General information

Clinical study is the generic term for all medical studies. This includes studies with drugs (also called clinical trials) or medical devices (e.g. cannulas), studies in which diagnostic procedures are examined, or observational studies. The latter are sometimes referred to as registry studies and mean studies that do not prescribe a specific treatment. Rather, observational studies are about collecting clinical data from patients, e.g. to find out more about the disease or the patient's care situation. All clinical trials are part of a lengthy, carefully planned and controlled process in cancer research. Their aim is to answer scientific questions and, above all, to improve the therapeutic results of a specific disease. Both higher healing rates and lower side effect rates are to be understood as improvements.

What are therapy studies?

In principle, healthy people and patients can take part in clinical studies. It is different in cancer therapy: Here, the study participants are usually cancer patients. If a patient receives study therapy as part of his treatment, it is a therapy study. A therapy study is a clinical study in which new forms of treatment - e.g. new drugs, combinations of drugs and therapeutic measures - to be examined exclusively on patients. As this applies to most studies in cancer treatment, the further explanations on this page refer to therapy studies. Much of the information also applies to other clinical trials. The so-called therapy optimization studies are a special form of therapy studies. Their aim is to further develop already established therapy methods for the benefit of the patient, in order to increase the chances of recovery or to improve the quality of life. The study treatment is often a modified treatment compared to the standard treatment, e.g. Modified dose concept in radiation therapy or new combinations of drugs that have already been approved. Since the difference to the standard treatment is usually not very great, the risk for study patients is correspondingly low.

Why are therapy studies being conducted?

In the past few decades, clinical studies have led to significant advances in the diagnosis and treatment of cancer, which ultimately also contributed to a significant improvement in the chances of survival in most forms of cancer. However, the results of the therapy are not yet satisfactory in most areas and further improvement is necessary. This applies to newly diagnosed diseases and especially to patients who suffer a relapse of their disease (relapse) or whose disease does not respond to the initial treatment. Carrying out therapy studies ensures that new forms of treatment are tested and evaluated in a controlled manner so that benefits can be convincingly demonstrated and then made available to the general public. It is conceivable that individual doctors, based on their personal experience, get the impression that one or the other treatment is promising. However, this cannot be checked without therapy studies, since it is necessary to show the advantages of a treatment on a sufficiently large number of patients as part of a precisely planned and evaluated study. Legal regulations and control mechanisms ensure that patient safety is guaranteed.

How are therapy studies conducted?

Strict legal regulations and guidelines apply to all clinical studies in Germany, which all doctors and other persons who treat patients in clinical studies or who take part in the development of clinical studies must adhere to. In addition, there is a precisely defined procedure that must be followed before new forms of treatment can be tested on patients and ultimately benefit all patients in standard care. Therapy studies are the last step in a research process that begins with scientific investigations in the laboratory (pre-clinical studies). Only when the results of the laboratory tests provide convincing data that speak for the advantages of a new drug may it be tested on the patient in an orderly step program - so-called phases. Before the start of the study, possible risks are strictly checked by ethics committees and authorities who pay particular attention to the safety of the study participants.

Phase I studies
In phase I studies, a new therapeutic method that has shown promising results in pre-clinical studies is being used for the first time in humans. In this first of three stages, the tolerance of the drug, its distribution and its breakdown in the body are first examined in a small group of patients. It should also be determined which dose can be safely administered. In Phase I trials, large amounts of blood and urine are taken and patients are closely monitored to obtain the data needed. Since unexpected side effects cannot be completely ruled out despite careful preliminary tests in the laboratory, only patients who have already exhausted all options of standard treatment are allowed to participate in phase I studies. At the same time, however, there is an opportunity to be the first to gain access to a new, effective drug.

Phase II studies
Based on the findings from phase I studies, the subsequent phase II analyzes the effectiveness of certain diseases, possibly also in combination with other drugs. The aim is also to confirm the previously determined dose and carefully examine any side effects.

Phase III studies
After completion of the phase II studies and determination of an optimal dose, reliable evidence of the efficacy and safety of the drug under investigation should be provided in phase III. For this purpose, the new therapy method is compared with a known standard treatment. So-called randomized tests are often carried out (see below). Many patients are included in phase III studies and the study is often multi-centered - that is, at numerous hospitals at the same time. If an advantage of the new therapy methods compared to the usual standard methods can be proven in the context of a phase III study, this can be taken over into the standard care and brings advantages for a large number of patients.

Study design
Since the results of a therapy study are of great importance for future treatment concepts, it must be guaranteed in any case that one can rely on the findings from the study. For this reason, we try to rule out external factors that could influence the results as far as possible. Various measures can be taken to this end, some of which are described below.

Inclusion and exclusion criteria
Each study has specific pre-defined guidelines that determine which patients can participate in the study. They are referred to as inclusion criteria (characteristics that must be present) and exclusion criteria (characteristics that prevent participation in the study). These criteria can e.g. The type of cancer, the stage of the disease, comorbidities, age, or cancer therapies already received. On the one hand, the definition of inclusion and exclusion criteria is necessary to ensure that only data from patients with comparable disease characteristics are used to answer the study question. On the other hand, it should be avoided that patients are exposed to great stress and risks when participating in the study, for example if certain concomitant diseases are present.

Randomization
In randomized therapy studies, patients are randomly assigned one of several, precisely defined treatments. The various treatment methods are referred to as therapy arms. Often, in randomized studies, the new therapeutic method to be tested is compared with the known standard treatment or a dummy drug (placebo). The random distribution to the therapy arms is carried out because, on the one hand, it is actually not known which of the examined treatment methods

How is patient safety guaranteed in studies?

