Changes

February to April 2024 — reviewed. A literature search was conducted in February 2024 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last version of this topic. The topic name has been changed from 'Ankylosing spondylitis' to 'Axial spondyloarthritis (including ankylosing spondylitis)' in line with current terminology in the literature. The recommendations have been updated in line with current evidence in the literature. A new section on Assessment has been added to the Diagnosis section. The topic structure has been amended to improve clarity and navigation. The Prescribing information section has been deleted, and links have been provided to relevant CKS topics instead.

Update

Goals

To support primary healthcare professionals to:

• Be aware of when to suspect a diagnosis of axial spondyloarthritis. 
• Arrange rheumatology referral if a diagnosis of axial spondyloarthritis is suspected.
• Provide advice on sources of information and support for the person and/or carers.
• Arrange follow-up in primary care and re-referral of uncontrolled disease or complications, depending on clinical judgement.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP - options for local implementation were found during the review of this topic. 

NICE quality standards

The NICE quality standards relevant to this CKS topic are:

• Adults with suspected axial or peripheral spondyloarthritis are referred to a rheumatologist.
• Adults with suspected axial spondyloarthritis and an X‑ray that does not show sacroiliitis have an MRI, using an inflammatory back pain protocol.
• Adults with axial spondyloarthritis are referred to a specialist physiotherapist for a structured exercise programme.
• Adults with spondyloarthritis are given information about their condition, which healthcare professionals will be involved with their care, and how and when to get in touch with them.

[NICE, 2018]

What is it?

• Spondyloarthritis is a term describing a group of clinically heterogeneous chronic inflammatory rheumatologic conditions that may cause musculoskeletal and extra-musculoskeletal manifestations. It may present with clinical features from one or more of the following categories, as features of axial and peripheral spondyloarthritis can overlap and coexist [NICE, 2017; Sieper, 2017; Ramiro, 2023]:
  • Axial skeleton (predominantly affects the sacroiliac joints and spine causing back pain and stiffness), subdivided into:
    • Radiographic axial spondyloarthritis — characterized by signs of sacroiliitis and structural changes on X-ray (also known as ankylosing spondylitis).
    • Non-radiographic axial spondyloarthritis — characterized by an absence of changes on X-ray, but there may be signs of sacroiliitis on MRI.
    • Note: radiographic and non-radiographic axial spondyloarthritis are increasingly felt to be part of the same disease spectrum with similar clinical presentations and responses to treatment [Ritchlin, 2021; Ramiro, 2023]. Non-radiographic axial spondyloarthritis may represent early forms of the disease, where some (but not all) people may eventually progress to show signs of radiographic changes [Navarro-Compan, 2021].
  • Peripheral joints and entheses — including psoriatic arthritis, reactive arthritis, or enteropathic spondyloarthritis; enthesitis (inflammation at the insertion of tendons, ligaments, or capsule into bone); and dactylitis [NICE, 2017; de Koning, 2018; Magrey, 2020; Ramiro, 2023]. See the CKS topic on Spondyloarthritis and psoriatic arthropathy for more information.
  • Extra-musculoskeletal manifestations — such as acute anterior uveitis, inflammatory bowel disease, and/or psoriasis, which may occur after initial presentation [Navarro-Compan, 2021; Ramiro, 2023]. See the CKS topics on Crohn's disease, Psoriasis, Ulcerative colitis, and Uveitis for more information.

What are the risk factors?

The pathophysiology of axial spondyloarthritis is not completely understood and is likely to be complex and multifactorial [Hwang, 2021]. It is thought to involve processes of axial inflammation, bone destruction, and new bone formation [Navarro-Compan, 2021].

