The guidelines manual

Abstract

Summary of a study, which may be published alone or as an introduction to a full scientific paper.

AGREE (appraisal of guidelines research and evaluation)

An international collaboration of researchers and policy makers whose aim is to improve the quality and effectiveness of clinical practice guidelines. The AGREE II instrument, developed by the group, is designed to assess the quality of clinical guidelines.

Algorithm (in guidelines)

A flow chart of the clinical decision pathway described in the guideline, where decision points are represented by boxes, linked with arrows.

Allocation concealment

The process used to prevent advance knowledge of group assignment in a randomised controlled trial. The allocation process should be uninfluenced by the person making the allocation, by being administered by someone who is not responsible for recruiting participants.

Applicability

The degree to which the results of an observation, study or review are likely to hold true in a particular clinical practice setting.

Arm (of a clinical study)

Subsection of participants within a study who receive one particular intervention (for example, the placebo arm).

Association

Statistical relationship between two or more events, characteristics or other variables. The relationship may or may not be causal.

Audit support

The provision of ready-to-use criteria, including exceptions, definitions and data source suggestions, in order to make the process of developing clinical audit projects easier. NICE provides audit support for all clinical guidelines.

Audit trail

Records of action to assess practice against standards. Also a record of actions (for example, changes to a draft guideline) so that the reasons are apparent to a third party.

Baseline

The initial set of measurements at the beginning of a study (after the period before the study starts when no treatment is given [the 'run-in' period], where applicable), with which subsequent results are compared.

Bias

Systematic (as opposed to random) deviation of the results of a study from the 'true' results, which is caused by the way the study is designed or conducted.

'Burden of disease' study

A study investigating the overall impact of diseases and injuries at the individual level, at the societal level or on the economic costs of diseases.

Centre for Clinical Practice (CCP)

The department at NICE that manages the development of clinical guidelines. It commissions one of the National Collaborating Centres or the Internal Clinical Guidelines Programme to develop each clinical guideline.

Class (of drugs)

A group of drugs with the same or similar mechanism of action; these drugs may or may not have the same basic chemical structure. However, there may be differences between drugs within a class (for example, in side-effect profile).

Clinical Adviser

A member of the Guideline Development Group who works closely with the National Collaborating Centre or Internal Clinical Guidelines Programme team to provide expert topic-specific support. Responsibilities of the Clinical Adviser may include working with the systematic reviewer on the detail of the evidence reviews or checking clinical and technical terminology in the full guideline.

Clinical effectiveness

The extent to which an intervention produces an overall health benefit in routine clinical practice.

Cochrane Review

A systematic review of the evidence from randomised controlled trials relating to a particular health problem or healthcare intervention, produced by the Cochrane Collaboration. Available electronically as part of the Cochrane Library.

Code of conduct (of the GDG)

A code of conduct developed by NICE for Guideline Development Group (GDG) members and other people who attend GDG meetings. This code sets out the responsibilities of NICE and the GDG, and the principles of transparency and confidentiality.

Comparability

Similarity of groups in terms of characteristics likely to affect study results (such as health status or age).

Comparator

The standard intervention against which an intervention is compared in a study. The comparator can be no intervention (for example, best supportive care).

Complementary therapy

Practices not generally recognised by the medical community as standard or conventional medical approaches, which are used to enhance or complement standard treatments.

Conceptual framework

A theoretical structure of assumptions, principles and rules that holds together the ideas comprising a broad concept.

Conceptual model

A descriptive model of a system based on qualitative assumptions about its elements, their interrelationships, and system boundaries.

Conflict of interest

An interest that might conflict, or be perceived to conflict, with duties and responsibilities to an organisation.

Confounding

In a study, confounding occurs when the effect of an intervention on an outcome is distorted as a result of an association between the population or intervention or outcome and another factor (the 'confounding variable' or 'confounder') that can influence the outcome independently of the intervention under investigation.

For example, a study of heart disease may look at a group of people that exercises regularly and a group that does not exercise. If the ages of the people in the two groups are different, then any difference in heart disease rates between the two groups could be because of age rather than exercise. Therefore age is a confounding factor.

