Evidence review for imaging to investigate the cause of pulsatile tinnitus

National Guideline Centre (UK)

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Evidence review for imaging to investigate the cause of pulsatile tinnitus

Tinnitus: assessment and management

Evidence review K

NICE Guideline, No. 155

Authors

National Guideline Centre (UK).

London: National Institute for Health and Care Excellence (NICE); 2020 Mar.

ISBN-13: 978-1-4731-3711-0

1. Imaging to investigate the cause of pulsatile tinnitus

1.1. Review question: What is the most clinical and cost-effective imaging method to investigate the cause of pulsatile tinnitus?

1.2. Introduction

In certain groups of individuals with tinnitus, it is important to image the head and neck to exclude an organic cause for their symptoms. The role of imaging is to detect specific pathology that is treatable. A variety of imaging modalities may be considered depending on the type of tinnitus and/or associated symptoms reported, particularly if the tinnitus is considered to be pulsatile in nature. Imaging modalities include ultrasound, computerised tomography, magnetic resonance imaging and angiography. A thorough history and clinical examination can direct the decision for imaging and the type of imaging.

Pulsatile tinnitus is heard as a regular rhythmical noise. It can occur at the same time as the heart beat (synchronous) or at a different interval (non-synchronous). Synchronous pulsatile tinnitus can be caused by a number of different causes such as irregular blood vessels, high blood pressure, raised intracranial pressure, anaemia and atherosclerosis. Vascular causes may be systemic, for example anaemia, or due to a vascular anomalies or pathology, for example arteriovenous malformation or fistula. Non-vascular pulsatile causes include paragangliomas, intracranial hypertension, osseous pathology and somatic causes. Middle ear pathology such as glomus tumours can also give rise to synchronous tinnitus. Non-synchronous pulsatile tinnitus may be caused by palatal myoclonus. If these conditions are identified they can then be treated, which should also improve the tinnitus.

Whilst it is crucial not to miss significant pathology, it is also important not to over-scan people where significant pathology is unlikely. Not only is this cost unnecessary, it maybe unpleasant and stressful for the person and possibly expose them to an unnecessary dose of ionising radiation or risk of adverse effects from the contrast agent.

1.3. PICO table

For full details see the review protocol in appendix A.

1.4. Clinical evidence

1.4.1. Included studies

No relevant randomised controlled trial evidence comparing imaging methods with other imaging methods or with no imaging method were identified. Consequently, non-randomised comparative studies were also assessed. However, no relevant studies were identified for inclusion.

1.4.2. Excluded studies

See the excluded studies list in appendix I.

1.5. Economic evidence

1.5.1. Included studies

No relevant health economic studies were identified.

1.5.2. Excluded studies

No health economic studies that were relevant to this question were excluded due to assessment of limited applicability or methodological limitations.

See also the health economic study selection flow chart in appendix G.

1.6. Unit Costs

1.7. Evidence statements

1.7.1. Clinical evidence statements

No relevant published evidence was identified.

1.7.2. Health economic evidence statements

No relevant economic evaluations were identified.

1.8. The committee’s discussion of the evidence

1.8.1. Interpreting the evidence

1.8.1.1. The outcomes that matter most

Tinnitus distress, annoyance and tinnitus severity were critical outcomes as they were thought to be common factors for people with tinnitus and impact their quality of life. Quality of life (tinnitus-related) and general quality of life were also critical outcomes due to their impact on the person with tinnitus. Mortality was another critical outcome.

Tinnitus loudness, anxiety, depression, sleep, safety, tolerability and side effects were thought to be important outcomes.

The committee did not prioritise diagnostic accuracy outcomes such as sensitivity and specificity because they felt it was more useful to know about the effect on tinnitus outcomes and cost effectiveness of including these scans in the pathway compared to each other or no scanning.

There was no outcome data for any of the outcomes.

1.8.1.2. The quality of the evidence

Randomised controlled trials (RCTs) and systematic reviews of RCTs were searched for and assessed for eligibility but no relevant RCT evidence was identified which matched the review protocol. Consequently, non-randomised comparative studies were also searched for and assessed for eligibility. No relevant non-randomised comparative studies were identified.

