Changes

June 2026 — minor update. Statistics regarding paraproteinaemias ammended/removed. 

Update

Goals

To support primary health care professionals to:

• Make a diagnosis of sensory neuropathy.
• Offer appropriate initial and subsequent management.
• Refer people with sensory neuropathy, when appropriate, to other healthcare professionals.

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.

NICE quality standards

Suspected neurological conditions: recognition and referral

• Adults with suspected dystonia are referred for neurological assessment.
• Adults diagnosed with a functional neurological disorder are supported to manage symptoms that are a part of the disorder in non-specialist care.
• Adults with suspected neurological conditions using NHS services experience care and treatment that is tailored to their needs and preferences.

[NICE, 2021]

QIPP — Options for local implementation

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

Definition

• Sensory neuropathy describes symptoms due to damage to sensory nerve fibres, including loss of sensation (numbness), tingling, burning, loss of temperature perception, pain, and loss of balance or coordination.
• The sensory neuropathies can be broadly divided into two subtypes, depending on the type of sensory nerve fibre affected:
  • Small fibre-predominant — caused by damage to small-diameter nerve fibres, which mediate temperature sensation and pain, and are thinly myelinated or unmyelinated.
    • Typically results in burning and shooting pain with paraesthesia, and may be associated with loss of thermal and nociceptive sensation and dysautonomia. 
  • Large fibre-predominant — caused by damage to large-diameter nerve fibres, which mediate vibration sensation, pressure, and proprioception, and are more heavily myelinated with rapid conduction velocity.
    • Typically results in difficulties with gait and balance coordination (ataxia) leading to falls.
  • Some diseases can lead to mixed polyneuropathy, affecting both small- and large-diameter fibres.
• Distal symmetrical polyneuropathy (DSP) is the most common presentation of sensory neuropathy, and describes a length-dependent peripheral nerve injury resulting in distal-predominant sensory loss, pain, and if severe, weakness, and gait instability.
• There are a number of underlying causes for sensory neuropathy.

[Mendell, 2003; Devigili, 2020; Gomatos, 2024; Ring, 2024]

Causes

• The most common causes of sensory neuropathy are:
  • Diabetes (and pre-diabetes).
  • Vitamin B12 deficiency.
  • Idiopathic.
• Other causes of sensory neuropathy include:
  • Alcohol misuse.
  • Other nutritional deficiencies  — thiamine (B1), pyridoxine (B6), folic acid, copper, and vitamin E.
  • Infections  — including HIV, Epstein-Barr virus, herpes simplex, varicella zoster, Lyme disease, hepatitis C, human T-cell lymphotropic virus infection (HTLV-1), and leprosy.
  • Immune-mediated conditions — including sarcoidosis, Sjögren's syndrome, systemic lupus erythematosus, coeliac disease, Guillain-Barré syndrome, and vasculitis.
  • Systemic disease — chronic kidney disease, liver disease, hypothyroidism, and amyloidosis.
  • Paraneoplastic disease — secondary to bronchial carcinoma, small cell lung carcinoma, Hodgkin's lymphoma, neuroendocrine tumours, breast cancer, ovarian cancer, and sarcoma.
  • Paraproteinaemias.
  • Medication side effects  — including cytotoxics, statins, metronidazole, fluoroquinolones, nitrofurantoin, leflunomide, reverse transcriptase inhibitors, levodopa, and phenytoin.
  • Toxin exposure — lead, arsenic, mercury, organophosphates, thallium, and nitrous oxide.
  • Genetic disorders — including Charcot-Marie Tooth disease (a group of hereditary peripheral neuropathies with different genetic causes), and hereditary sensory neuropathy (HSN).
  • Environmental — prolonged exposure to cold, vibration, or hypoxemia.
  • Other causes — fibromyalgia.