Consensus methods

Techniques that aim to reach an agreement on a particular issue. Formal consensus methods include Delphi and nominal group techniques, and consensus development conferences. In the development of clinical guidelines, consensus methods may be used where there is a lack of strong research evidence on a particular topic.

Control

An explicitly defined comparator against which the effects of an intervention are compared in a clinical study.

'Cost of illness' study

A study that measures the economic burden of a disease or diseases and estimates the maximum amount that could potentially be saved or gained if a disease was eradicated.

Decision-analytic model (and/or technique)

A model of how decisions are or should be made. This could be one of several models or techniques used to help people to make better decisions (for example, when considering the trade-off between costs, benefits and harms of diagnostic tests or interventions).

Decision tree

A method for helping people to make better decisions in situations of uncertainty. It illustrates the decision as a succession of possible actions and outcomes. It consists of the probabilities, costs and health consequences associated with each option. The overall effectiveness or cost-effectiveness of different actions can then be compared.

Delphi technique

A technique used for reaching agreement on a particular issue, without the participants meeting or interacting directly. It involves sending participants a series of questionnaires asking them to record their views. After the first questionnaire, participants are asked to give further views in the light of the group feedback. The judgements of the participants may be statistically aggregated.

Discounting

Costs and perhaps benefits incurred today have a higher value than costs and benefits occurring in the future. Discounting health benefits reflects individual preference for benefits to be experienced in the present rather than the future. Discounting costs reflects individual preference for costs to be experienced in the future rather than the present.

Discrete event simulation

A method that can be used to model the course of a disease (for example, to predict disease progression for the purposes of cost-effectiveness analysis).

Dosage

The prescribed amount of a drug to be taken, including the size and timing of the doses.

Effect (as in treatment effect, effect size)

The observed association between interventions and outcomes, or a statistic to summarise the strength of the observed association.

Equity

Fair distribution of resources or benefits.

Evidence

Information on which a decision or guidance is based. Evidence is obtained from a range of sources, including randomised controlled trials, observational studies and expert opinion (of healthcare and other professionals and/or patients).

Evidence profile

A table summarising, for each important clinical outcome, the quality of the evidence and the outcome data (part of the GRADE approach).

Exceptional update

Review of existing guidance carried out sooner than originally planned because new data have become available.

Exclusion criteria (clinical study)

Criteria that define who is not eligible to participate in a clinical study.

Exclusion criteria (literature review)

Explicit standards used to decide which studies should be excluded from consideration as potential sources of evidence.

Expert consensus

See 'Consensus methods'.

Extrapolation

In data analysis, predicting the value of a parameter outside the range of observed values.

Facilitator

A person whose role is to promote the effective functioning of a group.

Follow-up

Observation over a period of time of a person, group or initially defined population whose characteristics have been assessed in order to observe changes in health status or health-related variables.

Free-text terms

Data entered into a field without any formal or predefined structure other than the normal use of grammar and punctuation.

Generalisability

The extent to which the results of a study based on measurement in a particular patient population and/or a specific context hold true for another population and/or in a different context.

Generic name

The general non-proprietary name of a drug or device.

GRADE
(Grading of recommendations assessment, development and evaluation)

A systematic and explicit approach to grading the quality of evidence and the strength of recommendations.

Grading (of evidence)

A code given to a study or other evidence, indicating its quality.

Guideline consultation table

A table of all the comments received by NICE during guideline consultation. The Guideline Development Group considers the comments received, and the National Collaborating Centre or Internal Clinical Guidelines Programme then responds to the comments in the table.

Guideline Development Group (GDG)

A group of healthcare and other professionals, patients and carers, and technical staff who develop the recommendations for a clinical guideline. The guideline developer (National Collaborating Centre or Internal Clinical Guidelines Programme) responsible for developing a guideline recruits a GDG to work on the guideline. The guideline developer reviews the evidence and support the GDG. The GDG writes draft guidance, and then revises it after a consultation with stakeholders.

Handsearch/ handsearching

The planned searching of a journal page-by-page (by hand) to identify reports of studies to answer review questions.

Harms

Adverse effects of an intervention.

Healthcare professional member

A member of the Guideline Development Group with appropriate knowledge and skills to represent the perspective(s) of the healthcare professionals (and other professionals where relevant) involved in the care of patients affected by the guideline topic.