1.8.1.3. Benefits and harms

The committee noted that whilst no evidence was identified, the use of imaging to investigate pulsatile tinnitus is a crucial part of the management pathway and therefore consensus recommendations were made. The committee discussed that there is a risk of anxiety with any scan and healthcare professionals should take this into consideration when offering scans to people with tinnitus. Pulsatile tinnitus may be due to a benign cause, but it can also be due to a vascular malformation or abnormal intracranial pressure that can be potentially significant or life-threatening. Therefore, the committee agreed that imaging should be offered to all age groups with pulsatile tinnitus in order to detect significant and treatable lesions.

Synchronous pulsatile tinnitus

Synchronous pulsatile tinnitus can originate from a number of different causes such as raised intracranial pressure, irregular blood vessels, high blood pressure, anaemia and atherosclerosis. If these conditions are identified they can then be treated which should also improve the tinnitus.

Contrast-enhanced CT scan is more effective at detecting osseous pathology, while MR imaging is more suitable for detecting soft tissue or intracranial pathology. Therefore, the choice of initial imaging method will depend on the clinical suspicion of underlying pathology. For example, middle ear pathology or osseous abnormality such as glomus tumours can give rise to synchronous tinnitus. If this is suspected at examination and audiological assessment, a contrast enhanced CT scan of the temporal bone was considered by the committee to be the best next step to identify the cause.

Magnetic resonance angiography (MRA) can be used to identify or exclude significant and/or treatable disease such as vascular problems. The committee noted that it can also be used to assess the risk of stroke as well as other serious vascular and neurological complications. MRA does not involve ionising radiation, unlike CT scans, and therefore the committee considered this to be the first choice of investigation. Some people may not be able to have or to tolerate an MRA due to metal implants such as pacemakers, or claustrophobia. In these cases, contrast enhanced CT scans of the head, neck, temporal bone and IAM should be considered. CT scans are however associated with a risk from the radiation dose and a risk of sustaining a reaction from the contrast medium. The committee agreed that MRI of the head, neck, temporal bone and IAM with contrast should also be considered. The selection of MRA or MRI is based on experience and equipment available.

There may be instances (e.g. glomus tumour) when both CT and MR imaging can be helpful in improving diagnostic accuracy as they can be complementary in diagnosing and assessing the extent of the medical condition.

Angiography was not recommended by the committee because the committee considered that angiography is associated with a risk of stroke or heart attack, a risk of allergic reaction to the contrast medium and risk from the radiation dose.

Non-synchronous pulsatile tinnitus

Non- synchronous pulsatile tinnitus may be caused by palatal myoclonus. The committee considered that where this is a suspected pathology, an MRI of the head could be considered. MRI provides the most accurate method for investigating non-synchronous pulsatile tinnitus to exclude significant and/or treatable disease. The committee noted that the incidence of this medical condition is very low. Again, where MRI is not suitable, contrast enhanced CT of the head should be considered, although the risk from radiation dose and potential for adverse reaction to the contrast media means that MRI is preferred where possible.

1.8.1.4. Cost effectiveness and resource use

There were no economic evaluations available for this review question. The view of the committee was that all people with pulsatile tinnitus should be offered a scan because pulsatile tinnitus can occur due to serious causes such as irregular blood vessels, high blood pressure, raised intracranial pressure, anaemia and atherosclerosis, paragangliomas, osseous pathology and glomus tumours. A scan would be able to help identify the underlying cause of tinnitus and avoid later expenditure and morbidity that might occur if these conditions were left untreated.

The committee judged that a scan was imperative for the pulsatile tinnitus population but they were also mindful of the potential resource impact. One way that the committee considered cost-effectiveness in their recommendations is by ensuring clinicians are directed towards the most appropriate tests and thereby limiting unnecessary use of more expensive imaging modalities such as an MRI. For example, the committee has recommended using a contrast CT as the primary imaging test in people suspected for an osseous or middle ear abnormality.

Synchronous pulsatile tinnitus

The committee noted that examinations and audiological assessments may indicate suspicion of osseous or middle ear abnormality in people with synchronous pulsatile tinnitus. In these cases, the committee formed a consensus view that a contrast-enhanced CT scan of the temporal bone would be the preferred and more sensitive imaging modality for this abnormality. The committee were of the view that this recommendation would aid in preventing clinicians immediately opting for the more expensive MRI scan and thus help generate cost-savings.

