Research recommendations

Delirium assessment tools:
What is the diagnostic accuracy, and ease of implementation, of different delirium assessment tools:

• for people with pre-existing cognitive impairment, for example dementia, learning disability or severe depression
• for people who do not speak English as a first language
• in different settings, for example emergency departments, residential care homes or virtual consultations
• when delivered by different types of health and social care practitioners, for example healthcare assistants or allied health professionals such as paramedics?

Pharmacological prevention: In people in hospital who are at high risk of delirium, which medication (atypical antipsychotics, typical antipsychotics, benzodiazepines or acetylcholinesterase inhibitors), compared with placebo or each other, is more clinically and cost effective in preventing the development of delirium?

Pharmacological treatment: In people in hospital who have delirium, which is the most effective medication (atypical antipsychotics, typical antipsychotics or benzodiazepines) compared with placebo or each other for treating delirium?

Multicomponent intervention: For people in long-term care, is a multicomponent non-pharmacological intervention more clinically and cost effective than usual care in preventing the development of delirium?

Delirium in long-term care: How common is delirium and what are its adverse outcomes in people in long-term care?

Education programme: Does a staff education programme (compared with an educational leaflet or usual care) reduce the incidence of delirium and improve the recognition and recording of delirium in people in hospital?

Imaging options in occult hip fracture: In people with a continuing suspicion of a hip fracture but whose radiographs are normal, what is the clinical and cost effectiveness of CT compared with MRI, in confirming or excluding the fracture?

Anaesthesia: What is the clinical and cost effectiveness of regional versus general anaesthesia on postoperative morbidity in people with hip fracture?

Undisplaced intracapsular hip fractures: For people with undisplaced (or non-displaced) intracapsular hip fracture, what features should be used to characterise the injury and what are the optimal clinical and cost-effective management strategies?

Intensive rehabilitation therapies after hip fracture: What is the clinical and cost effectiveness of additional intensive physiotherapy and/or occupational therapy (for example, progressive resistance training) after hip fracture?

Early supported discharge in care home patients: What is the clinical and cost effectiveness of early supported discharge on mortality, quality of life and functional status in people with hip fracture who are admitted from a care home?

Long-term effectiveness of total hip replacement: What is the long-term clinical and cost effectiveness for adults (including different subgroups) undergoing total hip replacement compared with hemiarthroplasty for displaced intracapsular hip fracture?

Femoral component design: In adults undergoing hemiarthroplasty for displaced intracapsular hip fracture (including in different subgroups), which femoral component design has the best long-term outcomes?

Aside from mast cell tryptase, which other chemical inflammatory mediators offer potential as indicators of anaphylaxis?

What are the frequency, timing, severity and predictors of biphasic reactions in people who have received emergency treatment for anaphylaxis?

For how long should a person who has received emergency treatment for anaphylaxis be observed?

What is the annual incidence of anaphylaxis and its related outcomes within the UK?

For people who have experienced suspected anaphylaxis, what is the effect on health-related quality of life of (a) referral to specialist allergy services and (b) provision of adrenaline injectors, when compared with emergency treatment alone?

Newly diagnosed seizures (focal and generalised) – monotherapy: How do the newer AEDs compare in efficacy to the standard AEDs in the treatment of newly diagnosed epilepsy?

Epilepsy syndromes: What are the initial and add-on AEDs of choice in the treatment of the epilepsy syndromes with onset in childhood, for example, myoclonic-astatic epilepsy and Dravet syndrome?

Infantile spasms: Does treatment response relate to cause in infantile spasms? Does early treatment success in seizure control and resolution of the hypsarrhythmic EEG influence the long-term developmental and cognitive outcomes more than the underlying cause of the spasms?

Treatment of convulsive status epilepticus (that is, not just refractory): What is the most effective and safest AED to treat:

AEDs and pregnancy: What is the malformation rate and longer term neurodevelopmental outcome of children born to mothers who have taken AEDs during pregnancy?

What is the clinical and cost effectiveness of facilitated self-help for the treatment of mild anxiety and depressive disorders in autistic adults?

What structure and organisation of specialist autism teams are associated with improvements in care for autistic people?

What is the clinical and cost effectiveness of augmentative communication devices for autistic adults?

What is the most clinically and cost-effective tool for diagnosing peripheral arterial disease in people with diabetes?

What is the most clinically and cost-effective tool for establishing the severity of peripheral arterial disease and the impact on mortality, morbidity and limb amputation in people with diabetes?

Amitriptyline to prevent recurrent migraine:- Is amitriptyline a clinically and cost effective prophylactic treatment for recurrent migraine?

5-aminosalicylate (5-ASA) treatment:- Following successful medical induction of remission of Crohn's disease of the colon, is mesalazine more clinically and cost effective than no treatment?

What is the value of a key worker approach (defined by protocol and delivered in addition to usual care) for autistic children and young people in terms of parental satisfaction, functioning and stress and child psychopathology?

Is a group-based parent training intervention for parents or carers of autistic children and young people clinically and cost effective in reducing early and emerging behaviour that challenges in the short- and medium-term compared with treatment as usual?

What is the comparative clinical and cost effectiveness of pharmacological and psychosocial interventions for anxiety disorders in autistic children and young people?

Are comprehensive early interventions that combine multiple elements and are delivered by parents and teachers (for example, the Learning Experiences – an Alternative Program for Preschoolers and their Parents [LEAP] model) effective in managing the core features of autism and coexisting difficulties (such as adaptive behaviour and developmental skills) in pre‑school children?

What is the clinical effectiveness, cost effectiveness and tolerability of pharmacological monotherapy compared with combination therapy for treating neuropathic pain?

What is the clinical and cost effectiveness of alternative treatments as firstline treatment for trigeminal neuralgia compared with other better-tolerated pharmacological treatments?

Is response to pharmacological treatment predicted more reliably by underlying aetiology or by symptom characteristics?

What is the clinical and cost effectiveness of carbamazepine as initial treatment for trigeminal neuralgia compared with other pharmacological treatments?

What are the key factors, including additional care and support, that influence participation* and quality of life in people with neuropathic pain?

What is the impact of drug-related adverse effects on health economics and quality of life in neuropathic pain?

Is there a potential for dependence associated with pharmacological agents for neuropathic pain?

How should the symptomatic treatment of neuropathic pain relate to its cause?

Does early intervention to treat neuropathic pain reduce the likelihood of chronic pain?

What is the clinical and cost effectiveness of lidocaine patches for localised peripheral pain?

In people who experience symptoms of gastro-oesophageal reflux disease (GORD) or symptoms suggestive of GORD, what patient characteristics, risk factors and predictors indicate when endoscopy is needed to exclude Barrett's oesophagus?

What is the effectiveness of laparoscopic fundoplication compared with medical management in people with GORD that does not respond to optimal proton pump inhibitor (PPI) treatment?

What is the clinical effectiveness of double-dose PPIs in people with severe erosive reflux disease (Los Angeles classification grade C/D or Savary–Miller grade 3/4):

What specialist management is effective for people whose symptoms do not respond to PPIs despite optimum primary care, or for people whose symptoms return after surgery?

What specialist investigations should be conducted to exclude a diagnosis of functional dyspepsia in people with uninvestigated dyspepsia that does not respond to PPIs or H₂ receptor antagonists (H₂RAs) despite optimum primary care?

Dopamine: In people with acute heart failure, congestion and worsening renal function, does the addition of low‑dose dopamine to standard therapy lead to greater diuresis and renal protection compared with adding placebo to standard therapy?

Thiazide: In people with acute heart failure and persistent congestion, does the addition of a thiazide diuretic to standard therapy lead to greater diuresis compared with adding placebo to standard therapy?

Intra-aortic balloon counter‑pulsation: In people with acute heart failure and hypoperfusion syndrome, is the use of intra‑aortic balloon counter‑pulsation pump (IABP) better than the use of intravenous inotropes?

Ultrafiltration: In people with decompensated heart failure, fluid congestion and diuretic resistance, does ultrafiltration lead to more rapid and effective decongestion compared with continuing diuretic treatment?

Measurements for assessing health risks in adults: What are the most accurate and suitable measurements and boundary values to assess the health risks associated with overweight, obesity and central adiposity in adults of different ethnicities, particularly those from Black, Asian and minority ethnic family backgrounds?

Measurements for assessing health risks in children and young people: What are the most accurate and suitable measurements and boundary values to assess the health risk associated with overweight, obesity and central adiposity in children and young people of different ethnicities, particularly those from Black, Asian and minority ethnic family backgrounds?

Follow-up care after bariatric surgery: Do post-operative lifestyle intervention programmes (exercise, behavioural or dietary) improve weight loss and weight-loss maintenance following bariatric surgery?

What is the effectiveness and cost effectiveness of bariatric surgery in achieving weight loss and improving treatment outcomes in people who are unable to receive treatment for other health conditions (such as joint replacement surgery or fertility treatment) because they are living with obesity? 

Long-term outcomes of bariatric surgery on people with type 2 diabetes: What is the long-term effect of bariatric surgery on diabetes-related complications and quality of life in people with type 2 diabetes compared with optimal medical treatment?

What is the effectiveness and cost effectiveness of bariatric surgery in achieving weight loss and maintaining a healthier weight in adults from minority ethnic family backgrounds who are living with obesity? 

Bariatric surgery in children and young people: What are the long-term outcomes of bariatric surgery in children and young people living with obesity?

Obesity management for people with a condition associated with an increased risk of obesity: What is the best way to deliver obesity management interventions to people with particular conditions associated with increased risk of obesity (such as people with a physical disability that limits mobility, a learning disability or enduring mental health difficulties)?

Long-term effect of very-low-calorie diets on people with a BMI of 40 kg/m2 or more: What are the long-term effects of using very-low-calorie diets (VLCDs) versus low-calorie diets (LCDs) on weight and quality of life in patients with a body mass index (BMI) of 40 kg/m2 or more, including the impact on weight cycling?

Comparative risks for different generations of immigrants: Is the risk of ill health the same for first-, second- and third-generation immigrants from black, Asian and other minority ethnic groups at the same BMI and waist-to-height ratio thresholds?

Single cut-off points: What are the risks and benefits of developing single-figure cut-off points on BMI and waist-to-height ratio for black, Asian and other minority ethnic groups to help prevent diabetes and other conditions?

Awareness of risk among black, Asian and other minority ethnic groups: Are black, Asian and other minority ethnic groups aware that they are at the same risk of type 2 diabetes and mortality at a lower BMI, compared with the white population?

Practitioners and providers' awareness of risk in black, Asian and other minority ethnic groups: Are clinicians, practitioners and weight management service providers aware that black, Asian and other minority ethnic groups are at the same risk of type 2 diabetes and mortality at a lower BMI compared with the white population. If so, do they intervene at lower BMI and waist-to-height ratio thresholds?

Lifestyle interventions for black, Asian and other minority ethnic groups: How effective and cost effective are lifestyle interventions for people from black, Asian and other minority ethnic groups at different BMI and waist-to-height ratio thresholds, compared with the general population?

Long‑term consequences of planning birth in different settings: What are the long‑term consequences for women and babies of planning birth in different settings?

Education about the latent first stage of labour: Does enhanced education specifically about the latent first stage of labour increase the number of nulliparous women who wait until they are in established labour before attending the obstetric or midwifery unit (or calling the midwife to a home birth), compared with women who do not receive this education?

Postpartum haemorrhage: What is the most effective treatment for primary postpartum haemorrhage?

How safe are drugs used to treat bipolar disorder in pregnancy and the postnatal period?

Few women use contraception perfectly (that is, exactly in accordance with the product instructions) and consistently. Pregnancy rates during typical use reflect effectiveness of a method among women who use the method incorrectly or inconsistently. Few data are available on typical use of any contraceptive method among women in the UK. Much of the data on contraceptive effectiveness used in the guideline come from clinical trials or surveys undertaken in other countries such as the USA. Large prospective cohort studies are needed to compare the contraceptive effectiveness of LARC methods with non‑LARC methods during typical use in the UK.

Most women will need to use contraception for more than 30 years. Patterns of contraceptive use vary with age, ethnicity, marital status, fertility intention, education and lifestyle. Large prospective cohort studies are needed to identify:

In addition to individual circumstances and needs, a woman's choice and acceptance of LARC may be influenced by potential health disbenefits (side effects and risks) as well as non‑contraceptive benefits of LARC (such as alleviation of menorrhagia). Large population studies of appropriate design are needed to determine the effect of these factors on the uptake of LARC methods and the implications for NHS resources.

The effect of injectable contraceptives on bone mineral density in women who have used DMPA for longer than 2 years is uncertain. Adequately powered surveys or cross‑sectional studies are needed to examine the recovery of bone mineral density after discontinuation of DMPA after long‑term and very long‑term use. Studies are also needed to examine the risk of bone fractures in older women.

What is the clinical and cost effectiveness of using different thresholds of LDL‑C concentration in primary care case finding?

What are the long-term effects of statin therapy on sub-clinical atherosclerosis in children with FH who are treated with statin therapy?

What is the clinical effectiveness and safety of differing doses of lipid-modifying therapy in children with FH?

What are the appropriate indications, effectiveness and safety of LDL apheresis in people with heterozygous FH?

What are the implications of FH for the safety of a mother during pregnancy and what are the risks of fetal malformations attributable to pharmacological therapies

What is the utility of routine cardiovascular evaluation for asymptomatic people with FH?

What is the role of arm and shoulder specific exercises compared with and/or used as an adjunct to established lymphoedema treatments (such as compression garments and complex decongestive therapy)?

What is the impact and longer-term clinical outcomes of adding procalcitonin testing to standard clinical practice with protocol-driven care in the NHS, to guide the use of antibiotic treatment in people with confirmed or highly suspected sepsis in intensive care units and in people with suspected bacterial infections presenting to the emergency department?

What is the impact and longer-term clinical outcomes of adding procalcitonin testing to standard clinical practice with protocol-driven care in the NHS, to guide the use of antibiotic treatment in children having antibiotics for a suspected or proven infection in an intensive care unit?

What is the impact and longer-term clinical outcomes of adding procalcitonin testing to standard clinical practice with protocol-driven care in the NHS, to guide the use of antibiotic treatment in children and adults presenting to the emergency department with respiratory tract infection?

What is the impact and longer-term clinical outcomes of adding procalcitonin testing to standard clinical practice with protocol-driven care in the NHS, to guide the use of antibiotic treatment in adults presenting to the emergency department with exacerbations of chronic inflammatory respiratory conditions such as chronic obstructive pulmonary disease?

What is the impact of using the VivaScope 1500 and 3000 imaging systems in the clinical workflow of melanoma and basal cell carcinoma assessment in secondary care in England, particularly on excision rates, diagnostic accuracy, health related quality of life and associated NHS costs?

What proportion of people with melanoma who are referred into secondary care under the 2 week wait rule, have equivocal moles that are excised and have equivocal moles that are monitored?

How many confirmatory diagnostic biopsies are carried out before definitive treatment, in people who have a clinical diagnosis of basal cell carcinoma and which different modalities used to treat basal cell carcinoma?

What is the clinical effectiveness of using the VivaScope 1500 and 3000 imaging systems to define margins of lentigo maligna and basal cell carcinoma compared with histological margins determined by Mohs surgery?

What is the incidence of lentigo maligna diagnosed in England and which different therapies are used to treat lentigo maligna?