Health economist

A member of the Guideline Development Group with skills in economic analysis whose role is to advise on economic aspects of the clinical issues or questions, review economic literature, prioritise topics for further analysis and carry out additional cost-effectiveness analyses.

Health inequalities

The gap in health status and in access to health services between different social classes and ethnic groups, and between populations in different geographical areas. For more information, see the Department of Health website.

Health-related quality of life

A combination of a person's physical, mental and social well-being; not merely the absence of disease.

Health Technology Assessment report

Independent research information about the effectiveness, costs and broader impact of healthcare treatments and tests for those who plan, provide or receive care in the NHS. The Health Technology Assessment (HTA) programme is part of the National Institute for Health Research (NIHR).

Hypothesis

An unproven theory that can be tested by research.

Implementation

The process of putting guidance into practice.

Inclusion criteria (literature review)

Explicit criteria used to decide which studies should be considered as potential sources of evidence.

In confidence material

Information (for example, the findings of a research project) defined as 'confidential' because its public disclosure could have an impact on the commercial interests of a particular company ('commercial in confidence') or the academic interests of a research or professional organisation ('academic in confidence').

Incremental analysis

The analysis of additional costs and additional clinical outcomes with different interventions.

Incremental cost-effectiveness ratio (ICER)

The difference in the mean costs in the population of interest divided by the differences in the mean outcomes in the population of interest.

Index

In epidemiology and related sciences, this word usually means a rating scale (for example, a set of numbers derived from a series of observations of specified variables). Examples include the various health status indices, and scoring systems for severity or stage of cancer.

Index test

The test being evaluated in a study to compare it with the best available test (the reference standard).

Indication (specific)

The defined use of a technology as licensed by the Medicines and Healthcare products Regulatory Agency (MHRA).

Indirect treatment comparison

An analysis that compares interventions that have not been compared directly within a head-to-head, randomised trial.

Information specialists

Specialists, based either at NICE or within a National Collaborating Centre, with expertise in information retrieval who provide information to support the decision-making groups.

Internal validity

The degree to which the design and conduct of a study are likely to have prevented bias. (Definition from The Cochrane Collaboration website.)

Key clinical issues

The most important aspects of care that a clinical guideline will cover in order to ensure that it focuses on areas in which the NHS most needs advice. Key clinical issues relate to the effectiveness and cost effectiveness of interventions or tests that are being considered for a given population.

Licence

See 'Marketing authorisation'.

Likelihood ratio

The ratio of the probability that a person with a condition has a specified test result to the probability that a person without the condition has the same specified test result.

Marketing authorisation

An authorisation that covers all the main activities associated with the marketing of a medicinal product. Medicines that meet the standards of safety, quality and efficacy set by the Medicines and Healthcare products Regulatory Agency (MHRA) are granted a marketing authorisation (previously a product licence), which is normally necessary before they can be prescribed or sold.

Markov modelling

A decision-analytic technique that characterises the prognosis of a cohort of patients by assigning them to a fixed number of health states and then models transitions among health states.

Medical devices

All products, except medicines, used in healthcare for the diagnosis, prevention, monitoring or treatment of illness or disability.

Medicines and Healthcare products Regulatory Agency (MHRA)

The Executive Agency of the Department of Health responsible for protecting and promoting public health and patient safety by ensuring that medicines, healthcare products and medical equipment meet appropriate standards of safety, quality, performance and effectiveness, and are used safely.

MeSH (medical subject headings)

The US National Library of Medicine's controlled vocabulary thesaurus used for indexing articles from biomedical journals for databases such as MEDLINE.

Meta-analysis

The use of statistical techniques in a systematic review to integrate the results of included studies. (Definition from The Cochrane Collaboration website.)

Meta-ethnography

A process of identifying relevant findings or other statements from the literature and sorting them into a pattern of evidence on the subject being studied.

Mixed treatment comparison

An analysis that compares two or more interventions using a combination of direct evidence (from trials that directly compare the interventions of interest) and indirect evidence (from trials that do not compare the interventions of interest directly).

Model input

Information required for economic modelling. For clinical guidelines, this may include information about prognosis, adverse effects, quality of life, resource use or costs.