In those instances where there are no such suspicions but a person has synchronous pulsatile tinnitus, the committee formed a consensus view that an MRA or MRI of head, neck, temporal bone and IAM should be provided. This is because in these cases, MRI and MRA imaging techniques are more able to pick up soft tissue, vascular and other abnormalities and are associated with less harm than CT. The committee suggested that a CT of head, neck, temporal bone and IAM should however be used if MRI or MRA is not possible or cannot be tolerated. While a CT scan would be less sensitive than the MRA, the committee noted that it was still important for clinicians to rule out significant pathology as this would reduce later expenditure and avoidable complications.

The committee noted that the consensus recommendations on imaging modalities for synchronous tinnitus has the potential to be cost saving because it will limit the unnecessary use of more expensive imaging modalities (e.g. MRA or MRI).

Non-synchronous pulsatile tinnitus

Current practice for investigating non-synchronous pulsatile tinnitus is for an MRI of the head to be performed in cases where palatal myoclonus is thought to be the cause of the tinnitus. Therefore, the recommendation is not a change to practice and is expected to be cost-neutral to the NHS. Again, the committee noted that it was important all people with non-synchronous tinnitus are considered for imaging (preferably an MRI of the head or CT of the head if an MRI is contraindicated) to prevent avoidable complications and later expenditure.

1.8.2. Other factors the committee took into account

Whilst individuals may become anxious whilst waiting for scans and results, the clinician can minimise this anxiety by discussing openly the reasons for the scan, the risks and benefits of the scan and the possible outcomes. Most people with pulsatile tinnitus will appreciate having an investigation which will either indicate a condition to be treated or rule out any serious underlying cause for the tinnitus.

The committee noted that MRI is loud and some people may find this noise can affect their tinnitus. Radiology departments provide earplugs, if this is the case.

References

1.: Dawes PJ, Basiouny HE. Outcome of using magnetic resonance imaging as an initial screen to exclude vestibular schwannoma in patients presenting with unilateral tinnitus. Journal of Laryngology and Otology. 1999; 113(9):818–22 [PubMed: 10664684]
2.: De Ridder D, De Ridder L, Nowe V, Thierens H, Van De Heyning P, Moller A. Pulsatile tinnitus and the intrameatal vascular loop: Why do we not hear our carotids? Neurosurgery. 2005; 57(6):1213–1217 [PubMed: 16331169]
3.: Fortnum H, O’Neill C, Taylor R, Lenthall R, Nikolopoulos T, Lightfoot G et al. The role of magnetic resonance imaging in the identification of suspected acoustic neuroma: A systematic review of clinical and cost-effectiveness and natural history. Health Technology Assessment. 2009; 13(18) [PubMed: 19358774]
4.: Mundada P, Singh A, Lingam RK. CT arteriography and venography in the evaluation of pulsatile tinnitus with normal otoscopic examination. Laryngoscope. 2015; 125(4):979–984 [PubMed: 25379666]
5.: National Institute for Health and Care Excellence. Developing NICE guidelines: the manual [Updated October 2018] London. National Institute for Health and Care Excellence, 2014. Available from: https://www.nice.org.uk/process/pmg20/chapter/introduction-and-overview
6.: NHS Improvement. NHS reference costs 2017-18. 2017. Available from: https://improvement.nhs.uk/resources/reference-costs/#rc1718 Last accessed: 29/05/19
7.: Remley KB, Coit WE, Harnsberger HR, Smoker WR, Jacobs JM, McIff EB. Pulsatile tinnitus and the vascular tympanic membrane: CT, MR, and angiographic findings. Radiology. 1990; 174(2):383–9 [PubMed: 2296650]
8.: Seemann MD, Beltle J, Heuschmid M, Lowenheim H, Graf H, Claussen CD. Image fusion of CT and MRI for the visualization of the auditory and vestibular system. European Journal of Medical Research. 2005; 10(2):47–55 [PubMed: 15817422]
9.: Simonetti P, Oiticica J. Tinnitus neural mechanisms and structural changes in the brain: The contribution of neuroimaging research. International Archives of Otorhinolaryngology. 2015; 19(3):259–265 [PMC free article: PMC4490922] [PubMed: 26157502]
10.: Song JJ, De Ridder D, Van De Heyning P, Vanneste S. Mapping tinnitus-related brain activation: An activation-likelihood estimation metaanalysis of PET studies. Journal of Nuclear Medicine. 2012; 53(10):1550–1557 [PubMed: 22917883]
11.: Waldvogel D, Mattle HP, Sturzenegger M, Schroth G. Pulsatile tinnitus - A review of 84 patients. Journal of Neurology. 1998; 245(3):137–142 [PubMed: 9553842]

