Changes

October 2022 — this is a new CKS topic. A literature search was conducted in October 2022 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials. The recommendations have been made in line with current evidence in the literature. 

Update

Goals

To support primary healthcare professionals to:

• Recognize possible clinical features of long COVID.
• Assess a person with suspected long COVID.
• Offer management in primary care when appropriate.
• Provide relevant information and advice.
• Refer to secondary care or seek specialist advice when required.
• Provide appropriate follow-up.

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

No NICE quality standards were found during the review of this topic.

QIPP - Options for local implementation

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

What is it?

• Coronavirus disease is an infectious disease caused by a novel betacoronavirus known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The disease associated with it is now referred to as 'COVID-19' [WHO, 2022; UKHSA, 2022a].
• The following clinical case definitions can be used to identify and diagnose the long-term effects of COVID-19: 
  • Acute COVID-19 — signs and symptoms of infection consistent with COVID-19 for up to 4 weeks.
  • Ongoing symptomatic COVID-19 — signs and symptoms of COVID-19 infection from 4 weeks up to 12 weeks.
  • Post-COVID-19 syndrome — signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis. It usually presents with clusters of symptoms which may overlap, fluctuate, change over time, and affect any body system.
• Long COVID is a multi-system condition with a range of debilitating symptoms — signs and symptoms continue or develop after acute COVID-19, continue for more than 4 weeks, and are not explained by an alternative diagnosis.
  • It includes both ongoing symptomatic COVID-19 (from 4-12 weeks) and post-COVID-19 syndrome (12 weeks or more).
  • Long COVID may consist of a number of distinct syndromes, which can include post-ICU syndrome, post-viral fatigue syndrome, long-term COVID syndrome, and permanent organ damage. 

[NIHR, 2021; NHS England, 2022a; NICE, 2022]

How common is it?

• An estimated 2 million people in the UK were experiencing self-reported long COVID in July 2022. 
• Of people with self-reported long COVID:
  • 253,000 (13%) first had (or suspected they had) COVID-19 less than 12 weeks previously.
  • 1.7 million people (83%) at least 12 weeks previously.
  • 892,000 (45%) at least one year previously.
  • 429,000 (22%) at least two years previously.
• The most commonly reported symptoms were: 
  • Fatigue (62%).
  • Shortness of breath (37%).
  • Difficulty concentrating (33%).
  • Muscle ache (31%).
• The prevalence of self-reported long COVID was highest in: 
  • People aged 35 to 69 years.
  • Females.
  • People living in more deprived areas.
  • People working in social care.
  • People aged 16 years and over not working and not looking for work.
  • People with another activity-limiting health condition or disability.

[ONS, 2022]

What causes long COVID?

Post-COVID conditions are heterogeneous and may be attributable to a multiplicity of underlying pathophysiologic processes. Possible aetiologies include: 

• Organ damage resulting from acute phase infection.
• Complications from a dysregulated inflammatory state.
• Ongoing viral activity associated with an intra-host viral reservoir.
• Autoimmunity.
• Inadequate antibody response.

[CDC, 2022a]

What is the prognosis?

• The prognosis for people with long COVID is variable and it is not possible to predict who will recover within weeks and those who may develop a long-term condition.
• 12 weeks after infection there is a steady reduction in the number of people who have persistent symptoms.
• However, in people who have symptoms which persist for over 12 weeks many report that these problems are severely debilitating.
  • Around 70% of people report their ability to undertake daily activities is adversely affected, while 20% report that this has been 'limited a lot'.
• People who have had COVID-19 may be more likely to develop new health conditions such as diabetes mellitus, heart conditions, or neurological conditions compared with people who have not had COVID-19. 
  • In a retrospective cohort study, of 47,780 individuals in hospital with COVID-19 over the study period, diabetes, major adverse cardiovascular event, chronic kidney disease, and chronic liver disease were diagnosed after discharge in 4.9%, 4.8%, 1.5%, and 0.3% of individuals with COVID-19, respectively, occurring at rates of 127 (122 to 132) for diabetes, 126 (121 to 131) for a major adverse cardiovascular event, 39 (36 to 42) for chronic kidney disease, and 7 (6 to 9) for chronic liver disease diagnoses per 1000 person-years.
    • There were similar patterns for new onset diagnoses, but at lower rates of 29 (26 to 32) for diabetes, 66 (62 to 70) for a major adverse cardiovascular event, 15 (13 to 17) for chronic kidney disease and 4 (3 to 5) for chronic liver disease diagnoses per 1000 person-years [Ayoubkhani, 2021].
  • In a retrospective cohort study using electronic health records, among 236,379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17–34·07), with 12·84% (12·36–13·33) receiving their first such diagnosis [Taquet, 2021]. 
• People who have experienced multisystem inflammatory syndrome (MIS) during or after COVID-19 illness may be at higher risk for ongoing multiorgan system effects and post-COVID conditions [CDC, 2022b]. 
  • MIS in children is rare and occurs 2 to 6 weeks after infection. It develops in less than 0.1% of children with COVID-19 (median age 8.6 years) and requires intensive care support in 68% of cases. 
• A study of long COVID in children and young people found that up to 1 in 7 children and young people may have symptoms linked to the virus 15 weeks later.  

