Randomized controlled trial Health Dictionary

A controlled research study of the safety and effectiveness of drugs, devices or techniques that occurs in four phases, starting with the enrolment of a small number of people, to the later stages in which thousands of people are involved prior to approval by the licensing authorities (for example, the Food and Drug Administration).... clinical trial

A scienti?c study in which di?erent patients receive a di?erent drug, the same drug at a different dose, or a placebo – with neither the investigators assessing the outcome nor the subjects being treated knowing which of these the latter are receiving. The aim is to remove any hint of bias due to the investigators’ or patients’ preferences or preconceptions. The results are analysed after all the data have been collected and the code has been broken. Trials should have a separate supervising committee, the members of which know the code but do not take part in the study. Their job is to check the results at intervals so they can stop the trial if one arm of treatment is clearly better than another. Otherwise, it would be unethical to continue. (See INTERVENTION STUDY.)... double blind trial

One of a number of drugs subject to restricted use because of their potential for abuse. They include

opiates such as cocaine and morphine, amfetamine drugs, and barbiturate drugs. controlled trial A method of testing the effectiveness of new treatments or comparing different treatments. In a typical controlled drug trial, 2 comparable groups of patients suffering from the same illness are given courses of apparently identical treatment. However, only one group receives the new treatment; the second control group is given a placebo. Alternatively, the control group may be given an established drug that is already known to be effective. After a predetermined period, the 2 groups are assessed medically. Controlled trials must be conducted “blind’’ (the patients do not know which treatment they are receiving). In a “double-blind’’ trial, neither the patients nor the doctors who assess them know who is receiving which treatment. contusion Bruising to the skin and underlying tissues from an injury. convalescence The recovery period following an illness or surgery during which the patient regains strength before returning to normal activities.... controlled drug

(See EVIDENCE-BASED MEDICINE.) Clinical trials aim to evaluate the relative effects of di?erent health-care interventions. They are based on the idea that there must a fair comparison of the alternatives in order to know which is better. Threats to a fair comparison include the play of chance and bias, both of which can cause people to draw the wrong conclusions about how e?ective a treatment or procedure is.

An appreciation of the need to account for chance and bias has led to development of methods where new treatments are compared to either a PLACEBO or to the standard treatment (or both) in a controlled, randomised clinical trial. ‘Controlled’ means that there is a comparison group of patients not receiving the test intervention, and ‘randomised’ implies that patients have been assigned to one or other treatment group entirely by chance and not because of their doctor’s preference. If possible, trials are ‘double-blind’ – that is, neither the patient nor the investigator knows who is receiving which intervention until after the trial is over. All such trials must follow proper ethical standards with the procedure fully explained to patients and their consent obtained.

The conduct, e?ectiveness and duplication of clinical trials have long been subjects of debate. Apart from occasional discoveries of deliberately fraudulent research (see RESEARCH FRAUD AND MISCONDUCT), the structure of some trials are unsatisfactory, statistical analyses are sometimes disputed and major problems have been the – usually unwitting – duplication of trials and non-publication of some trials, restricting access to their ?ndings. Duplication occurs because no formal international mechanism exists to enable research workers to discover whether a clinical trial they are planning is already underway elsewhere or has been completed but never published, perhaps because the results were negative, or no journal was willing to publish it, or the authors or funding authorities decided not to submit it for publication.

In the mid 1980s a proposal was made for an international register of clinical trials. In 1991 the NHS launched a research and development initiative and, liaising with the COCHRANE COLLABORATION, set out to collect systematically data from published randomised clinical trials. In 1994 the NHS set up a Centre for Reviews and Dissemination which, among other responsibilities, maintains a database of research reviews to provide NHS sta? with relevant information.

These e?orts are hampered by availability of information about trials in progress and unpublished completed trials. With a view to improving accessibility of relevant information, the publishers of Current Science, in 1998, launched an online metaregister of ongoing randomised controlled trials.

Subsequently, in October 1999, the editors of the British Medical Journal and the Lancet argued that the case for an international register of all clinical trials prior to their launch was unanswerable. ‘The public’, they said, ‘has the right to know what research is being funded. Researchers and research funders don’t want to waste resources repeating trials already underway.’ Given the widening recognition of the importance to patients and doctors of the practice of EVIDENCE-BASED MEDICINE, the easy availability of information on planned, ongoing and completed clinical trials is vital. The register was ?nally set up in 2005.... clinical trials

A trial in which each of the groups involved will receive each of the treatments, but in a randomized order: that is, they will start in one arm of the trial, but will deliberately ‘cross over’ to the other arm(s) in turn.... crossover trial

