Glossary

Randomisation is a method of allocating or selecting without using any system. It is purely random. In clinical trials, participants are generally allocated to different arms of the trial (for example, to receive the study medicine or the placebo) randomly. This is a key part of the randomised controlled trial (RCT).

Randomisation in clinical trials means that each participant has an equal chance of being in any of the arms of the trial. It is an important method to reduce the risk of bias in the outcomes of the trial.

A randomised clinical trial is one that uses randomisation when allocating people to different arms of the study. For example, in a trial comparing a new medicine with a placebo, each person has an equal chance of being allocated to the medicine or to the placebo group.

A randomised controlled trial is a trial in which people are allocated at random (by chance alone) to receive one of several clinical interventions such as a new medicine. One of these interventions is the control group, for example a placebo may be given, no intervention at all, or the current best treatment available. This study is one of the simplest and most powerful tools in clinical research.

Participants in a trial who have been randomly (by chance) assigned to one intervention arm or another of that trial. Practical considerations, such as missing data over time, may lead to some participants not being included in the final analysis.

A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population. Rare disease are commonly defined as life-threatening or chronically debilitating diseases which are of such low prevalence (fewer than 1 in 2,000 people) that special combined efforts are needed to address them. Diseases that are statistically rare, but not also life-threatening, chronically debilitating, or inadequately treated, are excluded from this definition. A disease may be considered rare in one part of the world, or in a particular group of people, but still be common in another.

Most rare diseases are genetic so that most people show symptoms from childhood (although some rare diseases only become apparent later in life).

A subtype of attenuated vaccines containing genetic material from at least two different strains of the same pathogen.

Recombinant DNA, often shortened to rDNA, is an artificially made DNA strand that is formed by the combination of two or more gene sequences from different species. Recombinant DNA is engineered specifically for a purpose. For example, recombinant DNA can be used to change the genetic makeup of a bacterial cell in order to make it produce insulin. Recombinant genes, and the recombinant proteins they produce, have become widely used in medicine. They offer a novel method of managing some health conditions, such as the use of recombinant insulin in diabetes.

A recombinant gene is one which has been changed by the addition and/or removal of some of its sequence. This can happen naturally or may be done artificially in the laboratory.

Natural recombination happens when the chromosomes in parents interact and exchange genetic material so that their offspring inherit combinations that are different to both parents.

Recombination is one of the important causes of genetic diversity between generations and individuals.

A vaccine using an antigen produced using recombinant DNA technology.

Recruitment is the process used by investigators to enrol people (participants) into a clinical study. Recruitment is based on the inclusion and exclusion criteria that are documented in the study protocol.

Recurrence is the return of a sign, symptom, or disease after some time when the signs or symptoms could not be detected. It is applied to the return of symptoms of an incurable disease. For example, the reappearance of cancer cells at the same site as the original tumour, or in another location. The risk of a recurrence depends on many factors, including the type of illness and type and/or time of treatment.

When talking about biosimilar and generic medicines, a reference medicine is the existing medicine already on the market that biosimilar and generic medicines are developed to be similar to or copies of, respectively.

Regulatory affairs is a relatively new profession which developed from the desire of governments to protect public health by controlling the safety and efficacy of products in areas including human medicines, veterinary medicines, medical devices, pesticides, agrochemicals, cosmetics and complementary medicines. The Regulatory Affairs departments of pharmaceutical companies ensure that their companies comply with the regulations and laws governing medicinal products or medical devices. They are the key interface between the company and the regulatory authorities.

In clinical research, is the economic compensation for legitimate expenses incurred by a participant taking part in a specific research project.

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.

It is the extent to which an intervention does more good than harm compared to one or more alternative interventions, when provided under ideal circumstances.

The reliability of a measurement or tool is how consistent it is. A reliable measurement or tool will give the same result when repeated at random in the same patient or sample. In clinical trials, reliability is an important consideration in the choice of primary outcome measures (such as an improvement in certain symptoms). The reliability of measures should be formally assessed during the design of clinical trials.

Reliability is different to validity, which is the extent to which a measurement measures what it is supposed to.

Remission is a temporary end (or significant reduction) in the signs and symptoms of an incurable disease. A disease is said to be incurable if there is always a chance that the patient will become ill again, no matter how long they have been in remission.

In cancer, the term 'in remission' is often used. Partial remission means the cancer is still detectable, but tumours or smaller, or - as in leukaemia - when there is less cancer throughout the body. Complete remission means that cancer cannot be detected using tests or scans - but because there is always the chance that cancer cells are still present, patients are said to be in remission rather than cured.

Reproductive toxicology investigates the negative effects of a medicine that interfere with normal sexual function and fertility in adult males and females. Such negative effects include adverse effects on sexual function and fertility in adult males and females, as well as developmental toxicity in the offspring.

Medicine repurposing is taking an existing medicine and seeing whether it can be used as an effective treatment for another condition.