[CDC, 2022a; CDC, 2022b; Fainardi, 2022; Greenhalgh, 2022; NHS England, 2022a]

What are the risk factors?

• A meta-analysis identified the following risk factors for developing long-term effects of COVID-19: 
  • Female sex.
  • Poorer pre-pandemic mental health.
  • Poor general health.
  • Asthma.
  • People who are overweight or obese.
• Other studies identified the following additional risk factors:
  
  • Smoking or vaping.
  • Previous hospitalization for acute COVID-19.
  • Severe COVID-19 — these people were at greatest risk of neurological or psychiatric diagnoses.
  • Aged 70 years or more, white ethnicity — greater absolute risk of death, readmission, and multiorgan dysfunction after discharge.
    • However, younger patients and ethnic minority individuals had greater relative risks compared to people aged 70 or more and those in the white ethnic group, respectively, and a recent large retrospective matched cohort study found that black, mixed ethnicity and other minority ethnic backgrounds were at increased risk of persistent symptoms [Subramanian, 2022,]. 
• People who are not vaccinated against COVID-19 and become infected may be at higher risk of developing post-COVID conditions compared to people who were vaccinated and had breakthrough infections. A UKHSA rapid review found that: 
  • People who received two doses of a COVID-19 vaccine were less likely to develop long COVID symptoms, or they had symptoms for a shorter duration, compared to people who were unvaccinated. This is supported by a number of studies:
    • In a nested case-control study (n = 8400), fully vaccinated participants were about half as likely to have symptoms lasting ≥28 days than unvaccinated participants (odds ratio [OR] = 0.51, 95% CI: 0.32 to 0.82, p=0.005), whereas partially vaccinated participants were about as likely to have symptoms lasting ≥28 days than unvaccinated participants (OR = 1.04, 95% CI: 0.86 to 1.25, p=0.69), and fully vaccinated younger adults (18 to 59 years) were much less likely to have symptoms lasting ≥28 days than younger unvaccinated adults (OR = 0.21, 95% CI: 0.08 to 0.59, p=0.003).
    • In a retrospective cohort study, vaccinated cases (n = 16,035) were less likely to have at least 1 post-acute sequalae of COVID-19 at 6 months compared with unvaccinated cases (n =48,536, hazard ratio [HR] = 0.87, 95% confidence interval [CI]: 0.83 to 0.92).
    • In another retrospective cohort study (n = 240,648) cases who were vaccinated before diagnosis were much less likely to have any symptoms of long COVID between 12 and 20 weeks after diagnosis than cases who were unvaccinated up to 12 weeks after their diagnosis (OR = 0.22, 95% CI: 0.20 to 0.25, p<0.005), and even less likely to have more than 1 symptom of long COVID (OR = 0.11, 95% CI: 0.09 to 0.14, p<0.005).
    • In a cross-sectional study nested in a prospective cohort study (n = 951) compared with unvaccinated participants, participants with 2 or 3 doses of vaccine were 54% to 83% less likely to report 7 of the 10 most commonly reported symptoms.
    • In another cross-sectional study (n = 773) fully vaccinated (2 doses) participants were less likely to have long COVID symptoms (not stated if these were short-term, long-term or both) than unvaccinated participants (OR = 0.55, 95% CI: 0.37 to 0.85).
    • In a matched case-control study there was no association between vaccination (comparing participants with 2 doses of vaccine [n = 2996] with unvaccinated participants [n = 6957]) and the composite long COVID outcome in the 6 months after infection: hazard ratio (HR) = 1.00 (95% CI: 0.95 to 1.06); 64.9% and 65.6% of vaccinated and unvaccinated participants had a long COVID symptom respectively. However, participants with 2 doses of vaccine, when compared with unvaccinated participants, were less likely to be diagnosed with anosmia, fatigue, hair loss, interstitial lung disease, myalgia, or other pain.
  • People who were vaccinated after being infected with COVID-19 also reported a shorter duration of post-COVID symptoms compared to those who were unvaccinated. 
    • In a prospective cohort study (n = 66), which examined the effect of vaccination on long COVID symptoms in previously unvaccinated participants who were hospitalised with COVID-19 and either remained unvaccinated or were vaccinated, at 1 month after vaccination (or a matched time for unvaccinated cases), more vaccinated participants reported their symptoms improved than unvaccinated participants (23.2% versus 15.4%), and fewer vaccinated participants reported their symptoms worsened than unvaccinated participants (25.6% versus 14.3%, p=0.035 for all differences). A similar percentage of vaccinated and unvaccinated participants had unchanged symptoms (71.1% versus 70.3%).