Appendices

Appendix A. Review protocols

Table 3. Review protocol: Imaging method to investigate the cause of pulsatile tinnitus (PDF, 356K)

Table 4Health economic review protocol

Review question	All questions – health economic evidence
Objectives	To identify health economic studies relevant to any of the review questions.
Search criteria	Populations, interventions and comparators must be as specified in the clinical review protocol above. Studies must be of a relevant health economic study design (cost–utility analysis, cost-effectiveness analysis, cost–benefit analysis, cost–consequences analysis, comparative cost analysis). Studies must not be a letter, editorial or commentary, or a review of health economic evaluations. (Recent reviews will be ordered although not reviewed. The bibliographies will be checked for relevant studies, which will then be ordered.) Unpublished reports will not be considered unless submitted as part of a call for evidence. Studies must be in English.
Search strategy	A health economic study search will be undertaken using population-specific terms and a health economic study filter – see appendix B below.
Review strategy	Studies not meeting any of the search criteria above will be excluded. Studies published before 2003, abstract-only studies and studies from non-OECD countries or the USA will also be excluded. Each remaining study will be assessed for applicability and methodological limitations using the NICE economic evaluation checklist which can be found in appendix H of Developing NICE guidelines: the manual (2014).⁵ Inclusion and exclusion criteria If a study is rated as both ‘Directly applicable’ and with ‘Minor limitations’ then it will be included in the guideline. A health economic evidence table will be completed and it will be included in the health economic evidence profile. If a study is rated as either ‘Not applicable’ or with ‘Very serious limitations’ then it will usually be excluded from the guideline. If it is excluded then a health economic evidence table will not be completed and it will not be included in the health economic evidence profile. If a study is rated as ‘Partially applicable’, with ‘Potentially serious limitations’ or both then there is discretion over whether it should be included. Where there is discretion The health economist will make a decision based on the relative applicability and quality of the available evidence for that question, in discussion with the guideline committee if required. The ultimate aim is to include health economic studies that are helpful for decision-making in the context of the guideline and the current NHS setting. If several studies are considered of sufficiently high applicability and methodological quality that they could all be included, then the health economist, in discussion with the committee if required, may decide to include only the most applicable studies and to selectively exclude the remaining studies. All studies excluded on the basis of applicability or methodological limitations will be listed with explanation in the excluded health economic studies appendix below. The health economist will be guided by the following hierarchies. Setting: UK NHS (most applicable). OECD countries with predominantly public health insurance systems (for example, France, Germany, Sweden). OECD countries with predominantly private health insurance systems (for example, Switzerland). Studies set in non-OECD countries or in the USA will be excluded before being assessed for applicability and methodological limitations. Health economic study type: Cost–utility analysis (most applicable). Other type of full economic evaluation (cost–benefit analysis, cost-effectiveness analysis, cost–consequences analysis). Comparative cost analysis. Non-comparative cost analyses including cost-of-illness studies will be excluded before being assessed for applicability and methodological limitations. Year of analysis: The more recent the study, the more applicable it will be. Studies published in 2003 or later but that depend on unit costs and resource data entirely or predominantly from before 2003 will be rated as ‘Not applicable’. Studies published before 2003 will be excluded before being assessed for applicability and methodological limitations. Quality and relevance of effectiveness data used in the health economic analysis: The more closely the clinical effectiveness data used in the health economic analysis match with the outcomes of the studies included in the clinical review the more useful the analysis will be for decision-making in the guideline.

Appendix B. Literature search strategies

The literature searches for this review are detailed below and complied with the methodology outlined in Developing NICE guidelines: the manual.⁵

For more detailed information, please see the Methodology Review.

B.1. Clinical search literature search strategy

Searches were constructed using a PICO framework where population (P) terms were combined with Intervention (I) and in some cases Comparison (C) terms. Outcomes (O) are rarely used in search strategies for interventions as these concepts may not be well described in title, abstract or indexes and therefore difficult to retrieve. Search filters were applied to the search where appropriate.