• In genetically susceptible people, axial spondyloarthritis may be triggered by exogenous factors such as mechanical stress and infection, and endogenous factors such as disruption to the gut microbiome and loss of gut epithelial integrity, together with microdamage to entheseal and joint connective tissues. These factors may be involved in the onset and progression of the disease [Hwang, 2021; Navarro-Compan, 2021].
  • Genetic studies estimate a heritability of more than 90% for axial spondyloarthritis. The most important genetic risk factor is the presence of human leukocyte antigen B27 (HLA-B27), but other major histocompatibility complex (MHC) variants are also involved [Hwang, 2021; Navarro-Compan, 2021]. It most likely has a polygenic mode of inheritance [de Koning, 2018].
    • Men are more likely to be HLA-B27 positive than women. A lower prevalence of HLA-B27 is associated with a higher likelihood of peripheral features and extra-musculoskeletal manifestations (especially psoriasis) in axial spondyloarthritis [Navarro-Compan, 2021].
    • The absolute risk of developing spondyloarthritis if a person is HLA-B27 positive is estimated to be between 2–10% [Taurog, 2016]. The prevalence of spondyloarthritis across different geographic regions has been attributed to the background prevalence of HLA-B27 in different populations [de Koning, 2018].
    • Expert opinion in a review article cites evidence that first-degree relatives of people with radiographic axial spondyloarthritis have a 5.6- to 16-fold higher risk of developing disease than the general population [Magrey, 2020].
    • The presence of spondyloarthritis and related extra-musculoskeletal manifestations (anterior uveitis, psoriasis, and inflammatory bowel disease) in first and second-degree relatives is associated with an increased risk of developing spondyloarthritis [Poddubnyy, 2020].
  • In addition, damage to the skin caused by psoriasis, and to the intestinal mucosa caused by inflammatory bowel disease may facilitate exposure to pathogens [Navarro-Compan, 2021].
    • The presence of HLA-B27 positivity may result in susceptibility to axial spondyloarthritis by modifying the gut microbiome and presenting a variety of different peptides in the gut, introducing a microenvironment that leads to microbial imbalance, inflammation, and subsequent overproduction of interleukins and other proinflammatory mediators. In addition, gut permeability may be increased, which could allow greater systemic exposure to potentially pathogenic gut microbes [Hwang, 2021].
    • Subclinical gut inflammation has been linked to earlier disease onset and worse prognosis [Navarro-Compan, 2021].
  • A previous diagnosis of juvenile idiopathic arthritis also increases the risk of developing axial spondyloarthritis [NICE, 2017].
  • A history of current (but not previous) smoking appears to be a risk factor for developing axial spondyloarthritis and disease progression [Hwang, 2021; Ramiro, 2023].
    • This may be due to the proinflammatory and pro-oxidative effects of smoking, which contributes to disease onset in a genetically predisposed person and the possible progression of non-radiographic axial spondyloarthritis into radiographic disease.

How common is it?

Axial spondyloarthritis is widely underdiagnosed, and prevalence estimates in the literature are likely to be underestimates of true prevalence [Magrey, 2020]. The variation in prevalence estimates in the literature is due to different study populations, geographic settings, study methodology, data sources, and case definitions [Ritchlin, 2021].

• A retrospective study of people with axial spondyloarthritis (n = 1080) found [Feldtkeller, 2003]:
  • Disease typically developed in people younger than 45 years and had a peak age at onset of between 20 and 30 years.
  • There was an older average age of disease-onset in people who were human leukocyte antigen B27 (HLA-B27) negative compared to those who were HLA-B27 positive (27.7 years and 24.8 years respectively). The average age at diagnosis was 39.1 years and 33.2 years respectively. The average duration of diagnostic delay was 11.4 years and 8.5 years respectively.
• A review article cites evidence that [Navarro-Compan, 2021]:
  • The prevalence of radiographic axial spondyloarthritis ranges from 0.1–1.4%.
  • The prevalence of non-radiographic spondyloarthritis is increasing over time, which may be partially due to improved detection and diagnosis.
  • Radiographic axial spondyloarthritis is more common in men, with a male-to-female ratio of 2:1, whereas non-radiographic axial spondyloarthritis is equally prevalent in men and women.
  • Populations with a high background prevalence of HLA-B27, such as in Northern Europe, show higher rates of axial spondyloarthritis.
• A UK epidemiology study using Clinical Practice Research Datalink data, which identified 12,333 patients with ankylosing spondylitis, found [Crossfield, 2021]:
  • Incidence reduced from 0.72 to 0.39 per 10,000 patient-years from 1998 to 2007, and then increased to 0.57 per 10,000 patient-years in 2017, which may reflect increased recognition and diagnosis of the condition.
  • Prevalence increased from 0.13% to 0.18% between 1998 and 2017, particularly in women and people aged over 60 years.
  • The median time from symptom onset to rheumatology referral was 4.87 years.
  • The median time from symptom onset to diagnosis increased from 3.62 years to 8.31 years between 1998 and 2017.
• A US population-based cohort retrospective longitudinal study of young adults with new-onset inflammatory back pain (n = 124) followed up for a mean of 13.2 years found [Wang, 2018]:
  • 31% of people were diagnosed with spondyloarthritis over the follow-up period.
  • 12% of people received a non-spondyloarthritis diagnosis.
  • 47% of people had resolution of back pain symptoms.
• A systematic review of global data found that extra-musculoskeletal manifestations are common in people with ankylosing spondylitis, with pooled prevalence data for [Stolwijk, 2015]: 
  • Uveitis of 25.8% (95% CI 24.1 to 27.6).
  • Psoriasis of 9.3% (95% CI 8.1 to 10.6).
  • Inflammatory bowel disease of 6.8% (95% CI 6.1 to 7.7).

