The EUPATI Patient Academy website also contains a useful glossary of terms, which informs many of the definitions provided below, see https://www.eupati.eu/glossary/
Below we have provided explanations of some terms commonly encountered in our reports and in discussions about Health Technology Assessment.
The option to modify the design of an ongoing clinical trial is becoming increasingly common and is known as adaptive design. Data are evaluated before the trial is finished. This is known as interim analysis and might be carried out at several time points. Depending on the circumstances, this may lead to changes to the trial such as stopping one treatment arm or changing the number of participants in a group. The planned number of participants might be reduced if the interim analysis shows that a smaller sample size will still allow a valid result to be obtained. Alternatively, the sample size might be increased if that will allow a valid or reliable result to be obtained within a more acceptable period of time. Adaptive designs can save time and resources, and can reduce the exposure of study participants to the inferior treatment. Interim analyses and any anticipated changes to a trial should be described and justified in the study protocol to reduce the risk of bias.
Advanced therapy medicinal products (ATMP) are new medical products for human use based on genes (gene therapy), cells (cell therapy), or tissues (tissue engineering). They have huge potential and open the way for new treatments of a number of diseases or injuries, such as skin in burns victims, Alzheimer’s, cancer, or muscular dystrophy. CAR-T cells are an example of an ATMP.
Any untoward (not favourable) medical occurrence in a patient, or clinical trial participant receiving a medicine, and which does not necessarily have a causal relationship with this treatment. Adverse events can therefore be: any unfavourable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicine, whether or not considered related to the medicine.
An adverse reaction is any adverse event or experience related to a medicine for which a reasonable causal relationship with the medicine’s use is suspected. This is synonymous with adverse drug reaction (ADR).
In clinical research this refers to any of the treatment groups in a randomised trial. Many randomised trials have two ‘arms’ or groups, but some may have three or even more.
Best supportive care (BSC) is the treatment of choice when a cure is not achievable with existing treatments. It involves the management of disease-related symptoms.
Bioequivalence means that the identical active pharmaceutical ingredient of two medicines have the same rate and extent of absorption. The medicines produce the same effect at the required target. For example, a receptor in the brain can be a target for a medicine. Bioequivalence is often used to compare an original and generic version of a medicine, or two different formulations (for instance, tablet or oral suspension) of the same medicine.
A biologic medicine is any medicinal product manufactured in, extracted from, or synthesised in part from biological sources. Biologics can be composed of sugars, proteins, or nucleic acids; they may be complex combinations of sugars, proteins, or nucleic acids; or they may be living cells or tissues. Some of the oldest forms of biologics are extracted from the bodies of animals and other humans – such as whole blood and blood components. Some traditional biologics are now produced in the laboratory rather than from living tissue – for example, tissue for transplants, antibodies for passive immunisation, and insulation. Different from chemically synthesized pharmaceuticals, they include vaccines, blood or blood components, gene therapies, and living cells used in cell therapy.
A biosimilar medicine is a biological medicine which is similar to another biological medicine that has already been authorised for use. Biosimilar medicines are commonly known as biological generic medicines. The existing biological medicine is known as the ‘reference medicinal product’. Biosimilars may only be marketed after the patent for the reference medicinal product has expired, although they may be developed earlier. A biosimilar medicine and its reference medicinal product are expected to have the same safety and efficacy profile. Biosimilar medicines are developed to have the same mechanism of action, and to treat the same diseases as the reference medicinal product. Standards of the EU Good Manufacturing Practice (GMP) apply to the manufacture of biosimilar medicines in the same way as for any other biological medicinal product. Biosimilar medicines may offer a less costly alternative to existing biological medicinal products that have lost their exclusivity rights.
Blinding is a way of making sure that the people involved in a research study, such as the participants in clinical trials, do not know which trial arm they are assigned to. For example, in a trial with one treatment arm and one placebo arm, blinding means that the participants do not know if they are receiving the treatment or the placebo. Blinding is used to remove bias that can be caused intentionally or unintentionally if participants or the research team are aware of which trial group participants are in. Sometimes the term ‘single-blind’ is used to describe studies where the participants are unaware of which arm they are in, but the research team does know. In a double-blind trial, both the research team and participants do not know which participant is assigned to which arm. A blind trial is the opposite of an open or open-label trial.