    • In another prospective cohort study (n = 28,356) both the first and second vaccine doses were associated with reduced odds of reporting long COVID symptoms shortly after vaccination: first vaccine dose, OR = 0.87 (95% CI: 0.81 to 0.93, p<0.001); second vaccine dose: OR = 0.91 (95% CI: 0.86 to 0.97, p=0.003). The second vaccine dose was also associated with a long-term decrease in the odds of reporting long COVID symptoms (p=0.03). The results were similar for activity limiting long COVID (n=4,747 reported activity limiting long COVID): first vaccine dose: OR = 0.88 (95% CI: 0.81 to 0.96, p=0.003); second vaccine dose: OR = 0.91 (95% CI: 0.84 to 0.98, p=0.01). The second vaccine dose was also associated with a long-term decrease in the odds of reporting long COVID symptoms (p=0.03).  
    • In another prospective cohort study (n = 67) which asked healthcare workers in the UK with long COVID whether vaccination changed their long COVID symptoms several weeks after vaccination, 14 (21%) participants reported an improvement in one or more of their symptoms, 8 (12%) participants reported a worsening in symptoms, and 45 (67%) participants reported no change in their symptoms.
    • In another prospective cohort study (n = 910) long COVID symptoms were less severe in vaccinated compared with unvaccinated participants 120 days after recruitment (mean difference in COVID ST score = -1.8, 95% CI: -2.5 to -1.0), and more vaccinated than unvaccinated participants had remission of all long COVID symptoms (16.6% versus 7.5%, HR = 1.97, 95% CI: 1.23 to 3.15). The impact of long COVID on the lives of vaccinated participants was also less than unvaccinated participants (mean difference in COVID impact score = -3.3, 95% CI: -6.2 to -0.5), and fewer vaccinated participants found their symptoms unacceptable (38.9% versus 46.4%, risk difference = -7.5%, 95% CI: -14.4% to -0.5%).
    • In a retrospective cohort study (n = 240,648) cases who were vaccinated 0 to 4 weeks after diagnosis were much less likely to have any symptoms of long COVID between 12 and 20 weeks after diagnosis than cases who were unvaccinated up to 12 weeks after their diagnosis (OR = 0.38, 95% CI: 0.35 to 0.41, p<0.005), and even less likely to have more than one symptom of long COVID (OR = 0.19, 95% CI: 0.16 to 0.22, p<0.005). Cases who were vaccinated 4 to 8 weeks after diagnosis were less likely to have any symptoms of long COVID between 12 and 20 weeks after diagnosis than cases who were unvaccinated up to 12 weeks after their diagnosis (OR = 0.54, 95% CI: 0.51 to 0.57, p<0.005), and much less likely to have more than 1 symptom of long COVID (OR = 0.32, 95% CI: 0.29 to 0.35, p<0.005). Cases who were vaccinated 8 to 12 weeks after diagnosis were less likely to have any symptoms of long COVID between 12 and 20 weeks after diagnosis than cases who were unvaccinated up to 12 weeks after their diagnosis (OR = 0.75, 95% CI: 0.71 to 0.78, p<0.005), and much less likely to have more than one symptom of long COVID (OR = 0.46, 95% CI: 0.43 to 0.49, p<0.005).
    • In an online survey (n = 812) which asked people in the UK and elsewhere with long COVID (n = 812) whether their symptoms improved or worsened following vaccination 57% of participants reported an improvement in symptoms, 25% of participants reported no change in symptoms, while 19% of participants reported a worsening of symptoms.
    • In another online survey of French-speaking adults (n = 567) with post-acute sequelae of COVID-19 (n = 380), 117 (31%) reported a global worsening of symptoms (including fever/chills [74%], gastrointestinal symptoms [70%], paraesthesia [64%] and arthralgia [63%]), whereas 83 (21.8%) reported a global improvement in symptoms (including anosmia [62%] and brain fog [51%]), and 179 (47%) reported no change in symptoms following vaccination.
    • In another online survey which compared long-term symptom changes after receiving a COVID-19 vaccination in adults with (n = 100) and without a previous COVID-19 infection (n = 285) in the US, COVID-19 cases were more likely to report that the vaccine improved their long-term symptoms than adults who never tested positive for COVID-19 (28.7% versus 15.7%, p=0.023). However COVID-19 cases were also more likely to report that their symptoms worsened following the vaccination (although this was not statistically significant,16.1% versus 11.2%, p=0.27), and that their symptoms were gone before receiving the vaccine (28.4% versus 13.1%, p=0.007). Fewer COVID-19 cases reported that the vaccine did not affect their symptoms at all (26.4% versus 59.2%)
  • Two doses of the COVID-19 vaccine provided a high level of protection against long COVID compared to one dose or no doses.