What are the complications and associated conditions?

Possible complications associated with axial spondyloarthritis include:

• Limited spinal mobility and deformity — usually a late manifestation, due to axial synovitis and enthesitis causing new bone formation, irreversible structural damage, and possible bony fusion of vertebral joints. In severe cases, this can lead to the complete fusion of the axial skeleton [Taurog, 2016; Navarro-Compan, 2021].
• Osteoporosis and spinal fracture — the combination of spinal rigidity from the formation of syndesmophytes (bony growths in intervertebral joint ligaments) and osteoporosis within trabecular bone contributes to a spinal fracture rate of up to 10% in people with axial spondyloarthritis, which may occur with minimal or no trauma, and is associated with a high risk of spinal cord injury [Taurog, 2016; Ramiro, 2023]. See the CKS topic on Osteoporosis - prevention of fragility fractures for more information.
• Increased cardiovascular risk — cardiac complications also include aortic and non-aortic valvular heart disease and heart failure [Navarro-Compan, 2021]. See the CKS topic on CVD risk assessment and management for more information.
• Lung involvement — may cause restrictive lung disease as costovertebral involvement may decrease vital capacity [Navarro-Compan, 2021].
• Renal involvement — may be associated with the development of IgA nephropathy [Navarro-Compan, 2021].
• Impact on quality of life — may impact on work, educational, and social activities [Hamilton, 2017; Navarro-Compan, 2021; Ramiro, 2023]. There may be associated mental health issues including anxiety and depression due to chronic pain, stiffness, fatigue, and limitations in mobility and function [Danve, 2022; Zhao, 2023].
  • A cohort study undertaken in Wales of 570 people with ankylosing spondylitis reported on a health economic analysis based on patient-reported questionnaires and linked data [Cooksey, 2015].
    • It found the majority of costs were attributed to loss of working hours, early retirement, unpaid carer's time, and GP attendance.
    • 43% of people of working age were not working (due to ankylosing spondylitis symptoms in more than 70%); the mean age of retirement was 53.6 years; and 3.5% of work time was missed.

Possible extra-musculoskeletal manifestations associated with axial spondyloarthritis include:

• Anterior uveitis — this typically presents with acute unilateral painful red eye, photophobia, and blurred vision, and recurrence is common. It is the most common extra-musculoskeletal manifestation of axial spondyloarthritis, and may rarely be the first manifestation of the disease [Magrey, 2020; Navarro-Compan, 2021]. The lifetime prevalence is 30–40% in people with ankylosing spondylitis, particularly in men and people who are positive for HLA-B27 [Taurog, 2016]. See the CKS topic on Uveitis for more information.
• Psoriasis — this occurs in about 10% of people with axial spondyloarthritis [Magrey, 2020]. See the CKS topic on Psoriasis for more information.
• Inflammatory bowel disease — this occurs in about 4–6% of people with axial spondyloarthritis [Magrey, 2020]. See the CKS topics on Crohn's disease and Ulcerative colitis for more information.

What is the prognosis?

The natural history of axial spondyloarthritis is variable, but sustained disease activity may lead to irreversible structural damage [Navarro-Compan, 2021].

