A

Acronym

A short form of the title that forms an effable word. E.g. HAnd-suture versus STApling for closure of loop ileostomy (HASTA Study).

Active control

(see Controlled Study)

Allocation

Method how participants are allocated to the groups:

• Single arm study: there is no comparison group.
• Parallel distribution: There are several study groups conducted side by side in terms of time (i.e. multi-armed).
• Non-randomized controlled study: assignment to treatment groups not randomly; there is at least one comparison group.
• Randomized controlled study: assignment to treatment groups by chance; there is at least one comparison group.

Amendment

Change of the study protocol in written form. Substantial changes of the protocol require authorization by the competent authority and the ethics committee.

AMG (German medicinal products act/drug law)

(see Corresponding Law)

Arm (Intervention arm)

The term "arm" is understood as a treatment group. A study is single-arm if there is only one treatment group and no control group. Most studies have two or more arms (treatment groups).

Audit Trail

A system that tracks all changes in a data base. It records who changed which items and when. This allows changes to be tracked retrospectively. The public audit trail is visible to the public.

B

Baseline

Initial conditions (e.g. blood pressure, laboratory values) of a participant at the beginning of a study. The unaffected values are assessed and compared with the changes in the course of the study.

Basic research/physiological study

Research to gain new knowledge about immunology, immunobiology, cell and molecular biology or genetics of diseases.

BfArM (Federal Institute for Drugs and Medical Devices in Germany)(=competent authority)
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 studies, 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.

Bias

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). Studies with a small bias risk are regarded to be valid.

Blinding

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 studies the treatment group is not known to participants only. Participants and investigators are unaware of the allocation in double blind studies. 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.

Brief summary in lay language

Short description of the study in generally understandable language to inform patients and the public.

C

Clinical Study / Clinical Trial

The WHO generally defines a clinical study as an experimental investigation of an intervention (e.g. medical therapy, surgical procedure, psychotherapy or preventive care) under defined conditions. On the other hand, there are the "non-interventional studies".

Studies with pharmaceuticals and medical devices have their own definitions in the EU and Germany, as these are precisely regulated by corresponding laws:

According to European pharmaceutical legislation (Regulation (EU) No. 536/2014), the term "clinical study" includes interventional studies, which are called "clinical trial" (Klinische Prüfung) and "minimal interventional clinical trial" (Minimalinterventionelle Prüfung), and non-interventional studies. Further information on non-interventional studies with drugs (NIS, AWB, PASS) can be found, e.g., in the following document: Joint recommendations on AWB and PASS (German)

In medical device legislation (MDR 2017/745 and MPDG), a distinction is essentially made between “clinical investigations” (Klinische Prüfung) that are carried out for placing on the market as part of the so-called conformity assessment procedure and "other clinical investigations" (Sonstige Klinische Prüfungen) that serve to answer scientific or other questions.

In vitro diagnostics, a subgroup of medical devices, are referred to as "performance studies" (Leistungsstudien), which are specifically regulated in EU Regulation 2017/746 ("IVDR").

(updated 2023)

Compliance

The willingness and the cognitive ability of a participant to follow the given medical instructions.

Corresponding law

AMG: The Clinical Trial falls under the Medicinal Products Act 'Arzneimittelgesetz' which regulates the marketing of medicinal products and addresses the protection of humans in clinical trials in Section 6, as well as under EU regulation 536/2014 which came into effect on 31.01.2022.

MPDG / EU MDR: The Clinical Trial falls under the German Medical Devices Implementation Act 'Medizinprodukterecht-Durchführungsgesetz' (see chapter 4) and also under the EU Medical Device Regulation (see chapter VI). On 26.05.2021, these replaced the former German Medical Devices Act ‘Medizinproduktegesetz’ (MPG).

Non-AMG/non-MPDG: These so-called "other studies" are usually carried out under the German code of medical ethics for physicians (Berufsordnung § 15).

IVDR: Study falls under the EU In-vitro Diagnostics Regulation which addresses performance evaluation studies in chapter VI.

StrlSchV: Study falls under the German Radiation Protection Ordinance 'Strahlenschutzverordnung', which has taken over the regulations of the former German X-ray Ordinance 'Röntgenverordnung' (RöV) in its latest form since 31.12.2018.

GenTG: Study falls under the German Genetic Engineering Act 'Gentechnikgesetz'.