Table 5Database date parameters and filters used

Database	Dates searched	Search filter used
Medline (OVID)	1946 – 02 April 2019	Exclusions
Embase (OVID)	1974 – 02 April 2019	Exclusions
The Cochrane Library (Wiley)	Cochrane Reviews to 2019 Issue 4 of 12 CENTRAL to 2019 Issue 4 of 12 DARE, and NHSEED to 2015 Issue 2 of 4 HTA to 2016 Issue 4 of 4	None
CINAHL, Current Nursing and Allied Health Literature (EBSCO)	Inception – 02 April 2019	Exclusions

Medline (Ovid) search terms

1.	Tinnitus/
2.	tinnit*.ti,ab.
3.	1 or 2
4.	letter/
5.	editorial/
6.	news/
7.	exp historical article/
8.	Anecdotes as Topic/
9.	comment/
10.	case report/
11.	(letter or comment*).ti.
12.	or/4-11
13.	randomized controlled trial/ or random*.ti,ab.
14.	12 not 13
15.	animals/ not humans/
16.	exp Animals, Laboratory/
17.	exp Animal Experimentation/
18.	exp Models, Animal/
19.	exp Rodentia/
20.	(rat or rats or mouse or mice).ti.
21.	or/14-20
22.	3 not 21
23.	limit 22 to English language

Embase (Ovid) search terms

1.	tinnitus/
2.	tinnit*.ti,ab.
3.	1 or 2
4.	letter.pt. or letter/
5.	note.pt.
6.	editorial.pt.
7.	Case report/ or Case study/
8.	(letter or comment*).ti.
9.	or/4-8
10.	randomized controlled trial/ or random*.ti,ab.
11.	9 not 10
12.	animal/ not human/
13.	Nonhuman/
14.	exp Animal Experiment/
15.	exp Experimental animal/
16.	Animal model/
17.	exp Rodent/
18.	(rat or rats or mouse or mice).ti.
19.	or/11-18
20.	3 not 19
21.	limit 20 to English language

Cochrane Library (Wiley) search terms

#1.	MeSH descriptor: [Tinnitus] explode all trees
#2.	tinnit*:ti,ab
#3.	#1 or #2

CINAHL (EBSCO) search terms

S1.	(MH “Tinnitus”)
S2.	(MH “Tinnitus Retraining Therapy”)
S3.	tinnit*
S4.	S1 OR S2 OR S3
S5.	PT anecdote or PT audiovisual or PT bibliography or PT biography or PT book or PT book review or PT brief item or PT cartoon or PT commentary or PT computer program or PT editorial or PT games or PT glossary or PT historical material or PT interview or PT letter or PT listservs or PT masters thesis or PT obituary or PT pamphlet or PT pamphlet chapter or PT pictorial or PT poetry or PT proceedings or PT “questions and answers” or PT response or PT software or PT teaching materials or PT website
S6.	S4 NOT S5

B.2. Health Economics literature search strategy

Health economic evidence was identified by conducting a broad search relating to the tinnitus population in NHS Economic Evaluation Database (NHS EED – this ceased to be updated after March 2015) and the Health Technology Assessment database (HTA) with no date restrictions. NHS EED and HTA databases are hosted by the Centre for Research and Dissemination (CRD). Additional searches were run on Medline and Embase for health economics and quality of life studies.

Table 6Database date parameters and filters used

Database

Dates searched

Search filter used

Medline

2002 – 02 March 2019

Exclusions

Health economics studies

Quality of life studies

Embase

2002 – 02 March 2019

Exclusions

Health economics studies

Quality of life studies

Centre for Research and Dissemination (CRD)