Research Ethics Committee

Respect for persons is the concept that all people have the right to exercise their full autonomy. In research, this principle seeks to ensure that a participant's wishes are respected, even if they differ from those of the researcher.

A response variable is a measured outcome within a trial which can be influenced by other factors. For example, a trial might test if a new medicine is effective at reducing a certain heart disease symptom. In this case, the reduction in this symptom will be measured and this measurement will be a response variable (also known as a dependent variable). In contrast, the new medicine is known as the independent variable, which is tested to determine if it has caused a change in the dependent variable.

A retrospective case control study is one that uses existing data to compare two groups. For example, people who have developed a disease might be compared with a group of people who have not. The researcher will look at whether there is any difference in the two groups in their previous exposure to possible risk factors. This type of study is useful when studying risk factors for rare diseases, and is often used to create new hypotheses which can then be tested.

For example, there are fewer than 300 confirmed cases of new variant Creutzfeldt-Jakob disease (CJD), a degenerative, invariably fatal brain disorder. A cohort study that follows healthy people over time to see what risk factors lead to developing the disease would need to recruit a huge number of people in order for just one to develop symptoms (around 200,000). It would also take a very long time, because the period between infection and showing symptoms is thought to be between 10 and 30 years. A much better approach in this case would be to carry out a case control study, starting with people who already have a diagnosis of new variant CJD, and comparing their past exposure to possible risk factors with a group of people who do not have the disease.

The quality of being extremely thorough and careful. Scientific rigour is judged by how narrow, concise, and objective the design and analysis techniques of a research project are and how scrupulously the rules have been adhered to and applied to all decisions.

Risk is the probability of harm or injury occurring as a result of using a treatment in clinical practice or as part of a research study. The harm or injury may be physical, but can also be psychological, social, or economic. Risks may include experiencing side effects of the treatment, or taking a medication that is not as effective as the standard treatment (during a trial). In a trial, a new treatment may have side effects or risks that researchers do not expect. This is more likely in the early stages of clinical trials.

No clinical trial is risk free. Participants should be aware of both the benefits and the risks before they make a decision about whether or not to take part (see informed consent).

Risk assessment is one of the three pillars of risk management (together with safety specifications and the risk minimisation plan). It contains both routine and additional pharmacovigilance activities to characterise the safety profile of the medicinal product including what is known and not known. It does NOT include actions intended to reduce, prevent or mitigate risks.

Risk Evaluation and Management Strategy

A Risk Evaluation and Mitigation Strategy (REMS) is used in the United States, and is similar to the Risk Management Plan (RMP) in the EU.

A risk factor is a characteristic, condition or habit that increases a person™s chances to develop a particular disease or injury, for example, physical inactivity may, over time, contribute to weight gain, high blood pressure and high cholesterol levels. Risk factors include:

• behavioural (poor diet, smoking, alcohol consumption),
  
• biomedical (high weight, high blood pressure),
  
• environmental (social, economic, cultural),
  
• genetic (chromosomal abnormalities),
  
• demographic (age, gender, ethnicity).
  

Risk management is a process for identifying, assessing, prioritising, and taking the appropriate action to mitigate a risk. The objective of risk management is to continuously try to ensure that the benefits of a particular medicinal product (or a series of medicinal products) exceed the risks by the greatest achievable margin for the individual patient and for the target population as a whole.

A risk management plan provides a detailed description of the activities and interventions in place to prevent or minimise risks of using a medicine. Risk management plans outline how more knowledge about the safety and efficacy of a medicine will be generated, what are the risk factors for developing side effects, and how risk-minimisation measures will be monitored.

Risk management plans must be submitted by companies at the same time they apply for marketing authorisation in the European Union, although they must be continually updated and revised throughout the medicine™s lifetime. Risk management plans can also be requested by the EMA at other times, or whenever there is concern that a risk may be affecting the balance of benefits and risks for a particular medicine.

These are public health interventions intended to prevent or reduce the occurrence of adverse reactions associated with the exposure to a medicine, or to reduce their severity or impact on the patient should adverse reactions occur. Risk minimisation measures aim to optimise the safe and effective use of a medicinal product throughout its life cycle. Planning and implementing risk minimisation measures and assessing their effectiveness are key elements of risk management. Routine risk minimisation involves the use of the tools such as the Summary of Product Characteristics (SmPC), the package leaflet, the labelling, the pack size and design, and the legal (prescription) status of the product.

The majority of safety concerns may be adequately addressed by routine risk minimisation measures, but for some risks however, additional risk minimisation measures are necessary to manage risk and/or improve the benefit-risk balance of a medicinal product.

Routine pharmacovigilance activities are generally conducted for any medicine in development, where there are no special safety concerns. Activities might include safety evaluation incorporated into clinical trials, and the monitoring and reporting of adverse events. These activities are specified in European law on pharmacovigilance.