Glossary

A t-test is a statistical test that helps compare whether the average values of two groups of data are significantly different from each other. It is used to obtain a measure of the difference between the means (averages) of the groups, relative to the spread of data within each group.

The t-test helps decide whether a difference in mean values between two groups is due to random chance in a sample selection.

Refers to the patients the medicine is intended for.

A target product profile is a document that describes the features of a product (such as a medicine) that a company is planning or developing. The document can include a wide range of information such as dosage, how the product will be administered (for example this could be a patient taking a medicine by mouth, or a hospital nurse giving the medicine as an injection), formulation, clinical studies, adverse reactions (unwanted harmful effects) and contraindications (situations when the product should not be used).

The target product profile is written by the company developing the treatment, and if it is begun early it can help keep their development work properly focused on the end goal. A target product profile can also be used as a basis for discussions between the company and those regulatory authorities that will assess the product for release to market.

These are medicines designed in a manner that focuses the activity of the medication in certain parts of the body. The goal of a targeted medicine is to increase the length of time that the medicine interacts with the diseased tissue in a specific area of the body and spares other parts (e.g. affecting tumour cells rather than adjacent healthy cells). The advantages of a targeted release system are the reduction in the frequency of the dosages taken by the patient, having a more consistent effect of the medicine, reduction of side effects, and reduced fluctuation in medicine levels in the body.

Finnish National Institute for Health and Welfare. https://www.thl.fi"

Thalidomide is a medicine that was developed in the 1950s as a sedative. It was used later against nausea in pregnant women, but this resulted in the birth of about 10,000 infants with deformed limbs, and sometimes with other serious problems such as blindness, deafness, and heart problems. More than half of these children died. This crisis led to more structured regulations for the development and use of medicines. Currently, thalidomide is used to treat certain cancers, and to alleviate symptoms of leprosy.

Therapeutic alternatives are medicines that are chemically different from the one prescribed (used) but which have the same clinical effect. Therapeutic alternatives are not to be confused with generics.

Therapeutic indications are a description of the disease to be treated with a medicine, and the population for which the medicine is intended. They include the specifics about the disease, and restrictions to the patient population such as age, and whether the medicine is intended for symptom relief, cure or prevention, or whether it is for diagnostic use only.

Example statements from therapeutic indications:

• Symptomatic treatment of mild to moderately severe Alzheimer™s disease.
  
• Active substance X 40 mg is indicated for the prevention of post-operative nausea and vomiting (PONV) in adults.
  

Therapeutic indications must be clearly and concisely stated within the summary of product characteristics (SmPC) document that each medicine requires in the EU.

Therapeutic vaccines introduce antigens associated with an illness to teach the body to fight against a different illness.

A time-to-event endpoint is the time taken until a pre-defined event takes place, once groups in a trial start to receive treatment or placebo. There are several kinds of time-to-event endpoints. For example, time-to-progression (TTP) is the time between randomisation of people to groups within a trial, and disease progression. Disease progression in this case must be defined, and it must be specific and measurable. For example, the growth of a particular tumour type by a minimum amount may be used as an indicator of disease progression.

Time-to-Progress

Tissue Engineered Product; Tissue Engineered Medicine

The tolerability of the medicinal product represents the degree to which adverse effects can be 'tolerated' or accepted by a patient.

Toxicity is the degree to which a chemical or biological substance can damage a living organism. It can refer to harm to specific organs, tissues or cells, or to the whole organism.

Medicines development is a step-by-step process involving the evaluation of both animal and human safety information. Non-clinical safety studies (before human testing) should be able to identify potential toxic effects that might occur under the conditions of the later clinical trial.

A specific type of pharmacokinetics that studies what the body does to a medicinal product at toxic doses. These studies assess how a substance enters the body and what happens to it in the body depending on the absorption, distribution, metabolism and excretion of the substance. Toxicokinetic measurements that determine the severity of toxicity are:

• Duration and concentration of substance at the site of entry.
  
• Rate and amount that can be absorbed.
  
• Distribution in the body and concentration at specific sites.
  
• Metabolic efficiency and nature of the metabolites.
  
• Ability of the substance or its metabolites to pass through cell membranes and come into contact with specific cell components (e.g. DNA).
  
• The amount and duration of storage of the substance (or its metabolites) in body tissues.
  
• The rate and sites of excretion.

Different dose levels used in toxicokinetics, compared to pharmacokinetics, give rise to technological changes in such factors as solubility, stability, absorption, pre-systemic clearance, protein binding, and metabolism that may be influenced by dose size, and may give rise to profound differences in the design and interpretation of studies.