HTA - Inception – 31 Mar 2018

NHSEED - Inception to March 2015

None

Medline (Ovid) search terms

1.	Tinnitus/
2.	tinnit*.ti,ab.
3.	1 or 2
4.	letter/
5.	editorial/
6.	news/
7.	exp historical article/
8.	Anecdotes as Topic/
9.	comment/
10.	case report/
11.	(letter or comment*).ti.
12.	or/4-11
13.	randomized controlled trial/ or random*.ti,ab.
14.	12 not 13
15.	animals/ not humans/
16.	exp Animals, Laboratory/
17.	exp Animal Experimentation/
18.	exp Models, Animal/
19.	exp Rodentia/
20.	(rat or rats or mouse or mice).ti.
21.	or/14-20
22.	3 not 21
23.	limit 22 to English language
24.	Economics/
25.	Value of life/
26.	exp “Costs and Cost Analysis”/
27.	exp Economics, Hospital/
28.	exp Economics, Medical/
29.	Economics, Nursing/
30.	Economics, Pharmaceutical/
31.	exp “Fees and Charges”/
32.	exp Budgets/
33.	budget*.ti,ab.
34.	cost*.ti.
35.	(economic* or pharmaco?economic*).ti.
36.	(price* or pricing*).ti,ab.
37.	(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.
38.	(financ* or fee or fees).ti,ab.
39.	(value adj2 (money or monetary)).ti,ab.
40.	or/24-39
41.	quality-adjusted life years/
42.	sickness impact profile/
43.	(quality adj2 (wellbeing or well being)).ti,ab.
44.	sickness impact profile.ti,ab.
45.	disability adjusted life.ti,ab.
46.	(qal* or qtime* or qwb* or daly*).ti,ab.
47.	(euroqol* or eq5d* or eq 5*).ti,ab.
48.	(qol* or hql* or hqol* or h qol* or hrqol* or hr qol*).ti,ab.
49.	(health utility* or utility score* or disutilit* or utility value*).ti,ab.
50.	(hui or hui1 or hui2 or hui3).ti,ab.
51.	(health* year* equivalent* or hye or hyes).ti,ab.
52.	discrete choice*.ti,ab.
53.	rosser.ti,ab.
54.	(willingness to pay or time tradeoff or time trade off or tto or standard gamble*).ti,ab.
55.	(sf36* or sf 36* or short form 36* or shortform 36* or shortform36*).ti,ab.
56.	(sf20 or sf 20 or short form 20 or shortform 20 or shortform20).ti,ab.
57.	(sf12* or sf 12* or short form 12* or shortform 12* or shortform12*).ti,ab.
58.	(sf8* or sf 8* or short form 8* or shortform 8* or shortform8*).ti,ab.
59.	(sf6* or sf 6* or short form 6* or shortform 6* or shortform6*).ti,ab.
60.	or/41-59
61.	23 and (40 or 60)

Embase (Ovid) search terms

1.	tinnitus/
2.	tinnit*.ti,ab.
3.	1 or 2
4.	letter.pt. or letter/
5.	note.pt.
6.	editorial.pt.
7.	Case report/ or Case study/
8.	(letter or comment*).ti.
9.	or/4-8
10.	randomized controlled trial/ or random*.ti,ab.
11.	9 not 10
12.	animal/ not human/
13.	Nonhuman/
14.	exp Animal Experiment/
15.	exp Experimental animal/
16.	Animal model/
17.	exp Rodent/
18.	(rat or rats or mouse or mice).ti.
19.	or/11-18
20.	3 not 19
21.	health economics/
22.	exp economic evaluation/
23.	exp health care cost/
24.	exp fee/
25.	budget/
26.	funding/
27.	budget*.ti,ab.
28.	cost*.ti.
29.	(economic* or pharmaco?economic*).ti.
30.	(price* or pricing*).ti,ab.
31.	(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.
32.	(financ* or fee or fees).ti,ab.
33.	(value adj2 (money or monetary)).ti,ab.
34.	or/21-33
35.	quality adjusted life year/
36.	"quality of life index"/
37.	short form 12/ or short form 20/ or short form 36/ or short form 8/
38.	sickness impact profile/
39.	(quality adj2 (wellbeing or well being)).ti,ab.
40.	sickness impact profile.ti,ab.
41.	disability adjusted life.ti,ab.
42.	(qal* or qtime* or qwb* or daly*).ti,ab.
43.	(euroqol* or eq5d* or eq 5*).ti,ab.
44.	(qol* or hql* or hqol* or h qol* or hrqol* or hr qol*).ti,ab.
45.	(health utility* or utility score* or disutilit* or utility value*).ti,ab.
46.	(hui or hui1 or hui2 or hui3).ti,ab.
47.	(health* year* equivalent* or hye or hyes).ti,ab.
48.	discrete choice*.ti,ab.
49.	rosser.ti,ab.
50.	(willingness to pay or time tradeoff or time trade off or tto or standard gamble*).ti,ab.
51.	(sf36* or sf 36* or short form 36* or shortform 36* or shortform36*).ti,ab.
52.	(sf20 or sf 20 or short form 20 or shortform 20 or shortform20).ti,ab.
53.	(sf12* or sf 12* or short form 12* or shortform 12* or shortform12*).ti,ab.
54.	(sf8* or sf 8* or short form 8* or shortform 8* or shortform8*).ti,ab.
55.	(sf6* or sf 6* or short form 6* or shortform 6* or shortform6*).ti,ab.
56.	or/35-55
57.	20 and (34 or 56)
58.	limit 57 to English language