NICE recommends further research to quantify the impact of hypoglycaemia on quality of life for people with type 1 diabetes and their carers.
Future research should include adults and children and should capture the impact of persistent anxiety associated with the fear of catastrophic events related to severe hypoglycaemic events.

NICE recommends further research to investigate the clinical effectiveness of the integrated sensor-augmented insulin pump therapy systems in younger children and pregnant women. No data are currently available for these subgroups and their inclusion in future studies is encouraged.

NICE recommends that health economic models are developed to capture the impact of interventions on short-term outcomes such as hypoglycaemia. In addition, the feasibility of incorporating more recently developed risk prediction models for cardiovascular disease such as QRisk2 and observational data from registries such as the Swedish National Diabetes Register into health economic models for type 1 diabetes should be explored.

Further research into the analytical and clinical validity of the enzyme-linked immunosorbent assay (ELISA) kits (LISA-TRACKER, IDKmonitor and Promonitor) is recommended, specifically on:
- the best methods to measure tumour necrosis factor (TNF)-alpha-inhibitor levels in the presence of antibodies to TNF-alpha inhibitors
- developing primary reference standards
- the accuracy for predicting clinical state
- clinically meaningful thresholds.

Further research is recommended on clinical outcomes associated with using the ELISA kits (LISA-TRACKER, IDKmonitor and Promonitor) in people whose Crohn's disease is losing response to a TNF-alpha inhibitor. This could be through a prospective study, for local audit, or for submission to a registry. (The IBD Registry is being adapted to receive data on TNF-alpha inhibitor levels and antibodies against TNF-alpha inhibitors).

Further research is recommended on clinical outcomes associated with using the ELISA kits (LISA-TRACKER, IDKmonitor and Promonitor) to monitor TNF-alpha-inhibitor levels and antibodies to a TNF-alpha inhibitor in people with Crohn's disease whose disease responds to treatment with TNF-alpha inhibitors. This should be evaluated using prospective studies.

Further research is recommended on the use of repeat PlGF-based testing (Triage PlGF test and Elecsys immunoassay sFlt-1/PlGF ratio), with standard clinical assessment, in women presenting with suspected pre-eclampsia between 20 weeks and 34 weeks plus 6 days of gestation, who have had a negative PlGF-based test result (Triage PlGF test result of 100 picograms/ml or more; Elecsys immunoassay sFlt 1/PlGF ratio of less than 38) that was used to rule-out pre-eclampsia. This should include:
- exploration of the different scenarios in which repeat testing may be indicated
- the appropriate intervals between PlGF-based tests
- the diagnostic accuracy of PlGF-based testing in women with suspected pre-eclampsia who have previously had 1 or more negative PlGF-based test results.

Further research is recommended on the use of the Triage PlGF test and Elecsys immunoassay sFlt-1/PlGF ratio, with standard clinical assessment, to rule-in pre-eclampsia in women presenting with suspected pre-eclampsia between 20 weeks and 34 weeks plus 6 days of gestation. This should specifically investigate how a positive PlGF-based test result (Triage PlGF test result of 12 picograms/ml or less; Elecsys immunoassay sFlt 1/PlGF ratio of greater than 38) used to rule-in pre-eclampsia would affect management decisions on time to delivery and the outcomes associated with this.

Further research is recommended on using ImmunoCAP ISAC 112 for diagnosing allergy and clinical outcomes associated with using allergy testing for people with allergy that is difficult to diagnose, specifically in people with:
- idiopathic anaphylaxis
- multiple allergies and multiple sensitisations
- plant-derived food allergy
- seafood allergy, but who have a positive history and negative diagnostic test results.

Further research is recommended on alternative postpartum testing strategies that do not include cord blood typing of all babies born to rhesus-D (D) negative women.

Further research is recommended on resource use and clinical effects associated with using the xTAG Gastrointestinal Pathogen Panel, the FilmArray GI Panel and the Faecal Pathogens B assay.

Further research is recommended on patient acceptability of using virtual chromoendoscopy for real-time assessment of diminutive polyps compared with assessment using histopathology

Data collection and analysis are recommended to monitor the effect on endoscopy and histopathology services of using virtual chromoendoscopy instead of  histopathology to assess diminutive polyps. Measures may include:
- the length of time to do colonoscopies
- the number of polyps sent for histopathology analysis
- cost savings or workload reductions associated with reductions in histopathology.

NICE recommended further research into the clinical effectiveness of BCM – Body Composition Monitor-guided fluid management in people with chronic kidney disease having dialysis. It noted that the ongoing BISTRO study will assess the effect of the device in people aged 18 years or over having haemodialysis. Further research should collect clinical-outcome data in the following populations:
- adults (aged 18 years and over) having peritoneal dialysis
- babies, children and young people (aged under 18 years) having haemodialysis
- babies, children and young people (aged under 18 years) having peritoneal dialysis.

NICE recommended that data on the effect of BCM – Body Composition Monitor-guided monitoring on health-related quality of life is collected and published. Prospective within-patient studies, which record quality of life and symptoms before and after having BCM – Body Composition Monitor-guided fluid management should be considered.

NICE considered that further research is needed to determine whether faecal haemoglobin levels are influenced by age, sex and medicines that increase the risk of gastrointestinal bleeding. It noted that these data could be used to further develop risk scores that include variables such as age, sex and symptoms to help determine pre-test probability. The data could also be combined with faecal haemoglobin concentration to refine management after the use of faecal immunochemical tests in primary care.

NICE noted advice from clinical experts that there is variability between the faecal immunochemical tests. This may affect the number of positive and negative results reported by the tests when a single threshold is used. It recommended further research to investigate the variability between technologies and encouraged the companies to make sure that results can be standardised for use in a symptomatic population.

Further diagnostic accuracy studies, or analyses of existing data sets, are recommended to assess the accuracy of the tests included in this assessment in the following subgroups:
- people who are premenopausal
- people who are postmenopausal
- people with suspected early stage ovarian cancer, that is, disease apparently confined to the pelvis.
Future studies should be done in populations that are representative of people with suspected ovarian cancer who are assessed in NHS secondary care.

Further research is recommended to assess:
- inter-observer reproducibility of tests involving ultrasound scans (the ADNEX model and Simple Rules)
- changes in clinical management based on test results from the ADNEX model, Overa (MIA2G), ROMA and Simple Rules.

Further research is recommended to assess the diagnostic accuracy of the tests included in this assessment when used in combination; for example sequentially.

The committee recommended that further studies should be done in a HPV primary screening setting. These studies should incorporate clinical outcome data and be designed to minimise verification bias. Future studies should consider measuring variability and should also take into account HPV genotyping status when possible, so that the difference in accuracy in a population vaccinated against HPV types 16 and 18 can be better understood.

The  committee recommended that data should be collected to show how the results of the technologies affect decision-making, including biopsy decisions and decisions to
discharge people with a negative colposcopy examination back to routine screening.

Further research is needed to understand the effect of having the additional information provided by the adjunctive colposcopy technologies on anxiety for people having a colposcopy, when this information is shown to a person during the examination.

The committee recommended that further research is needed to better understand the natural history of low-volume cervical intraepithelial neoplasia (CIN) 2 lesions.

Further research on the routine adoption of Actim Partus and PartoSure to help diagnose preterm labour in women with intact membranes when transvaginal ultrasound measurement of cervical length is needed on the accuracy of the tests and their effect on clinical outcomes. Centres using the tests to help diagnose preterm labour in women with intact membranes are encouraged to take part in studies to address the research considerations (see the guidance sections 5.12 to 5.16). Data are needed on:
- the impact of gestational age on the accuracy of the tests
- how the tests affect clinical decision-making
- the effect of the tests on outcomes for mother and baby

The committee recommended further research to determine if using the lead‑I electrocardiogram (ECG) devices in primary care for people with signs or symptoms of atrial fibrillation, and an irregular pulse, increases the number of people with atrial fibrillation (including paroxysmal) detected, ompared with current practice (that is, a 12‑lead ECG done later). The committee considered the feasibility of collecting data to see if using the lead‑I ECG devices increased the detection of atrial fibrillation that would be missed if only 12‑lead ECGs done later were available. It noted that even if a lead‑I ECG is used and atrial fibrillation is detected, a subsequent 12‑lead ECG would still be done to check for structural cardiac abnormalities and inform further management decisions. The committee concluded that practices using lead‑I ECG devices could determine the number of additional cases of atrial fibrillation detected by the devices. This can be done by identifying people with a confirmed positive lead‑I ECG for atrial fibrillation who subsequently had a 12‑lead ECG that was negative because the atrial fibrillation had stopped. The committee also considered that data collected on the time between the initial lead‑I ECG and the subsequent 12‑lead ECG would be useful.

The committee recommended that data should be collected to evaluate the system impact of adopting the lead‑I ECGs on both primary and secondary care. In particular, data should be collected on how ECGs generated by the devices would be interpreted in practice, including staff time needed to interpret the ECG traces and associated costs.

Further primary research is recommended on the clinical effectiveness of using ELISA tests for therapeutic monitoring of TNF‑alpha inhibitors in people with rheumatoid arthritis.

secondary research is recommended to understand the clinical validity of enzyme-linked immunosorbent assay (ELISA) tests, that is the correlation between ELISA test results and health outcomes or states, such as remission, response, low or high disease activity or flares in rheumatoid arthritis

Secondary research is recommended to understand the comparative performance of different ELISA tests for therapeutic monitoring of tumour necrosis factor (TNF)‑alpha inhibitors in rheumatoid arthritis

The committee recommended further research on the incidence and effect of post-contrast acute kidney injury (PC‑AKI) in people with eGFR less than 30 ml/min/1.73 m2.

The committee recommended that a suitable risk factor screening tool for identifying risk of PC‑AKI for use across the NHS in people presenting for an outpatient CT scan with contrast agent is developed or an existing tool is validated.

The committee recommended studies to collect data on the rates of cancelled CT scans, whether cancelled appointments are filled and the effect on patients' experience before and after the introduction of point-of-care (POC) creatinine devices to radiology departments.

The committee recommended that further research is needed to measure the wider effects on public health and the costs of antimicrobial stewardship associated with different classes of antibiotics used in different healthcare settings. This will help to inform the development of technologies to guide more targeted use of antibiotics and wider UK antimicrobial resistance policy.

Companies should specify patient populations in the NHS who could benefit from test-guided preventive care for acute kidney injury. Further research is then recommended in these populations to assess the clinical effectiveness of defined care bundles designed to prevent or reduce the effect of acute kidney injury in the NHS. Research should be done in children, young people and adults, but specific considerations may be needed for children and young people when care differs from that for an adult population (see section 4.11).

Further research is recommended to assess the effect of test-guided preventive care (see section 5.1) on clinical outcomes (such as length of stay in hospital, mortality and need for renal replacement therapy and progression to chronic kidney disease). Research should be done in children, young people and adults, but specific considerations may be needed for children and young people when care differs from that for an adult population. Studies should investigate the effects of both positive and negative test results on clinical decisions and subsequent care.

Further research is recommended on the diagnostic performance of the TriageTrue high-sensitivity troponin test using samples at point of care.

Further research is recommended on how using sex-specific 99th percentile thresholds affects treatment decisions and clinical outcomes for men and women.

Further research is recommended to assess the diagnostic yield of the BioMonitor 2‑AF and Confirm Rx (or later devices) for atrial fibrillation when used in people who have had a cryptogenic stroke. The committee noted that existing ongoing research may provide further data for these devices (see section 3.51 and section 4.19).

Further data collection and research are recommended to understand how SeHCAT (tauroselcholic [75 selenium] acid) test results affect clinical decision making.

Further data collection and research are recommended to assess clinical outcomes after positive and negative SeHCAT test results. This research should focus on clinical outcomes relevant to people with chronic diarrhoea, such as severity of symptoms, including urgency. Clinical outcomes should be measured in the short and long term.

Further data collection and research are recommended to assess the effectiveness of treatment options for bile acid diarrhoea. Consideration should be given to how well the treatments are tolerated and how they affect the severity of symptoms in the longer term.

Further data collection and research are recommended to better understand the health-related quality of life in people with bile acid diarrhoea. Consideration should be given to how quality of life differs before and after a positive or negative test and diagnosis, and how it is affected by treatment and symptom severity.

The committee recommends more research on:

• the accuracy of PredictSURE IBD and IBDX tests in identifying people at high or low risk of following a severe course of Crohn's disease
• how PredictSURE IBD and IBDX tests, when used alongside clinical features, affect clinical decisions about whether step-up or top-down treatment is offered
• the clinical outcomes and costs resulting from a top-down treatment strategy compared with a step-up treatment strategy
• how PredictSURE IBD and IBDX tests affect clinical outcomes once someone has been assigned to top-down or step-up treatment, considering the different pathways that children and adults may follow.

Further research is recommended on:

• The accuracy of EarlyCDT Lung, and the validity of the risk models used to combine EarlyCDT Lung results with the Brock and the Herder risk models.
• The impact of EarlyCDT Lung on clinical management decisions.

A large retrospective audit is recommended to:

• Understand how patient and nodule characteristics impact on malignancy prevalence and disease progression.
• Understand current practice regarding clinical management of people with intermediate-risk lung nodules.
• Determine the clinical consequences of CT surveillance, including the likelihood of disease progression during CT surveillance.
• Determine the likelihood and impact of unnecessary biopsy or resection of indolent and benign nodules
• If existing data on these points is limited or not routinely collected, a prospective data collection should be undertaken to obtain it.

A high-quality test accuracy study is needed for the BRAHMS sFlt‑1 Kryptor/BRAHMS PLGF plus Kryptor PE ratio test, using thresholds defined by the company, done in a population independent from that used to establish the test's thresholds, and with the test used as intended in the NHS.

Further research is recommended on repeat PLGF (placental growth factor)‑based testing, with standard clinical assessment, in women presenting with suspected preterm pre-eclampsia, who have had a previous PLGF‑based test result (see section 3.7). This should include:

- exploring the different scenarios in which repeat testing may be indicated

- the appropriate intervals between PLGF‑based tests

- the diagnostic accuracy of repeat PLGF‑based testing in women with suspected preterm pre-eclampsia.

Further research is recommended into how well the tests work when women are pregnant with more than 1 baby to find out if different cut-offs are needed (see section 3.15).

Further research is recommended on:
• the impact of LiverMultiScan test results on decisions about care, such as the decision to do a liver biopsy, or on adherence to lifestyle interventions (see section 3.5)
• the test accuracy of LiverMultiScan compared with biopsy, or the prognostic ability of LiverMultiScan to predict clinical outcomes (see section 3.19).

Further research is recommended on:
• the impact of magnetic resonance elastography (MRE) test results on decisions about care, such as the decision to do a liver biopsy, or on adherence to lifestyle interventions (see section 3.5)
• the test accuracy of MRE to assess the level of fibrosis or presence of cirrhosis compared with biopsy at thresholds specified by the company, or the prognostic ability of MRE to predict clinical outcomes (see section 3.20).

There is uncertainty about how much remote monitoring devices would affect resource use in the NHS and personal social services. Some impacts may not have been included in the external assessment group's (EAG) model because of a lack of data (see section 3.12), including resource use related to carers (see section 3.13). Adopting the technologies may change how care is provided (see section 3.4) so their effect on resources is hard to estimate without direct data. So, the committee recommended collecting data on how much using the devices affects resource use, to inform cost-effectiveness estimates. Data on time dedicated to training and spent reviewing device results should also be collected. The broader impact on services provided by Parkinson's specialist teams and carers should be considered.

