submitted to the authorities. The corresponding results will then be used for the application of authorisation.

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Backgroundinformation: Phases of clinical trials

In general, there are several different phases of clinical trials, which may actually show some overlap for specific clinical developments. For example, some Phase I studies in the field of regenerative medicine are not acceptable to be conducted with healthy volunteers, such that those cases typically start with so-called Phase-I/IIA studies.

In controlled clinical trials (starting from Phase IIB), the participating patient are divided in two groups, of which one is treated with the drug under consideration, and the other group serves as control. This group receives – if possible – a placebo, i.e., a preparation whose optical appearance is identical to the real one. A blind test means that the patient is not informed whether he/she belongs to one group or the other. The test is called double-blind if neither patient nor physician knows whether a real drug or a placebo is applied. Are the patients distributed by chance, the trial is called randomised. Furthermore, the trial is called multicentric if more than one clinical institution is involved.

• Phase I trials are the first stage of testing in humans where the safety of healthy probands is of particular importance

• Phase IIA trials are pilot studies to verify efficacy and safety in a selected group of patients and to assess dosing requirements

• Phase IIB trails are controlled clinical efficacy and safety assessments of selected indications

• Phase III trials are the “approval studies” and are controlled, blind or double-bind, often multicentric, and are performed on large patient groups.

• Phase IIIB trials are additional rarely performed studies to obtain additional data for the authorisation, or to support marketing claims

• Phase IV trials are post-authorisation studies and serve for the purpose of marketing

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