[Mendell, 2003; Sghirlanzoni, 2005; Auer-Grumbach, 2008; Barrell, 2019; Devigili, 2020; Jones, 2020; BMJ Best Practice, 2024; BNF, 2024; Gomatos, 2024; Ring, 2024]

Prevalence

• Rates of sensory neuropathy in the general population have been estimated at between 1% and 3%, rising to 7% in older adults.
• Peripheral neuropathy is one of the most common neurological conditions encountered in primary care.
• In the UK, approximately one in every 10 people aged over 55 years experiences peripheral neuropathy.
• Peripheral neuropathy is observed in up to 50% of people with diabetes.
• Charcot-Marie-Tooth disease is the most common inherited neurological disorder, and affects approximately 1 in every 2500 people worldwide.
• A study using information from the UK Clinical Practice Research Database (CPRD) between 2010 and 2019 found the prevalence of Charcot-Marie-Tooth disease to be 29.5/100,00 and Guillain-Barré syndrome to be 40.1/100,00. 

[Barrell, 2019; Carey, 2021; NHS, 2022; BMJ Best Practice, 2024; Gomatos, 2024; Ring, 2024]

Risk factors

As well as the underlying causes of sensory neuropathy, other risk factors include:

• Advancing age.
• Sex — sensory neuropathy is slightly more common in females
• Occupation — exposure to certain occupational chemicals/toxins (lead, arsenic, mercury, organophosphates, thallium, and nitrous oxide) can cause sensory neuropathy, as can vibration and temperature extremes.
• Family history — there are a number of underlying genetic causes with dominant and recessive inheritance patterns.

[Mendell, 2003; Auer-Grumbach, 2008; Barrell, 2019; Jones, 2020; BMJ Best Practice, 2024; Gomatos, 2024; Ring, 2024]

Complications

The complications of sensory neuropathy include:

• Reduced quality of life due to neuropathic pain, and effects on sleep and mental wellbeing.
• Injury due to loss of protective sensation (such as burns, traumatic skin injury, and retention of foreign objects) — this may then lead to infection and in severe cases, sepsis, and gangrene.
  • Sensory neuropathy associated with diabetes is a significant risk factor for lower limb amputation.
  • The overall risk of diabetic foot ulceration is approximately 2% per year, rising to 7% per year in people with sensory neuropathy.
• Falls due to effects on gait and balance.

[Barrell, 2019; BMJ Best Practice, 2024; Gomatos, 2024; Ring, 2024]

Prognosis

• The prognosis of sensory neuropathy depends on the underlying cause, as well as other factors, including the longevity of symptoms prior to seeking medical attention.
  • Treatment of any identified underlying cause may cause symptoms to subside or improve.
  • Charcot-Marie-Tooth disease is progressive, with no effective therapies apart from bracing and corrective surgery.
• Appropriate management of the sequelae of sensory neuropathy can improve the person's long-term prognosis and quality of life, such as:
  • Fall prevention strategies.
  • Regular assessment (and appropriate management) of sleep patterns, pain level, and mental health.
  • Education regarding the importance of regular foot inspection for people with diabetes.

[Barrell, 2019; BMJ Best Practice, 2024; Gomatos, 2024; Ring, 2024]

When should I suspect sensory neuropathy?

• Suspect sensory neuropathy if the person reports typically stocking/glove pattern of:
  • Numbness.
  • Paraesthesia — burning, tingling, pins and needles, or electric shock sensation.
  • Lack of temperature perception.
• Additional features that may be reported include:
  • Hyperalgesia — increased sensitivity to painful stimuli.
  • Allodynia — pain resulting from innocuous stimuli. 
  • Imbalance.
  • Gait incoordination (possibly leading to falls).
  • Clinical features suggestive of the underlying causes of sensory neuropathy.

How should I assess a person with suspected sensory neuropathy?