A technique whereby a patient can deliver an analgesic substance (see ANALGESICS) in amounts related to the extent of the PAIN that he or she is suffering. For example, to combat post-operative pain, some hospitals use devices which allow patients to give themselves small intravenous amounts of opiates when they are needed. Pain is more e?ectively controlled if it is not allowed to reach a high level, a situation which tends to happen when patients receive analgesics only on ward drug rounds or when they ask the nursing sta? for them.... patient-controlled analgesia

A method of comparing the results between two or more groups of patients intentionally subjected to di?erent methods of treatment – or sometimes of prevention. Those subjects entering the trial have to give their informed permission. They are allocated to their respective groups using random numbers, with one group (controls) receiving no active treatment, instead receiving either PLACEBO or a traditional treatment. Preferably, neither the subject nor the assessor should know which ‘regimen’ is allocated to which subject: this is known as a double-blind trial.... randomised controlled trial

See “blinding”.... single-blind trial

See “blinding”.... triple-blind trial

A form of controlled trial that evaluates the effectiveness of a drug, or other treatment, in which subjects are randomly allocated to one of the study groups.

This random allocation means individuals are equally likely to be selected for the particular treatment being investigated or for the control group of the trial.... randomized controlled trials

In the United Kingdom, controlled drugs are those preparations referred to under the Misuse of Drugs Act 1971. The Act prohibits activities related to the manufacture, supply and possession of these drugs, and they are classi?ed into three groups which determine the penalties for o?ences involving their misuse. For example, class A includes COCAINE, DIAMORPHINE, MORPHINE, LSD (see LYSERGIC ACID DIETHYLAMIDE and PETHIDINE HYDROCHLORIDE. Class B includes AMPHETAMINES, BARBITURATES and CODEINE. Class C includes drugs related to amphetamines such as diethylpropion and chlorphentermine, meprobamate and most BENZODIAZEPINES and CANNABIS.

The Misuse of Drugs Regulations 1985 de?ne the classes of person authorised to supply and possess controlled drugs, and lay down the conditions under which these activities may be carried out. In the Regulations, drugs are divided into ?ve schedules specifying the requirements for supply, possession, prescribing and record-keeping. Schedule I contains drugs which are not used as medicines. Schedules II and III contain drugs which are subject to the prescription requirements of the Act (see below). They are distinguished in the British National Formulary (BNF) by the symbol CD and they include morphine, diamorphine (heroin), other opioid analgesics, barbiturates, amphetamines, cocaine and diethylpropion. Schedules IV and V contain drugs such as the benzodiazepines which are subject to minimal control. A full list of the drugs in each schedule can be found in the BNF.

Prescriptions for drugs in schedules II and III must be signed and dated by the prescriber, who must give his or her address. The prescription must be in the prescriber’s own handwriting and provide the name and address of the patient and the total quantity of the preparation in both words and ?gures. The pharmacist is not allowed to dispense a controlled drug unless all the information required by law is given on the prescription.

Until 1997 the Misuse of Drugs (Noti?cation and Supply of Addicts) Regulations 1973 governed the noti?cation of addicts. This was required in respect of the following commonly used drugs: cocaine, dextromoramide, diamorphine, dipipanone, hydrocodeine, hydromorphone, levorphanol, methadone, morphine, opium, oxycodone, pethidine, phenazocine and piritranide.

In 1997 the Misuse of Drugs (Supply to Addicts) Regulations 1997 revoked the 1973 requirement for noti?cation. Doctors are now expected to report (on a standard form) cases of drug misuse to their local Drug Misuse Database (DMD). Noti?cation by the doctor should be made when a patient ?rst presents with a drug problem or when he or she visits again after a gap of six months or more. All types of misuse should be reported: this includes opioids, benzodiazepines and central nervous system stimulants. The data in the DMD are anonymised, which means that doctors cannot check on possible multiple prescribing for drug addicts.

The 1997 Regulations restrict the prescribing of diamorphine (heroin), Diconal® (a morphine-based drug) or cocaine to medical practitioners holding a special licence issued by the Home Secretary.

Fuller details about the prescription of controlled drugs are in the British National Formulary, updated twice a year, and available on the Internet (see www.bnf.org).... controlled drugs

A test on human volunteers of the effectiveness and safety of a drug. A trial can also involve systematic comparison of alternative forms of medical or surgical treatment for a particular disorder. Patients involved in clinical trials have to give their consent, and the trials are approved and supervised by an ethics committee.... trial, clinical

see intervention study.... blind trial

(COS) see superovulation.... controlled ovarian stimulation

see intervention study.... controlled trial

see intervention study.... cross-over trial