How much using remote monitoring devices to guide decisions about care affects symptoms, and therefore health-related quality of life, is uncertain. How long after using the devices any impact would last is also uncertain. This had a sizeable influence on cost-effectiveness estimates (see section 3.10). Data on this came from studies that did not represent likely NHS practice (see section 3.6), which is itself uncertain (see section 3.3), and from assumptions made by the EAG because of lack of data. For its model, the EAG used a published algorithm from Chandler et al. (2020) to estimate quality-adjusted life years (QALYs) from the Unified Parkinson's Disease Rating Scale (UPDRS) domain scores. The clinical experts said that health-related quality of life questionnaires like the PDQ‑39 are increasingly used in trials to assess health-related quality of life for people with Parkinson's disease. The committee also recognised that the effect of the devices on the health-related quality of life of carers had not been included in the EAG's model because of a lack of data (see section 3.13).

How frequently the remote monitoring devices were modelled as being used substantially affected the cost-effectiveness estimates in the EAG's model (see section 3.9). There are many ways the devices could be used in the NHS (see section 3.3) and no data was available to compare different approaches. So, it is currently not possible to highlight particular approaches that are likely to be more clinically and cost effective. Centres using the devices should therefore collect data on how often they are used and under what circumstances. For example, regularly in advance of scheduled review appointments, to indicate when such appointments are needed, or targeted to people having issues with symptoms. This will help assess the clinical and cost effectiveness of the different uses of the devices in NHS practice.

The committee recommends more research on diagnostic accuracy in people with leg ulcers. The following considerations should be made when doing this research:

The committee recommends collecting further data on the impact of the automated devices on time to treatment for people with leg ulcers to reduce uncertainty in the economic modelling.

The committee recommends collecting further data on clinical outcomes such as time to healing, and incorrect use of compression and its associated adverse consequences when possible.

Further research is recommended to determine the impact of MRI fusion biopsy systems compared with cognitive fusion biopsy on the detection of different grades of prostate cancer.

Further data collection or research is recommended on the impact of implementing MRI fusion biopsy systems on the rate at which biopsies can be done, capacity resources and waiting times for this procedure.

NICE encourages the company, NHS England and treatment centres to collect more evidence, particularly on the longer-term benefits and costs of eliglustat and enzyme replacement therapy for treating type 1 Gaucher disease.

In its evaluation of burosumab, the committee noted substantial uncertainty in several areas, and agreed that further research into the treatment benefit of burosumab in young people aged 13 years and over would relieve some of the clinical uncertainty in an age group covered by the marketing authorisation.

The committee also noted that the additional evidence exploring the relationship between radiological measures of bone defects (that is, the Rickets Severity Score and the Radiographic Global Impression of Change) and health-related quality of life would help to address several key uncertainties in the economic analysis.

Evidence on the progression of X-linked hypophosphataemia (XLH) over time and the long-term benefits of burosumab would also be valuable.

More research is needed on the following artificial intelligence (AI)‑derived software to analyse chest X‑rays alongside clinician review for suspected lung cancer in adults referred from primary care:

More research is needed on the following key outcomes:

More research is needed on using the following digital weight-management technologies:

NICE encourages further research into coronary sinus narrowing device implantation for refractory angina. This should report details of patient selection and long-term patient outcomes, including survival. 

Evidence on the efficacy of transanal total mesorectal excision of the rectum is adequate. Evidence on its safety is inconsistent. It also shows the potential for major safety concerns, including damage to adjacent structures and seeding of malignancy. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Further research, which could be randomised controlled trials or registry data, should report details of patient selection, including tumour type, use of neoadjuvant chemoradiotherapy and all complications, including malignancy dissemination.

Evidence on the safety and efficacy of endobronchial nerve ablation for chronic obstructive pulmonary disease (COPD) is inadequate in quantity. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Further research should be randomised controlled trials comparing the procedure with sham treatment. It should report details of patient selection, and short and long-term functional outcomes including lung functional outcomes, quality of life and patient-reported outcomes, incidence of exacerbations and hospital admissions, and all adverse events.

Evidence on the safety of endoscopic balloon dilation for subglottic or tracheal stenosis is adequate. The most serious complication related to the procedure, independent of age, is tracheal laceration but this is well recognised. For adults, evidence on the efficacy of the procedure is limited. So, it should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

NICE encourages further research on insertion of an epiretinal prosthesis for retinitis pigmentosa. Outcomes should include the impact on quality of life and activities of day-to-day living, and durability of implants. NICE may update the guidance on publication of further evidence.

NICE encourages further research into radiofrequency ablation for gastric antral vascular ectasia and collaborative publication of data from local audit. Patient selection should be clearly documented, including details of prior treatments. Outcomes should include success and duration of effect in controlling bleeding and the effect of this on the need for blood transfusion. All complications should be reported. NICE may update the guidance on publication of further evidence.

NICE encourages further research into hysteroscopic morcellation of uterine leiomyomas (fibroids) which could include data collection with publication of the findings, particularly of safety outcomes. Patient selection should be clearly described. Outcomes should include symptom relief, quality of life, recurrence rates and information about fertility and subsequent pregnancies. All complications should be documented. NICE may update the guidance on publication of further evidence.

NICE encourages further research comparing ultrasound-enhanced, catheter-directed thrombolysis for deep vein thrombosis against catheter-directed thrombolysis alone. Patient selection should be documented, including the duration and extent of thrombosis. The dose of thrombolytic agent used and the duration of thrombolysis should be reported, together with all complications. Outcome measures should include the success of thrombolysis (complete, partial or failed) and long-term sequelae. NICE may update the guidance on publication of further evidence.

NICE encourages further research into ultrasound-enhanced, catheter-directed
thrombolysis for pulmonary embolism. Ideally this should include comparative studies against catheter-directed thrombolysis alone. Patient selection should be  documented. The dose of thrombolytic agent used and the duration of thrombolysis should be reported, together with all complications. Outcome measures should include the success of thrombolysis (complete, partial or failed) and long-term sequelae. NICE may update the guidance on publication of further evidence.

NICE encourages further research on sphenopalatine ganglion stimulation for chronic cluster headache. Reported outcomes should include long-term efficacy and device durability.

Further research into joint distraction for knee osteoarthritis without alignment  correction should include comparative studies against existing forms of management. Studies should record patient selection, joint space measurements in the medium to long term, functional outcomes, quality of life and complications. They should also report the nature and timing of any further surgery on the knee. NICE may update the guidance on publication of further evidence.

NICE encourages further research into transcranial direct current stimulation (tDCS) for depression, which should document how patients were selected and any other treatments they were having. It should describe the precise method and regime used for administering tDCS. Outcome measures should include the duration of effect. NICE may update the guidance on publication of further evidence.

NICE encourages further research into preoperative high dose rate brachytherapy for rectal cancer. Trials should be designed to provide clear data on the efficacy of this procedure, whether or not other adjunctive treatments are used. Research should document adjunctive treatments and details of patient selection. Outcomes should include local recurrence, survival, disease-free survival and quality of life. NICE may update the guidance on publication of further evidence.

NICE encourages further research into low-energy contact X-ray brachytherapy (CXB) for early-stage rectal cancer. Research should clearly describe details of patient selection and treatment intent. It should document adjunctive treatments and subsequent procedures. Outcomes should include local recurrence, survival, disease-free survival and quality of life. NICE may update the guidance on publication of further evidence.

Further research on implanting a baroreceptor stimulation device for resistant hypertension should document patient selection in detail and should specify the devices and techniques used, and any adjunctive therapies. It should describe the changes in blood pressure that are considered to result from baroreceptor stimulation, and those that might be caused by other factors. Outcomes should include the duration of effect of baroreceptor stimulation; device durability; and the complications of hypertension, such as myocardial infarction and stroke.

NICE encourages further research on subretinal prosthesis system for retinitis pigmentosa. Outcomes should include the impact on quality of life and activities of day-to-day living, and durability of implants. NICE may update the guidance on publication of further evidence.

Further research into joint distraction for ankle osteoarthritis should include comparative studies against the natural history of the disease and against other forms of management. Studies should record patient selection, pain relief, functional outcomes, complications, and quality of life in the long term. They should also report the nature and timing of any further surgery on the ankle.
Minimising loss to follow-up is of particular importance. NICE may update the guidance on publication of further evidence.

NICE encourages further research into radiofrequency ablation for symptomatic Morton's neuroma. Further research should include details of patient selection and previous treatments. Studies should compare the procedure against other non-surgical treatments, such as steroid injections.
Outcome measures should include pain relief, the duration of treatment effect, and the need for subsequent treatments.

Current evidence on the safety and efficacy of electrical stimulation of the lower oesophageal sphincter for treating gastro-oesophageal reflux disease (GORD) is limited in quantity and quality. Therefore, this procedure should only be used in the context of research.

NICE encourages further research into transapical transcatheter mitral valve-in-valve implantation for a failed surgically implanted mitral valve bioprosthesis. This may include prospective observational studies. Studies should include details on patient selection, functional outcomes, quality of life, survival and complications. Studies should report long-term follow-up of clinical outcomes and valve durability. NICE may update this guidance on publication of further evidence.

NICE encourages further research into percutaneous electrothermal treatment of the intervertebral disc  annulus. Further research should document details of patient selection, including the duration of their symptoms. It should report precise details of the technique used for treatment. Outcome measures should include pain relief and quality of life. Long-term follow-up data should include details of any subsequent procedures.

NICE encourages further research into percutaneous intradiscal radiofrequency treatment of the intervertebral disc nucleus for low back pain. Further research should include details of patient selection, the duration of patients' symptoms, and a precise account of the technique used for treatment. Outcome measures should include pain relief and quality of life. Long-term follow-up data should
include details of any subsequent procedures.

Further research on angioplasty and stenting to treat peripheral arterial disease causing refractory erectile dysfunction should provide clear details of patient selection. Efficacy outcomes should include procedural success (as measured by arterial imaging and blood-flow measurement), validated scoring systems of erectile dysfunction, and the duration of treatment effect. All complications should be reported. NICE may update the guidance on publication of further evidence.

NICE encourages further research on endovascular aneurysm sealing for abdominal aortic aneurysmthis procedure in the form of controlled clinical trials, observational studies and analysis of registry data. Details about patient selection, including anatomical details, should be clearly documented.
Research should compare the procedure with conventional stent graft endovascular aneurysm repair. All complications should be reported. Long-term outcomes should be described as data become available. NICE may update the guidance on publication of further evidence.

NICE encourages further research into normothermic extracorporeal preservation of hearts for transplantation following donation after brainstem death. Outcomes should include primary graft function, graft function in the long term and device-related complications.

Further research on endoscopic carbon dioxide laser cricopharyngeal myotomy for relief of oropharyngeal dysphagia could include the publication of collaborative audit data. Reports should separate outcomes for different groups of patients; in particular for patients with primary neuromuscular dysfunction alone, those with associated phargyngeal diverticula and those with dysphagia caused by radiotherapy. Outcome measures should include dysphagia scores, quality of life, long-term outcomes and the need for further treatment. All complications should be reported. NICE may update this guidance on publication of further evidence.

NICE encourages further research on corticosteroid-eluting bioabsorbable stent or spacer insertion during endoscopic sinus surgery and, specifically, controlled studies designed for between-patient (rather than within-patient) comparisons. Outcomes should include symptom scores, quality of life and the need for retreatment in the long term. All complications should be reported. NICE may update this guidance on publication of further evidence.

NICE encourages further research on transcutaneous stimulation of the cervical branch of the vagus nerve for cluster headache and migraine. Studies should describe whether the procedure is used for treatment or prevention, and whether it is used for cluster headache or migraine. Clinicians should clearly document details of patient selection and the treatment regimen. Outcome measures should include changes in the number and severity of cluster headache or migraine episodes, medication use, quality of life in the short and long term, side effects, acceptability, and device  durability. NICE may update this guidance on publication of further evidence.

NICE encourages further research into balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension. Details of patient selection, all complications, and subsequent treatments and interventions for pulmonary hypertension should be collected. Reports should include quality-of-life outcomes, long-term efficacy outcomes and survival. NICE may update the guidance on publication of further evidence.

Current evidence on the efficacy and safety of biodegradable subacromial spacer insertion for rotator cuff tears is limited in quantity and quality. Therefore, this procedure should only be used in the context of research.

NICE encourages further research on transcutaneous electrical stimulation of the supraorbital nerve for treating and preventing migraine. Data should be collected for all patients not entered into controlled trials. Studies should describe clearly whether the procedure is used for treatment or prevention. They should include details of patient selection and the dose and frequency of use. Outcome measures should include the number and severity of migraine episodes, quality of life in the short and long term and any changes in medication. The development of any complications after starting treatment should be documented. NICE may update the guidance on publication of further evidence.

NICE encourages further data collection, including randomised controlled trials on microstructural scaffold insertion without autologous cell implantation for repairing symptomatic chondral knee defects. Studies should clearly describe patient selection, clinical indications and adjunctive treatments. Outcome measures should include symptom relief, functional ability, long-term outcomes measured by appropriate imaging techniques and patient-reported outcomes.

NICE encourages further research and publication on efficacy of miniature lens system implantation for advanced age-related macular degeneration (AMD) which patients may benefit and on safety and efficacy outcomes, particularly longer-term results. NICE may update the guidance on publication of further evidence.

NICE encourages further research into single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) for treating morbid obesity, particularly research examining long-term outcomes. NICE may update the guidance on publication of further evidence.

NICE encourages further research into epiduroscopic lumbar discectomy through the sacral hiatus for sciatica and may update the guidance on publication of further evidence. Research studies should include details of patient selection, complications and long-term results.

NICE encourages further research into extracorporeal shockwave therapy (ESWT) for Achilles tendinopathy, which may include comparative data collection. Studies should clearly describe patient selection, treatment protocols, use of local anaesthesia and the type and duration of energy applied (see section 3). Studies should include validated outcome measures and have a minimum of 1 year of follow-up. NICE may update the guidance on publication of further evidence.

Current evidence on the safety and efficacy of irreversible electroporation for treating prostate cancer is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. Studies should include randomised controlled trials comparing the procedure with current standards of care. They should report details of patient selection and short- and long-term outcomes, including patient-reported outcomes and the effect on any future prostate surgery.

NICE encourages further research into radiation therapy for early Dupuytren's disease, including randomised controlled trials. Because of the uncertainty over the natural history of the disease, this should include studies comparing the long-term efficacy of radiation therapy with no radiation therapy. Studies should include details of patient selection, stage of disease progression, duration and types of treatment, patient-reported outcomes, and long-term efficacy and safety data. NICE may update the guidance on publication of further evidence.

Further research into extraurethral (noncircumferential) retropubic adjustable compression devices for stress urinary incontinence in women should include detailed safety outcomes, long-term results and patient-reported outcome measures. NICE may update the guidance on publication of further evidence.

Further research, preferably in the form of randomised controlled trials, should assess the effect of the procedure on local tumour control, patient survival, pain
control and quality of life.

NICE encourages further research and data collection on endoscopic full thickness removal of non-lifting colonic polyps and may update the guidance on publication of further evidence. This should include safety and efficacy outcomes such as perforation, bleeding, the need for immediate re-intervention, inadequate resection and longer-term follow-up of patients found to have malignant disease.

Clinicians are encouraged to collect long-term data on clinical outcomes and patient-reported quality-of-life outcomes using validated scales. NICE may update the guidance on publication of further evidence.