Costs within a particular timeframe and related to a particular healthcare budget rather than a country’s overall budget. This assumes robust data on epidemiology and treatment patterns, along with assumptions of uptake and displacement of current treatments.
As a component of a dossier submitted for HTA assessment, clinical effectiveness is a measure of how well a particular treatment works in the practice of medicine. It depends on the application of the best knowledge derived from research, clinical experience, and patient preferences.
In medicine, clinical efficacy indicates a positive therapeutic effect. If efficacy is established, an intervention is likely to be at least as good as other available interventions to which it will have been compared. When talking in terms of efficacy versus effectiveness, efficacy measures how well a treatment works in clinical trials or laboratory studies. Effectiveness, on the other hand, relates to how well a treatment works in the practice of medicine.
Method of providing an unlicensed medicine prior to final approval by a regulatory (competent) authority for use in humans. This procedure is used with very sick individuals who have no other treatment options. Often, case-by-case approval must be obtained for compassionate use of a medicine or therapy.
In the context of pharmacoeconomics, cost effectiveness is studied by looking at the results of different interventions by measuring a single outcome, usually in ‘natural’ units (for example, life-years gained, deaths avoided, heart attacks avoided, or cases detected). Alternative interventions are then compared in terms of cost per (natural) unit of effectiveness in order to assess how it provides value for money. This economic evaluation helps decision-makers to determine where to allocate limited healthcare resources. Cost effectiveness, however, is only one of a number of criteria that should be used to determine whether or not interventions are made available. Other issues, such as equity, needs, and priorities should also be part of the decision-making process.
A European Public Assessment Report (EPAR) is an assessment produced for all medicines where marketing authorisation is sought through the centralised procedure at the European Medicines Agency (EMA). It is a series of documents, and includes: a lay summary, details about the marketing authorisation holder, product information (such as the package leaflet and summary of product characteristics), details about the assessment carried out at EMA. EPARs are published on the EMA’s website once the European Commission has issued a decision regarding a marketing authorisation.
The European network for Health Technology Assessment was established to create a network for HTA across Europe, developing a framework (HTA Core Model®) by which a technology (for example a new medicine) can be assessed. It facilitates efficient use of resources, creating a sustainable system of knowledge, and promoting good practice in HTA methods and processes. The network connects public national HTA bodies, research institutions and health ministries, to exchange information and to support policy decisions by member states.
Expanded Access Program
An Expanded Access Program (EAP) is a method of providing access to a licensed but not yet reimbursed medicine, where the manufacturer provides the treatment free of charge to a group of patients, usually with specific clinical characteristics and usually for a defined and limited period of time.
A generic medicine is a medicine that is developed to be the same as a medicine that has already been authorised, called the ‘reference medicine’. A generic medicine contains the same active substances as the reference medicine, and it is used at the same doses to treat the same diseases. However, a generic medicine’s inactive ingredients, name, appearance, and packaging can be different from the reference medicine’s. Generic medicines are manufactured according to the same quality standards as all other medicines. A company can only develop a generic medicine for marketing once the period of exclusivity on the reference medicine has expired. This is usually 10 years from the date of first authorisation. Each medicine has an approved name called the generic name. A group of medicines that have similar actions often have similar-sounding generic names. For example, phenoxymethylpenicillin, ampicillin, amoxicillin, and flucloxacillin are in the same group of antibiotics.
Health technology assessment aims to inform decision making by health care policy makers. It is a systematic process that considers health technologies (such as medicines) and can involve a review of: clinical evidence compared to existing models of care, cost effectiveness, social and ethical impacts on the health care system and the lives of patients. The process advises whether or not a health technology should be used, and if so, how it is best used and which patients are most likely to benefit from it. Assessments vary, but most look at the health benefits and risks of using the technology. They can also look at costs and any other wider impacts that the technology may have on a population or on a society. They can also look at the relationship between costs and benefits and risks, and make determinations about value for money.