• Expert opinion in a review article states that the disease course of axial spondyloarthritis may involve relapses and long remission periods [Poddubnyy, 2020]. A British Society for Rheumatology (BSR) joint guideline notes that flares of axial spondyloarthritis typically last for an average of 2–3 weeks in people on treatment [Hamilton, 2017].
• A review article cites evidence from studies that in about 5–10% of people, non-radiographic disease will evolve into radiographic disease over 2 years, increasing to 5–30% over 10 years [Magrey, 2020]. 
• An international guideline notes that radiographic and non-radiographic axial spondyloarthritis are increasingly felt to be part of the same disease spectrum with similar clinical presentations and burden of disease, including the presence of comorbidities, treatment received, and response. It states that structural damage progression tends to occur slowly [Ramiro, 2023].
• Predictors of a good prognosis of axial spondyloarthritis and positive response to specialist treatment include [Taurog, 2016]:  
  • Young age at diagnosis.
  • Short disease duration.
  • High baseline level of inflammatory markers.
  • Low baseline level of functional impairment.
• Expert opinion in a review article notes that about 60–65% of people with axial spondyloarthritis achieve clinical response after treatment with a first biological disease-modifying anti-rheumatic drug (DMARD). It notes that a poorer prognosis may be associated with factors such as longer disease duration, higher disease activity and level of inflammation, reduced physical functioning, and engagement in physically demanding work [Navarro-Compan, 2021].

When should I suspect a diagnosis of axial spondyloarthritis?

Axial spondyloarthritis can present with varied and non-specific clinical features and can be challenging to diagnose, leading to a potentially delayed or missed diagnosis. Signs and symptoms may be musculoskeletal or extra-articular in origin.

• Suspect a diagnosis of axial spondyloarthritis if a person has low back pain and spinal stiffness starting before the age of 45 years and lasting longer than 3 months, plus four or more of the following additional criteria:
  • Low back pain starting before the age of 35 years (increased likelihood of spondyloarthritis compared with onset before the age of 45 years).
  • Symptoms that wake the person during the second half of the night.
  • Buttock pain — variable location, may alternate with hip pain.
    • Pain and stiffness usually involve the lower spine and the buttocks, but any level of the spine can be affected.
  • Improvement with movement and exercise, not relieved by rest.
  • Improvement within 48 hours of taking a nonsteroidal anti-inflammatory drug (NSAID).
  • Family history of spondyloarthritis in a first-degree relative.
  • Current or past history of peripheral arthritis — typically asymmetrical oligoarthritis of the ankle, knee, and/or hip. See the CKS topic on Spondyloarthritis and psoriatic arthropathy for more information.
  • Current or past history of peripheral enthesitis — especially if persistent and/or in multiple sites; may present with pain, stiffness, and/or swelling at the Achilles tendon and plantar fascia insertions and patellar and quadriceps tendon insertions, for example. See the CKS topics on Plantar fasciitis and Spondyloarthritis and psoriatic arthropathy for more information. 
  • Current or past history of psoriasis (including nail changes). See the CKS topic on Psoriasis for more information.
• Consider a diagnosis of spondyloarthritis if a person presents with other extra-musculoskeletal or peripheral features, such as:
  • Acute anterior uveitis. See the CKS topic on Uveitis for more information.
  • Psoriasis. See the CKS topics on Psoriasis and Spondyloarthritis and psoriatic arthropathy for more information.
  • Inflammatory bowel disease. See the CKS topics on Crohn's disease and Ulcerative colitis for more information.
  • Recent gastrointestinal or genitourinary infection — may present with reactive arthritis.
  • Dactylitis — rare; may present with painful, diffuse swelling of a whole finger or toe due to a combination of synovitis, tenosynovitis, and enthesitis. See the CKS topic on Spondyloarthritis and psoriatic arthropathy for more information.
• Do not rule out a diagnosis of axial spondyloarthritis on the basis of the presence or absence of an individual symptom or sign.

How should I assess a person with suspected axial spondyloarthritis?