[NICE, 2021; CDC, 2022b; UKHSA, 2022b]

What are the signs and symptoms?

• The signs and symptoms after acute COVID-19 are highly variable and wide-ranging, and may fluctuate, with exacerbations triggered by physical or mental stress. 
  • Some people experience multi-organ effects or autoimmune conditions. 
  • There may be evolution of symptoms including permanence of symptoms, and the development of new symptoms or conditions. 
  • There may be a worsening of pre-existing symptoms or conditions. 
• The most commonly reported symptoms include, but are not limited to: 
  • Generalized symptoms
    • Fatigue — some people develop post-exertional malaise, or post-exertional symptom exacerbation. For more information, see the CKS topic on Tiredness/fatigue in adults.
    • Fever.
    • Pain.
  • Cardiovascular symptoms
    • Chest pain — this may be positional, or occur on exertion. 
    • Chest tightness.
    • Palpitations.
  • Dermatological symptoms
    • Hair loss.
    • Skin rashes — for example, urticaria. 
  • Ear, nose and throat symptoms
    • Dizziness.
    • Earache.
    • Loss of taste and/or smell — loss of enjoyment of food and mealtimes. Phantosmia or parosmia may be present. In a large European study of people with COVID-19 who experienced olfactory and taste disorders, at 2 and 6 months, 75% and 95% of patients recovered olfaction, respectively. A poor prognosis for olfactory recovery was statistically related to the severity of the baseline olfactory objective evaluation.
    • Nasal congestion.
    • Sore throat — throat may also be dry with a sensation of choking, or altered voice. 
    • Tinnitus.
  • Gastrointestinal symptoms
    • Abdominal pain.
    • Diarrhoea.
    • Nausea and vomiting.
    • Weight loss and reduced appetite.
  • Musculoskeletal symptoms
    • Joint pain and/or muscle pain — generalized, focal or regional pain. May be in coathanger distribution, and may progress to chronic pain.
  • Neurological symptoms
    • Autonomic dysfunction — palpitations, dizziness, orthostatic tachycardia, gastrointestinal disturbance, generalized pain. 
    • Cognitive impairment — ‘brain fog’, loss of concentration, memory issues, poor problem-solving and executive function, mental fatigue. 
    • Delirium (in older populations).
    • Dizziness and vertigo.
    • Headache.
    • Mobility impairment.
    • Peripheral neuropathy symptoms (pins and needles and numbness).
    • Sleep disturbance — unrefreshing sleep, vivid dreams or nightmares. 
    • Visual disturbance.
  • Psychological/psychiatric symptoms
    • Anxiety.
    • Depression.
    • Post-traumatic stress disorder — this may be experienced by people who were treated in the intensive care unit. People treated in ICU may have overlapping symptoms from post-intensive care syndrome (PICS) and long COVID. 
  • Respiratory symptoms
    • Breathlessness — predominantly with physical activity. The severity of dyspnoea does not seem to be closely related to the initial severity of COVID-19. Dyspnoea has a major effect on quality of life and socioeconomic status, as it can affect the person's ability to return to work. 
    • Cough — this can persist for weeks or months and potentially alter quality of life. 
• Multisystem inflammatory syndrome in children (MIS-C) presents with several multisystemic manifestations — the most common involve the gastrointestinal tract, skin, mucous membranes and the cardiovascular system. In some cases the clinical picture may resemble Kawasaki disease, especially in cases with shock, toxic shock syndrome and macrophage activation syndrome. 

How should I assess a person with suspected long COVID?

