The ABC of Clinical Trial Terms

^{Published: 09.06.2021}

 

Clinical studies operate with technical terms that are often difficult to understand. We explain the most important terms.

 

Adverse Event

Adverse Event (AE) is any untoward medical occurrence in a patient during a clinical trial. This adverse event can occur either with or without connection to the investigated therapy. The temporal context, i.e. the occurrence during the clinical trial, plays a decisive role here.

 

BfArM

The Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte - BfArM) is a higher federal authority that is subordinate to the Federal Ministry of Health. The tasks of the BfArM include the approval of finished medicinal products, the registration of homeopathic medicinal products, the monitoring of trade in narcotics and work on the medical and technical safety, suitability and performance of medical devices.

 

BYOD (Bring your own device)

The abbreviation BYOD stands for "Bring your own device" and means that patients' private devices are used within clinical trials. The advantage of this method is that patients do not have to familiarize themselves with other people's devices and there is no need for lengthy training. This saves a considerable amount of time during the study, as fewer educational sessions are required.

 

 

Clinical Trials

The clinical trial is considered the most important instrument of clinical research, as it tests a treatment procedure, such as new medication or therapeutic approaches, on an experimental basis. The trial takes place under previously defined conditions. There are different types of studies, such as randomized or placebo-controlled trials.

 

CTMS

The abbreviation CTMS stands for "Clinical Trial Management System". The software supports the management of clinical trials in all phases, such as planning, preparation, implementation or evaluation.

 

Declaration of Helsinki

The Declaration of Helsinki defines ethical principles for medical research involving human subjects. It is based on the 1964 General Assembly of the World Medical Association. Since then, the wording has been revised several times, most recently in 2013. Although the declaration is not binding, it is regarded as the standard for medical ethics.

 

Digital Twin / Avatar

Digital twins are increasingly being used in the digitalization of clinical studies. For this purpose, the participant in a study is digitally depicted with all their characteristics. This avatar can be used in trials with pain patients or diabetics in particular. Sensors on the participant's body feed it with the physiological data of the real person in real time. Artificial Intelligence uses this data to generate recommendations for treatment, such as the dosage of medication.

 

Drop-out-Rate

The drop-out rate is the number of patients who leave a clinical trial prematurely for personal or other reasons. A drop-out rate that is too high jeopardizes the results of a study. If too few patients take part in a study, the results will be less meaningful.

 

eCRF

The abbreviation eCRF stands for "electronic case report form". This is an electronic data collection form for clinical studies. Doctors use it to document the patient visit data required for the clinical study. Data is entered and maintained online in the eCRF. Among other things, this makes data collection significantly faster and less error-prone. In addition, all information is stored in one place and can be easily accessed online by the responsible personel. Alcedis developed Germany's first web-based eCRF in 1998.

Find out in our interview with Alcedis founder Dr. Elke Heidrich-Lorsbach how the eCRF was developed in 1998 and what challenges the company faced.

 

ePRO

The abbreviation stands for "electronic patient reported outcomes". Data and feedback from patients are essential for the success of clinical trials. With the help of digital questionnaires or surveys, patients can enter this data directly via their smartphone or a tablet provided in the clinic. This approach guarantees significantly higher data quality and a better participation rate.

 

Ethics Committee

The Ethics Committee clarifies ethical and legal admissibility in connection with medical research on humans and the import of embryonic stem cells. Legislation and the Code of Medical Practice clearly define the commission's remit. The Ethics Committee always has the rights and safety of patients in mind and examines all documents that are relevant for a clinical study. The ethics committee is made up of interdisciplinary members, including doctors, scientists and lawyers. Aspects from different disciplines are therefore taken into account.

 

Exclusion and Inclusion Criteria

Exclusion and inclusion criteria determine whether a person may participate in a clinical trial before it starts. Exclusion criteria are factors that study participants must not have. Inclusion criteria define characteristics that a patient must have. These vary greatly depending on the study and can range from age and gender to the disease progression.

 

German Medicinal Products Act (AMG)

The German Medicinal Products Act regulates the authorization, manufacture and trade of medicinal products. Its purpose is to ensure the safety of medicinal products. The law has existed since 1961 and has been amended and changed several times since then in order to adapt to medical progress.

 

Good Clinical Practice

The GCP Regulation came into effect on August 9, 2004. It is regarded as the implementation of the GCP principles in German law. The "Good Clinical Practice" sets out ethical and scientific quality requirements that apply to the planning, conduct and recording of clinical trials.

Originally, there were various country- and region-specific GCP rules that were adapted between the USA, Europe and Japan as part of the ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use). The ICH GCP has been applied since 2014 in the adopted EU Regulation 536/2014.

Compliance with "Good Clinical Practice" is intended to protect the rights, safety and well-being of participants in clinical trials and guarantee credible results (EU Directive 2001/20, Article 1, Clause (2)).

 

Lost to follow-up

In the case of lost to follow-up, contact is broken off between a study participant and the supervising doctor. As a result, the person no longer actively participates in the study and no longer counts as an active participant who offers added value to the study. Reasons for this discontinuation can be, for example, a move or the death of the participant.

The difference to the drop-out rate can be seen in the time frame: Termination of study participation is referred to as lost to follow-up, even if the break does not occur until the end of active study participation at the follow-up appointments. The drop-out rate is only recorded during the active study period.

 

Monitoring

In clinical trials, monitoring ensures, among other things, compliance with the protocol, legal requirements and their adequate documentation. There are two types of monitoring:

• Remote-Monitoring/ Online-Monitoring: This monitoring is primarily carried out using the eCRF (electronic questionnaire).
• On-site Monitoring: On-site monitoring takes place at the study centers.

