Clinical Trials

Clinical trials are research studies that are generally open to healthy volunteers and patients. In cancer clinical trials, the situation is different: study participants are usually cancer patients. For example: If patients receive the new type of treatment under investigation as part of their treatment plan, then they are more than likely taking part in a cancer treatment study. A cancer treatment study is therefore a clinical trial in which new forms of cancer treatment are tested on cancer patients only. New forms of treatment can include new drugs, combinations of drugs, new approaches to cancer therapy or a combination of these. Since the criteria just described apply to most studies dealing with cancer treatment, the rest of the information covered on this page will mainly refer to this type of research. However, please keep in mind, most of the information found here generally applies to other types of clinical trials as well.

A special type of cancer treatment study is a therapy optimization study (TOPs). The aim of therapy optimization studies is to further develop therapy options already in use; however, their focus is on increasing patient chances of cure and bettering patient quality of life. In these types of studies, drugs with proven efficacy are often used and tested in combination with other drugs; or, they are used and tested in combination with other forms of treatment such as radiation, surgery, or chemotherapy. Since the difference in comparison to standard treatment procedures in therapy optimization studies is usually not very large, the amount of risk involved for study patients can therefore be said to be correspondingly low.

Over the past decades, clinical trials have led to significant progress in the diagnosis and treatment of cancer which, in turn, has contributed to improving patient chances of survival for most forms of cancer.

Nevertheless, most cancers still remain difficult to treat successfully. This is especially true when either treating patients with newly-diagnosed diseases or treating patients who have either suffered a relapse and/or have not responded to initial treatment.

Cancer treatment studies ensure that new forms of treatment are tested, evaluated and verified under controlled procedures before being approved of for use in clinical care. Before this can happen, promising new approaches to treatment need to be proven first through cancer treatment studies conducted on a sufficiently large number of patients and within the context of a precisely planned and executed study, where legal regulations and control mechanisms are in place to ensure patient safety.

All clinical trials in Germany are subject to strict legal regulations and guidelines, which must be observed by all physicians and all other persons who are either involved in treating patients in clinical trials and/or who participate in developing clinical trials. In addition, clearly defined procedures must also be followed before new forms of treatment can begin to be tested on patients and eventually be part of a process that will later benefit all patients in regular care. Cancer treatment studies are thus the final step in a rather long research process, which begins with pre-clinical trials or, put in another way, scientific investigations performed first in the laboratory.

Only after the results of the pre-clinical trials performed in the laboratory produce convincing results that clearly show possible favorable benefits of a new drug, may it be tested on patients within the framework of a staged program also known as phases of a clinical trial. All possible risks are strictly reviewed by ethics committees and government authorities before a study is approved of and can begin. It is the job of these authorities to pay particular attention to the safety of the study’s participants.

Phase I Clinical Trials

Only when a new cancer treatment procedure has shown promising results in pre-clinical laboratory tests, will it enter Phase I of a clinical trial and be approved for first-time testing on patients. In tthis first of three trial phases, a small group of patients are administered a drug to find out how well they tolerate, absorb, metabolize and excrete the drug. The goal of this phase is to determine which dose can be safely administered. To obtain data, patients are closely monitored and several blood and urine samples are taken. Although new drugs undergo careful stages of pre-testing in the laboratory, unexpected side effects still cannot be completely ruled out. Therefore, only patients who have exhausted all standard options for therapy may participate in Phase I clinical trials and so receive access to a new and potentially effective new drug.

Phase II Clinical Trials

In Phase II trials, doctors want to know more about the results they collected in Phase I. Therefore, Phase II clinical trials researchers analyze drug efficacy or, in other words, how effective the drug is in treating specific cancer types. Sometimes combinations of drugs are tested. Researchers also want to confirm the dosages they gave in the previous Phase I trial and to investigate the side effects in more detail.

Phase III Clinical Trials

After finishing Phase II clinical trials and having determined an optimal dosage, Phase III aims to provide reliable proof of efficacy and safety of the drug under investigation. In Phase III, researchers compare the new treatment with the standard treatment. To do so, they frequently conduct randomized trials (please see below). Phase III studies involve many patients and the study is often conducted simultaneously in multiple trial centers, for example, at a large number of hospitals. If new treatment procedures in a Phase III trial are shown to be more advantageous over established standard procedures, it can be adopted into standard care procedures and benefit a large number of patients.

Study design

Ensuring the reliability of results is of great importance in finding new ways to treat cancer. For this reason, researchers try to exclude external factors that could possibly influence the results of a trial. There are several ways to do this, some of which are described below.

