Glossary

• Absorption
  The process by which medications reach the blood stream when administered other than intravenously.
• ACR
  American College of Rheumatology
• Approved drugs
  In the USA, the Food and Drug Administration (FDA) must approve a substance as a drug before it can be marketed. The approval process involves several steps including pre-clinical laboratory and animal studies, clinical trials for safety and efficacy, filing of a New Drug Application by the manufacturer of the drug, FDA review of the application, and FDA approval/rejection of the application.
• ATP
  Adenosine 5’-triphosphate (ATP) is a multifunctional nucleotide whose principle function is the transport of chemical energy within living cells.
• Bioequivalence
  Scientific basis on which drugs with the same active ingredient(s) are compared. To be considered bioequivalent, the bioavailability of two products must not differ significantly when the two products are given in studies at the same dosage under similar conditions.
• Blinded study
  One in which the subject, the investigator, or anyone assessing the outcome is unaware of the treatment assignment(s).
• CCM (Circadian cytokine modulators)
  Circadian cytokine modulators are drugs that modify the levels of pro-inflammatory cytokines at specific times of the day when they will have specific therapeutic effects (see Circadian Rhythm).
• Centralised Procedure
  A Community registration procedure created by Council Regulation (EEC) No. 2309/93 for the authorisation of medicinal products, for which there is a single application, a single evaluation and a single authorisation allowing direct access to the single market of the European Community. The single scientific evaluation is made by a review team that is lead by a Rapporteur and Co-rapporteur (both CHMP members) on behalf of all EU Member States and is undertaken in 210 days. The opinion of the CHMP is transmitted to the European Commission to be transformed in a further 90 days into a single marketing authorisation applicable to the whole European Union. This procedure is compulsory for medicinal products derived from biotechnology, and available at the request of companies for other innovative new products. Applications are submitted directly to the EMEA.
• Circadian Rhythm
  A circadian rhythm is a roughly-24-hour cycle in the physiological processes of living beings. In a strict sense, circadian rhythms are endogenously generated, although they can be modulated by external cues, primarily daylight.
• Clinical efficacy
  Power or capacity to produce a desired effect (i.e., appropriate pharmacological activity in a specified indication) in humans.
• Clinical endpoint
  See Endpoint.
• Clinical investigator
  A medical researcher in charge of carrying out a clinical trial’s protocol.
• Clinical pharmacology
  Science that deals with the characteristics, effects, properties, reactions, and uses of drugs, particularly their therapeutic value in humans, including their toxicology, safety, pharmacodynamics, and pharmacokinetics (ADME).
• Clinical significance
  Change in a subject’s clinical condition regarded as important. Some statistically significant changes are small and have no clinical significance.
• Clinical trial
  A clinical trial is a research study that answers specific questions about new therapies or new ways of using known treatments. Clinical trials (also called medical/clinical research and research studies) are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people. Trials occur in four phases: Phase I tests a new drug or treatment in a small group; Phase II expands the study to a larger group of people; Phase III expands the study to an even larger group of people; and Phase IV takes place after the drug or treatment has been licensed and marketed.
• Comparative study
  A study in which the investigative drug is compared against another product, either an active drug or a placebo.
• Cmax concentration
  Used in pharmacokinetics and bioequivalence to indicate maximum plasma concentration for a drug.
• Controlled trials
  In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo. This allows the comparison of efficacy and safety of the experimental drug to the control treatments.
• CRO
  Contract Research Organisation: provides services to the pharmaceutical industry and may be specialised in the conduct of clinical trials.
• DMARD
  Disease-modifying anti-rheumatic drugs.
• DMOAD
  Disease modifying osteoarthritis drugs.
• Dose
  The amount of drug administered to a patient or test subject at one time or the total quantity administered.
• Dose-ranging study
  A clinical trial in which two or more doses of an agent (such as a drug) are tested against each other to determine which dose works best and is least harmful. This is typically Phase II of the clinical development of a drug.
• Double-blind study
  A clinical trial design in which neither the participating individuals nor the study staff knows which participants are receiving the experimental drug and which are receiving a placebo (or another therapy). Double-blind trials are thought to produce objective results, since the expectations of the doctor and the participant about the experimental drug do not affect the outcome.