• Note: The most common presentation of sensory neuropathy is distal symmetrical polyneuropathy (DSP) — suggested by distal-predominant sensory loss, pain, and, if severe, weakness and gait instability. 
• Be aware of the differential diagnoses of sensory neuropathy, and the clinical features of rarer neuropathies that require more urgent assessment.
• Take a history, paying particular attention to:
  • The person's age — younger onset can be associated with hereditary neuropathies, as well as nutritional deficiency or toxic exposures (such as heavy metals).
  • Time-course of symptom onset — rapid progression is atypical (such as progression of sensory symptoms from toes to knees, and/or gait difficulties within 6 months of symptom onset).
    • Paraneoplastic causes tend to be of acute onset.
    • Acute/subacute progression may be associated with toxic exposures or infectious causes.
    • Sensory neuropathy caused by diabetes/pre-diabetes tends to be chronic and slowly progressive.
    • Inherited neuropathies are slowly progressive with symptoms generally starting in childhood.
    • Ataxia at the onset of symptoms is atypical.
  • Presence/absence of accompanying motor and/or autonomic symptoms, such as:
    • Changes in strength, such as the ability to stand from a seated position, climbing stairs, or dragging feet when walking — suggests motor weakness, particularly if symptoms are persistent rather than just experienced with activity. Motor-predominant symptoms are suggestive of an underlying cause that might require prompt assessment
    • Orthostatic hypotension, postural dizziness, constipation, diarrhoea, bladder dysfunction, dry mouth, eyes, and skin, temperature dysregulation, or erectile dysfunction — suggest autonomic dysfunction. Prominent autonomic features require prompt assessment to rule out a serious underlying cause.
  • Whether symptoms are length-dependent — the typical length-dependent pattern involves symptoms that start in the toes and ascend over time, with fingertips being affected only once lower extremity symptoms have reached the knees.
    • If the person has symptoms affecting both the upper and lower extremities, it is important to determine the timeline and order of onset.
    • The presence of symptoms that presented in all four extremities simultaneously, or that started in the upper limbs or face, is a red flag for a potential serious underlying cause.
  • Whether symptoms are symmetrical — Most neuropathies are symmetrical. Ask about whether symptoms were symmetrical at onset and whether this has changed.
  • Possible underlying causes, being aware that idiopathic sensory neuropathy constitutes up to 40% of cases. Consider relevant co-morbidities (or whether the person requires further investigation), particularly:
    • Diabetes.
    • Vitamin B12 deficiency (ask about the person's diet).
    • Alcohol misuse.
    • Medication exposure. 
    • Family history.
    • Occupational/environmental exposures.
    • A history of infectious diseases.
    • Paraproteinaemias.
• Examine the person.
  • Inspect the hands and feet, looking for:
    • Muscle atrophy.
    • Ulceration.
    • Contractures.
    • High foot arches and hammer toes — associated with some hereditary neuropathies.
  • Perform a neurological examination.
    • Assess the person's gait, with particular attention to ataxia and weakness (including foot drop).
    • Carry out a motor examination, assessing strength of upper extremities (deltoids, biceps, triceps, and finger abduction) and lower extremities (hip and knee flexion, knee extension, ankle plantarflexion, and ankle dorsiflexion).
    • Carry out a sensory examination, assessing pinprick sensation starting distally in the affected extremities.
    • Assess vibration perception of the upper and lower extremities using a tuning fork.
    • Assess reflexes in the upper and lower extremities.
    • Be aware that DSP is suggested by a symmetric stocking–glove pattern sensory loss, diminished or absent Achilles deep tendon reflexes, and absent or mild distal weakness. In advanced, chronic DSP motor findings that may be present include weakness of big toe extension which can progress to mild weakness in the ankle dorsiflexors.
  • Consider additional investigations, depending on clinical judgement.

Which investigations should I consider?

• Initial investigations (to determine whether the person has a common underlying cause of sensory neuropathy) include:
  
  • HbA1C and fasting glucose.
  • Vitamin B12.
• Additional investigations that can be considered, depending on the history and examination findings, include:
  
  • Renal function.
  • Liver function.
  • Thyroid function.
  • Rheumatologic screening (to test for connective tissue diseases and vasculitis).
  • Coeliac serology.
  • Other vitamin levels as appropriate (such as vitamin B2, vitamin B3, and vitamin E).
  • Heavy metals.
  • Screening for infectious diseases, such as:
    • HIV.
    • Epstein-Barr virus.
    • Herpes simplex
    • Varicella zoster.
    • Lyme disease.
    • Hepatitis C.
    • Human T-cell lymphotropic virus infection (HTLV-1).
    • Leprosy (if the person's history suggests possible exposure).
  • Serum protein electrophoresis — to test for paraproteinaemias. 
  • Genetic testing (for inherited neuropathies).