Inclusion and exclusion criteria

Each study has a set of pre-defined criteria that determine who is eligible to participate in the clinical trial. They are called inclusion criteria (factors that must be present) and exclusion criteria (factors that prevent participation in the study). These factors can include, for example, the type and stage of the disease, other illnesses and/or conditions, age or previous treatment history. Defining inclusion and exclusion criteria is necessary, because it ensures that only data of patients with comparable disease characteristics is used to answer the research question. Choosing relevant criteria also considers the health of the patient. It might be harmful or too big of a burden for patients who have other illnesses or conditions to participate in a trial, for example.

Randomization

In randomized clinical trials, patients are randomly assigned one of several accurately defined treatments. Each of the different treatments are called treatment arms. In randomized trials, the new treatment is often compared with the standard treatment, or a dummy drug (placebo).
Randomly distributing groups of patients into separate therapy arms is done for two reasons: one, it is not yet known which of the treatment methods will yield better results. And two, it ensures an equal distribution of patients with certain characteristics into different therapy arms. This is important because certain characteristics like, for example, age or sub-type of cancer, can have an influence on clinical trial results.

Blinding

If patients know they are receiving a presumably more effective treatment, it can lead to a measurable improvement in symptoms and/or their general well-being. Likewise, knowledge of receiving a supposedly less effective treatment can lead to a measurable worsening of disease symptoms or well-being. This phenomenon can falsify the results of clinical trials. Therefore, patients in blind randomized trials are initially placed in groups without knowing which drug they will be receiving. Only at the end of the trial are patients told how they were treated.

But not only are patients subject to bias. Physicians can also conduct a clinical trial with certain expectations that can have an influence on the results of a trial. For example, knowing that a new drug is being administered may unconsciously influence researchers in their evaluation of its efficacy and its side effects. Therefore, in double-blind trials, neither the patient nor the physician knows what treatment the patient will be receiving.

Keeping patients safe is the main concern when planning clinical trials. Thus, patients are constantly monitored during the trial. In Germany, all clinical trials about medicinal products are subject to the regulations of the German Drug Law (AMG). These regulations are primarily made to protect patients. The AMG is binding for all investigators in clinical trials. All physicians, who accompany participating patients, are trained in and act in accordance to the rules of Good Clinical Practice (GCP). These are internationally recognized rules for conducting clinical trials, which are based on ethical and scientific principles. They focus on criteria to ensure the quality of clinical trials results as well as on informing and protecting the participants.

Before a clinical trial can begin, it must be reviewed and cleared by various authorities and commissions, who act on the basis of medical, scientific and ethical principles.

Ethics Committee

Ethics committees are independent, qualified bodies made up of persons from various professional groups (e.g. scientists, doctors or lawyers and patient committees). Before a clinical trial can begin, an ethics committee assesses it in terms of its medical, scientific and ethical value and checks whether all legal requirements have been met. The clinical trial will only receive approval if patient rights and safety are guaranteed. The ethics committee is kept informed of the clinical trial's progress throughout its implementation and can withdraw its approval if, for example, too many unexpected risks arise for the patients.

Authorities

Clinical trials involving medicinal products must also be approved of by a higher federal authority, either the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI). Like the ethics committee, the BfArM or the PEI can also withdraw their approval if it becomes apparent during the course of the study that patient safety cannot be guaranteed.
In addition, participating clinics and physicians are registered with the county of their federal state. These local authorities have the power to review the execution of the trial at the respective clinic.

Participant insurance

Participant insurance is taken out to ensure that financial losses resulting from participation in the clinical trial will be compensated by the insurance company. The exact insurance terms and conditions are handed out to the patient by the investigating physician.

Study protocol

For every clinical trial there is an investigating physician who is in charge of planning, executing and evaluating the trial. Before the trial begins, the investigating physician writes what is called a study protocol or research plan. Study protocols usually contain the following information:

• Justification
• Study objectives
• Number of patients to be treated
• Inclusion and exclusion criteria
• Description of the treatment in the trial
• List of necessary examinations to be performed
• Information on anticipated side effects
• Data to be collected
• Patient information

Before a clinical trial begins, the study protocol is submitted to an ethics committee and the responsible higher federal authority for approval. All participating physicians use the same study protocol. Using the same study protocol ensures that all patients are treated in the same way and that the information obtained can be combined and compared.