TFG: Study falls under the German Transfusion Act 'Transfusionsgesetz'

Controlled Study

In controlled trials, there are one or more groups that are compared to the group of the intervention being studied. The comparison group can be, for example, a historical control, or a group that remains untreated or receives a placebo. A group that receives standard therapy or a comparator in different doses or dosage forms is called an active control.

CRO (Contract Research Organization)

Contract research organizations perform tasks concerning the conduct of clinical studys on behalf of the sponsor.

Crossover design

(see Assignment)

Cross-sectional study

A study in which participants are evaluated at a particular point in time, i.e. an examination is only carried out once.

D

Declaration of Helsinki

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 studies.

DRKS-ID

Unique identification number automatically assigned by the DRKS to identify a study in the register.

Drop-out

Participants that withdraw from a study because they do not want to participate any more or because one or several exclusion criteria foreclose subjects from participating in a study for their own protection.

E

Efficacy

Efficacy is a reproducible effect in a defined and optimal setting.

Endpoint

Endpoints of a clinical study. Before a study starts all outcomes have to be defined in the study 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 study. Further endpoints are called secondary outcomes.

Epidemiological study

An epidemiological study examines the relationship between exposure to a risk factor (or to a protective factor) and the occurrence of illness. Most epidemiological studies are non-interventional (see study type non-interventional).

Ethics Committee

An ethics committee (EC) is 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 studies/trials must be submitted to ethics committees and evaluated with approval. The committee reviews the study protocol, investigators' qualifications, study site as well as the potential benefit for the study participants.

Since the EU Regulation (EU) No. 536/2014 came into force and after the expiry of the transitional period on 31.01.2023, the competent EC for clinical trials with medicinal products is determined via a business allocation plan. Now there is only one national competent EC. The location of the trial centre in the case of monocentre trials or the location of the former Principal Coordinating Investigator (PCI) in the case of multicentre trials has thus become irrelevant. Applications for authorisation are submitted to the member states via a common EU portal (CTIS). Both, the higher federal authorities and the ethics committees are involved in the approval procedure.
For all other studies (like medical device trials or studies performed under the German code of medical ethics), there is still a lead ethics committee held primarily responsible if a study has several trial centres in different areas of responsibility. It is determined by the location of the head of the clinical trial. The vote of the lead ethics committee applies to the entire study in Germany.

Exclusion criteria

List of indications, concomitant diseases and attendant circumstances (e.g. pregnancy, age etc.) that exclude a potential subject from participating in a study.

F

Factorial

(see Assignment)

Source of monetary or material support

Study 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 studies sponsored by institutional budgets are paid with the PI's/sponsor's budget.

Follow up

Check-ups, e.g. physical examinations, assessments of health-related variables after an intervention. Results are relevant for final evaluations.

G

GCP

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting studies that involve the participation of human subjects.

H

Health economics

A branch of economics concerned with the economic aspects of health care.

Health services research

Is usually concerned with need, demand, supply, structure, process, output and attributable outcomes of health services, subsystems and huge institutions or programmes.

Historical control

Patient's records of subjects treated in the past and used as a comparison group.

I

ICD

ICD stands for "International Statistical Classification of Diseases and Related Health Problems". The ICD-10-GM has been adapted to the conditions in Germany (GM stands for German Modification).  In addition to the currently valid version ICD-10, the new version ICD-11 came into force in January 2022. Both versions can be used for a transition period of 5 years. Until ICD-11 is introduced in Germany, coding will continue according to ICD-10.

ICH (International Conference on Harmonisation)

International conference that publishes guidelines (e.g. GCP) to adapt the drug laws and medical devices acts of Europe, Japan and the United States.

ICTRP (International Clinical Trials Registry Platform)

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.

IST/IIT (Investigator Sponsored Trial/Investigator Initiated Trial)

A study in which the responsibility for initiating and organising the study (the sponsorship) does not lie with a pharmaceutical manufacturer, but with a scientist/physician/study leader (or their institution). More detailed information can be found in the FAQ "Is my clinical trial an IST/IIT?".

ICF (Informed Consent Form), IC (Informed Consent)

The "Patient information and consent form" serves to document the performed information of the study participants and their consent to participate in the study. It consists of two parts:

The patient/proband information informs the potential study participants in written form about the benefits and risks of participation and possibly existing treatment alternatives. After handout and sufficient reflection time, counselling and information must be provided by the investigator/study director. This is part of the patients' rights in Germany.