What else could it be?

• Uncommon neuropathies that may present with sensory features include:
  • Guillain-Barre syndrome (acute inflammatory demyelinating polyneuropathy [AIDP]) — suggested by rapidly ascending symmetric weakness and sensory symptoms with acute onset (within 4 weeks) that was often preceded by an infection.
    • Can quickly progress to quadriplegia and respiratory failure.
  • Chronic inflammatory demyelinating polyneuropathy (CIDP) — suggested by proximal and distal motor and sensory symptoms with subacute progression (within 8 weeks).
  • Amyloid neuropathy — suggested by prominent autonomic dysfunction with painful sensory or sensorimotor peripheral neuropathy that progresses within weeks to months. 
  • Sensory neuronopathy — suggested by non–length-dependent asymmetric sensory loss, and gait ataxia. The most common underlying causes are paraneoplastic (particularly small-cell lung carcinoma) and Sjögren's syndrome.  
  • Mononeuritis multiplex — suggested by a patchy, asymmetric pattern of weakness and numbness. The most common underlying cause is vasculitis, which may be caused by polyarteritis nodosa, microscopic polyangiitis, rheumatoid arthritis, systemic lupus erythematosus, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, cryoglobulinemia (often associated with hepatitis C), Sjögren's syndrome, sarcoidosis, or infectious vasculopathy.
  • Diabetic lumbosacral radiculoplexus neuropathy (DLRPN) — in a person with type 2 diabetes, suggested by acute/subacute severe proximal leg pain followed by atrophy and weakness and progressive involvement of the contralateral limb and distal muscles.
  • Neuropathies presenting with symmetric, motor-predominant features include:
    • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes).
    • Distal acquired demyelinating symmetric neuropathy.
    • Genetic forms of motor neuron disease (such as spinal muscular atrophy and spinal bulbar muscular atrophy).
    • Lead poisoning — can present with abdominal pain, encephalopathy, and weakness of wrists and finger extensors.
  • Neuropathies presenting with asymmetric, motor-predominant features include:
    • Amyotrophic lateral sclerosis (ALS) — suggested by a combination of upper (spasticity and/or hyperreflexia) and lower motor neuron dysfunction (fasciculations, muscle atrophy, and weakness). Onset typically begins in one limb (80% of cases) or with bulbar dysfunction,  and progresses to other body segments.
    • Primary lateral sclerosis — variant of ALS with pure upper motor neuron involvement.
    • Progressive muscular atrophy — variant of ALS with pure lower motor neuron involvement.
    • Multifocal motor neuropathy — suggested by progressive, distal predominant weakness primarily affecting the upper extremities.
  • Porphyric neuropathy — suggested by acute/subacute motor neuropathy mimicking Guillain-Barre syndrome, with a prodrome of abdominal pain and psychosis.
• Conditions with symptoms that might overlap those of sensory neuropathy include:
  • Nerve root compression (radiculopathy) — suggested by distal symmetric sensory or sensorimotor symptoms, with low back pain and pain radiating from the back to the legs. See the CKS topic on  Sciatica (lumbar radiculopathy) for more information.
  • Spinal cord pathology (myelopathy) — suggested by distal symmetric sensory or sensorimotor symptoms, with hyperreflexia, spasticity (stiffness and resistance of the limbs to passive movement on examination), or decreased pain and temperature sensation below a particular level of the body.
  • Brain and central nervous system cancers — suggested by proximal neuropathy. See the CKS topic on Brain and central nervous system cancers - recognition and referral for more information.
  • Carpal tunnel syndrome — suggested by episodic wrist pain and paraesthesia involving the first three fingers, which is often provoked by repetitive movement, or sleep. See the CKS topic on Carpal tunnel syndrome for more information. 
  • Chronic pain — can cause give-way weakness on examination, due to pain inhibiting motor function. See the CKS topic on Chronic pain for more information.
  • Migraine with aura — suggested by sensory symptoms that occur with or without headache, are fully reversible, develop over at least 5 minutes, and last between 5 and 60 minutes. See the CKS topics on Headache - assessment and Migraine for more information.
  • Head injury — see the CKS topic on Head injury for more information.
  • Multiple sclerosis — see the CKS topic on Multiple sclerosis for more information.
  • Neuropathic pain including post-herpetic neuralgia; trigeminal neuralgia and other causes of facial pain. See the CKS topics on Post-herpetic neuralgia and Trigeminal neuralgia for more information.