Patient informed consent

Prior to receiving treatment in a clinical trial, patients must be given detailed information about all aspects of the trial, foreseeable risks, advantages and disadvantages as well as other treatment options available in both spoken and written form. Patient rights as a participant in a clinical trial are also explained and the confidential treatment of patient data is also assured. In addition, the patient receives information in written form and is asked to read it thoroughly and discuss it with relatives and friends prior to signing. Patients are given sufficient time to consider their decisions and, after additional questions have been answered, are asked for their decision.
Only if patients, after being properly informed, agree to participate in the trial and confirm with their signature, will they be admitted to a clinical trial. If a patient does not want to participate in the clinical trial, a physician will then suggest alternative treatment options.

Conducting the Clinical Trial

Cancer treatment studies are usually carried out at specialty clinics or in specialty practices. Trial participants are taken care of by physicians, nurses and research staff who have been specially trained in how to conduct the trial. In addition to other duties, they ensure that the regulations governing the study protocol are followed as closely as possible. They also carefully record how the patient is affected by the treatment, all examinations results and side effects (if they occur).

Patients are first thoroughly examined only after they have given their written consent. The purpose of the first examination is to verify that all inclusion criteria have been met and no exclusion criteria exist. In most trials, women who are still in their child-bearing years are obliged to take a pregnancy test in order to eliminate the possibility of an existing pregnancy. Only when these examinations have been completed will patients be included in the trial.

During the trial, participants are examined at precisely defined times (rounds). Generally, all participants are monitored particularly carefully throughout the course of the trial. Therefore, more time may have to be planned in for frequent visits to the doctor’s and additional examinations. Additional tests are done primarily in the best interest of the patient and primarily serve to steadily monitor the patient’s condition throughout the course of treatment. Patients can inquire about the number and type of examinations they will need to have done before consenting to participate. In most cases, physicians contact their patients to collect information on how well they are feeling usually some time after the trial has ended. 

Clinical trial patients may also always inquire about how the trial is progressing. Since trial participation is voluntary, patients can leave the trial at any time without having to give a reason and without having to fear receiving no further treatment. However, if patients wish to discontinue their participation in the trial, they should seek consultation with the treating physician immediately and should not simply discontinue taking medication!

Most of the time, deciding whether to participate in a clinical trial frequently has to be made at an especially challenging time for the patient. Usually a patient has just received the diagnosis and is not feeling particularly well. Still, the chances for repressing the disease best means treatment must be started directly after diagnosis. Despite maybe feeling under pressure, patients should still take time for careful consideration and arrive at a decision only after they have gathered enough information and assistance in understanding what the trial is about and what it could mean for them. We hope the information below will be of assistance in this difficult process:

• Obtain enough information about the disease and treatment options, e.g. through information material by the UCT, the German Cancer Aid or other professional societies
• Talk with a trusted physician, family and friends
• Discuss the trial in depth with the treating physician (patient education)

Possible further sources of information are local hospitals, the family doctor, members of the trial’s ethics committee, books and information services on the Internet. Patients should also talk to doctors and nursing staff to find out more about the experience and expertise of the institution where they will be treated. Making a decision on whether to participate in a clinical trial also requires careful consideration of some possible advantages and disadvantages:

Possible advantages

• Treatment and care by highly-qualified and trained specialists
• Exact information about the planned treatment and its advantages and disadvantages
• For therapy optimization studies, a network of experts is available who can be called upon if necessary
• Access to new treatments before they become available to the public
• Particularly close and regular monitoring of patient health and well-being
• An opportunity to contribute to the advancement of cancer research

Possible disadvantages

• New drugs and/or types of treatment may have unanticipated side effects or risks
• The new treatment method under investigation may not result in any advantages or may even produce worse results than the standard treatment
• Close monitoring of the participant’s health condition means frequent visits to the doctor
• Unpleasant examinations may be carried out more frequently (e.g. blood tests)
• A particular trial may not be conducted at every hospital, so treatment may not be available close to home. 

• What clinical trials are available to me?
• What is the treatment / drug called? 
• What is the purpose of this clinical trial?
• What kind of treatments and other procedures (e.g. tests, scans, etc.) will I have during the clinical trial? How often will they take place?
• How long will the clinical trial last? Can I participate as an outpatient?
• What are the possible advantages of participating in this clinical trial?
• What are the possible risks of participating in this clinical trial?
• Will I be able to take my everyday medication during this clinical trial?
• Are there any other alternative treatment options compared with participating in this clinical trial? How will these tests and procedures be different from the ones needed for the standard treatments?
• Who is backing this clinical trial financially?
• How will I be insured during this clinical trial?
• What do I have to do in order to participate in this clinical trial?