Clinicians are encouraged to collect long-term data on clinical outcomes and patient-reported quality-of-life outcomes using validated scales. NICE may update the guidance on publication of further evidence into infracoccygeal sacropexy using mesh to repair uterine prolapse.

NICE encourages further research into laparoscopic insertion of a magnetic titanium ring for gastro-oesophageal reflux disease (GORD), and may update the guidance on publication of further evidence. Long-term outcome data and comparative trials with other anti-reflux surgery would be helpful.

NICE encourages further research into radiofrequency treatment for haemorrhoids, preferably randomised controlled trials. It may update the guidance on publication of further evidence. Outcomes should include pain, secondary haemorrhage, recurrence rate, the need for repeat procedures and quality-of-life measures. Details of patient selection should also be reported.

Further research on high-intensity focused ultrasound for symptomatic breast fibroadenoma should include publication of patient-reported outcome measures and studies with long-term follow-up.

Further research should give details of patient selection, patient-reported outcomes and long-term effects including survival and quality of life. NICE may update the guidance on publication of further evidence.

Further research on the safety and efficacy of total distal radioulnar joint replacement for symptomatic joint instability or arthritis should provide information on patient selection, and continue to collect long-term outcomes. NICE may update the guidance on publication of further evidence.

NICE encourages further research into processed nerve allografts to repair peripheral nerve discontinuities. This should include information on the type of nerve repaired, the anatomical site, the size of the defect, patient reported outcome measures, functional outcomes, time to recovery and long-term outcomes (12 months to 18 months).

Further research including the use of observational data from registries should provide information on patient selection, safety outcomes, quality of life, long-term
outcomes and the position of the procedure in the treatment pathway. NICE may update the guidance on publication of further evidence.

NICE encourages further research into transcutaneous microwave ablation for severe primary axillary hyperhidrosis and may update the guidance on publication of further evidence. Further research should include information on patient selection, objective measures of physiological effect, patient-reported outcome measures and long-term outcomes.

NICE encourages further research into total artificial heart implantation as a bridge to transplantation for end-stage refractory biventricular heart failure, including well matched comparative studies. NICE may update the guidance on publication of further evidence.

Further research on aortic valve reconstruction with processed bovine pericardium should address patient selection and report long-term outcomes, particularly the durability of the valve.

Further research on unilateral MRI-guided focused ultrasound thalamotomy for moderate to severe tremor in Parkinson's disease, which could include randomised controlled trials, should address patient selection and report on long-term follow-up.

Further research on laparoscopic mesh pectopexy for apical prolapse of the uterus or vagina should include details of patient selection and long-term outcomes.

Further research on robot-assisted kidney transplant should include studies comparing robot-assisted kidney transplant with open surgery. This should collect data on patient selection, warm ischaemia times, the need for conversion to open surgery, graft function, and long-term graft and patient survival.

The evidence on efficacy of nerve transfer to partially restore upper limb function in tetraplegia is limited in quantity. There are no major safety concerns. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.

NICE encourages further research into microinvasive subconjunctival insertion of a trans-scleral gelatin stent for primary open-angle glaucoma, including randomised studies. Further research should include details of patient selection and long-term outcomes.

NICE encourages the peer-reviewed publication of all further research for percutaneous balloon valvuloplasty for fetal critical aortic stenosis. Further research could be in the form of controlled trials, analysis of registry data or other observational studies. It should address patient selection, timing of the intervention and the natural history of the disease.

Further research on endoscopic bipolar radiofrequency ablation for treating biliary obstruction caused by cancer should address: patient selection, relief of biliary obstruction, quality of life and survival.

Further research on the efficacy and safety of intranasal phototherapy for allergic rhinitis should include: details of patient selection including medication use; underlying medical conditions; the intensity, duration and wavelength of light used; patient-reported outcomes; comparison with existing treatments; and the effects of repeated long-term use. NICE may update the guidance if further evidence is published.

Further research on the safety of unilateral MRI-guided focused ultrasound thalamotomy for treatment-resistant essential tremor, which could include randomised controlled trials, should address patient selection, report on functional improvement and quality of life, and provide long-term follow-up data.

Research on the safety and efficacy of superior capsular augmentation for massive rotator cuff tears should address patient selection, type of graft and technique used,
long-term outcomes including shoulder function, and patient-reported outcome measures.

Further research in low-intensity pulsed ultrasound to promote healing of fresh fractures at high risk of non-healing should include details of patient selection, fracture site, and risk factors and comorbidities that delay fracture healing.

NICE encourages further research into low-intensity pulsed ultrasound to promote healing of delayed-union and non-union fractures. Further research should include details of patient selection, fracture site, and risk factors and comorbidities that delay fracture healing.

Further research in people who could have conventional cardiac pacemaker implantation should report the patient selection criteria and compare leadless pacemakers with conventional pacemakers. Follow-up should be for at least 5 years and outcomes should include adverse events, symptom relief, quality of life and device durability in the long-term.

Further research in superior rectal artery embolisation for haemorrhoids should report details of patient selection, and follow-up efficacy (including symptom relief), need for subsequent treatments, quality of life and safety outcomes for at least 1 year.

NICE encourages further research into intravesical microwave hyperthermia and chemotherapy for non-muscle-invasive bladder cancer. Research should include randomised controlled trials, which stratify patients by risk and give adequate follow-up. They should report frequency of adverse events, patientreported outcome measures, overall and disease-free survival and quality of life.

NICE encourages further research into transurethral water jet ablation for lower urinary tract symptoms caused by benign prostatic hyperplasia and may update the guidance on publication of further evidence. Further research should report long-term follow-up and include reintervention rates.

Further research on selective internal radiation therapy (SIRT) for unresectable primary intrahepatic cholangiocarcinoma in the form of prospective studies, including randomised controlled trials, should address patient selection, quality-of-life outcomes and overall survival. Patient selection for the research studies should be done by a
multidisciplinary team. The procedure should only be done in specialist centres by clinicians trained and experienced in managing cholangiocarcinoma.

Clinicians should enter details about all patients having selective internal radiation therapy (SIRT) for unresectable primary intrahepatic cholangiocarcinoma onto a suitable registry.

Further research on subcutaneous automated low-flow pump implantation for refractory ascites should report details of patient selection, the frequency of pump-related complications, and the need for regular albumin infusions.

Further research on percutaneous insertion of a temporary heart pump for left ventricular haemodynamic support in high-risk percutaneous coronary interventions should report details of patient selection and subsequent management.

Further research on transcutaneous neuromuscular electrical stimulation for oropharyngeal dysphagia in adults should address patient selection, variations in technique, the need for retreatments and long-term outcomes.

Further research on ex-situ machine perfusion for extracorporeal preservation of livers for transplantation should report the exact method of perfusion used (such as
hypothermic or normothermic), graft survival and the use of marginal grafts.

Further research on platelet-rich plasma injections for knee osteoarthritis should be in the form of randomised controlled trials with medium- to long-term follow-up, including validated measures of knee function and patient-reported outcomes.

Further research on electrically stimulated intravesical chemotherapy for nonmuscle-invasive bladder cancer should include randomised controlled trials compared with
standard care, which should report details of patient selection.

Further research, ideally in the form of randomised controlled trials, on the safety and efficacy of prostatic urethral temporary implant insertion for lower urinary tract symptoms caused by benign prostatic hyperplasia should report details of patient selection (including prostate size and the amount of median lobe enlargement), improvement in lower urinary tract symptoms in the short term and long term, re-intervention rates, and outcome measures of sexual function using established methods.

Further research should include details of patient selection, durability and the incidence of complications. Outcomes should be published.

Further research should report details of patient selection, nodule size and position, and whether the nodule is cystic.

Current evidence on the safety and efficacy of radially emitting laser fibre treatment of an anal fistula is limited in quantity and quality. Therefore, although there are no major safety concerns, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.

The evidence on percutaneous insertion of a cerebral protection device to prevent cerebral embolism during TAVI raises no major safety concerns other than those associated with the TAVI procedure. However, the evidence on efficacy for preventing TAVI-related stroke is inconclusive. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.

Current evidence on the safety of percutaneous mechanical thrombectomy for acute deep vein thrombosis (DVT) of the leg shows there are well-recognised but infrequent complications.

Current evidence on the safety of percutaneous mechanical thrombectomy for acute deep vein thrombosis (DVT) of the leg shows there are well-recognised but infrequent complications.

Current evidence on the safety and efficacy of bronchoscopic thermal vapour ablation for upper-lobe emphysema is inadequate in quantity and quality. Therefore the procedure should only be used in the context of research.

Current evidence on the safety and efficacy of valve-in-valve transcatheter aortic valve implantation (ViV‑TAVI) for aortic bioprosthetic dysfunction is adequate to support the use of this procedure provided that standard arrangements are in place for clinical governance, consent and audit.

The evidence on the safety of reinforcement of a permanent stoma with a synthetic or biological mesh to prevent a parastomal hernia shows there are serious but well-recognised complications. The evidence on efficacy is limited in quantity and quality. Therefore, this procedure should not be used unless special arrangements are in place for clinical governance, consent, and audit or research.

The evidence on cardiac contractility modulation device implantation for heart failure raises no major safety concerns. However, the evidence on efficacy is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research.

The evidence on the safety of transurethral laser ablation for recurrent non-muscle-invasive bladder cancer shows that there are no major safety concerns. However, current evidence on its efficacy is limited in quality and quantity. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.

Current evidence on the safety of ultrasound-guided high‑intensity transcutaneous focused ultrasound for symptomatic uterine fibroids shows there are well-recognised complications including skin burns. The evidence on efficacy is limited in quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.

Current evidence on the safety and efficacy of endovascular insertion of an intrasaccular wire-mesh blood-flow disruption device for intracranial aneurysms is adequate to support the use of this procedure provided that standard arrangements are in place for clinical governance, consent and audit.

Current evidence on the safety and efficacy of low-energy contact X‑ray brachytherapy (the Papillon technique) for locally advanced rectal cancer is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research.

Current evidence on the safety and efficacy of implant insertion for prominent ears is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research.

Evidence on the safety and efficacy of high-intensity focused ultrasound for glaucoma is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research.

Evidence on the safety and efficacy of midcarpal hemiarthroplasty for wrist arthritis is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research.

Evidence on the safety of irreversible electroporation for primary liver cancer shows serious but infrequent and well-recognised complications. Evidence on its efficacy is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research.

NICE may update this guidance after 3 years or sooner if important new information becomes available, including evidence on:

• the epidemiology of CJD, including data on the prevalence of CJD and its infectivity in the UK population
• the transmission of CJD by surgical instruments, including cases of CJD in which surgery is a possible route of transmission
• the cost effectiveness of single-use instruments for use in interventional procedures on high-risk tissues
• commercially available decontmination methods that are safe and cost effective against prions
• the systems for, and cost effectiveness of, maintaining set integrity and traceability of instruments.

Evidence on the efficacy of open prenatal repair of open neural tube defects in the fetus is adequate in quantity and quality. However, evidence on its safety shows serious but well recognised safety concerns for the mother and fetus. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.

Evidence on the safety and efficacy of fetoscopic prenatal repair of open neural tube defects in the fetus is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. This could be in the form of randomised controlled trials or published registry data.

Bilateral cervicosacropexy (CESA) or vaginosacropexy (VASA) using mesh for pelvic organ prolapse

MRI-guided laser interstitial thermal therapy for drug-resistant epilepsy Interventional procedures guidance

Selective internal radiation therapy for unresectable colorectal metastases in the liver

Evidence on the safety and efficacy of artificial iris implant insertion for acquired aniridia is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE website.

Evidence on the safety of transcranial magnetic stimulation for obsessive-compulsive disorder raises no major safety concerns. However, evidence on its efficacy is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE website.

1.1Evidence on the safety of electrical stimulation to improve muscle strength in chronic respiratory conditions, chronic heart failure and chronic kidney disease shows no major safety concerns.

Further research should describe patient selection and clearly define the target area of the brain. Outcomes should include reduction in seizure frequency and improvement in the epilepsy seizure outcome scale, quality of life, reduction in concomitant medication and hospital admissions.

NICE encourages further research into implanted vagus nerve stimulation for treatment-resistant depression, in the form of randomised controlled trials with a placebo or sham stimulation arm. Studies should report details of patient selection. Outcomes should include validated depression rating scales, patient-reported quality of life, time to onset of effect and duration of effect, and any changes in concurrent treatments.

Evidence on the safety of pressurised intraperitoneal aerosol chemotherapy for peritoneal carcinomatosis shows that this procedure can cause serious but well-recognised side effects. Evidence on its efficacy is inadequate in quality. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE website.

Evidence on the safety and efficacy of balloon cryoablation for Barrett's oesophagus is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. This could be in the form of randomised controlled trials or published registry data. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of balloon cryoablation for squamous dysplasia of the oesophagus is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. This could be in the form of randomised controlled trials or published registry data. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety of the swallowable gastric balloon capsule for weight loss shows infrequent but potentially serious adverse events:

Evidence on the safety of repetitive short-pulse transscleral cyclophotocoagulation for glaucoma shows no major safety concerns. Evidence on efficacy is inadequate in quality. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE website.

Evidence on the safety and efficacy of permanent His-bundle pacemaker implantation for treating heart failure is inadequate in quality and quantity.
Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

The evidence on transvaginal laser therapy for stress urinary incontinence does not show any short-term safety concerns. Evidence on long-term safety and
efficacy is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research. Find out what only in research means onthe NICE interventional procedures guidance page.

The evidence on transvaginal laser therapy for urogenital atrophy does not show any short-term safety concerns. Evidence on long-term safety and efficacy is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of inducing and maintaining normothermia using temperature modulation devices to improve outcomes after stroke or subarachnoid haemorrhage is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety of magnetic resonance therapy for knee osteoarthritis shows no major safety concerns. Evidence on efficacy is inadequate in quality and quantity and shows no benefit over placebo. Therefore, this procedure should not be used unless it is part of a research study. Further research should be in the form of appropriately powered randomised controlled trials comparing the procedure with placebo. It should report patient selection and treatment protocols, including the number of sessions and magnetic field strength.

Evidence on the safety of laparoscopic removal of uterine fibroids with power morcellation shows potentially serious complications. In particular there is a risk of spreading undiagnosed malignant tissue, which has higher prevalence in people who are postmenopausal or over 50. Evidence on the procedure's efficacy is limited in quantity. Therefore, further research should report details of patient selection, surgical technique (including any containment system used) and long-term outcomes.

Evidence on the safety and efficacy of lateral elbow resurfacing for arthritis is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Further research, which could include case series with long-term follow up, should report range of motion, patient-reported outcomes and complications.

NICE encourages further research into transapical transcatheter mitral valvein-valve implantation for a failed surgically implanted mitral valve bioprosthesis. Studies should include details on patient selection, type and size of valve used, functional outcomes (New York Heart Association functional class, mitral valve regurgitation), quality of life, patient-reported outcome measures, survival and complications. Studies should report long-term follow up of clinical outcomes and valve durability. NICE may update this guidance on publication of further evidence.

NICE encourages further research into transapical transcatheter mitral valvein-ring implantation after failed annuloplasty for mitral valve repair. Studies should include details on patient selection, type and size of valve used, functional outcomes (New York Heart Association functional class, mitral valve regurgitation), quality of life, patient-reported outcome measures, survival and complications. Studies should report long-term follow up of clinical outcomes and valve durability. NICE may update this guidance on publication of further evidence.