Health-Related Quality of Life considers many different aspects related to a person’s perception of quality of life affected by health status. These include physical, psychological, functional, and social aspects.
Life years (LY) gained is a measure in health economics. It expresses the additional number of years of life that a person lives as a result of receiving a treatment.
A patient-reported outcome (PRO) is a measure of the experience or view of a participant in a clinical study. It is not a clinical measure, or an assessment made by anyone else involved in the study. PROs are commonly collected by asking patients to fill in questionnaires, or by interviewing patients. Questionnaires or interview guides used as part of clinical studies should undergo extensive testing to ensure they are reliable and valid. PROs can be used to assess, for example, symptoms as experienced by the patient, disability, quality of life, and other health perceptions. There are many published PRO questionnaires dealing with aspects of quality of life. some have been developed for specific conditions or treatments. Some are designed to be general, such as the ‘EuroQoL’ or ‘EQ-5D’, which has been translated into many languages and used extensively in clinical trials. PRO is often used interchangeably with the term patient-reported outcome measure (PROM).
The quality-adjusted life year (QALY) is a measure in health economics. It expresses the additional number of years which a person lives as a result of receiving a treatment, and takes into account the quality of life of those years. It does this by measuring how important various factors are to patients, such as symptoms, pain, and psychological health. The calculation of QALYs is a common approach used by health technology assessment (HTA) bodies, which advise about the ‘usefulness’ of treatments and, in some countries, about whether treatments should be funded by (for example) government health departments.
Quality of Life (QoL) is a measure in health economics. It expresses the effect of factors such as symptoms, pain, psychological health, and wellbeing on people’s lives. Health-related quality of life (HRQoL) measures are used to calculate the likely impact of treatments on the lives of patients.
It can be defined as the extent to which an intervention does more good than harm compared to one or more alternative interventions for achieving the desired results, when provided under the usual circumstances of health care practice.
Treatment that is accepted by medical experts as a proper treatment for a certain type of disease and that is widely used by healthcare professionals. Also called best practice, standard medical care, and standard therapy.
In order to market a medicine, a submission (an application) must be made to the relevant regulatory authority, for example the European Medicines Agency (EMA). Submissions provide comprehensive information about the medicine, its formulation, the trials it has undergone, its intended use, and its risks and benefits.
The Summary of Product Characteristics (SmPC) is a document approved as part of the marketing authorisation of each medicine. It is aimed at healthcare professionals and includes information such as: How to use the medicine; What the medicine should be used to treat (therapeutic indications); Dose; Method of administration; In what conditions the medicine should not be used (contraindications); Special warnings; The medicine’s mechanism of action; and Any undesirable effects. The SmPC contains more detail than the Package Leaflet (PL). See www.ipha.ie or www.hpra.ie for access to Irish SmPCs.
The endpoint in a clinical trial is an event such as the occurrence of a disease, or symptom, or a particular laboratory result. Once someone reaches the endpoint, they are generally excluded from further research in the trial. A surrogate endpoint (or marker) is a measure which in itself is not the outcome that the study treatment aims to elicit. For example, blood pressure is used as a surrogate endpoint in trials because it is a risk factor for heart attacks and strokes – even though in itself blood pressure might not be important for patients. Surrogate endpoints are useful if it would take a very long time for clinical endpoints to appear. Surrogate endpoints must be proven to be valid markers of clinical endpoints when they are used in clinical trials.
Utility, or usefulness, is the (perceived) ability of something to satisfy needs or wants. In health economics, utilities measure the strength of patient preferences. For example, how important various factors are to patients, such as symptoms, pain, and psychological health. The impact of new treatments on those factors, and therefore on quality of life (QoL), can then be calculated. This is a common approach used by health technology assessment (HTA) bodies, which advise on whether treatments should be funded by (for example) government health departments.