Glossary of key terms
The following glossaries were used as sources of information: German Network for Evidence Based Medicine, German Cochrane Centre, National Cancer Institute, Clinical Data Interchange Standards Consortium (CDISC), International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), WHO Health Systems Performance, Food and Drug Administration (FDA).
The control group receives an intervention to be compared with the investigated intervention e.g. standard treatment.
Method how participants are allocated to the groups:
Single arm study: there is no comparison group.
Non-randomized controlled trial: assignment to treatment groups not randomly; there is at least one comparison group.
Randomized controlled trial: assignment to treatment groups by chance; there is at least one comparison group.
Approval of the ethics committee. A trial must not be started before approval of the (leading) ethics committee.
The following kinds of assignment can be chosen:
Single (group): there is no comparison group
Parallel: concurrent comparison between at least two treatments
Crossover: there are several groups (at least two), which receive every or at least several treatments in different sequences
Factorial: concurrent comparison between several treatments and their combinations
A system that tracks all changes in a data base. It records who changed which items and when. The public audit trail is visible to the public.
Initial conditions (e.g. blood pressure, laboratory values) of a participant at the beginning of a trial. The unaffected values are assessed and compared with the changes in the course of the trial.
Research to gain new knowledge about immunology, immunobiology, cell and molecular biology or genetics of diseases.
Falsification, systematic error: A deviation in results or inferences from the truth. A bias leads either to an over- or underestimation of the efficacy of an intervention. The main reasons for bias are due to study design and performance. They lead to systematic differences between the groups that are compared (selection bias), in the assessment of the outcome (measurement bias), or withdrawals of participants (attrition bias). Trials with a small bias risk are regarded to be valid.
Concealment of allocation (therapy or control). Allocation is not known to participants, investigators, nursing staff or statisticians involved in a clinical trial. The aim is to prevent that the response to treatment, manner of investigator or the statistical evaluation is influenced by the awareness of the intervention group. In single blind trials the treatment group is not known to participants only. Participants and investigators are unaware of the allocation in double blind trials. Blinding of investigators and participants is not always possible (e.g. if a surgical intervention is compared with a drug). In general a blinding of statisticians is possible.
Short description of the trial in generally understandable language to inform patients and the public.
A clinical trial is the experimental investigation of an intervention (e.g. medical therapy, surgical procedure, psychotherapy or preventive care) under defined conditions.
The willingness and the cognitive ability of a participant to follow the given medical instructions.
Contract research organizations perform tasks concerning the conduct of clinical trials on behalf of the sponsor.
Controlled trials have at least one or more comparison group/s to be compared with the investigated intervention. A comparison group can be a historical control or a group receiving no treatment or standard therapy or placebo. A control group can also be treated with the investigational intervention in different dosages or pharmaceutical forms.
German medicinal products act/drug law (AMG): 'Arzneimittelgesetz'
German medical devices act (MPG): 'Medizinproduktegesetz'
Non-AMG/non-MPG: none of the above
German X-ray ordinance (RöV): 'Röntgenverordnung'
German radiation protection ordinance (StrlSchV): 'Strahlenschutzverordnung'
German genetic engineering act (GenTG): 'Gentechnikgesetz'
German transfusion act (TFG): 'Transfusionsgesetz'
Other: laws or acts which are not listed here
Statement of the World Medical Association on ethical principles concerning medical research in human beings. It names essential rights and interests of patients to ensure the well-being of participants in clinical trials.
Unique identification number automatically assigned by the DRKS to identify a trial in the register.
Participants that withdraw from a trial because they do not want to participate any more or because one or several exclusion criteria foreclose subjects from participating in a trial for their own protection.
Efficacy is a reproducible effect in a defined and optimal setting.
An epidemiological trial examines the relationship between exposure to a risk factor (or to a protective factor) and the occurrence of illness. Most epidemiological trials are non-interventional (see study type non-interventional).
An independent board that consists of healthcare professionals and persons not working for the health care sector. The aim is to protect ethical principles in medical research and associated fields.
Clinical trials have to be approved by an ethics committee. It reviews the trial protocol, investigators' qualifications, study site, the potential benefit for participants and more.
In Germany the main responsibility lies with the leading ethics committee. In case of several study sites the ethics committee which is responsible for the site of the lead principal investigator is the leading one.
The approval of the leading ethics committee refers to the whole clinical trial.
List of indications, concomitant diseases and attendant circumstances (e.g. pregnancy, age etc.) that exclude a potential subject from participating in a trial.
The Federal Institute for Drugs and Medical Devices (BfArM, Bundesinstitut für Arzneimittel und Medizinprodukte) is an independent higher federal authority within the portfolio of the Federal Ministry of Health. The main tasks of the BfArM are the approval of clinical trials, licensing and registering of medicinal products, pharmacovigilance as well as monitoring the legal traffic of medicinal products. The BfArM is responsible for risk monitoring of medical devices as well.
The second higher federal authority in Germany is the Paul-Ehrlich-Institut (PEI). It is the competent authority for marketing authorizations of vaccines, sera and other medicinal products for human use.
Check-ups, e.g. physical examinations, assessments of health-related variables after an intervention. Results are relevant for final evaluations.
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects.
(see corresponding law)
Regulates medical devices trading and guarantees safety, suitability and performance levels of medical devices.
Regulates the legal traffic of medicinal products in Germany.
A trial can be concerned with depression, breast cancer or heart attack etc.
A branch of economics concerned with the economic aspects of health care.
Is usually concerned with need, demand, supply, structure, process, output and attributable outcomes of health services, subsystems and huge institutions or programmes.
Patient's records of subjects treated in the past and used as a comparison group.
(see informed consent)
International conference that publishes guidelines (e.g. GCP) to adapt the drug laws and medical devices acts of Europe, Japan and the United States.
Internet platform of the World Health Organization (WHO). It provides information about the registry network and a search portal, in which the data of all participating registries are combined.
All characteristics that a potential subject must meet to be eligible for participation in a trial (e.g. age).
Participants have to sign the informed consent before they can be enrolled into a clinical trial. Before they give their agreement to participate they have to be informed by the investigator of all aspects of the trial that are relevant to the subject's decision to participate.
The patients are statistically analysed in the initially allocated treatment group.
An intervention is a treatment. Interventions include but are not restricted to medical therapies like drugs, radiological procedures, surgical procedures, psychotherapy and other therapies like physiotherapy and preventive care (e.g. vaccination).
An intervention arm is a treatment group. Single arm trials have only one treatment group and no comparison group. Most trials have two or more arms (treatment groups).
A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial or to cause a specific reaction in humans. This includes products with a marketing authorization if used or assembled (formulated or packaged) in a way different from the approved form, or if used for an unapproved indication, or if used to gain further information about an approved use.
Usually a physician responsible for conducting a clinical trial with human subjects at a study site (in case of psychotherapy the psychotherapist). If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and is called the principal investigator. In case of multiple sites a lead principal investigator (LPI) or principal coordinating investigator (PCI) is designated by the sponsor.
A trial, which was initiated by a researcher. Independent from financing the trial the sponsorship underlies the responsibility of the researcher or his institution. That means that he or it takes responsibility for the initiation, management and financing of a clinical trial.
Terms to describe main objectives of trials to improve ease of access to trials in the register (retrieval by keyword).
Inclusion criterion that a potential subject must meet to be eligible for participation in a trial. The indicated maximum age must not be exceeded by Participants.
Inclusion criterion that a potential subject must meet to be eligible for participation in a trial. Participants' age must not be below the indicated minimum age.
Trial is conducted at one study site only.
(see corresponding law)
Trial is conducted at least at two study sites.
All study sites are located in one country.
(see corresponding law)
Endpoints of a clinical trial. Before a trial starts all outcomes have to be defined in the trial protocol. It must be indicated which parameter (what), at which time point (when) and using which measuring method, questionnaire etc. (how) is assessed. The main endpoint is the primary outcome of a trial. Further endpoints are called secondary outcomes.
The Paul-Ehrlich-Institut is an independent higher federal authority responsible for the approval of clinical trial applications and licensing and registration of allergens, blood products, vaccines, sera and gene transfer medicinal products. The second competent authority in Germany is the BfArM (Federal Institute for Drugs and Medical Devices in Germany).
Trial that examines the influence of individual genetic characteristics (genes) on the efficacy of drugs.
Short description of the different study phases
Exploration of human material (e.g. tissue samples or biomarker determinations). In certain cases first trials in humans intended to assess new candidate therapeutic and imaging agents. These tests are conducted with subtherapeutic doses (microdosing). First results in the fields of pharmacokinetics and pharmacodynamics.
First drug testing in human subjects in a small group of healthy volunteers or carefully chosen patients (for certain indications where trials with healthy volunteers are not possible, e.g. cancer or HIV/AIDS) under defined conditions to investigate safety, pharmacokinetics and pharmacodynamics.
Phase II: therapeutic exploration
The drug to be investigated is tested in a small group of patients suffering from a disease that is supposed to be affected by the drug. Therapeutic dose, efficacy, side effects and clinical toxicity are assessed. Phase II trials can be divided into Phase IIa and Phase IIb.
Phase IIa: Clinical pilot trial primarily to evaluate safety.
Phase IIb: Trial to evaluate efficacy and especially therapeutic dose and safety.
Phase III: therapeutic confirmation
The drug is tested within a large trial to investigate efficacy and safety. Phase I to III trials are required for application at regulatory agencies (in order to obtain approval). Phase III trials can be divided into phase IIIa and phase IIIb trials.
Phase IV: therapeutic implementation
Carried out after licensing of a drug. These trials are restricted to approved indication, dosages, pharmaceutical forms and target population to evaluate rare side effects.
(see principal investigator)
A therapeutic effect measured in the placebo treated group.
Trial to investigate interventions for prevention of diseases e.g. vaccination.
Main target variable of a trial (see outcome).
WHO approved Primary Registries have to meet specific criteria for content, quality and validity, accessibility, unambiguous identification of trials, technical capacity, quality management and administration. They must have a national or regional remit or the support of government. Primary Registries submit all trials to the WHO Central Repository (ICTRP) to enable a global search for clinical trials.
The aim is to predict a course of a disease, pathogenesis and event of disease. Variables are identified to make a statement about disease prognosis (e.g. tumour marker level).
Falsification of data concerning a specific aspect. Bias is caused by the circumstance that positive results are more likely to be published than those with negative or weak results.
Randomization is the allocation of participants to intervention groups or arms by chance. An allocation is by chance if a well recognized statistical technique has been used and if allocation is not based on human decision or predictable processes.
(see recruitment status)
Indicates the current stage of a trial, whether participants are currently being recruited or not.
Trial investigating how symptom-free diseases can be diagnosed in an early stage in widely implemented diagnostic procedures.
Secondary objective of a trial to supplement the main objective (primary outcome).
(see intervention arm)
Trial can be funded commercially, publicly, by private sponsors or by an institutional budget. A commercial sponsor could be the pharmaceutical industry. The BMBF (Federal Ministry of Education and Research) and the DFG (German Research Foundation) are public sponsors in Germany. Foundations and study societies are private sponsors and trials sponsored by institutional budgets are paid with the PI's/sponsor's budget.
An individual, company, institution, or organization (legal person) which takes responsibility for the initiation, management, and financing of a clinical trial with human subjects.
In German trials only one sponsor is defined (primary sponsor) but in some countries the law provides secondary sponsors. The WHO requires the primary sponsor and secondary sponsors if applicable.
Please note: A sponsor in clinical trials is not identical with the source of monetary or material support!
A trial is terminated when the last patient had the last visit.
(see investigational product)
A study site is e.g. a hospital or physician's office where all study-related activities are performed.
Participants are exposed to an intervention (medication, surgery, radiation etc.).
Participants are not exposed to an intervention.
Supportive care trials investigate supporting and accompanying therapies.
All medical interventions used to remedy or mitigate health disorders and diseases (drugs, radiation, surgery etc.).
A short form of the title that forms an effable word. E.g. HAnd-suture versus STApling for closure of loop ileostomy (HASTA Trial).
The protocol describes the scientific background, study design, outcomes, methodology, inclusion and exclusion criteria, termination criteria and important contact details of the planned trial. Substantial changes of the protocol (amendments) require authorization by the ethics committee and where appropriate by the competent authority as well.
(GCP-V §3 Nr.11)
Disclosure of trial participants to their treatment allocation (provide study participants with their study medication status: placebo or investigational treatment/active substance).
A single arm trial without comparison group/s (standard therapy, placebo, investigational product in other dosages etc.) is uncontrolled.
The UTN is an unambiguous identification number for clinical trials. The sponsor or principal investigator should obtain the UTN from the WHO website (http://www.who.int/trialsearch/utn.aspx) as soon as possible when planning a trial. The UTN should become part of the trial's identity number (e.g. in the trial protocol) and be used whenever information about the trial is communicated. The UTN is a worldwide identifying number but not a registration number. For this reason the UTN should be provided as a secondary ID when registering a trial.
Investigational drug used in a clinical trial containing an active substance, in contrast to placebos.