Evidence on the safety of genicular artery embolisation for pain from knee osteoarthritis shows no major safety concerns in the short term. Evidence on its efficacy and long-term safety is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page. Research should preferably be randomised controlled trials against sham and current best practice. It should report details of patient selection and identify those who would most benefit from this procedure. It should also report details of the technique used, long-term safety, and patient-reported outcomes. The procedure should only be done by interventional radiologists with specific training in this technique.

Evidence on the safety and efficacy of laparoscopic renal denervation for loin pain haematuria syndrome is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page. Further research should report details of patient selection, technique used and long-term follow-up outcomes

NICE encourages further research, preferably randomised controlled trials, into percutaneous endovascular forearm arteriovenous fistula creation for haemodialysis access. This should report details of patient selection, particularly about vascular anatomy, technique used, need for training, patency of the fistula and its subsequent ease of use, and quality of life.

Evidence on the safety of microwave ablation for treating primary lung cancer and metastases in the lung is adequate but shows it can cause infrequent serious complications. Evidence on its efficacy shows it reduces tumour size. But the evidence on improvement in survival, long-term outcomes and quality of life is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Further research should be randomised controlled trials or disease registry studies. It should report patient selection, disease progression and quality of life, and take account of the effectiveness of managing oligometastatic disease in patients.

Evidence on the safety and efficacy of intramedullary distraction for lower limb lengthening is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page. This guidance is not intended to cover this procedure for bilateral lower limb lengthening for people with short stature.

Evidence on the safety and efficacy of percutaneous insertion of a cystic duct stent after cholecystostomy for acute calculous cholecystitis is inadequate in quality and quantity. But because patients would otherwise need permanent external drainage, the procedure can be considered for this condition, as long as special arrangements for clinical governance, consent, and audit or research are in place. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety of liposuction for chronic lipoedema is inadequate but raises concerns of major adverse events such as fluid imbalance, fat embolism, deep vein thrombosis, and toxicity from local anaesthetic agents. Evidence on the efficacy is also inadequate, based mainly on retrospective studies with methodological limitations. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of intramedullary distraction for upper limb lengthening is inadequate in quantity and quality. But because this is a rare condition with limited alternative treatments, the procedure can be considered as long as special arrangements for clinical governance, consent, and audit or research are in place. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Further research, which could be registry data, should report details of patient selection, device selection, technique used, procedural outcomes, long-term outcomes including quality of life, the need for repeat interventions or surgery and complication rates.

Evidence is adequate on the short-term safety and efficacy of personalised external aortic root support (PEARS) using mesh to prevent aortic root expansion and aortic dissection in people with Marfan syndrome. Evidence on long-term outcomes is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Further research should report details of patient selection, including aortic diameter, and long-term outcomes, including evidence of disease progression, such as dilation and dissection of the aortic root.

For people with unfavourable aneurysm morphology needing an endovascular aortic aneurysm repair (EVAR) as a primary procedure, or for people with an existing EVAR who need a secondary procedure, evidence on the safety of using endoanchoring systems is adequate. Evidence on efficacy is limited in quantity and quality. Therefore, for these people, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

For people with favourable aneurysm morphology needing an EVAR as a primary procedure, evidence on the safety of using endoanchoring systems is adequate. However, evidence on efficacy is inadequate in quantity and quality. Therefore, for these people, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of supercapsular percutaneously assisted total hip arthroplasty for osteoarthritis is limited in quality and quantity. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

For people with severe and symptomatic tricuspid regurgitation, evidence on the efficacy of transcatheter tricuspid valve annuloplasty is limited in quantity and quality. Evidence on its safety shows there are serious but well-recognised complications. Therefore, for these people, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

For people with mild or moderate tricuspid regurgitation, evidence on the safety and efficacy of transcatheter tricuspid valve annuloplasty is inadequate in quantity and quality. Therefore, for these people, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

For people with severe and symptomatic tricuspid regurgitation, evidence on the efficacy of transcatheter tricuspid valve leaflet repair is limited in quantity and quality. Evidence on its safety shows there are serious but well-recognised complications. Therefore, for these people, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

For people with mild or moderate tricuspid regurgitation, evidence on the safety and efficacy of transcatheter tricuspid valve leaflet repair is inadequate in quantity and quality. Therefore, for these people, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the efficacy of bioresorbable stent implantation to treat coronary artery disease is inadequate. Evidence on its safety has shown an increased risk of serious complications in the longer term. This includes an increased risk of myocardial infarction and death with some types of bioresorbable stents. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of aortic remodelling hybrid stent insertion during surgical repair of an acute type A aortic dissection is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the efficacy of focal resurfacing implants to treat articular cartilage damage in the knee is limited in quality and quantity. Short-term evidence shows no major safety concerns, but long-term evidence on safety is limited in quality and quantity. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety of transcutaneous electrical neuromuscular stimulation for urinary incontinence raises no major safety concerns. Evidence on its efficacy is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of prostatic urethral temporary implant insertion for lower urinary tract symptoms caused by benign prostatic hyperplasia is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of removal, preservation and subsequent reimplantation of ovarian tissue to prevent symptoms from the menopause is inadequate in quality and quantity. Therefore, this procedure should not be done unless it is part of a formal research study, with appropriate governance and ethics approval. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the efficacy and safety of neurostimulation of lumbar muscles for refractory non-specific chronic low back pain is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

The evidence for treating an acute migraine attack is adequate but, for treating subsequent attacks, is limited in quality and quantity. So, for treating acute migraine, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

The evidence for preventing migraine is inadequate in quality. So, for preventing migraine, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of YAG laser vitreolysis for symptomatic vitreous floaters is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety of extracorporeal shockwave therapy for calcific tendinopathy in the shoulder shows no major safety concerns in the short term. Evidence on efficacy is inadequate. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page

Evidence on the safety of ab interno canaloplasty for open-angle glaucoma shows no major safety concerns. Evidence on the efficacy is limited in quality and quantity, particularly in the long term. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety of long-term tunnelled peritoneal drainage catheter insertion for refractory ascites in cirrhosis is limited but shows well-recognised complications. Evidence on the efficacy is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of percutaneous image-guided cryoablation of peripheral neuroma for chronic pain is inadequate in quality and quantity. Therefore, this procedure should only be used in the
context of research. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of transvenous obliteration of gastric varices is adequate in the short term but limited in the long term. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of biodegradable spacer insertion to reduce rectal toxicity during radiotherapy for prostate cancer is limited in quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety of endoluminal gastroplication for gastro-oesophageal reflux disease is adequate. However, evidence on its efficacy is inadequate in quality, particularly in terms of patient selection and long-term outcomes. Therefore, this procedure should be used only
in research. Find out what only in research means on the NICE interventional procedures guidance page.

Percutaneous transluminal renal sympathetic denervation for resistant hypertension should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of percutaneous thoracic duct embolisation for persistent chyle leak is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety of focal therapy using high-intensity focused ultrasound for localised prostate cancer is adequate, but evidence on its efficacy is limited. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of radiofrequency ablation for palliation of painful spinal metastases is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Find out what special arrangements mean on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of daytime intraoral neuromuscular electrical tongue stimulation using a removable device for obstructive sleep apnoea is inadequate in quality and quantity. So, this procedure should be used only in research. Find out what only in research means on the NICE interventional procedures guidance page.

Evidence on the safety and efficacy of endoscopic ultrasound-guided biliary drainage (EUS-BD) for biliary obstruction caused by distal malignant disease is adequate to support using this procedure. This is provided that standard arrangements are in place for clinical governance, consent and audit. Find out what standard arrangements mean on the NICE interventional procedures guidance page.

Minimally invasive fusionless posterior-approach surgery to correct idiopathic scoliosis in children and young people should be used only in research. Find out what only in research means on the NICE interventional procedures guidance page.

Further research should ideally be in the form of randomised controlled trials. Details of patient selection, the procedure and long-term outcomes should be reported.

Further research should report details of patient selection, duration of the effect (including whether repeat procedures are needed), and long term outcomes.

Further research should report:

Research should report:

Further research should include details of patient selection and report longer term outcomes.

Further research should be in the form of randomised controlled trials or registries. It should report:

Middle meningeal artery embolisation for chronic subdural haematomas should be used only in research. Find out what only in research means on the NICE interventional procedures guidance page.

Research is recommended to address uncertainties about the claimed patient and system benefits of using Parafricta Bootees and Undergarments.

Research is recommended on HumiGard compared with standard insufflation gases in patients having laparoscopic or open surgery alongside general measures to reduce the risk of perioperative hypothermia (described in section 2.5). Research should report on the comparative rate of surgical site infections and other complications associated with hypothermia and normothermia, as well as related resource use.

NICE concluded that the cost consequences of using HumiGard in abdominal surgery are very uncertain, and that further research is needed on resource use.

Further research is needed on the benefits and consequences of detecting preclinical diabetic peripheral neuropathy.

Research is recommended to address uncertainties about the claimed benefits of using Mepilex Border Heel and Sacrum dressings. This research should also explore issues such as:
- the incidence of heel and sacrum pressure ulcers in NHS acute care settings
- criteria for patient selection to reduce pressure ulcer incidence with Mepilex Border Heel and Sacrum dressings in addition to standard care.
NICE will consider reviewing this guidance when substantive new evidence becomes available.

Further evidence to address the uncertainties in the current clinical evidence,
including the impact of gammaCore on all treatments and care as well as its
long-term benefits, would be welcome.

Episcissors-60 show promise for mediolateral episiotomy. But there is currently not enough evidence to support the case for routine adoption in the NHS.

Research is recommended to address uncertainties about the efficacy and safety of using Episcissors-60. This research should:

- determine if using Episcissors-60 in addition to other care bundle measures is more effective in achieving an optimal episiotomy angle and in preventing episiotomy-related obstetric anal sphincter injuries (OASI) than standard episiotomy scissors

- include patient-reported outcome measures

- address potential equality considerations by ensuring patients at greatest risk of OASI are recruited

- determine the relative cost of using Episcissors-60 compared with standard episiotomy scissors.

Further evidence to address uncertainties about the relative clinical and cost effectiveness of UroLift compared with Rezum, especially in the NHS, would be welcome. This should include:

• exploring long-term clinical outcomes and reintervention rates after UroLift

• assessing the suitability of UroLift for prostates larger than 80 ml and for those with an obstructive median lobe.

A randomised controlled trial is recommended to compare DyeVert Systems with standard care. The aim of this research would be to address uncertainties about whether using DyeVert Systems reduces AKI incidence and rate of renal replacement therapy after using contrast media. This must include people with stage 4 chronic kidney disease (with an estimated glomerular filtration rate [eGFR] under 30 ml/min/1.73 m2), who are at risk of AKI and need elective coronary or peripheral angiography.

Endo-SPONGE shows promise for treating low rectal anastomotic leaks. However, there is not enough good-quality evidence to support the case for routine adoption in the NHS. Further evidence in the form of real-world data collection is recommended to address uncertainties about selection criteria, patient-reported outcome measures, stoma reversal and bowel function recovery compared with other treatments. Find out more in the section on further research in this guidance.

Further research is recommended to identify any health conditions or groups of patients that would benefit more from inhaled sedation with Sedaconda ACD-S than from standard care

Additional research could help address uncertainties in the evidence, although the case for cost savings remains unlikely.

Although the committee acknowledged that the Game et al. (2018) RCT was well conducted, it felt that additional research could help resolve some uncertainties around the cost and clinical case for 3C Patch. Specifically, research identifying the most appropriate stopping rule, and the associated clinical outcomes of implementing the rule, would help address key uncertainties within the cost case. Additional collection of resource use data on unhealed hard-to-heal ulcers could also reduce uncertainty in the cost case. Further to this, evidence could be collected on an UrgoStart-experienced population, as this would be reflective of current NHS care. Clinical experts thought a trial on this population would be feasible. The committee concluded that although further research could be done, on balance it was unlikely to result in a cost-saving case for 3C Patch based on the decision problem evaluated in this guidance

Randomised controlled trials comparing Prontosan with saline or water in the NHS are needed.

The committee concluded that further research is needed to address the uncertainties about the clinical effectiveness of Prontosan compared with saline or water. It recommended that randomised controlled trials should be done in the NHS. These should compare Prontosan with saline or water in different types of chronic wounds. The randomised controlled trial needs to be well designed to detect clinically meaningful results in subgroups (for example, pressure ulcers or venous leg ulcers). The committee agreed that a key outcome should be time to complete wound healing. The number of dressing changes should also be recorded for each wound included in the study. Other important outcomes should include pain and wound odour, measured using patient reported outcome measures (PROMs).

Further good quality evidence is needed to address uncertainties about myCOPD's clinical benefits and its effect on healthcare resource use. myCOPD has potential for clinical benefits, but more evidence is needed to reduce uncertainties. The committee considered that comparative evidence is needed to show the clinical benefits of using myCOPD in 2 populations:

• people using it to self-manage COPD
• people referred to pulmonary rehabilitation

For self-management, a randomised controlled trial is preferred to show the clinical benefits of myCOPD. This could be powered based on the encouraging results in the RESCUE study. However, a high-quality comparative observational study designed to minimise bias in the results may provide acceptable evidence. Outcomes such as rates of exacerbations, hospital readmissions and unscheduled care appointments should be considered alongside patient-reported outcomes such as health-related quality of life. For pulmonary rehabilitation, further evidence is needed to show the clinical benefits of myCOPD. This could be a randomised controlled trial which is powered based on the encouraging results in the TROOPER study or a well-designed comparative observational study. Key outcomes will be the CAT score and 6-minute walk test, ideally supported by additional longer-term outcomes such as rates of exacerbations and hospital admissions.

Real-world data could be used to inform the uptake rates in the economic modelling. It should also include qualitative data on patient experience using myCOPD such as patient preferences and adherence.

More research is recommended on UroShield for preventing catheter associated urinary tract infections (UTIs). It has potential to provide significant patient and healthcare system benefits but uncertainties in the evidence need to be addressed.

Research should be comparative, and it should address uncertainties about the effectiveness of UroShield in preventing catheter-associated UTIs and other catheter-related complaints such as blockages. Find out more in the further research section of this guidance.

More research or data collection is recommended on Sleepio for people who are eligible for face-to-face cognitive behavioural therapy for insomnia (CBT-I) in primary care. This is because there is limited clinical evidence to show how effective Sleepio is compared with face-to-face CBT-I. A real-world study is suggested to compare the effectiveness of Sleepio with face-to-face CBT-I.

Given the limited evidence available, the original guidance committee noted that it would be beneficial to routinely collect data on all ureteric stent placement procedures. This was ideally in collaboration with a national professional society such as the British Association of Urological Surgeons. Clinical experts confirmed that an NHS registry for stent procedures has not been set up since the original guidance, and the evidence base remains limited with no prospective data available. The committee for this guidance update considered it important to further emphasise the need for collecting data using a national database or clinical registry on ureteric stent procedures. The prospective data collection should cover information about patient selection, choice of stent placement procedure and stent used, and adverse events such as
stent migration and encrustation rates. It concluded that this should form part of its recommendations in section 1 of the guidance, and agreed that such data collection should be used to help inform the most appropriate patient population for Memokath 051.

Long-term real-world data is needed on AposHealth's clinical effectiveness and cost benefit

Long term real-world data is needed on AposHealth's clinical effectiveness and cost benefit

What are the symptoms of GORD in infants, children and young people with a neurodisability?