Narrative summary

Summary of findings given as a written description.

Negative predictive value

The proportion of people with a negative test result who do not have the disease or characteristic.

Net benefit estimate

An estimate of the amount of money remaining after all payments made are subtracted from all payments received. This is a source of information used in the economic evidence profile for a clinical guideline.

NICE guideline

The version of a clinical guideline that presents the recommendations from the full guideline in a format that focuses on implementation by healthcare professionals and NHS organisations.

Nominal-group technique

A technique used to reach agreement on a particular issue. It uses a variety of postal and direct contact techniques, with individual judgements being aggregated statistically to derive the group judgement.

Observational study

Retrospective or prospective study in which the investigator observes the natural course of events with or without control groups (for example, cohort studies and case–control studies).

Off-label prescribing

A situation where a drug is used to treat a condition or disease for which the drug regulatory authority has not granted a marketing authorisation for that particular use. Off-label prescribing is particularly common in pregnant women and in children and young people, as these groups have often been excluded from clinical trials during drug development.

Opportunity cost

The opportunity cost of investing in a healthcare intervention is the other healthcare programmes that are displaced by its introduction. This may be best measured by the health benefits that could have been achieved had the money been spent on the next best alternative healthcare intervention.

Patient and carer member

A member of the Guideline Development Group with knowledge of the issues that are important to patients and carers.

Personal social services

Care services for vulnerable people, including those with special needs because of old age or physical disability and children in need of care and protection. Examples are residential care homes for the elderly, home help and home care services, and social workers who provide help and support for a wide range of people. (Department of Health definition.)

PICO (population, intervention, comparison and outcome) framework

A structured approach for developing review questions that divides each question into four components: the population (the population under study); the interventions (what is being done); the comparators (other main treatment options); and the outcomes (measures of how effective the interventions have been).

Positive predictive value

The proportion of people with a positive test result who actually have the disease or characteristic.

Primary research

Study generating original data

Prognosis

A probable course or outcome of a disease. Prognostic factors are patient or disease characteristics that influence the course. Good prognosis is associated with low rate of undesirable outcomes; poor prognosis is associated with a high rate of undesirable outcomes.

Project manager

The National Collaborating Centre or Internal Clinical Guidelines Programme staff member who oversees and facilitates the clinical guideline development process.

Proprietary name

The brand name given by the manufacturer to a drug or device it produces.

Prospective cohort study

An observational study that takes a group (cohort) of patients and follows their progress over time in order to measure outcomes such as disease or mortality rates and make comparisons according to the treatments or interventions that patients received. Prospective cohorts are assembled in the present and followed into the future.

QUADAS-2 (quality assessment of diagnostic accuracy studies-2)

A tool for the quality assessment of studies on the accuracy of diagnostic technologies.

Quality of life

See 'Health-related quality of life'.

Quorum

The smallest number of group members that must be present to constitute a valid meeting. The quorum of a Guideline Development Group is 50% of appointed members. No business relating to the formulation of guideline recommendations may be conducted unless the quorum is reached.

Receiver operating characteristic (ROC) curve

A plot of test sensitivity versus (1 − specificity), used to summarise the results of studies of diagnostic test accuracy.

Recommendations

Formal, numbered paragraphs in NICE clinical guidelines that give specific advice on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

Reference case

When estimating clinical and cost effectiveness in a technology appraisal, the reference case specifies the methods that are considered by NICE to be the most appropriate for the Appraisal Committee's purpose and are also consistent with an NHS objective of maximising health gain from limited resources.

Reference standard (or gold standard)

A method, procedure or measurement that is widely accepted as being the best available to test for or treat a disease.

Relative risk reduction

The proportional reduction in risk between experimental and control participants in a trial.

Remit

The brief given by the Department of Health or the NHS Commissioning Board at the beginning of the clinical guideline development process. This defines core areas of care that the guideline needs to address.

Research recommendation

Recommendations for future research covering questions relating to an uncertainty or evidence gap that has been identified during the guideline development process.

Resource implication

The likely impact in terms of finance, workforce or other NHS resources.

Review of the literature

An article that summarises the evidence contained in a number of different individual studies and draws conclusions about their findings. It may or may not be systematically researched and developed.

Review protocol

A document that outlines the background, objectives and planned methods for a systematic review.

Review question

A structured question about treatment and care that is formulated from a key clinical issue in the scope to guide the systematic review. See also PICO framework.

Scope consultation table

A table of all the comments received by NICE during consultation on the guideline scope and responses. It is published on the NICE website with the final scope.

Scope notes (bibliographic databases)

Scope notes provide additional information about database indexing terms (for example, when the term was first used for indexing, how the term is applied in the database, and 'used-for' terms and 'see-related' terms).

Scoping group

A group led by the National Collaborating Centre or Internal Clinical Guidelines Programme with input from the Guideline Development Group (GDG) Chair (and the GDG Clinical Adviser if applicable), NICE, and patient and carer groups. The role of the group is to:

Scoping search

A search of the literature undertaken at the scoping stage to identify previous clinical guidelines, health technology assessment reports, key systematic reviews and economic evaluations relevant to the guideline topic.

Search filter

A collection of search terms designed to retrieve selections of records (for example, records of research using a specific study design or on a specific topic).

Selection bias

1. Systematic differences between comparison groups in prognosis or responsiveness to treatment. Random allocation with adequate concealment of allocation protects against selection bias. Other means of selecting who receives the intervention are more prone to bias because decisions may be related to prognosis or responsiveness to treatment.

2. A systematic error in reviews due to how studies are selected for inclusion. Reporting bias is an example of this.

3. A systematic difference in characteristics between those who are selected for study and those who are not. This affects external validity but not internal validity.

(Definitions from The Cochrane Collaboration website.)

Sensitivity (of a test)

The proportion of people classified as positive by the reference standard who are correctly identified by the study test.

Sensitivity analysis

A means of representing uncertainty in the results of economic evaluations. Uncertainty may arise from missing data, imprecise estimates or methodological controversy. Sensitivity analysis also allows for exploring the applicability of results to other settings. The analysis is repeated using different assumptions to examine the effect on the results.

Deterministic sensitivity analysis: tests the impact of potential bias resulting from the selection of data sources for key model parameters.

One-way sensitivity analysis (univariate analysis): each parameter is varied individually in order to isolate the consequences of each parameter on the results of the study.

Probabilistic sensitivity analysis: probability distributions are assigned to the uncertain parameters and are incorporated into evaluation models based on decision analytical techniques (for example, Monte Carlo simulation).

Service delivery guidance

Recommendations on service delivery aimed primarily at health service commissioners. Service delivery guidance focuses on the broad configuration and provision of clinical services.

Specificity (of a test)

The proportion of people classified as negative by the reference standard who are correctly identified by the study test.

Stakeholder scoping workshop

Workshop attended by registered stakeholders before consultation on the guideline scope, to discuss the key clinical issues identified by the scoping group.

Stochastic analysis

A cost-effectiveness analysis in which both costs and effects are determined from data sampled from the same patients in a study.

Study quality

The extent to which a study has conformed to recognised good practice in the design and execution of its research methods.

Synthesis of evidence

A generic term to describe methods used for summarising (comparing and contrasting) evidence in order to address a defined review question. This can include systematic review (with or without meta-analysis), and qualitative and narrative summaries.

Systematic review

Research that summarises the evidence on a clearly formulated review question according to a predefined protocol using systematic and explicit methods to identify, select and appraise relevant studies, and to extract, collate and report their findings. It may or may not use statistical meta-analysis.

Technology assessment

The process of evaluating the clinical, economic and other evidence relating to use of a technology in order to formulate guidance on its most efficient use.

'Test and treat' study

A study that compares outcomes of patients after a diagnostic test (in combination with a management strategy) with those of patients who receive the usual diagnostic or management strategy.

Time horizon

The time span that reflects the period over which the main differences between interventions in health effects and use of healthcare resources are expected to be experienced, taking into account the limitations of supportive evidence.

Treatment allocation

The process by which study participants are allocated to a treatment group.

Treatment options

The choices of intervention available.

Workplan

A document prepared by the National Collaborating Centre (NCC) or Internal Clinical Guidelines Programme that sets out the methods and timelines for each guideline. It is an internal document that provides the reference from which the progress of the work can be assessed.