Only when all questions have been clarified the study participants can sign the consent form and thus be enrolled in the study.

Inclusion criteria

All characteristics that a potential subject must meet to be eligible for participation in a study (e.g. age).

Informed Consent (IC), Informed Consent Form (ICF)

(see ICF (Informed Consent Form), IC (Informed Consent))

Indication (Health condition or problem studied)

A trial could look at depression, breast cancer or heart attack etc.

Intention to treat analysis

In the statistical evaluation of a study, the participants are evaluated in the treatment group to which they were originally assigned after inclusion, regardless of which treatment they actually received in the further course.

Intervention

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).

Interventional study

(see Study type interventional)

Intervention arm

(see Arm)

Investigational product

A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical study 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.

Publication bias

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.

Investigator

Usually a physician responsible for conducting a clinical study with human subjects at a study site (in case of psychotherapy the psychotherapist).
If a study is conducted by a team of individuals at a study site, the investigator is the responsible leader of the team and is called the principal investigator.
In case the study is conducted at multiple sites in Germany a lead principal investigator (LPI) or principal coordinating investigator (PCI) is designated by the sponsor (see e.g. MPDG §30).
For clinical drug trials according to AMG & EU Regulation 536/2014 the following applies: The "investigator" is a person responsible for the conduct of a clinical trial at a trial site. The "principal investigator" is an investigator who is the responsible head of a team of investigators conducting the clinical trial at a trial site. The term LPI/PCI in multicentre trials was abolished by the EU Regulation.

Investigator sponsored/initiated trial (IST/IIT)

(See IST/IIT)

L

Longitudinal Study

In a longitudinal study, a survey is conducted several times at intervals, usually over a long period of months or years. The data generated in the different survey waves are compared with each other.

Lead principal investigator (LPI), Principal Coordinating Investigator (PCI)

(see Investigator)

Principal Coordinating Investigator (PCI), Lead principal investigator (LPI)

(see Investigator)

LPLV

Stands for “Last Patient Last Visit” and defines the time point “study closing”.

M

Masking

(see Blinding)

Monocenter study

Study is conducted at one study site only.

MPDG and MDR

(see Corresponding law)

Multicenter study

Study is conducted at least at two study sites.

N

Non-AMG/non-MPDG

(see Corresponding law)

Non-interventional study

(see Study type non-interventional)

O

Observational study

(see Study type non-interventional)

Outcome

(see Endpoint)

P

Parallel assignment

(see assignment)

Partner Registry

WHO Partner Registries submit study records to their associated WHO Primary Registry. Partner Registries have to meet the same criteria for content, quality and validity as Primary Registries.

Patient information

(see ICF)

Patient or disease register

A patient register is used to record patients and their disease course in a collection.

The term patient registry usually refers to a database system for recording patients and their treatment data that can be assigned to a specific type of disease or patient group.

Paul-Ehrlich-Institut

(see PEI)

PCI (principal coordinating investigator)

(see lead principal investigator (LPI))

PEI (Paul-Ehrlich-Institut)

The Paul-Ehrlich-Institut is an independent higher federal authority responsible for the approval of clinical study 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).

Pharmacogenetics study

Study that examines the influence of individual genetic characteristics (genes) on the efficacy of drugs.

Pharmacogenomics Study

The study deals with the question of which genes/gene products were influenced by the active substance in their regulation.

Phase of a study

Short description of the different study phases

Phase 0

Exploration of human material (e.g. tissue samples or biomarker determinations). In certain cases first studies 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.

Phase I

First drug testing in human subjects in a small group of healthy volunteers or carefully chosen patients (for certain indications where studies 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 studies can be divided into Phase IIa and Phase IIb.

Phase IIa: Clinical pilot study primarily to evaluate safety.

Phase IIb: Study to evaluate efficacy and especially therapeutic dose and safety.

Phase III: therapeutic confirmation

The drug is tested within a large study to investigate efficacy and safety. Phase I to III studies are required for application at regulatory agencies (in order to obtain approval). Phase III studies can be divided into phase IIIa and phase IIIb studies.