The safety of patients in therapy studies is taken into account as an essential point when planning a therapy study and is constantly monitored during the study. In Germany, the regulations of the Medicines Act (AMG), which are primarily intended to protect patients, apply to all therapeutic studies with medicinal products. The AMG is mandatory for study doctors. All doctors who accompany patients while participating in a therapy study are also specially trained and act according to the rules of so-called "good clinical practice" (GCP). These are internationally recognized rules for conducting clinical studies based on ethical and scientific aspects. The focus is on criteria for ensuring the quality of the study results as well as information and protection of study participants. Before a clinical study can begin, it must be examined and approved by various authorities and commissions based on medical, scientific and ethical criteria.

Ethics Committee
Ethics committees are independent, qualified bodies made up of people from various professional groups, e.g. Put together scientists, doctors or lawyers and patient representatives. Before the start of a clinical study, an ethics committee assesses its medical, scientific and ethical significance and checks whether all legal requirements are met. The study will only be approved if the rights and safety of patients are also protected. The ethics committee will also be informed of the progress of the study while the study is being carried out and can withdraw its approval if e.g. too many unexpected risks for the patient arise.

Authorities
Studies with medicinal products must also be approved by a higher federal authority - either the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI). Like the ethics committees, the BfArM or the PEI can also withdraw their approval if it turns out during the implementation that the safety of the patients is not guaranteed. In addition, the study assistance of the locally responsible doctors in a clinic is registered with the administrative district of the respective federal states. These local authorities have the opportunity to check the conduct of the study at the treatment center themselves.

Subject insurance
Subject insurance is taken out to ensure that financial losses resulting from the study therapy are compensated by the insurance company. The study doctor gives the patient the exact insurance conditions.

How do therapy studies work in practice?

Study protocol
Every study has a study director who is responsible for planning, carrying out and evaluating it. Before the start of the study, the study director writes a plan for the study, the study protocol. Therapy protocols usually contain the following components:

• Reason
• aims
• Number of patients to be treated
• Inclusion and exclusion criteria
• Description of the study therapy
• List of necessary examinations
• Information on expected side effects
• Data to be collected
• Patient information

Study protocols are submitted to the ethics committee and the competent higher federal authority for approval before the study begins. All of the doctors participating in the study use the same protocol. This ensures that all patients are treated in the same way and that the information obtained can be combined and compared.

Patient education and consent
Before treatment in a study, the patient concerned must be informed in detail orally about all aspects of the study, foreseeable risks, advantages and disadvantages and other treatment options. The rights of the patient as a participant in a therapy study are also explained and the confidential treatment of patient data is guaranteed. The patient also receives written information and is asked to read it carefully and discuss it with relatives and friends. The patient is given sufficient time to consider his decision and - after additional questions have been answered - is asked to make a decision about whether to participate in the study. Only if the patient - well informed - agrees to participate in the study and confirms this with his signature, can he be treated in a therapy study. If the patient does not agree, his doctor will suggest an alternative treatment option.

Study implementation
Therapy studies are usually carried out at specialized clinics or in specialized practices. Doctors, nurses and study staff who were specially trained for this study look after the study participants. They ensure that the regulations of the study protocol are adhered to as precisely as possible. They are also responsible for ensuring that the course of therapy, all test results and possible side effects are continuously documented in writing. After giving consent, a patient is first examined in detail. Above all, it is checked whether all inclusion criteria have been met and there are no exclusion criteria. Most studies require a pregnancy test to be performed in women of conceptual age in order to rule out an existing pregnancy. Admission to the study can only take place when these examinations have been completed. In the course of the study, patients are examined at precisely specified times (visits). In general, a patient's health will be monitored particularly carefully while participating in the study. It is therefore possible that additional doctor visits and examinations will be required. These are primarily used to better monitor the course of treatment and are therefore ultimately in the best interests of the patient. Patients can find out about the number and type of examinations before participating in the study. Most studies also provide for patients to be contacted by their doctor even after the study therapy has ended, in order to gain information about their long-term condition. Study patients have the opportunity to find out about the progress of the study at any time. Since participation in the study is voluntary, patients can terminate their participation in the study at any time and without giving reasons, without any disadvantages for further treatment. In this case, however, the patient should urgently consult the attending study doctor and not simply stop taking the medication.

Should I take part in a clinical trial?

The decision to participate in a study often has to be made at a time when the patient concerned is particularly stressed by the opening of the diagnosis and his state of health. In many cases, treatment must be started quickly in order to reduce the disease. Nevertheless, it is necessary to make use of all available information and help and to make a decision yourself after careful consideration. The following can be helpful:

Information about the disease and treatment options, e.g. the German Cancer Aid or other specialist societies, discussions with the doctor you trust, with relatives and friends, information talks about the therapy study with the treating doctor (patient information). Other possible sources of information are local hospitals, the general practitioner, the relevant ethics committee, books and internet information services. In addition, patients should speak to doctors and nurses and find out about the experience and expertise of the facility where they are being treated. When deciding for or against participating in a study, there are also some possible advantages and disadvantages that must be weighed against each other:

Possible benefits

• Treatment and care by qualified specialists
• precise information about the planned treatment and its advantages and disadvantages
• Access to new treatments before they are widely available
• particularly close monitoring of the state of health
• Opportunity to contribute to advancement in cancer research

Possible disadvantages

• New drugs and treatments can have unpredictable side effects or risks
• the therapeutic method examined may not offer any advantages or even bring worse results than the known standard therapy
• The close monitoring of the state of health means that there are more frequent visits to the doctor
• there may be more frequent unpleasant examinations (e.g. blood tests)
• as a particular study is not carried out in every hospital, treatment may not be available close to home