If a person has a suspected diagnosis of axial spondyloarthritis:

• Ask about:
  • Any axial, peripheral, and/or extra-musculoskeletal symptoms, including timescale, onset, severity, and impact on mobility and daily functioning.
  • The characteristics of any back or neck pain or stiffness.
    • Back pain typically has an insidious onset and inflammatory features such as morning stiffness lasting for 30 minutes or more.
    • Pain and stiffness usually involve the lower spine and the buttocks, but any level of the spine can be affected.
    • Be aware that up to one-third of affected people present with mechanical back pain. See the CKS topic on Back pain - low (without radiculopathy) for more information.
  • Clinical features suggesting an alternative or co-existing diagnosis, such as trauma preceding back pain.
  • Clinical features suggesting any complications or associated conditions.
  • Any history of other comorbidities such as enthesitis, arthritis, dactylitis, fatigue, weight loss, and psychosocial impact.
  • Any risk factors including family history of axial spondyloarthritis or extra-musculoskeletal manifestations, previous juvenile idiopathic arthritis, and smoking status.
  • Any treatments tried, and symptom response to nonsteroidal anti-inflammatory drugs (NSAIDs).
• Examine the person for signs of:
  • Inflammatory arthritis (tender or swollen joints); enthesitis (such as tender, stiff, or swollen Achilles tendon or plantar fascia insertion); dactylitis (diffuse swelling or a whole finger or toe); or psoriasis skin lesions.
  • Limitation of spinal movement (typically only seen in later stages of disease).
• Consider arranging investigations in primary care, depending on clinical judgement and local referral pathways, such as:
  • Blood tests for full blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and human leukocyte antigen B27 (HLA-B27).
    • Do not rule out a diagnosis of spondyloarthritis on the basis of normal CRP and ESR results.
    • Arrange an HLA-B27 blood test if a person has three additional diagnostic criteria present. Do not rule out a diagnosis of spondyloarthritis solely on the basis of a negative HLA-B27 result.
  • Plain X-ray of the sacroiliac joints to assess for sacroiliitis.
    • Signs of joint space narrowing, sclerosis, erosive changes, and partial or total fusion of the joint (ankylosis) may be seen on X-ray in late disease.
  • Plain X-ray and/or ultrasound of any other axial or peripheral symptomatic sites. See the CKS topic on Spondyloarthritis and psoriatic arthropathy for more information.
    • Be aware that a diagnosis of non-radiographic axial spondyloarthritis should not be ruled out if plain X-ray(s) are normal.
• Do not rule out a diagnosis of axial spondyloarthritis on the basis of the presence or absence of an individual test result.

What else might it be?

Other conditions that may present similarly to axial spondyloarthritis include:

• Mechanical back pain, which typically comes on after a recognised trauma and is worse after exercise or at the end of the day. See the CKS topic on Back pain - low (without radiculopathy) for more information.
• Osteoarthritis — including degenerative disc disease, spondylosis, degenerative changes in the intervertebral (facet) joints, osteoarthritis of sacroiliac joints, and spinal stenosis. See the CKS topic on Osteoarthritis for more information.
• Rheumatoid arthritis. See the CKS topic on Rheumatoid arthritis for more information.
• Spinal fracture.
• Infectious sacroiliitis.
• Bone metastasis. See the CKS topic on Bone and soft tissue sarcoma - recognition and referral for more information.
• Primary bone tumours. See the CKS topic on Bone and soft tissue sarcoma - recognition and referral for more information.
• Hypermobility and/or fibromyalgia. See the CKS topic on Chronic pain for more information.

Scenario: Suspected axial spondyloarthritis (including ankylosing spondylitis)

From age 16 years onwards.

Scenario: Confirmed axial spondyloarthritis (including ankylosing spondylitis)

From age 16 years onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines and systematic reviews on primary care management of ankylosing spondylitis.

Search dates

April 2019 - February 2024

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 4th April 2019). These were combined with filters to identify guidelines, systematic reviews and primary care relevant literature in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases.

S3    S1 OR S2 
S2    AB ( spondyloarthrit* or spondylitis or spondyloarthropath* ) OR TI ( spondyloarthrit* or spondylitis or spondyloarthropath* ) 
S1    (MH "Spondylitis, Ankylosing") 

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.