  • Stroke and transient ischaemic attack (TIA) — suggested by gait unsteadiness, recurrent limb or facial weakness, sensory loss, speech, swallowing, and language problems. See the CKS topic on Stroke and TIA for more information.
  • Functional neurological disorder — recurrent numbness and altered sensation be part of presentation of this disorder.
• The underlying causes of sensory neuropathy include:
  • Diabetes (especially if poorly controlled) — see the CKS topics on Diabetes type 1 and Diabetes type 2 for more information.
  • Vitamin B12 deficiency — see the CKS topic on Anaemia - B12 and folate deficiency for more information.
  • Alcohol use disorder — see the CKS topic on Alcohol - problem drinking for more information.
  • Drug toxicity/side effects — suspect if the person is taking cytotoxics, statins, metronidazole, fluoroquinolones, nitrofurantoin, leflunomide, reverse transcriptase inhibitors, levodopa, phenytoin.
  • Other nutritional deficiencies — such as deficiencies of thiamine (B1), pyridoxine (B6), folic acid, copper, and vitamin E. See the CKS topic on Anaemia - B12 and folate deficiency for more information.
  • Infectious causes — such as HIV, Epstein-Barr virus, herpes simplex, varicella zoster, Lyme disease, hepatitis C, HTLV-1, and leprosy. See the CKS topics on HIV infection and AIDS, Glandular fever (infectious mononucleosis), Herpes simplex, Shingles, Lyme disease, and Hepatitis C for more information..
  • Immune mediated conditions — such as sarcoidosis, vasculitis, Sjögren syndrome, systemic lupus erythematosus, and coeliac disease. See the CKS topics on Sarcoidosis and Coeliac disease for further information.
  • Systemic disease (hypothyroidism, chronic kidney disease, liver disease) — see the CKS topics on Chronic kidney disease, Hypothyroidism, Jaundice in adults, Non-alcoholic fatty liver disease (NAFLD), and Cirrhosis for more information.
  • Paraneoplastic disease and lymphoma. See the CKS topics on Breast cancer - recognition and referral, Haematological cancers - recognition and referral, Lung and pleural cancers - recognition and referral, Ovarian cancer, and Bone and soft tissue sarcoma - recognition and referral for more information.
  • Toxic exposure — suspect if the person reports possible occupational or environmental exposure to lead, arsenic, mercury, organophosphates, thallium, or nitrous oxide.
  • Fibromyalgia — see the CKS topic on Tiredness/fatigue in adults for further information.
  • Genetic disorders — Charcot-Marie-Tooth (CMT) disease, hereditary sensory neuropathy, familial amyloid polyneuropathy. Suspect CMT if there is distal weakness and painless sensory loss with onset in the first 2 decades. Often associated with high arched feet (pes cavus), hammertoes, and distal leg atrophy.
  • Environmental exposures — such as prolonged exposure to cold, vibration, or hypoxemia.
  • Paraproteinaemias — see the CKS topic on Multiple myeloma for more information.

Scenario: Sensory neuropathy

From age 18 years onwards.

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of sensory neuropathy

Unrestricted - October 2024

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• exp sensory neuropathy/, peripheral neuropathy/, polyneuropathy.tw.

• 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
• Health Protection Agency
• World Health Organization
• National Guidelines Clearinghouse
• Guidelines International Network
• TRIP database
• GAIN
• NHS Scotland National Patient Pathways
• New Zealand Guidelines Group
• 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
• University of Michigan Medical School
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• UK Ambulance Service Clinical Practice Guidelines
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work(occupational health practice)

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

• 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

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

• Drug & amp; Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

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

• Healthtalkonline
• BMJ - Patient Journeys

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

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.

• 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.

• 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.

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.

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.

• Animal studies
• Original research is not written in English

• 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

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.

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.

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.

None.