 

Observational Study

The main difference between an observational study and an interventional study is that the observational study has no influence on the treatment of a patient and does not carry out any examinations that do not correspond to clinical routine. There is therefore no randomization to different study arms, as randomization already constitutes an intervention.

 

Patient Centricity

If a study follows the patient-centric approach, the needs of the patient and, if applicable, their social environment are given high priority. Patients are actively involved in the clinical trial, can make suggestions for improvement or exchange information with other participants and doctors via social networks. A patient-centred approach can also minimize the drop-out rate of a study.

 

Patient Retention

Patient retention stands for patient commitment and is intended to minimize the drop-out rate in clinical trials. Patient retention is realized through a good bond with the study participants. The aim is for study participants to be loyal to their practice or clinic.

 

PEI (Paul-Ehrlich-Institut)

The Paul-Ehrlich-Institut controls medicinal products for humans and animals. Its areas of responsibility include vaccines, allergens, advanced therapy medicinal products and genetically engineered blood components.

The PEI has a wide range of tasks, including approving clinical trials of medicinal products for human use, ensuring the safety of medicinal products and publishing information for patients and consumers.

 

Pharmaceutical Quality

Medication must be of high quality in order to achieve therapeutic success. The pharmaceutical company is responsible for maintaining this quality. Among other things, the company must prove that medicinal products are subject to permanent process controls and that a sufficiently high level of purity is guaranteed. To this end, the company undertakes to disclose the entire manufacturing process.

 

Placebo Effect

If a therapeutic effect occurs in patients after they have received treatment in the form of dummy preparations, this is known in science as the placebo effect. This is mainly used for psychosomatic illnesses when no causal therapy has any prospect of success. Placebos also help to determine the true effect of a substance when the test group is compared with a placebo group. This is because the symptoms of the placebo group often also improve. One reason for this may be that many symptoms improve on their own over time. Thus, simply believing in the effectiveness of a medication can reduce patients' symptoms.

 

Plugins

In collaboration with various partners, Alcedis has developed around 45 plugins. These support, facilitate and accelerate many phases of a clinical trial. For example, there are plugins for various areas such as user support, simplified data collection or documentation aids. This can also minimize the susceptibility to errors within clinical trials.

In the following blog article we have summarized the functionality of the plugins developed by Alcedis. Find out more about them here:

Blog: eCRF-Plugins - Drug Accountability, eFeasability and more

 

Randomized Intervention Studies

Randomized means randomly assigned. In a clinical context, patients are randomly assigned to treatment groups.

An intervention study can be an experimental clinical trial. The conditions of the trial are specified by the principal investigator. If the methods described are combined, it is a randomized intervention study. In addition to experimental clinical trials, there are also single-arm interventional trials in which no control arm is examined.

 

Sponsor

The sponsor initiates and organizes a clinical study. He also takes care of the financial means to realize the study. The sponsor therefore bears overall responsibility for the research project. This includes, among other things:

• Financing

• Insurance

• Contracts

• Assignment of responsibilities

• Auditor information

 

Study Phase

The course of a clinical trial is divided into different phases:

Phase-0-study: This phase of the clinical trial is not required by law, as often only small doses of the active substance are tested on healthy volunteers.

Phase-I-study: In this study, the safety and tolerability of the medication is tested by giving the medication to healthy participants for the first time. However, an exception is made in the field of oncology. Here, medication is administered directly to ill patients.

Phase-II-study: The active substance is now being tested for the first time on patients suffering from the condition that the medication is intended to treat.

Phase-III-study: The medication is being tested on a larger group of test subjects in order to test its broad efficacy.

Phase-IV-study: This study is being conducted with medication that has already been approved. It is investigating the further risk-benefit assessment in a larger patient population.

 

Telemedicine

Telemedicine enables interaction between doctor and patient, even though there is physical separation. This is carried out with the help of communication technologies. Telemedicine has been used more and more frequently in the medical field, for example in diagnostics or clinical studies, especially since the start of the coronavirus pandemic.

Clinical studies primarily use information and communication technologies such as video calls or smartwatches for telemedicine. The use of digital devices often reduces the workload for participants in a clinical trial. Vital data is collected using wearables, for example, and sent to the study doctor.

Find out how telemedicine brings more flexibility to clinical trials in our blog post: Digitization as an opportunity for clinical trials.

 

Trial Schedule

Both the legal requirements and the ethical principles formulated in the Declaration of Helsinki and the ICH-GCP guideline require a trial protocol for every research project. This is to ensure that the results of a clinical study are comparable, evaluable and reproducible because all participating study centers use the same methods.

 

Virtual Patient

Several virtual patients can be created from the sum of all patient data from a clinical study. Due to the mix of different patient data, these are not assigned to a specific person. Nevertheless, virtual patients have similar characteristics to study participants, including age, gender and disease progression. This allows treatments to be simulated and what-if scenarios to be created. In addition, the targeted use of virtual patients means that fewer real patients could take part in a study in the future, meaning that studies could be completed much more quickly.

 

Wearables

Small computer systems that are integrated into clothing or worn directly on the body are known as wearables. These include smartwatches, for example. Wearables are also increasingly being integrated into clinical studies in order to collect more comprehensive data, such as the continuous monitoring of vital signs in real time and thus generate faster and more accurate results. The technology also makes it possible to transmit the data directly to study centers and evaluate it there.