NHS EED and HTA (CRD) search terms

#1.	MeSH DESCRIPTOR Tinnitus EXPLODE ALL TREES
#2.	(tinnit*)
#3.	#1 OR #2

Appendix C. Clinical evidence selection

Figure 1Flow chart of clinical study selection for the review of imaging method to investigate the cause of pulsatile tinnitus

Appendix D. Clinical evidence tables

No evidence identified.

Appendix E. Forest plots

No evidence identified.

Appendix F. GRADE tables

No evidence identified.

Appendix G. Health economic evidence selection

Figure 2Flow chart of health economic study selection for the guideline

* Non-relevant population, intervention, comparison, design or setting; non-English language

Appendix H. Excluded studies

H.1. Excluded clinical studies

Table 7Studies excluded from the clinical review

Reference	Reason for exclusion
Dawes 1999¹	No relevant outcomes (details of diagnoses reported)
De Ridder 2005²	Incorrect comparison (MRI for pulsatile versus non-pulsatile tinnitus); no relevant outcomes
Fortnum 2009³	Systematic review of non-RCTs
Mundada 2015⁴	No relevant outcomes (details of diagnoses reported)
Remley 1990⁷	No relevant outcomes (details of diagnoses reported)
Seemann 2005⁸	No relevant outcomes (details of diagnoses reported)
Simonetti 2015⁹	Systematic review; incorrect comparisons (functional studies comparing people with tinnitus versus people without tinnitus)
Song 2012¹⁰	Meta-analysis; incorrect comparison (people with tinnitus versus people without tinnitus)
Waldvogel 1998¹¹	No relevant outcomes (details of diagnoses reported)

H.2. Excluded health economic studies

None.

Appendix I

This appendix is not available from the publisher at this time.

Tables

Table 1PICO characteristics of review question

Population	Children, young people and adults with pulsatile tinnitus. Strata: People presenting with isolated pulsatile tinnitus People presenting with pulsatile tinnitus plus other conditions Synchronous and non-synchronous (including somatic) pulsatile tinnitus Unilateral and bilateral
Intervention(s)	CT/A scan MRI/A scan Angiography Ultrasound scan
Comparison(s)	CT/A scan MRI/A scan Angiography Ultrasound No imaging
Outcomes	Mortality (critical) Tinnitus severity (critical) Impact of tinnitus (critical): Tinnitus distress Tinnitus annoyance Health related QoL(critical): QoL (tinnitus) QoL Tinnitus percept (important): Tinnitus loudness Other co-occurring complaints (important): Depression Anxiety Anxiety and depression Sleep Adverse events (important): Safety Tolerability Side effects
Study design	Systematic review of RCTs RCT If there is an inadequate amount of RCT data, non-randomised comparative studies will be considered.

Table 2Unit costs of imaging techniques for non-pulsatile tinnitus

Imaging Modality^(a)	Contrast	Number of areas^(b)	Code	Costs
Computerised Tomography	With Contrast	Two areas	RD24Z	£106
Magnetic Resonance Imaging	Without Contrast	Two areas	RD04Z	£152
Magnetic Resonance Imaging	With Contrast	Two Areas	RD05Z	£202

(a): The committee provided the names of the key imaging techniques used for people with pulsatile tinnitus and the required contrast for each test. The costs were subsequently sourced from NHS reference costs.⁶

Final

Diagnostic test and treat evidence review

This evidence review was developed by the National Guideline Centre

Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and, where appropriate, their carer or guardian.

Local commissioners and providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.

NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.

Bookshelf ID: NBK557029PMID: 32437109