• Efficacy
  (Of a drug or treatment). The maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed. In the procedure mandated by the FDA, Phase II clinical trials gauge efficacy, and Phase III trials confirm it.
• EMEA (European Medicines Agency)
  The EMEA created by Council Regulation (EEC) No. 2309/93 of 22 July 1993 is based in Canary Wharf, London. The Agency is responsible for coordinating the existing scientific resources put at its disposal by the competent authorities of the Member States for the evaluation and supervision of medicinal products. (Formerly the European Agency for the Evaluation of Medicinal Products until May 2004.)
• Endpoint
  Overall outcome that the protocol is designed to evaluate. Common endpoints are improvement of patient’s clinical symptoms or measurements, such as blood pressure measurements.
• Epidemiology
  The branch of medical science that deals with the study of incidence and distribution and control of a disease in a population.
• EURO15
  Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxemburg, the Netherlands, Portugal, Spain, Sweden, United Kingdom.
• Food and Drug Administration (FDA)
  The U.S. Department of Health and Human Services agency responsible for ensuring the safety and effectiveness of all drugs, biologics, vaccines, and medical devices.
• GINA
  Global Initiative for Asthma.
• IB
  Investigator’s brochure.
• IL-6
  Interleukin-6, a cytokine involved in the processes of inflammation. In rheumatoid arthritis and PMR, IL6 is one of the cytokines released in increased amounts that appears to be responsible for the stiffness and pain experienced by patients.
• Incidence
  The extent or rate of occurrence, especially the number of new cases of a disease in a population over a period of time.
• Indication
  The specific primary disease for which the investigational product is being administered.
• Investigational New Drug (IND)
  A new drug that is used in a clinical investigation. In the USA, the FDA requires that an IND application be completed and approved before any clinical study can begin on US soil.
• International Non-proprietary Name (INN)
  When a molecule is shown to have some useful activity, it is given an international non-proprietary name (INN) based on internationally agreed rules, which is submitted for approval to a special committee at the World Health Organisation.
• Label
  Description of a drug product/device that includes: the indication,who should use it, adverse events, and instructions for use.
• Marketing Authorisation Application (MAA)
  Across all European markets, plus Australia, New Zealand, South Africa, and Israel (exceptions amongst major markets include USA, Canada, China and Japan), the Marketing Authorisation Application (MAA) is a common document used as the basis for a marketing application (an application for approval to market the product based on a full review of all quality, safety, and efficacy data, including clinical study reports. In the USA, the New Drug Application (NDA) is the MAA equivalent. In Canada, the New Drug Submission (NDS) is the MAA equivalent.
• Morning stiffness of the joints
  Morning stiffness is one of the most debilitating symptoms of rheumatoid arthritis and PMR. It is thought to be caused by a peak in proinflammatory cytokines, such as IL6, in the early hours of the morning.
• Mutual Recognition Procedure (MRP)
  A community registration procedure described by Council Directive 75/319/EEC (as amended) for the authorisation of medicinal products. Mutual Recognition Procedure: One of the routes for seeking regulatory approval in the European Union. A submission is first made to an EU Member State authority that assesses the submission, grants a national approval and prepares an assessment report. This report is circulated by the initial authority to the other (concerned) Member States who are expected to recognize this decision and grant their own national authorisation within a period of 90 days following the initial approval. The 90-day period is used to resolve any issues between Member States. If serious objections are raised then the application is referred to CHMP for arbitration leading to a binding decision.
• Multicenter trial/ Multicenter study
  Clinical trial conducted according to a single protocol, but at more than one site, and therefore, carried out by more than one investigator.
• New Drug Application (NDA)
  An NDA is the document used in the USA as the basis for a marketing application (an application for approval to market the product based on a full review of all quality, safety, and efficacy data, including clinical study reports).
• National Institute for Health and Clinical Excellence (NICE)
  NICE is the health technology assessment body in the UK providing guidance to clinicians relating to authorised treatments, devices, diagnostics and techniques. Decisions by NICE can influence reimbursement practices in other parts of the EU.
• Open study, Open-label study
  A trial in which both subjects and investigators know which product each subject is receiving; opposite of a blinded or double-blind study.