What is the effectiveness and cost effectiveness of a trial of hydrolysed formula in formula‑fed infants with frequent regurgitation associated with marked distress?

In infants, children and young people with overt or occult reflux, is fundoplication effective in reducing acid reflux as determined by oesophageal pH monitoring?

Medication for promoting de-escalation:- Which medication is effective in promoting de-escalation in people who are identified as likely to demonstrate significant  violence?

Violence related to drug or alcohol misuse:- What is the best environment in which to contain violence in people who have misused drugs or alcohol?

Advance statements and decisions:- What forms of management of violence and aggression do service users prefer and do advance statements and decisions have an important role in management and prevention?

Content and nature of effective de-escalation:- What is the content and nature of effective de-escalatory actions, interactions and activities used by mental health nurses, including the most effective and efficient means of training nurses to use
them in a timely and appropriate way?

Long duration or very frequent manual restraint:- In what circumstances and how often are long-duration or repeated manual restraint used, and what alternatives are there that are safer and more effective?

Analgesics:- What is the clinical and cost effectiveness of analgesic drugs other than non-steroidal antiinflammatory drugs (NSAIDs) in adults with rheumatoid arthritis (RA) whose pain or stiffness control is not adequate?

Short-term bridging treatment with glucocorticoids:- What is the clinical and cost effectiveness of short-term bridging treatment with glucocorticoids for adults with RA starting a new disease-modifying anti-rheumatic drug (DMARD), including the most effective dosing strategy and mode of administration?

Ultrasound in monitoring:- What is the clinical and cost effectiveness of using ultrasound to monitor disease in adults with RA when clinical examination is inconclusive or inconsistent with other signs of disease activity?

Ultrasound in diagnosis:- What is the clinical and cost effectiveness of using ultrasound in addition to clinical assessment when there is uncertainty about the diagnosis in adults with suspected RA?

Management of poor prognosis:- What is the clinical and cost effectiveness of managing RA with a poor prognosis (identified as presence of anti-cyclic citrullinated peptide [CCP] antibodies or evidence of erosions on X-ray at diagnosis) with a different strategy from that used for standard management of RA?

Subcutaneous methotrexate:- What is the clinical and cost effectiveness of subcutaneous methotrexate compared with oral methotrexate for adults with early onset RA starting a new DMARD?

Surgery to the breast:- What is the optimum tumour-free margin width after breast-conserving surgery for women with ductal carcinoma in situ (DCIS) and invasive breast cancer?

Efectiveness of 26 Gy in 5 fractions over 1 week regimen in people receiving nodal irradiation- What is the effectiveness of radiotherapy given in 26 Gy in 5 fractions over 1 week compared with 40 Gy in 15 fractions over 3 weeks in people with early or locally advanced invasive breast cancer who are also offered nodal irradiation?

Adjuvant bisphosphonate therapy:- Which groups of people with early and locally advanced breast cancer would benefit from the use of adjuvant bisphosphonates?

Breast reconstruction:- What are the long-term outcomes for breast reconstruction in women having radiotherapy to the chest wall?

Neoadjuvant endocrine therapy in premenopausal women:- Is neoadjuvant endocrine therapy safe in premenopausal women with early breast cancer?

Neoadjuvant endocrine therapy in postmenopausal women:- Is there a benefit for neoadjuvant endocrine therapy in postmenopausal women with early breast cancer?

Neoadjuvant treatment:- What are the indications for postmastectomy radiotherapy after neoadjuvant chemotherapy?

What is the most effective and cost-effective way of delivering the intervention (for example, type of physiotherapy or exercise, mode of delivery, number of sessions) to reduce arm and shoulder problems after breast cancer surgery or radiotherapy, and what is the acceptability of the intervention for different groups, such as:

women, men, trans people and non-binary people

people from minority ethnic family backgrounds

people with learning disabilities or cognitive impairment, or physical disabilities, or both

neurodiverse people?

Strategies to reduce arm and shoulder problems- What is the most effective and cost-effective way of delivering the intervention (for example, type of physiotherapy or exercise, mode of delivery, number of sessions) to reduce arm and shoulder problems after breast cancer surgery or radiotherapy, and what is the acceptability of the intervention for different groups, such as:

women, men, trans people and non-binary people

people from minority ethnic family backgrounds

people with learning disabilities or cognitive impairment, or physical disabilities, or both

neurodiverse people?

What is the adherence to, and satisfaction with, different intervention formats (for example, individual, group, virtual, and face to face) to reduce arm and shoulder problems after breast cancer surgery or radiotherapy, and what is the impact of greater adherence on effectiveness for different groups, such as:

women, men, trans people and non-binary people

people from minority ethnic family backgrounds

people with learning disabilities or cognitive impairment, or physical disabilities, or both

neurodiverse people?

What is the adherence to, and satisfaction with, different intervention formats (for example, individual, group, virtual, and face to face) to reduce arm and shoulder problems after breast cancer surgery or radiotherapy, and what is the impact of greater adherence on effectiveness for different groups, such as:

women, men, trans people and non-binary people

people from minority ethnic family backgrounds

people with learning disabilities or cognitive impairment, or physical disabilities, or both

neurodiverse people?

Effectivness of 26 Gy in 5 fractions over 1 week regimen in people receiving breast construction- What is the effectiveness of radiotherapy given in 26 Gy in 5 fractions over 1 week compared with 40 Gy in 15 fractions over 3 weeks in people with early or locally advanced invasive breast cancer who are offered breast reconstruction? 

Referral within a formal care pathway:- Is referral from a community pharmacy within a formal local care pathway framework more effective and cost effective than signposting alone in improving access to, and uptake of, services by underserved groups and the general population?

Health and wellbeing interventions:- How effective and cost effective are awareness raising, advice and education or behavioural support interventions delivered by community pharmacy teams to improve health and behavioural outcomes in underserved groups and the general population?

Addressing health inequalities:- What are the barriers to and facilitators for increasing access to community pharmacy services by underserved groups? How should health and wellbeing interventions be tailored to increase service uptake in underserved groups?

Characteristics of a person delivering an intervention:- How do the professional characteristics of pharmacy staff affect the effectiveness and cost effectiveness of delivering information, advice, education or behavioural support to underserved groups and the general population? (Characteristics include, for example, job roles such as health champion, as well as competencies and level of training.)

Patient activation:- How effective and cost effective is advice, education or behavioural support offered by community pharmacy teams to improve patient activation and measures of behaviour and health changes, particularly in areas where activation levels are lower? This includes evaluating factors such as frequency, intensity and duration of the intervention.

People in eligible groups:- What are the important messages and how should they be tailored and delivered to encourage and sustain flu vaccination uptake in eligible groups?

Underserved groups:- What are the most effective and cost-effective ways of reaching underserved groups and removing barriers to access in order to increase their uptake of flu vaccination?

Carers:- In what context is it cost effective to increase uptake of flu vaccination among carers?

Opt-out strategies for front-line health and social care staff:- Are opt-out strategies effective and cost effective at increasing uptake of flu vaccination among front-line health and social care staff?

Community-based models of flu vaccination:- What models of community-based flu vaccination provision (for example, community pharmacies, community nursing and midwifery teams and outreach services) are effective and cost-effective for increasing uptake in eligible groups?

Diagnosis of chronic pancreatitis:- In people with suspected (or under investigation for) chronic pancreatitis, whose diagnosis has not been confirmed by the use of 'first-line' tests (for example, CT scan, ultrasound scan, upper gastrointestinal [GI] endoscopy or combinations of these), what is the accuracy of magnetic resonance cholangiopancreatography (MRCP) with or without secretin and endoscopic ultrasound to identify whether chronic pancreatitis is present?

Speed of intravenous fluid resuscitation for people with acute pancreatitis:- What is the most clinically effective and cost-effective speed of administration of intravenous fluid for resuscitation in people with acute pancreatitis?

Pain management: chronic pancreatitis:- Is the long-term use of opioids more clinically effective and cost effective than non-opioid analgesia (including non-pharmacological analgesia) in people with chronic pain due to chronic pancreatitis?

Pain management: small duct disease:- What is the most clinically effective and cost-effective intervention for managing small duct disease (in the absence of pancreatic duct obstruction, inflammatory mass or pseudocyst) in people with chronic pancreatitis presenting with pain?

Management of type 3c diabetes:- What is the most clinically effective and cost-effective insulin regimen to minimise hypo- and hyperglycaemia for type 3c diabetes secondary to pancreatitis?

Non-clinical interventions:- How effective and cost effective are non-clinical interventions to reduce suicidal behaviours?

Supporting people bereaved or affected by a suicide:- How effective and cost effective are interventions to support people in the community who are bereaved or affected by a suicide?

Suicide prevention in custodial and detention settings:- What interventions are effective and cost effective in reducing suicide rates in custodial and residential settings?

Training:- How effective and cost effective is gatekeeper training in preventing suicides?

Diuretic therapy for managing fluid overload in people with advanced heart failure in the community:-  In people with advanced heart failure and significant peripheral fluid overload, what is the clinical and cost effectiveness of oral, subcutaneous and intravenous diuretic therapy in the community?

Cardiac MRI versus other imaging techniques for diagnosing heart failure:- What is the optimal imaging technique for the diagnosis of heart failure?

The impact of atrial fibrillation on the natriuretic peptide threshold for diagnosing heart failure:- What is the optimal NT-proBNP threshold for the diagnosis of heart failure in people with atrial fibrillation?

The impact of advanced kidney disease on the natriuretic peptide threshold for diagnosing heart failure:- What are the optimal NT-proBNP thresholds for diagnosing heart failure in people with stage IIIb, IV or V chronic kidney disease?

Risk tools for predicting non-sudden death in heart failure:- What is the most accurate prognostic risk tool in predicting 1-year mortality from heart failure at specific clinically relevant thresholds (for example, sensitivity, specificity, negative predictive value and positive predictive value at a threshold of 50% risk of mortality at 1 year)?

Cardiac assessment:- What is the clinical and cost effectiveness of cardiac assessment before transplantation?

Timing of pre-emptive transplant:- What is the most clinical and cost-effective strategy for timing of pre-emptive transplantation?

Acute haemodialysis versus acute peritoneal dialysis:- What is the clinical and cost effectiveness of initial haemodialysis versus initial peritoneal dialysis for people who start dialysis in an unplanned way?

Frequency of review:- What is the most clinical and cost-effective frequency of review for people on peritoneal dialysis, haemodiafiltration, haemodialysis or conservative management?

Coordinating care:- What is the clinical and cost effectiveness of having keyworkers present in the context of renal replacement therapy (RRT)?

Training and support for practitioners:- What is the effectiveness and cost effectiveness of different training programmes on the Mental Capacity Act 2005 at improving practice for practitioners involved in supporting decision-making, conducting capacity assessments and making best interests decisions?

Targeted interventions to support and improve decision-making capacity for treatment:- What is the effectiveness and cost effectiveness of different targeted interventions (speech and language therapy and psychological and psychosocial interventions) to support and improve decision-making capacity for treatment in specific groups?

Advocacy and support for decision-making:- What is the effectiveness, cost effectiveness and acceptability of advocacy as a means of supporting people to make decisions?

Using mental capacity assessment tools to assess capacity:- What is the accuracy and/or effectiveness, cost effectiveness and acceptability of mental capacity assessment tools that are compliant with the Mental Capacity Act 2005?

Components of a mental capacity assessment:- What are the components of an effective assessment of mental capacity to make a decision (for example checklists, memory aids or standardised documentation)?

Preventing behaviour that challenges from developing in children aged under 5 years with a learning disability:- Can positive behaviour support provided for children aged under 5 years with a learning disability reduce the risk of developing behaviour that challenges?

Interventions to reduce the frequency and extent of moderate to severe behaviour that challenges in community settings:- Are interventions based on the science and practice of applied behaviour analysis or antipsychotic medication, or a combination of these, effective in reducing the frequency and severity of behaviour that challenges shown by adults with a learning disability?

Locally accessible care: - Does providing care where people live compared with out-of-area placement lead to improvements in both the clinical and cost effectiveness of care for people with a learning disability and behaviour that challenges?

Factors associated with sustained, high-quality residential care:- What factors (including service organisation and management, staff composition, training and
supervision, and the content of care and support) are associated with sustained high-quality residential care for people with a learning disability and behaviour that challenges?

Pulmonary rehabilitation during hospital admission:- In people with COPD, does pulmonary rehabilitation during hospital admission for exacerbation and/or in the early recovery period (within 1 month of an exacerbation) improve quality of life and reduce hospitalisations and exacerbations compared with a later (defined as after 1 month)
pulmonary rehabilitation programme, and in which groups is it most clinically and cost effective?

Pulmonary hypertension:- What are the most clinical and cost-effective treatments for pulmonary hypertension in people with COPD?

Mucolytic therapy:- In people with COPD, does mucolytic drug therapy prevent exacerbations in comparison with placebo and other therapies?

Multidimensional assessment of outcomes- How can the individual factors associated with COPD prognosis (collected from a range of sources including primary care, imaging and pulmonary rehabilitation results) be combined into a multidimensional analysis that provides accurate and useful information on prognosis?

Inhaled therapies for people with COPD and asthma- What is the clinical and cost effectiveness of inhaled therapies (bronchodilators and/or inhaled corticosteroids) in people with both stable COPD and asthma?

Inhaled corticosteroid responsiveness:- What features predict inhaled corticosteroid responsiveness most accurately in people with COPD?

Prophylactic antibiotics for preventing exacerbations:- Which subgroups of people with stable COPD who are at high risk of exacerbations are most likely to benefit from prophylactic antibiotics?

Diagnosing COPD: -  What are the characteristics of people diagnosed with COPD as a result of an incidental finding of
emphysema on a CT scan, compared with those diagnosed with symptoms?

Prophylactic antibiotics for preventing exacerbations: - What is the long-term clinical and cost effectiveness of prophylactic antibiotics for people with stable COPD who are at high risk of exacerbations?

Prophylactic antibiotics for preventing exacerbations:- What is the comparative effectiveness of different antibiotics, doses and regimens of prophylactic antibiotics for people with stable COPD who are at high risk of exacerbations?

Prophylactic antibiotics for preventing exacerbations:- What is the comparative effectiveness of seasonal versus continuous prophylactic antibiotics for people with stable COPD who are at high risk of exacerbations?

Stepped care for post-traumatic stress disorder:- What is the clinical and cost effectiveness of stepped care for post-traumatic stress disorder (PTSD)?

Sequencing and further line treatment:- What is the clinical and cost effectiveness of sequencing and further line treatment in PTSD?

Trauma-informed approaches:- What is the clinical and cost effectiveness of trauma-informed care or trauma-informed approaches?

Personalisation and risk markers:- What prognostic and prescriptive factors are important in determining the choice of PTSD treatment?

Complex PTSD:- What is the clinical and cost effectiveness of interventions to deliver stabilisation and reintegration for people with complex PTSD?

Emotional freedom techniques:- What is the clinical and cost effectiveness of emotional freedom techniques (EFT) for the treatment of PTSD in adults?

Metabolic assessment:- What is the clinical and cost effectiveness of full metabolic assessment compared with standard advice alone, in people with recurrent calcium oxalate stones?

Alpha blockers and ureteroscopy- What is the clinical and cost effectiveness of tamsulosin as an adjunct to ureteroscopy?