Phase IV: therapeutic implementation

Carried out after licensing of a drug. These studies are restricted to approved indication, dosages, pharmaceutical forms and target population to evaluate rare side effects.

PI (Principal Investigator)

see Investigator

Placebo

Sham therapy used within a clinical study e.g. a pill without pharmacological active substance. A placebo must have the same appearance as the active therapy (verum) to be an appropriate comparator.

Placebo effect

A measurable therapeutic effect observed in the group of study participants treated with the placebo.

Positive vote/Approval

Approval of a study by the ethics committee. A clinical study may not be started without the approval of the responsible ethics committee.

Prevention study

Study to investigate interventions for prevention of diseases e.g. vaccination.

Primary outcome

Main target variable of a study

(see also Outcome)

Primary Registry

WHO approved Primary Registries have to meet specific criteria for content, quality and validity, accessibility, unambiguous identification of studies, technical capacity, quality management and administration. They must have a national or regional remit or the support of government. Primary Registries submit all studies to the WHO Central Repository (ICTRP) to enable a global search for clinical studies.

Primary sponsor

(see sponsor)

Principal Investigator (PI)

(see Investigator)

Principal coordinating investigator (PCI)

(see lead principal investigator (LPI))

Prognosis study

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).

Prospective study

In prospective studies (e.g. cohort or intervention study), the data is produced after the study has started.

Protocol (Study Protocol)

The protocol describes the scientific background, study design, outcomes, methodology, inclusion and exclusion criteria, termination criteria and important contact details of the planned study. Substantial changes of the protocol (amendments) require authorization by the ethics committee and where appropriate by the competent authority as well.

R

Randomization

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.

Recruitment

Recruitment is the process of finding study participants and including them in a study. Pre-screening involves searching for suitable study participants who are likely to meet the requirements for the study. In this process, the available patient files are roughly reviewed and/or the patients are approached directly. If a patient agrees to participate in the study, the study usually begins with a screening visit, in which the inclusion and exclusion criteria are checked conscientiously and, if necessary, invasively (e.g. by taking blood samples).

The recruitment status shows whether participants are still being sought for the study or whether recruitment has already been completed.

Registrant in DRKS

Person who makes the entry of a study in the DRKS and is responsible for updates, etc. Should usually be the sponsor/principal investigator, but this task can be delegated.

Retrospective observation

In retrospective studies, material is analysed (e.g. examination findings, X-rays, data) that is already available at the start of the study.

S

Screening study

A Screening Study investigates how symptom-free diseases can be diagnosed in an early stage in widely implemented diagnostic procedures.

Secondary outcome

Secondary objective of a trial to supplement the main objective (primary outcome).

(see also Outcome)

Secondary sponsor

(see Sponsor)

Single arm study

(see Arm)

Sponsor

According to EU Regulation 536/2014 for drug studies and EU Regulation 2017/745 for medical devices, the "sponsor" is an individual, company, institution or organisation, which takes responsibility for the initiation, for the management and for setting up the financing of the clinical trial.

In German studies, 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 studies is not identical with the source of monetary or material support!

Study closing

A trial is terminated when the last patient had the last visit. For retrospective data evaluations applies the date when the evaluation was finished.

Study type non-interventional

Participants are not exposed to an intervention.

Study medication/drug

(see investigational product)

Study type interventional

Participants are exposed to an intervention (medication, surgery, radiation etc.).

Study type non-interventional

Participants are not exposed to an intervention.

Study site

A study site is e.g. a hospital or physician's office where all study-related activities are performed.

Supportive Care

Supportive care studies examine accompanying and supportive measures (see Therapy).

T

Target variable

(see Outcome)

Therapy

All medical interventions used to remedy or mitigate health disorders and diseases (drugs, radiation, surgery etc.).

U

Unblinding (GCP-V §3 Nr.11)

Disclosure of study participants to their treatment allocation (provide study participants with their study medication status: placebo or investigational treatment/active substance).

Uncontrolled study

A single arm study without comparison group/s (standard therapy, placebo, investigational product in other dosages etc.) is uncontrolled.

UTN (Universal Trial Number)

The UTN is an unambiguous identification number for clinical studies. The sponsor or principal investigator should obtain the UTN from the WHO website (https://trialsearch.who.int/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.

V

Verum

Investigational drug used in a clinical trial containing an active substance, in contrast to placebos.