• Take a comprehensive medical history and ask about: 
  • History of acute COVID-19 (suspected or confirmed).
  • The nature, and severity of previous and current symptoms.
    • Discuss the person’s experience of their symptoms and how their life and activities have been affected, including work, education, mobility and independence.
    • Ask about any feelings of worry or distress. 
  • Timing and duration of symptoms since the start of acute COVID-19.
  • Specific triggers. 
  • History of other health conditions.
  • Comorbidities. 
  • Social circumstances. 
  • Exacerbation of pre-existing conditions.
• Conduct a physical examination depending on the presenting symptoms, including: 
  • Physical symptoms. For people with:
    • Breathlessness, see the section on Assessment in the CKS topic on Breathlessness. 
    • Chest pain, see the section on Assessment in the CKS topic on Chest pain. 
    • Cough, see the section on Assessment in the CKS topic on Cough. 
    • Delirium, see the section on Assessment in the CKS topic on Delirium. 
    • Diarrhoea, see the CKS topic on Diarrhoea - adult assessment.
    • Dizziness and vertigo, see the section on Assessment in the CKS topic on Vertigo.
    • Fatigue, see the section on Assessment in the CKS topic on Tiredness/fatigue in adults.
    • Headache, see the CKS topic on Headache - assessment. 
    • Postural symptoms, for example, palpitations or dizziness on standing, carry out lying and standing blood pressure and heart rate recordings (3‑minute active stand test for orthostatic hypotension, or 10 minutes if postural orthostatic tachycardia syndrome [POTS], or other forms of orthostatic intolerance are suspected). For more information, see the CKS topics on Palpitations and Blackouts.
    • Tinnitus, see the section on Assessment in the CKS topic Tinnitus.
  • Cognitive symptoms.
    • If the person reports new cognitive symptoms, use a validated screening tool to measure any impairment and impact. For more information on cognitive assessment tools see the CKS topic on Dementia.
  • Psychological and psychiatric symptoms. 
    • In children and young people consider using a psychosocial screening tool such as the HEADDSS assessment tool to identify psychosocial risks and resilience factors. 
    • For more information, see the section on Assessment in the CKS topic on Depression, and the section on Assessment in the topic on Generalized Anxiety Disorder.
    • For people with post-traumatic stress disorder, see the section on Assessment in the CKS topic on Post-traumatic stress disorder.
  • Functional abilities.
• Offer tests and investigations tailored to people’s signs and symptoms to exclude an acute, life‑threatening complications, or symptomatic COVID‑19, post‑COVID‑19 syndrome new diagnoses.
• Be aware that people may have wide-ranging and fluctuating symptoms following an acute COVID‑19 infection, which may vary in nature over time. 
  • Gradual decline, deconditioning, worsening frailty or dementia, or loss of interest in eating and drinking in older people, can be signs of ongoing symptomatic COVID‑19 or suspected post‑COVID‑19 syndrome. 
• It is not possible to predict whether a person is likely to develop post‑COVID‑19 syndrome based on their symptoms (or clusters of symptoms) or were admitted to hospital during an acute COVID‑19 infection. 

What investigations should I consider for a person with suspect long COVID?

• Offer tests and investigations depending on the person's signs and symptoms.  
  • Note: no laboratory test can definitely distinguish post-COVID presentations from other conditions. 
• If clinically indicated, offer blood tests, which may include the following: 
  • Full blood count.
  • Kidney and liver function tests.
  • C‑reactive protein.
  • Ferritin.
  • B‑type natriuretic peptide (BNP).
  • HbA1c.
  • Thyroid function tests.
  • Lipid profile.
  • Vitamin D levels. 
• Other investigations which may be useful to determine disease severity and exclude other conditions include: 
  • An exercise tolerance test suited to the person’s ability (for example, the 1‑minute sit‑to‑stand test).
    • During the exercise test, record the level of breathlessness, heart rate and oxygen saturation. 
    • Follow appropriate protocols to carry out the test safely.
  • Chest X-ray.Offer a chest X-ray 12 weeks after acute COVID-19 if the person has continuing respiratory symptoms and it is clinically indicated.
    • Chest X-ray appearances alone should not determine the need for referral for further care. 
  • Electrocardiography. 
• If another diagnosis unrelated to COVID-19 is suspected, offer investigations and referral in line with relevant national or local guidance. 
• Be aware that clinical evaluation, blood tests, chest X-rays, and electrocardiography may all be normal.

Scenario: Suspected long COVID

From birth onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of long-term effects of coronavirus (long COVID).

Search dates

Unrestricted - October 2022

Key search terms

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

• exp Coronavirus, COVID-19, long*COVID, post-covid syndrome.

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
• 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
• Institute for Clinical Systems Improvement
• 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
• Patient UK Guideline links
• 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)

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

• Bandolier
• 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

• Healthtalkonline
• BMJ - Patient Journeys
• Patient.co.uk - Patient Support Groups

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)
• LactMed
• 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.

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

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.

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.