Preventive treatment following shockwave lithotripsy:- What is the clinical and cost effectiveness of empirical potassium citrate or bendroflumethiazide as preventive treatment for people with small residual fragments following shockwave lithotripsy for renal and ureteric stones?

Frequency of follow-up imaging:- What is the clinical and cost effectiveness of 6-monthly imaging for 3 years for people with recurrent calcium renal or ureteric stones?

Non-steroidal anti-inflammatory drugs (NSAIDs) – route of administration:- What is the most clinically and cost effective route of administration for NSAIDs in the management of acute pain thought to be due to renal or ureteric stones?

Method of botulinum toxin type A injection in treating focal spasticity:- Is guided botulinum toxin type A injection using electrical localisation (electrostimulation or
electromyography) of muscles more clinically and cost effective than ultrasound-guided injections or clinical positioning for localisation of injections in treating focal spasticity in adults with cerebral palsy?

Selective dorsal rhizotomy treatment to reduce spasticity:- What is the clinical and cost effectiveness of selective dorsal rhizotomy compared with intrathecal baclofen to reduce spasticity in adults with cerebral palsy?

Detection and management of respiratory disorders in primary and community care:- Can detection and management of respiratory disorders in adults with cerebral palsy be improved in primary and community care?

Prophylactic antibiotics for respiratory disorders:- Are prophylactic antibiotics clinically and cost effective in the management of respiratory symptoms in adults with cerebral palsy with significant respiratory comorbidity?

Splinting to improve or maintain posture or function:- What is the optimum regimen for splints applied to the upper limb in adults with cerebral palsy to improve or maintain posture or function?

Augmentative and alternative communication systems:- Are augmentative and alternative communication systems clinically and cost effective in promoting  communication for adults with cerebral palsy who have communication difficulties?

Age thresholds in cancer: Longitudinal studies should be carried out to identify and quantify factors in adults that are associated with development of specific cancers at a younger age than the norm. They should be designed to inform age thresholds in clinical guidance. The primary outcome should be likelihood ratios and positive predictive values for cancer occurring in younger age groups.

Primary care testing: Diagnostic accuracy studies of tests accessible to primary care should be carried out for a given cancer in symptomatic people. Priority areas for research should include tests for people with cough, non-visible haematuria, suspected prostate cancer, suspected pancreatic cancer, suspected cancer in childhood and young people and other suspected rare cancers. Outcomes of interest are the performance characteristics of the test, particularly sensitivity, specificity and positive and negative predictive values.

Patient experience: Qualitative studies are needed to assess the key issues in patient experience and patient information needs in the cancer diagnostic pathway, particularly in the interval between first presentation to primary care and first appointment in secondary care. Outcomes of interest are patient satisfaction, quality of life and patient perception of the quality of care and information.

Prostate-specific antigen testing: What is the diagnostic accuracy of using age-adjusted and fixed prostate-specific antigen thresholds for people with symptoms of prostate cancer, including those at high risk of developing prostate cancer (such as those with an African family background or a family history of prostate cancer)?

Does caesarean section protect against cerebral haemorrhage in women with a history of subarachnoid haemorrhage or cerebrovascular malformation?

Does the use of ultrasound of the lumbar spine improve siting of regional anaesthetic needles in pregnant women with a BMI over 30 kg/m² at the booking appointment?

Is obesity an independent risk factor for perinatal morbidity and mortality?

What clinical features and laboratory investigations can be used to better stratify risk for women in labour with signs of sepsis (including fever and tachycardia)?

What is the clinical and cost effectiveness of intermittent auscultation compared with continuous cardiotocography for women in labour who have had a previous caesarean section?

What is the effectiveness and cost effectiveness of immunotherapy in people with stage IIIA-N2 non‑small‑cell lung cancer following multimodality treatment including surgery?

What is the effectiveness and cost effectiveness of immunotherapy in people with stage IIIA-N2 non-small-cell lung cancer following multimodality treatment including surgery?

Stereotactic ablative radiotherapy compared with surgery: What is the effectiveness and cost effectiveness of stereotactic ablative radiotherapy (SABR) compared with surgery (for example, sublobar, wedge resection, lobectomy) for people with non-small-cell lung cancer (stage I and IIA) in whom surgery is suitable?

What is the effectiveness and cost effectiveness of routinely performing contrast-enhanced brain CT at the time of initial diagnosis and/or staging CT?

Prophylactic cranial irradiation compared with routine MRI follow-up in extensive-stage small-cell lung cancer: What is the effectiveness and cost effectiveness of prophylactic cranial irradiation compared with routine MRI follow-up in people with extensive-stage small-cell lung cancer without brain metastases?

What is the effectiveness and safety of anticholinergic medicines for overactive bladder in older women?

What is the effectiveness of colpocleisis compared with sacrospinous fixation for pelvic organ prolapse in elderly women?

What is the effectiveness of ultrasound-guided visualisation compared with clinical assessment to identify complications after mesh surgery for stress urinary incontinence or pelvic organ prolapse in women?

What are the long-term outcomes, including patient satisfaction, from the use of pessaries compared with surgery for pelvic organ prolapse in women?

What are the long-term risks of mesh surgery compared with non-mesh surgery for stress urinary incontinence and pelvic organ prolapse in women?

What is the long-term effectiveness of bladder wall injection with botulinum toxin type A for overactive bladder in women?

What is the most effective surgical management for women with both stress urinary incontinence and pelvic organ prolapse, including the sequence of interventions?

What is the effectiveness of pain management for women who present with chronic pain 3 months after mesh surgery for stress urinary incontinence or pelvic organ prolapse?

What is the effectiveness of high-pressure non-invasive positive pressure ventilation (NIPPV) compared with continuous positive airways pressure (CPAP) flow driver as the primary mode of ventilation?

What is the best technique for delivering surfactant in a minimally invasive manner? 

What is the effectiveness of diuretics compared with placebo in preventing bronchopulmonary dysplasia (BPD) in preterm babies on respiratory support?

Does targeting higher oxygen saturations of 92% to 97% in preterm babies lead to improved survival without significant complications?

What is the most effective combination of an analgesic with a neuromuscular blocker, or an analgesic with an anaesthetic agent, for premedication in preterm babies requiring elective or semi-elective intubation? 

What is the clinical effectiveness of preoperative nasal decolonisation using mupirocin in combination with a chlorhexidine body wash in the whole population?

Does the use of barbed sutures for wound closure reduce the incidence of surgical site infection? 

Which closure method or technique is the most effective for reducing surgical site infections in patients undergoing emergency surgery?

Is the use of chlorhexidine body wash associated with increased antimicrobial resistance?

What is the clinical and cost effectiveness of chlorhexidine in alcohol at different concentrations in the prevention of surgical site infection when applied to the skin before incision?

Is the application of antiseptics and antibiotics in the operative field before wound closure, clinically and cost effective in reducing surgical site infection rates?

Which patient groups, contamination groups and which layers gain the most benefit from the use of triclosan-coated or triclosan-impregnated sutures?

What is the contribution to clinical effectiveness of the timing of nasal decolonisation and body wash for the prevention of surgical site infection?

What is the effectiveness of decolonisation using alternative interventions in combination with nasal decolonisation in the prevention of surgical site infections when chlorhexidine is contraindicated?

What is the clinical and cost effectiveness of a double application of antiseptic to the skin at the surgical site compared with a single application? 

What is the clinical and cost effectiveness of different modes of applying skin antiseptic before incision in the prevention of surgical site infection?

Early pregnancy assessment units: A national evaluation of early pregnancy assessment unit service provision should be carried out to identify factors affecting outcomes. Factors should include whether care is provided in a dedicated unit, staffing configuration and opening hours of dedicated services. Outcomes should include both process (service) outcomes and pregnancy-related outcomes. Data collected should be used to analyse the cost effectiveness of early pregnancy assessment units compared with other models of care.

Ultrasound for determining a viable intrauterine pregnancy: How does the timing and frequency of ultrasound examination affect diagnosis and outcomes of early pregnancy complications, including women's experience and cost effectiveness?

Effectiveness of progestogens in women with recurrent miscarriage: What is the clinical and cost effectiveness of progesterone for improving outcomes in women with unexplained recurrent miscarriage?

Effectiveness of different progestogens in women at risk of miscarriage: What is the clinical and cost effectiveness of vaginal micronised progesterone versus other progesterone preparations in improving outcomes in women at risk of miscarriage?

Management of miscarriage: In women with confirmed miscarriage, does the type of management strategy (expectant, medical and surgical) impact on women's experience, including psychological and emotional outcomes?

Comparison between expectant, medical or surgical management of ectopic pregnancy: In women with ectopic pregnancy, does the type of intervention impact on women's experience, including psychological and emotional outcomes?

Impact of intensive blood pressure lowering on people who are frail: What is the efficacy and safety of intensive interventions to lower blood pressure compared with less intensive interventions for people with acute intracerebral haemorrhage who are frail at presentation?

Impact of intensive interventions to lower blood pressure on cognitive function, functional ability and quality of life: What are the long-term effects of intensive interventions to lower blood pressure on cognitive function, functional ability and quality of life compared with standard interventions in people with acute intracerebral haemorrhage?

MRI brain scanning: Does early MRI brain scanning improve outcomes after suspected transient ischaemic attack (TIA)?

Avoidance of aspiration pneumonia: Does the withdrawal of oral liquids or the use of modified (thickened) oral fluids prevent the development of aspiration pneumonia after an acute stroke?

Aspirin and anticoagulant treatment for acute ischaemic stroke: Does modified-release dipyridamole or clopidogrel with aspirin improve outcome compared with aspirin alone when administered early after acute ischaemic stroke?

Aspirin treatment in acute ischaemic stroke: Should a person who has a stroke or a TIA and is already taking aspirin be prescribed the same or an increased dose of aspirin after the stroke?

Early mobilisation and optimum positioning of people with acute stroke: How safe and effective is very early mobilisation delivered by appropriately trained healthcare professionals after stroke?

Safety and efficacy of carotid stenting: What is the safety and efficacy of carotid stenting compared with carotid endarterectomy when these procedures are carried out within 2 weeks of TIA or recovered stroke?

What are the benefits, risk and cost effectiveness of enteral nutrition in maintaining remission in the post-surgical period of Crohn's disease?

How can the implementation of the recommendations made in this guideline be evaluated?

How can outcome measures relating to workplace health and wellbeing be measured?

How can the effectiveness of workplace health policies and programmes be measured?

How can the design and reporting of the outcomes used in intervention studies be improved, so researchers can identify 'active ingredients'? Which validated tools are effective at consistently measuring success, especially in relation to health and wellbeing, performance, productivity and in economic terms?

What are the most effective and cost-effective interventions to maintain and improve the health and wellbeing of older employees?

What are the most effective and cost-effective interventions to help older employees stay in or re-enter work? For example, to overcome the problems of a change in job specification?

What are the most effective and cost-effective interventions to help older employees plan and prepare for retirement?

What are the most effective and cost-effective interventions to challenge stereotypes and change employers' and workforce attitudes towards older employees?

In a mild-to-moderate first presentation or inflammatory exacerbation of proctitis that is resistant to standard treatment, what is the effectiveness of topical immunomodulators, such as tacrolimus, in achieving clinical remission and what is the most effective formulation (suppository/ointment)?

What is the effectiveness of oral tacrolimus and systemic (intramuscular/subcutaneous/oral) methotrexate in the induction of remission in mild-to-moderate ulcerative colitis unresponsive to aminosalicylates?

What is the clinical and cost effectiveness of prednisolone, budesonide, and beclometasone in addition to aminosalicylates compared with each other and with aminosalicylate monotherapy for the induction of remission for people with mild-to-moderate ulcerative colitis?

What is the clinical and cost effectiveness of prednisolone compared with aminosalicylates for the induction of remission for people with moderate ulcerative colitis?

What is the clinical and cost effectiveness of prednisolone plus an aminosalicylate compared with beclometasone plus an aminosalicylate for induction of remission for people with moderate ulcerative colitis?

What are the benefits, risks and cost effectiveness of methotrexate, ciclosporin, tacrolimus, adalimumab and infliximab compared with each other and with placebo for induction of remission for people with subacute ulcerative colitis that is refractory to systemic corticosteroids?

Cancers insufficiently researched in primary care: Observational studies of symptomatic primary care patients should be used to estimate the positive predictive value of different symptoms for specific cancers. Priority areas for research are those where the evidence base is currently insufficient and should include prostate cancer, pancreatic cancer, cancer in childhood and young people and other rare cancers. Outcomes of interest are positive predictive values and likelihood ratios for cancer.

What is the most suitable surveillance protocol (including the role of digital rectal examination [DRE] and prostate-specific antigen [PSA] measures) for people for whom active surveillance is appropriate, as assessed by multiparametric MRI and biopsy, when there are no clinical concerns during follow‑up?

What is the most clinically and cost-effective follow‑up protocol for people with prostate cancer who have had radical treatment, with specific regard to risk stratification, duration of follow‑up, frequency of follow‑up appointments, the type of examination or blood tests, and the roles of primary and secondary care in follow‑up?

What is the most clinically and cost-effective pathway for diagnosing clinically significant prostate cancer?

What is the most clinically and cost-effective pathway for diagnosing clinically significant prostate cancer?

What is the natural history of people with a Likert score on MRI of less than 3 without biopsy at long-term follow‑up?

Staging investigations for CPG 3 prostate cancer: What is the diagnostic accuracy of staging investigations for CPG 3 prostate cancer?

What is the prognostic value of different risk stratification methods for people with locally advanced prostate cancer?

In patients with negative MRI (Likert score 1 or 2), what is the next best diagnostic investigation to rule out clinically significant prostate cancer?

What is the diagnostic accuracy of transperineal mapping biopsy compared with transperineal non-mapping biopsy in the diagnosis of clinically significant prostate cancer?

What is the effectiveness and cost effectiveness of different scheduling of zoledronic acid in the prevention and reduction of skeletal events in people with hormone-refractory prostate cancer?

What is the clinical utility of bone turnover markers in the diagnosis and management of primary hyperparathyroidism?

What is the best and most cost-effective management strategy for people whose first surgery for primary hyperparathyroidism is not successful?

What are the long-term outcomes of different management strategies for primary hyperparathyroidism? Which strategies are most cost effective?

What are the optimal management strategies for primary hyperparathyroidism during pregnancy?

What is the clinical and cost effectiveness, post-treatment and at longer-term follow‑up, of psychological therapies in children aged 5 to 11 years with mild or moderate to severe depression?

What is the clinical and cost effectiveness, post-treatment and at longer-term follow‑up, of supported digital cognitive–behavioural therapy (CBT) compared with unsupported digital CBT in young people aged 12 to 18 years with mild depression, and what are the key components of the interventions that influence effectiveness?

What is the clinical and cost effectiveness, post-treatment and at longer-term follow‑up, of family therapy, psychodynamic psychotherapy and interpersonal psychotherapy for adolescents (IPT‑A) compared with each other and with individual CBT in young people aged 12 to 18 years with moderate to severe depression?

What is the clinical and cost effectiveness, post-treatment and at longer-term follow‑up, of a brief psychosocial intervention as reported by the IMPACT trial, but delivered by practitioners other than psychiatrists and in other settings, including primary care, to young people aged 12 to 18 years with mild or moderate to severe depression?

What is the clinical and cost effectiveness, post treatment and at longer-term follow‑up, of behavioural activation compared with other psychological therapies in children aged 5 to 11 years and young people aged 12 to 18 years with mild or moderate to severe depression?