Toxicology is the study of the toxic effects of substances on living organisms. It includes symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people. The main criterion regarding the toxicity of a substance is the dose, i.e. the amount of exposure to the substance.

Toxoid vaccines use an inactivated toxin of a pathogenic micro-organism to stimulate a response by the immune system.

TQTc stands for 'thorough QT/QTc study'. The test studies the effect of a compound on the electrical activity of the heart. In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QT interval represents the electrical activity associated with the contraction and relaxation of the heart chambers. A lengthened QT interval is used as an (imperfect) biomarker to assess the risk that a medicine may provoke arrhythmia.

Transcription is the process by which genetic information is transferred from DNA to RNA (this is accomplished by an enzyme called RNA polymerase). This RNA will in turn serve as a template to create a protein.

To produce proteins, genes are first transcribed™ into messenger RNA (mRNA). The transcriptome represents the whole set of mRNA molecules present in a specific cell or tissue at a certain time. By analysing the transcriptome, researchers can determine when each gene is turned on or off in a cell or tissue, how that type of cell normally functions, and how changes in the normal level of gene activity may be altered by or contribute to disease.

Transdermal meaning through the skin™ is a route of medicine administration to deliver a specific dose of medication through the skin and into the bloodstream e.g. transdermal patches or ointments. Examples include nicotine patches and scopolamine patches for motion sickness.

Transfer of blood or blood components (red and white blood cells, plasma, clotting factors, or platelets) into the bloodstream intravenously.

A transgenic organism (otherwise known as a genetically modified organism (GMO)) is an organism whose genetic material has been altered. Genetic modifications are made to produce certain traits (such as disease resistance in crops) or to cause the organism to produce specific biological products (for example, bacteria have been altered in order to produce insulin for diabetes treatment, and plants have been altered to make antibodies for blood-clotting factors).

Transgenic organisms are used in the production of medicines, in new forms of medicine such as gene therapy, and in agriculture.

Genetic modification is also a useful tool for scientists in many areas of research, including those who study the mechanisms of human and other diseases.

In the field of genetics, translation is the process by which a protein is made from messenger RNA (mRNA). During translation, an RNA sequence is read and translated into the code of amino acids, which are the building blocks of proteins.

Treatment emergent adverse events (TEAE) are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment.

In medicines development terminology, an adverse event (AE) is any undesirable event that occurs after a participant officially consents to take part in a trial (and could occur before treatment begins). An adverse event may or may not be associated with the medicine under investigation, but must be documented because it happened during the trial period.

A treatment emergent adverse event (TEAE) is an adverse event that occurs only once treatment has started.

In a clinical trial, the treatment group (as opposed to the control group) usually refers to the group of participants that receives the treatment under investigation. The treatment group is also known as the treatment arm™.

A trial arm is a group of participants that receives the same interventions, or no intervention, according to the study protocol. Many randomised trials have two arms, but some may have three or even more. This is decided before the trial begins.

Trials with several arms (multi-arm) allow more than one treatment to be tested at once, and can reduce the costs and time needed during clinical development. Multi-arm, multi-stage (MAMS) trials take this idea a step further and allow the recruitment of participants in a particular arm to be stopped partway through if that treatment is not producing satisfactory results. MAMS can also allow for new treatments to be added to the trial as they become ready for testing.

Type I Error occurs in statistical hypothesis testing when a null hypothesis, which is actually true, is incorrectly rejected. Type I errors are also known as 'false positives' they are the detection of a positive effect where no effect actually exists.

As a stark example, Type I errors could kill a patient - for instance, if a study incorrectly found that the standard of care was not better than the new treatment, and consequently the new treatment was given to patients, the results may be catastrophic.

Type I errors cannot be completely avoided, but researchers should decide on an acceptable level of risk of Type I error when designing clinical trials. A number of statistical methods can be used to control the Type I error rate. The methods to be sued in a clinical trial should be detailed in the study protocol or the statistical analysis plan for that trial.

Type II Error occurs in statistical hypothesis testing when the null hypothesis is incorrectly accepted. Type II errors are also known as 'false negatives' they are the failure to detect a positive effect where the effect does exist.

Type II errors mean that potentially valuable research goes to waste. As no positive effect is detected, research may be halted. This research may have been useful, but as no further study takes place, no harm is done to patients.

Type II errors cannot be completely avoided, but researchers should decide on an acceptable level of risk of Type II error when designing clinical trials. To reduce the risk of Type II errors to acceptable levels, the power or sample size (the number of participants in a study) can be increased.