• Pharmacodynamics
  A study of a pharmacological or clinical effect of a medicine in individuals to describe the relation of the effect to dose or drug concentration. A pharmacodynamic effect can be a potentially adverse effect (anticholinergic effect with a tricyclic), a measure of activity thought to be related to clinical benefit (various measures of beta-blockade, effect on ECG intervals, inhibition of ACE or of angiotensin I or II response), a short term desired effect, often a surrogate endpoint (blood pressure, cholesterol), or the ultimate intended clinical benefit (effects on pain, depression, sudden death).
• Pharmacokinetics (PK)
  A study of how a medicine is handled by the body, usually involving measurement of blood concentrations in relation to the drug and its metabolite(s) (sometimes concentrations in urine or tissues) as a function of time. Pharmacokinetic studies are used to characterize absorption, distribution, metabolism and excretion of a drug, either in blood or in other pertinent locations. When combined with pharmacodynamic measures (a PK/PD study) it can characterize the relation of blood concentrations to the extent and timing of pharmacodynamic effects.
• Pharmacoeconomics
  Branch of economics that applies cost-benefit, cost-utility, costminimization and cost-effective analyses to compare the economics of different pharmaceutical products or to compare drug therapy to other treatments.
• Preclinical studies
  Refers to the testing of experimental drugs in a test tube or in animals; the testing that occurs before trials in humans may be carried out.
• Primary endpoint
  The primary endpoint also called “primary research question” is the single main question to be answered in a given clinical trial. The statistical planning for the trial (i.e., calculation of the number of patients needed) is based on the primary endpoint.
• Prevalence
  The percentage of population which is affected by a disease.
• Phase I trials
  Initial studies to determine the metabolism and pharmacologic actions of drugs in humans and the side effects associated with increasing doses. Phase I trials are usually conducted with healthy volunteers.
• Phase II trials
  Controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study. Several doses of the drug are studied to evaluate the most appropriate dose for the next phase of development.
• Phase III trials
  In Phase III trials, the experimental drug or treatment is given to a larger amount of patients (often more than 1,000) to confirm its effectiveness, monitor side effects, to compare it to commonly used treatments and to collect information that will allow the experimental drug or treatment to be used safely. These studies serve as a basis for marketing approval (see NDA, MAA).
• Phase IV trials
  Studies conducted after marketing approval of a drug to delineate additional information including the drug’s risks, benefits and optimal use. Additional indications or patient populations may be studied.
• Placebo
  A placebo is an inactive pill, liquid or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment’s effectiveness.
• Prednisone, low dose (LDP)
  Defined by the American College of Rheumatology as a less than 10 mg/day dosage of prednisone. In recent years, studies have shown that the maintenance dose should be below 7.5 mg or as low as possible, usually around 5 mg to control side effects.
• Proof of concept
  Proof of concept refers to the first trials in humans with the target disease for the experimental drug. Such clinical trials seek to demonstrate that a new drug is clinically effective in the treatment of the particular disease (see Phase II trials).
• Protocol
  Plan for the precise procedure to be followed in a clinical trial, including planned and actual timing of events, choice of control group, method of allocating treatments and blinding methods. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. Before a clinical study can commence, the protocol must be approved by an independent ethics committee and the responsible national regulatory authority.
• Randomization
  A method based on chance by which study participants are assigned to a treatment group. Randomization minimizes the differences among groups by theoretically equally distributing people with particular characteristics among all the trial arms.
• Randomized trial
  A study in which participants are randomly assigned to one of two or more treatment arms of a clinical trial including a placebo arm if required.
• Safety
  In clinical trials, this refers to an absence of harmful side effects resulting from use of the product and may be assessed by laboratory testing of biological samples, special tests and procedures, psychiatric evaluation, and/or physical examination of subjects.
• SmPC/ SPC
  Summary of product characteristics - In order to obtain a marketing authorization in the EU, a Summary of Product Characteristics (SPC) in accordance with Article 11 of Directive 2001/83/EC must be included in the application.
• Standard treatment
  An approved treatment currently in wide use and considered to be effective in the treatment of a specific disease or condition.
• Standards of care
  Treatment regimen or medical management based on state of the art participant care.
• Statistical significance
  The probability that an event or difference did not occur by chance alone. In clinical trials, the level of statistical significance depends on the number of participants studied and the observations made, as well as the magnitude of differences observed.
• Study endpoint
  A primary or secondary outcome used to judge the effectiveness or safety of a treatment.
• Tmax
  The time after dosing when Cmax concentration occurs.