What components of alcohol education delivery contribute to its effectiveness for children and young people aged 11 to 18 in full-time education, and those with special educational needs and disabilities (SEND) up to the age of 25?

How effective and cost effective are individual, compared with group, education-based interventions for children and young people aged 11 to 18 in full-time education who are thought to be vulnerable to alcohol misuse?

How effective and cost effective are universal, education-based alcohol interventions for children and young people aged 11 to 25 with SEND?

How effective and cost effective are education-based alcohol interventions targeted at children and young people aged 11 to 25 with SEND who are thought to be vulnerable to alcohol misuse?

How effective are education-based alcohol prevention interventions (universal or targeted) for children and young people aged 11 to 25 with SEND in full-time education?

What methods and techniques help secondary schools and providers to effectively engage with parents and carers as part of a whole-school approach to promote and support alcohol education?

Automated blood pressure monitoring in people with atrial fibrillation: Which automated blood pressure monitors are suitable for people with hypertension and atrial fibrillation?

Thresholds for interventions in adults aged under 40: In adults aged under 40 with hypertension (with or without type 2 diabetes), what are the appropriate risk and blood pressure thresholds for starting treatment?

Blood pressure targets for people aged over 80: What is the optimum blood pressure target for people aged over 80 with treated primary hypertension (with or without cardiovascular disease)?

Step 1 treatment: Are there subgroups of people with hypertension who should start on dual therapy?

Relaxation therapies: What is the clinical and cost effectiveness of relaxation therapies for managing primary hypertension in adults in terms of reducing cardiovascular events and improving quality of life?

Same-day hospital specialist assessment: Which people with extreme hypertension (220/120 mmHg or higher) or emergency symptoms should be referred for same-day hospital specialist assessment?

Blood pressure targets for people with aortic aneurysm: What are the optimal blood pressure targets in adults with hypertension and aortic aneurysm, and does this vary by age?

Blood pressure targets for people with prior ischaemic or haemorrhagic stroke: What are the optimal blood pressure targets in adults with prior ischaemic or haemorrhagic stroke, and does this vary by age?

What is the most accurate prenatal screening marker for TAPS, including middle cerebral artery peak systolic velocity (MCA‑PSV)?

Monitoring and response biomarkers: Can biomarkers accurately classify recurrence, progression and response to treatment?

Safety, prognostic and predictive biomarkers: Can biomarkers be used for risk stratification and treatment planning for people with melanoma?

Effectiveness of localised treatments: What is the effectiveness of localised treatment for people with stages III and IV melanoma?

Histological margins: What is the optimal histological excision margin in stage 0 melanoma?

Surveillance strategies: How frequently should surveillance imaging be conducted, and which imaging modality should be used for people with stage IIB to IIIC melanoma?

Survivorship: What are the experiences of people who are living with, through and beyond a melanoma diagnosis in terms of survivorship and their disease journey?

Techniques for confirming a diagnosis in people with suspected atypical Spitzoid melanocytic lesions: In people with reported atypical Spitzoid lesions, how effective are fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH) and tests to detect driver mutations compared with histopathological examination alone in predicting disease specific survival?

This should be investigated ina prospective diagnostic study. Secondary outcomes should include sensitivity, specificity, accuracy, positive predictive value, disease specific survival and progression free survival.

Surgical excision for people with lentigo maligna: For people with lentigo maligna (stage 0 in sun damaged skin, usually on the face) how effective is Mohs micrographic surgery, compared with excision with a 0.5 cm clinical margin, in preventing biopsy proven local recurrence at 5 years?

This should be investigated in a randomised controlled trial. Secondary outcomes should include cosmetic and functional outcomes.

Vitamin D supplementation: In people with stage I to III melanoma does vitamin D supplementation improve overall survival?

This should be investigated in a placebo controlled randomised trial. Secondary outcomes should include disease specific survival and toxicity, including the development of renal stones and hypercalcaemia.

The effect of drug therapy for concurrent conditions on melanoma survival: In people diagnosed with melanoma what is the effect of drug therapy to treat concurrent conditions on disease specific survival?

This should be investigated in a national prospective cohort study. Secondary outcomes should include overall survival and quality of life.

What is the optimal antibiotic prophylaxis regimen for women who are having a surgical abortion?

What are the most effective and acceptable methods of cervical priming before dilatation and evacuation after 16⁺⁰ weeks' gestation?

Should women having a surgical abortion up to and including 10⁺⁰ weeks' gestation have anti-D prophylaxis if they are RhD (or D) negative?

For women who are having medical abortion between 10⁺¹ and 12⁺⁰ weeks, what is the efficacy and acceptability of expulsion at home compared with expulsion in a clinical setting?

What local anaesthetic techniques are most effective for women having surgical abortion?

What is the effectiveness and safety of regimens using mifepristone and misoprostol for women who are having medical abortion after 23⁺⁶ weeks' gestation, particularly for those who have had a previous caesarean section or uterine surgery?

What is the optimal regimen for general anaesthesia for women having surgical abortion?

Does early review of service provision and referral to additional specialist palliative care services improve outcomes for adults with progressive non-cancer disease thought to be approaching the end of their life?

Which of the electronic information-sharing systems perform best for the care of people approaching the end of their life?

What are the benefits of planned, regular community-based reviews compared with as-required review of non-cancer patients approaching the end of their life?

What is the optimal way of discharging people approaching the end of their life from hospitals back to their place of residence?

Symptoms and signs of serious illness: The Guideline Development Group (GDG) recommends a UK-based epidemiological study on the symptoms and signs of serious illness.

Management by remote assessment: The GDG recommends that a UK study is undertaken to determine the validity of symptoms reported on remote assessment for children with fever.

Diagnosis: The GDG recommends that a UK study of the performance characteristics and cost-effectiveness of procalcitonin versus C-reactive protein in identifying serious bacterial infection in children with fever without apparent source be carried out.

Antipyretics: The GDG recommends that studies are conducted in primary care and secondary care to determine whether examination or re-examination after a dose of antipyretic medication is of benefit in differentiating children with serious illness from those with other conditions.

Home-based antipyretic use: The GDG recommends studies on home-based antipyretic use and parental perception of distress caused by fever. [2013]

Thermometers and the detection of fever: Measuring temperature in young babies: tympanic versus axilla electronic versus axilla chemical dot versus temporal artery.

Management according to risk of serious illness: The GDG recommends that research is carried out on referral patterns between primary and secondary care for children with fever, so the health economic impact of this and future guidelines can be estimated.

Signs and symptoms of Kawasaki disease: Which signs and symptoms (or combinations of signs and symptoms) predict a diagnosis of Kawasaki disease in children under 5 presenting with fever lasting 5 days or more?

For adults with fibromyalgia or persistent treatment-resistant neuropathic pain, what is the clinical and cost effectiveness of cannabidiol (CBD), containing no, or traces of, delta-9-tetrahydrocannabinol (THC), as an add-on to standard treatment?

For children and young people with intractable cancer-related pain and pain associated with specific diseases (such as epidermolysis bullosa), what is the clinical and cost effectiveness of cannabis-based medicinal products as an add-on to standard treatment to improve symptoms compared with treatment with standard care?

What is the clinical and cost effectiveness of CBD in epileptic disorders in children, young people and adults?

Does the addition of THC to CBD have an effect on seizure frequency, brain structure and neuropsychological performance when compared with both CBD alone and placebo in epileptic disorders in children, young people and adults?

What is the clinical and cost effectiveness of cannabis-based medicinal products other than THC: CBD spray for children, young people and adults with spasticity? In particular, what is the impact of spasticity on improvements in quality of life?

What is the clinical and cost effectiveness of cannabis-based medicinal products as an add-on treatment for adults with chemotherapy-induced nausea and vomiting which persists with optimised conventional antiemetics?

What is the clinical and cost effectiveness of cannabis-based medicinal products as an add-on treatment in babies, children and young people with chemotherapy-induced nausea or vomiting which persists with optimised conventional antiemetics?

What is the clinical and cost effectiveness of cannabis-based medicinal products as an add-on treatment for adults with persistent nausea or vomiting not caused by chemotherapy which hasn't fully responded to optimised conventional antiemetics?

What is the clinical and cost effectiveness of cannabis-based medicinal products as an add-on treatment for babies, children and young people with persistent nausea or vomiting not caused by chemotherapy which hasn't fully responded to optimised conventional antiemetics?

What is the clinical and cost effectiveness of levothyroxine (T4) and liothyronine (T3) combination therapy compared with T4 alone for people with hypothyroidism whose symptoms have not responded sufficiently to T4 alone? Does DiO2 polymorphism affect the response to combination therapy with T4 and T3?

What is the clinical and cost effectiveness of iodine for people with subclinical hypothyroidism?

What is the clinical and cost effectiveness of selenium for people with subclinical hypothyroidism?

What is the clinical and cost effectiveness of treatment (antithyroid drugs or radioactive iodine) for improving long-term health outcomes for people with subclinical hyperthyroidism?

Are there subgroups of people with Graves' disease who have a particularly good response to antithyroid drugs?

What is the long-term clinical and cost effectiveness, including safety, of radioactive iodine for hyperthyroidism?

What is the clinical and cost effectiveness of dosimetry-guided radioactive iodine strategies for hyperthyroidism?

What is the clinical and cost effectiveness of different durations of antithyroid drug regimens for people with T3 thyrotoxicosis due to Graves' disease?

What is the clinical and cost effectiveness of levothyroxine for people under 65 with symptomatic subclinical hypothyroidism?

What is the clinical and cost effectiveness of a block and replace regimen compared with a titration regimen of antithyroid drugs for Graves' disease?

What is the clinical and cost effectiveness of percutaneous thermal ablation for benign thyroid nodules?

What interventions are effective and cost effective in supporting return to work, in all workplaces including micro-, small- and medium-sized organisations, after long-term sickness absence in the UK?

What interventions are effective and cost effective in supporting return to work after recurrent short-term sickness absence in the UK?

For people with common mental health conditions, what interventions are effective and cost effective in reducing long-term sickness absence and supporting return to work in the UK?

For people with common mental health conditions, what interventions are effective and cost effective in reducing recurrent short-term sickness absence and supporting return to work in the UK?

What are the challenges and potential solutions for UK employers and employees in micro-, small- and medium-sized organisations (which may not have easy access to additional services such as employee assistance programmes or occupational health services) in ensuring sickness policy is managed effectively and facilitating return to work?

Which interventions are effective and cost effective in supporting people working in organisations where employees are not centrally located to return to work after long-term sickness absence in the UK?

What is the clinical and cost effectiveness of antibiotics for the management of acute diverticulitis in primary care?

What is the most clinically and cost-effective conservative management for preventing diverticular disease in people with diverticulosis?

What is the most clinically and cost-effective treatment for diverticular disease?

What information and support do people with diverticulosis, diverticular disease or acute diverticulitis need?

What are the clinically and cost-effective surgical approaches to managing complicated acute diverticulitis, including timing of surgery (elective or emergency)?

What are the risk factors for diverticulosis progressing to diverticular disease?

Can risk of contrast-induced acute kidney injury be stratified by eGFR thresholds?

What is the relative effectiveness and cost effectiveness of different oral fluids and different oral fluid regimens, both with and without oral N-acetylcysteine, at preventing contrast-induced acute kidney injury?

What is the health impact of exposure to individual air pollutants alone or combined with each other in the home?

What is the effectiveness and cost effectiveness of interventions to improve indoor air quality at home for people without pre‑existing health conditions?

What is the minimum air exchange rate to minimise the health effects of poor indoor air quality in the home?

What are the emission profiles of indoor air pollutants released from building materials in a lived-in home environment?

What interventions are effective and cost effective at raising awareness of the health risks of damp and mould in the home?

How can damp and mould in the home be prevented?

How is damp and mould in the home best identified?

How is damp and mould in the home best fixed?

How can tenants be best made aware of whose responsibility it is to make any changes needed as a result of damp and mould in the home?

Reducing antimicrobial resistance:- What interventions, systems and processes are effective and cost effective in reducing antimicrobial resistance without causing harm to patients?

Decision-making:- What interventions, systems and processes are effective and cost effective in changing health and social care practitioners' decision-making and ensuring appropriate antimicrobial stewardship?

What is the effectiveness, cost effectiveness and acceptability of the whole family approach to carers' assessments?

What is the effectiveness of personal health and social care budgets in supporting carers to return to work, education or training?

What training, support or interventions help to reduce caring-related accidents or incidents?

What is the effectiveness, cost effectiveness and acceptability of carer passport schemes?

What is the effectiveness, cost effectiveness and acceptability of social prescribing for carers?

What is the cost effectiveness and safety of non-surgical ablation and stereotactic body radiotherapy compared to resection for people with metastatic colorectal cancer in the lung amenable to local treatment?

What is the effectiveness and safety of sacral nerve stimulation and transanal irrigation compared to symptomatic treatment for people with major low anterior resection syndrome?

What is the clinical effectiveness of topical treatments (antibiotics and antiseptics) compared with oral antibiotics for the treatment of infected leg ulcer?

For which people with impetigo are antiseptics as effective as antibiotics?

What are the information and support needs of parents and carers with babies on parenteral nutrition?

What is the optimal ratio of non-nitrogen energy to nitrogen in parenteral nutrition for preterm and term babies?

What is the optimal timeframe for starting parenteral nutrition in term babies who are critically ill or require surgery?

What overall osmolality (or concentration of calcium and glucose/dextrose) in parenteral nutrition can determine whether to administer centrally or peripherally?

What is the clinical and cost effectiveness of cognitive behavioural therapy (CBT) for adults with tinnitus delivered by appropriately trained healthcare professionals other than psychologists (for example, audiologists)?

What is the clinical and cost effectiveness of amplification devices for people who are d/Deaf or who have a severe-to-profound hearing loss?

What is the clinical and cost effectiveness of psychological therapies for people who are d/Deaf or who have a severe-to-profound hearing loss and tinnitus-related distress?

What is the clinical and cost effectiveness of fitting amplification devices(s) in people with tinnitus who have hearing loss but no perceived hearing difficulties?

What is the clinical and cost effectiveness of a combination management strategy consisting of sound therapy and tinnitus support?

What is the clinical and cost effectiveness of a combination management strategy consisting of sound therapy and tinnitus support?

What is the optimal method for assessing tinnitus in general practice (including consultation questions, physical examinations and questionnaires)?

What is the clinical, cost effectiveness and safety of neuromodulation interventions for treating tinnitus in adults?

What is the clinical and cost effectiveness of psychological therapies for children and young people who have tinnitus-related distress?

What is the most clinically and cost-effective tinnitus questionnaire to assess tinnitus in children and young people?

What is the most clinically and cost-effective tinnitus questionnaire to assess tinnitus in people with a learning disability or cognitive impairment?

What is the most clinically and cost-effective tinnitus questionnaire to assess tinnitus in people who are d/Deaf or who have a severe-to-profound hearing loss?

Are relaxation strategies clinically and cost effective for the management of tinnitus for children, young people and adults?

What are the most effective and cost-effective frequencies for monitoring people with unruptured abdominal aortic aneurysms (AAA) of different diameters, and what is the optimal AAA threshold size (inner-to-inner maximum anterior-posterior diameter on ultrasound) for repair?

What is the effectiveness and cost effectiveness of complex endovascular aneurysm repair (EVAR) versus open surgical repair in people for whom open surgical repair is suitable for: