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  • Open Access

Patient-reported outcome measures used in patients with primary sclerosing cholangitis: a systematic review

  • 1,
  • 2,
  • 2,
  • 2Email author,
  • 2, 3,
  • 4,
  • 5,
  • 6,
  • 3, 4 and
  • 2, 3
Health and Quality of Life Outcomes201816:133

https://doi.org/10.1186/s12955-018-0951-6

  • Received: 21 September 2017
  • Accepted: 4 June 2018
  • Published:

Abstract

Background

Primary Sclerosing Cholangitis (PSC) is a rare chronic, cholestatic liver condition in which patients can experience a range of debilitating symptoms. Patient reported outcome measures (PROMs) could provide a valuable insight into the impact of PSC on patient quality of life and symptoms. A previous review has been conducted on the quality of life instruments used in liver transplant recipients. However, there has been no comprehensive review evaluating PROM use or measurement properties in PSC patients’ to-date. The aim of the systematic review was to: (a) To identify and categorise which PROMs are currently being used in research involving the PSC population (b) To investigate the measurement properties of PROMs used in PSC.

Methods

A systematic review of Medline, EMBASE and CINAHL, from inception to February 2018, was undertaken. The methodological quality of included studies was assessed using the Consensus-based Standards for selection of health Measurement Instruments (COSMIN) checklist.

Results

Thirty-seven studies were identified, which included 36 different PROMs. Seven PROMs were generic, 10 disease-specific, 17 symptom-specific measures and 2 measures on dietary intake. The most common PROMs were the Short form-36 (SF-36) (n = 15) and Chronic liver disease questionnaire (CLDQ) (n = 6). Only three studies evaluated measurement properties, two studies evaluated the National Institute of Diabetes Digestive and Kidney Diseases Liver Transplant (NIDDK-QA) and one study evaluated the PSC PRO; however, according to the COSMIN guidelines, methodological quality was poor for the NIDDK-QA studies and fair for the PSC PRO study.

Conclusion

A wide variety of PROMs have been used to assess health-related quality of life and symptom burden in patients with PSC; however only two measures (NIDDK-QA and PSC PRO) have been formally validated in this population. The newly developed PSC PRO requires further validation in PSC patients with diverse demographics, comorbidities and at different stages of disease; however this is a promising new measure with which to assess the impact of PSC on patient quality of life and symptoms.

Keywords

  • Primary sclerosing cholangitis
  • Cholestasis
  • Patient reported outcome measures (PROMs)
  • PROSPERO (Registration Number: CRD42016036544).

Background

Primary Sclerosing Cholangitis (PSC) is a chronic, cholestatic liver condition that results in inflammation and fibrosis that can involve the entire biliary tree [1]. PSC is a progressive disorder and can lead to cirrhosis, portal hypertension and liver failure [1].

Approximately 1 in 100,000 people in the general population is affected with PSC per year in Europe and the United States [2]. The disease occurs at any age, but is more prevalent in adults between the ages of 30–60 years and is more common in men than in women. Approximately 70–80% of patients with PSC have an associated inflammatory bowel disease (IBD) such as ulcerative colitis or Crohn’s disease [3]. Currently, there is no known licensed medication to prevent the progression of PSC, which if left untreated can result in increasing disability and even death [4]. In patients with end-stage PSC liver disease, the only therapeutic option currently available is a liver transplant [4].

Although overall disease progression can be slow, patients with PSC can experience a range of debilitating symptoms. In the early stage of the disease, symptoms include tiredness or fatigue. In more advanced cases, symptoms include pruritus, jaundice, abdominal pain, weight loss, fevers, hyperpigmentation, vitamin deficiencies and metabolic bone disease [5]; all of which can have a significant impact on health-related quality of life (HRQOL) [6, 7].

Increasingly in chronic diseases and terminal illness, it is recognised that maintaining HRQOL is an important consideration when the treatment is aimed at maintenance rather than a cure, or the treatment has a high level of toxicity [8]. Many of the current therapeutic interventions in PSC are aimed at managing symptoms. Measuring the impact of these interventions and preserving HRQOL is an important aspect of PSC care. This requires patient reported outcome measures (PROMs) that are sensitive enough to capture changes in HRQOL or symptoms over time.

Increasingly, PROMs use has demonstrated a positive contribution to clinical practice and research [9]. In clinical practice, aggregate level PROM data can help us to understand the burden of chronic medical conditions, identify health inequalities [10] and determine new areas for therapeutic interventions. They can also play a key role in benchmarking and audit. [11] At an individual patient level, PROMs can be used to monitor the response, adverse effects and benefits of treatments in routine practice, [12] facilitating communication between clinicians and patients regarding their HRQOL, symptom management and control [1315].

A previous review investigating the quality of life (QOL) instruments used in liver transplant recipients has been conducted [16]. However, to date, no comprehensive review of PROMs used in PSC patients has been undertaken. There is a clear need to evaluate the measurement properties of the PROMs currently used in this population to determine the optimal measures for use in future research and routine care. Therefore the objectives of this systematic review were to: (a) identify and categorise PROMs currently used in research involving the PSC population; and (b) investigate their measurement properties, to help inform the selection of PROMs for use in future PSC research and routine practice.

Methods

The following guidelines were used, where applicable, to inform the conduct and reporting of this study: (i) the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [17] guidance (see Additional file 1 for the PRISMA checklist), (ii) COnsensus based Standards for the selection of health Measurement INstruments (COSMIN) guidance [18] and (iii) the updated method guidelines for systematic reviews in Cochrane collaboration back review group [19]. The study was registered with PROSPERO (Registration Number: CRD42016036544).

Search strategy

A systematic search was conducted on the following electronic databases: Medline, EMBASE and CINAHL from inception to 15 February 2018. The search terms “Primary sclerosing cholangitis” and “Patient reported outcome measures” were used, alongside synonyms and related terms (see Additional file 2 for the full search strategy). These terms were combined with the COSMIN search filters developed by VU University Medical Centre Amsterdam and University of Oxford (available on COSMIN website: http://www.cosmin.nl/). In addition, papers included in the full text review were subjected to a hand search of reference lists [20, 21].

Inclusion criteria

Studies were eligible if:
  1. a)

    PROMs were included in the study meeting the FDA definition [22].

     
  2. b)

    Study participants were patients with PSC.

     

In addition:

c) Studies that evaluated at least one measurement property (i.e. reliability, validity, responsiveness, interpretability) were included in the COSMIN quality review.

No restriction was placed on age or gender of participants or language, publication date or country of origin of the study.

Selection of studies

Two reviewers (FI/GT or GT/GK) independently screened studies according to their title and abstract to determine eligibility. Following this, the full text of potentially eligible studies was retrieved and screened independently by two independent reviewers (FI/GT or GT/GK). The protocol planned that discrepancies would be discussed with a third investigator (MG or DK or AS) to reach consensus; however, this was not required.

Data extraction

The two independent reviewers (GT plus FI, GK or AS) independently extracted the data from each study using a predefined form (including study design and patient level characteristics). Information regarding each PROM was extracted, including: constructs, therapeutic area, domains, number of items, scoring method, recall period, administration, completion time, data collection, cost/permission and measurement properties (reliability, validity, responsiveness, interpretability).

Content comparison of included PROMs

A summary of PROMs used in studies of PSC patients, including an overview of included domains and specific content was prepared. The PROMs were categorised according to their domains to facilitate comparison of the measures that have been used in PSC studies to-date.

Quality assessment

The COSMIN checklist [23] was used to assess the methodological quality of studies that reported on the measurement properties of PROMs used in the study. Two reviewers (FI/GT or GT/AW) independently completed the COSMIN checklist. The protocol planned that discrepancies would be discussed with a third reviewer; however, this was not required. Each measurement property was scored according to the quality of reporting by the publication, using a four-point rating scale: ‘excellent’, ‘good’, ‘fair’ and ‘poor’. The methodological quality of each study was rated by taking the lowest score (worst score counts method) per domain. For example, if any of the items of the domain reliability was scored ‘poor’, the overall score for regarding the methodological quality of reliability was rated as ‘poor’.

Evidence synthesis

Synthesis of measurement property evidence was performed using standardised criteria developed by Terwee 2011 [23]. The summary of the overall evidence of measurement properties of the PROMs was determined by the number of studies, the methodological quality of the studies, and consistency of the findings. Based on these factors the overall rating of a measurement property per PROM was ranked as “+” positive, “?” indeterminate or “-” negative and combined with an assessment of the overall level of supporting evidence (strong, moderate, limited, conflicting, unknown) as proposed by the Cochrane Back Review Group [24].

Results

Study selection

In total, 8074 studies were identified, 5893 remained after duplicate removal and 150 remained after reviewing titles and abstracts (Fig. 1). Following review of the 150 full texts, 37 studies, containing 36 different PROMs, were included.
Fig. 1
Fig. 1

PRISMA flowchart describing the identification, selection and inclusion of studies on PROM assessment in Primary sclerosing Cholangitis

Table 1 summarises the general characteristics of the included studies. The study designs included 17 cross-sectional studies, five randomised controlled trials (RCTs), four case-control studies, two validation study, two pilot study, two before and after study, one cost-effectiveness study, one case matched study, one longitudinal study, one cohort study and one retrospective case series study.
Table 1

Characteristics of included studies

Author (Year) (Reference)

Country

Study design

Sample size (PSC cases)

Mean age (SD) year

Gender (Male n %)

Disease stage

Mayo risk score / MELD Score

IBD (Yes/No (n (%))

LT (Yes/No (n (%))

PROM

Rationale for Assessment

PROM administration

Gavaler (1991) [66]

USA

Cross- sectional study

23 (23)

Quiescent group: 34.7 (6.2) Symptomatic group: 39.8 (1.6)

15 (65%)

Symptomatic UC:

Mild: 7 (40%)

Moderate: 8 (47%)

Severe: 2 (13%)

NR

Yes (23 (100%))

Yes (23 (100%))

Study questionnaire: symptoms of UC

A

Postal & telephone

Gross (1999) [26]

USA

Before & after study

157 (92)

Total sample: 50 (10)

31 (34%)

NR

MRS: Mean 5.3

NR

Yes (157 (100%))

NIDDK-QA, pilot version NIDDKQA

A

Clinic

Kim (2000) [28]

USA

Validation study

96 (17)

45 (9.3)

7 (41%)

PSC undergoing LT: 17 (100%)

MRS: mean (SD) = −0.1(1.0)

NR

PSC patients undergoing LT: 17 (100%)

NIDDK-QA, SF- 36

D

Clinic

Bharucha (2000) [67]

USA

Pilot study

20 (20)

44 (11)

12 (60%)

Early stage (1–2): 10 (50%),

Late stage (3–4): 10 (50%)

MRS: mean (SD) = 2.87 (0.95)

Yes (14 (70%))

No

Grading system fatigue & pruritus

B

Unclear

Younossi (2000) [38]

USA

Cross-sectional study

104 (29)

Total sample:: 55 (12)

Total sample 28 (97%)

NR

NR

NR

No

SF- 36, CLDQ

A

Unclear

Younossi (2001) [39]

USA

Cross-sectional study

353 (45)

Total sample: 54 (11)

Total sample 38 (30%)

Total sample: Child-pugh class: no cirrhosis: 47 (13%)

class A: 43 (12%)

class B-27 (8%) class C-4 (1%)

NR

NR

NR

SF-36, CLDQ

A

Clinic

Longworth (2003) [45]

England and Wales

Cost effectiveness study

347 (70)

NR

48 (69%)

NR

Of 41 patients MELD score median/IQR = 10/6–16

NR

Yes (45) 64%))

EuroQol EQ. 5D

C

Postal

Bjornsson (2004) [44]

England & Sweden

RCT

93 (20)

NR

13 (65%)

Cirrhosis: 5 (1%),Ludwig’s fibrosis score stage 1: 9 (44%), stage 2: 4(21%), stage 3:6(30%)

NR

Yes (16 (80%))

No

PGWB, FIS, BDI, GSRS, Rome ll modular QA

A

Postal

Ter Borg (2004) [36]

Netherlands

RCT

33 (11)

NR

10 (91%)

NR

NR

NR

No

VAS, FFSS, MFI

B

NR

Ter Borg (2005) [48]

Netherlands

Cross-sectional study

72 (27)

45 (NR)

19 (70%)

Cirrhosis: 15 (56%)

NR

Yes (2 (7%)

NR

VAS, FFSS, SF-36

A

NR

Olsson (2005) [33]

Sweden, Norway, Denmark

RCT

198 (198)

UDCA: 43.6(12.7) Placebo: 43.1 (11.2)

139 (70%)

NR

NR

Yes (168 (85%))

NR

SF- 36

B

Unclear

Gorgun (2005) [21]

USA

Case matched study

65 (65)

43.37 (11.2)

45 (69%)

NR

NR

Yes

(65 (100%))

No

FPQ, CGQOL

A

 

Mansour-Ghanaei (2006) [49]

Iran

RCT

34 (6)

Total sample: 53.97 (11.93)

NR

NR

NR

NR

NR

VAS

B

Unclear

Mayo (2007) [50]

USA

RCT

21 (4)

Total sample: 53.97 (11.93)

Total sample 5 (15%)

NR

aTotal sample MELD mean (range): 11(6–24)

NR

NR

VAS, IDS-SR30

B

Unclear

Van os (2007) [52]

Netherlands

Cross-sectional study

92(37)

43.8(12.3)

24 (65%)

Cirrhosis: 5 (13.5%)

NR)

NR

NR

BDI, SADS

A

Postal

Tillman (2009) [37]

Germany

Cross-sectional study

511(13)

42 (NR)

NR

NR

NR

NR

NR

SF- 36, FIS, WHOQOL-BREF, HADS

A

In clinic

Ananthakrishnan (2010) [47]

USA

Case-control study

26 (26)

40.7 (14.8)

21 (80.8%)

NR

MELD score mean (range) 8 (6–20)

Yes (26(100%))

No

SIBDQ, HBI, UCAI

A

Outpatient clinic

Aberg (2012) [30]

Finland

Cross-sectional study

401 (56)

53 (9)

36 (64%)

NR

NR

NR

Yes (56 (100%))

15D, ad hoc questionnaire

A

Postal

Benito De Valle (2012) [29]

England & Sweden

Cross-sectional study

182 (182)

160 patients no LT: 50 (16)

112 (70%)

Small duct disease: 17 (11%), Liver cirrhosis: 12 (8%), Decompensated liver disease: 9 (6%)

MRS mean (SD): 0.34 (1.10)

Yes (126 (79%))

Yes (22 (12%))

SF-36, CLDQ, FIS, HADS

A

Postal

Hagstrom (2012) [68]

Sweden

Cross-sectional study

96 (96)

47 (13)

63 (66%)

Cases child pugh score of 10, significant fibrosis: 26 (27%), non-significant fibrosis: 70 (73%)

NR

Yes (73 (76%))

Yes (12 (12.5%))

LDH

A

Interview

Gulati (2013) [25]

USA

Cross-sectional study

40 (24)

Total sample: 11.6 (4.5)

17 (43%)

Total sample: Cirrhosis 22 (55%)

NR

Total sample: Yes (16 (65%))

No

 

A

Unclear

Block (2014) [69]

Norway & Sweden

Case-control study

48 (48)

NR

40 (83%)

NR

NR

48

Yes (IPAA: 11, IRA: 7)

OS

A

Scheduled follow up visit

Gotthardt (2014) [6]

Germany

Cross-sectional study

113

(113)

43.6 (14.2)

81 (71.7%)

NR

MRS n: low/intermediate/ high =48 (42%) / 25 (22%) / 5 (4%)

Yes (71 (63%))

NR

SF 36, PHQ-9

A

Postal

Hov (2014) [70]

Norway

Case-control study

240

(240)

NR

171 (71%)

NR

NR

Yes (183 (77%))

Yes (94 (39%))

Study questionnaire

A

Postal

Pavlides (2014) [34]

England

Retrospective case note review

40 (PSC-IPAA = 21 & PSC-UC = 19)

NR

31 (78%)

PSC-IPAA had dysplasia: 2 (5%)

NR

Yes (19 (47.5%))

No

OS, CGQOL, FSFI, IIEF

A

Postal

Raszeja-Wyszomirska (2014) [35]

Poland

Cross-sectional study

102 (102)

36 (12)

73 (72%)

Cirrhosis: 30 (29%)

NR

Yes (65 (64%))

NR

SF 36, PBC-40, PBC-27

A

Unclear

Cheung (2015) [32]

Canada

Cross-sectional study

162 (99)

46.1 (15.1)

50 (51%)

Cirrhosis: 47 (48%), Decompensated liver disease: 16 (16%)

NR

Yes (74)

No

SF-36, PBC-40, PHQ-9, LDQOL, SIBDQ, 10 peered-reviewed QA on emotional and psychosocial

A

Postal or clinic

Dyson (2015) [20]

USA

Cross-sectional study

40 (40)

51 (13)

31 (78%)

NR

NR

Yes (24 (60%))

NR

FIS, ESS, HADs, COMPASS

A

Postal

Eaton (2015) [71]

Canada & USA

Case-control study

1000

(1000)

NR

619 (72%)

NR

NR

Yes (741 ((74%))

Yes (450 ((45%))

HHQ

A

Postal or clinic

Haapamaki (2015) [31]

Finland

Cross-sectional study

341

(341)

43.3 (13.7)

183 (54%)

ERC-score mean (SD): 5.9 (3.4)

NR

Yes (237 (69.5%))

Yes (9 (2.6%))

15D, study questionnaire

A

ERC examination at the HUGH endoscopy unit

Kalaitzakis (2015) [27]

England and Sweden

Cross-sectional study

163

(163)

No LT: 50 (16)

No LT

122 (75%)

No LT Small-duct disease: 15 (10%), Diver cirrhosis: 11 (8%), Decompensated liver disease: 8 (6%)

No LT MRS: mean (SD) = 0.11(1.42)

No LT Yes (116 (71%))

Yes (19 (12%))

SF 36, SF-6D, CLDQ, study questionnaire

A, C

Unclear

Raszeja-Wyszomirska (2015) [41]

Poland

Cross-sectional study

33 (33)

35.3 (13.38)

11 (33%)

Cirrhosis: 6 (18%)

NR

Yes (22 (67%)

NR

SF 36, PBC-40, PBC-27

A

NR

Carbone (2017) [46]

Italy

Longitudinal study

227 (64)

50(11)

39 (66%)

NR

NR

NR

NR

EQ-5D

A

Clinic

Kempinska (2017) [40]

Poland

Cohort study

275 (275)

Median 55, range 28–90

182 (66%)

NR

NR

NR

NR

SF 36, PBC-40, PBC-27

A

NR

Kittanamongkolchai (2017) [51]

USA

Before and after study

13 (5)

46.4 (13.2)

1 (20%)

NR

NR

NR

NR

Pruritus numerical rating scale

B

Physician administered

Tabibian (2017) [42]

USA

Pilot study

16 (16)

40 (NR)

13 (81%)

All patients had stage 1–3 PSC

NR

13 (81%)

NR

FFSS, 5-D itch scale, CLDQ, SF-36

B

NR

Younossi (2017) [43]

USA

Validation study

102 (102)

44 (13)

33 (32%)

Cirrhosis: 37 (39%)

NR

67 (68%)

NR

PSC PRO, SF-36, CLDQ, PBC-40, 5-D Itch

D

ePRO website

15D 15-dimensional health-related quality of life measure, 5-D Itch Five dimensions Itch, BDI Beck Depression Inventory, CGQOL Cleveland global quality of life questionnaire, CLDQ Chronic liver disease questionnaire, COMPASS Composite Autonomic Symptom Scale, ESS Epworth Sleepiness Scale, EQ. 5D EuroQol EQ. 5D, FFSS Fisk Fatigue Severity Scale, FIS Fatigue Impact Scale, FSFI Female Sexual Satisfaction Index, GSRS Gastrointestinal Symptom Rating Scale, HADS Hospital anxiety and depression scale, HBI Harvey-Bradshaw Index, HHQ Health Habits and History Questionnaires, IBD Inflammatory Bowel Disease, IDS-SR30 30-item Inventory of Depressive Symptomatology-self report, IIEF International index of erectile function, LDH Lifetime drinking history, LDQOL Liver Disease Quality of Life Questionnaire, LT Liver Transplant, MELD Model For End-Stage Liver Disease, MFI Multidimensional Fatigue Inventory, MRS Mayo Risk Score, NIDDK-QA National institute of diabetes and digestive and kidney disease liver transplant questionnaire, NR Not Reported, OS Oresland Scale, PBC-40 Primary Biliary Cirrhosis, PF Pouch Function Questionnaire, PGWB Psychological general well-being index, PHQ-9 Patient Health Questionnaire, PSC PRO Primary Sclerosing Cholangitis patient-reported outcome, RCT Randomised Controlled Trial, SADS Schedule for Affective Disorders and Schizophrenia, SD Standard Deviation, SF-36 Short form 36, SIBDQ Short Inflammatory Bowel Disease Questionnaire, UC Ulcerative Colitis, UCAI UC Activity Index, VAS Visual Analogue Scale, WHOQOL-BREF World Health Organization Quality of Life assessment instrument

aRationale for assessment: A; Burden (HRQOL /symptom) of disease, B: Effectiveness of treatment, C: Cost Effectiveness/Health Utilities, D:Validation of a Patient Reported Outcome Measure, (PROM)

Twenty seven of the 37 included studies used PROMs to examine the impact of PSC on patients and seven of these measured the effectiveness of treatments: one study evaluated the cost-effectiveness of liver transplantation, one study assessed health utilities and two were validation studies of the PROMs: the National Institute of Diabetes Digestive and Kidney Diseases Liver Transplant (NIDDK-QA) and the Primary Sclerosing Cholangitis Patient Reported Outcome (PSC PRO).

In total, 3742 patients with PSC were recruited to the included studies (sample size range n = 4–1000). All participants were adults, with the exception of one study [25] which included patients with the mean age of 11.6 years. Studies were heterogeneous in terms of population demographic characteristics. In the thirty-five studies that reported gender, the proportion of PSC patients who were males ranged from 15 to 97%. Five studies reported a relatively wide range of mean Mayo risk scores (− 0.1 to 2.87) for PSC patients, a score which estimates patient survival in PSC [6, 2629]. Twenty-four studies described the proportion of IBD in PSC patients, ranging from 7 to 100%. In 12 studies, the percentage of PSC patients who had received a liver transplant ranged from 12 to 100%.

Characteristics of PROMs

Characteristics of the 36 included PROMs are presented in Table 2. The most frequently used PROM was the Short Form 36 health survey (SF-36) (n = 15), followed by the Chronic Liver Disease Questionnaire (CLDQ) (n = 6) and the Primary Biliary Cirrhosis (PBC)-40 (n = 5). All other PROMs were used in ≤3 studies (Table 1).
Table 2

Characteristics of included PROMs

PROM

Construct

Therapeutic area

Domains

Total No. of items

Scoring method

Recall period

Administration

Completion time

Data collectiona

Cost & permissionb

15 D ©

HRQOL

Generic

Mobility,Vision,Hearing, Breathing, Sleeping, Eating, Speech, Elimination, Usual Activities, Mental function,Discomfort, symptoms, Depression, Distress, Vitality, Sexual Activity

15

1 to 5 levels

Present health status

Self-administered

5–10 min

PP

A, B

5-D Itch

Pruritus

Severity of symptoms

Duration, Degree, Direction, Disability, Distribution

5

0–5 (0 being least problematic and 5 most problematic)

Last 2 weeks

Self-administered

< 5 min

PP

Unknown

BDI

Psychological functioning (incl. coping)

Psychology/ Behaviour

Cognitive-affective, Somatic

21

Higher score = greater depression

Last 2 weeks including today

Self-administered/ Interviewer-administered

5–10 min

E, PP

B,D

CGQOL

HRQOL

Disease specific (IBD)

Unknown

3

0–1.0 (1 being the best)

Unknown

Unknown

Unknown

PP

Unknown

CLDQ

HRQOL

Digestive System Diseases

Abdominal symptoms, Fatigue, Systemic symptoms, Activity, Emotional function, Worry

29

Higher score = better QoL

Last two weeks

Self-administered

10 min

E, PP

B,D

COMPASS

Autonomic nervous system diseases

Signs and symptoms

Orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder and pupilometer

31

Higher score = higher autonomic symptom severity

In past year/ past 5 years

Self-administered

No information

PP

No information

EQ -5D

HRQOL

Generic

Mobility, Self-care, Usual activities, Pain/discomfort, Anxiety/depression

5 + VAS (20 cm)

Higher score = better QoL

Today

Interviewer-administeredProxy-ratedSelf-administered

A few minutes

E, PP, IVR, T

B,D

ESS

Sleep disorder

Signs and symptoms

Sleep

8

Higher score = higher sleepiness

Over recent times

Self-administered

2–3 min

E, PP

A,B

FFSS

HRQOL

Signs & symptoms

Fatigue

9

High score = higher fatigue

Past two weeks

Self-administered

<  5 min

E, PP

B,D

FIS

Symptoms of fatigue

Pathological Conditions, Signs and Symptoms

Cognitive functioning, Physical functioning, Psychosocial functioning

40

Lower score = less fatigue

Past four weeks

Self -administered

10 min

PP

A,B

FSFI

Signs and symptoms

Female Urogenital Diseases & Pregnancy

Desire, Arousal, Lubrication, Orgasm, Global satisfaction, Pain

19

Higher score = better functioning

During the past 4 weeks

Self-administered

Information not found

E, PP

C

Grading system for fatigue & pruritus

Fatigue and Pruritus

Severity of symptoms

Unknown

Unknown

Pruritus, grades 0 -no, 1-mild, 2- sleep interference,3-

substantial sleep disturbance

Fatigue, grade 0- no; 1- present, but no interference with activity; 2-extra rest required & activity limited 3- patient unable to work a full day.

Unknown

Unknown

Unknown

Unknown

Unknown

GSRS

Signs and symptoms

Signs & symptoms, Digestive system diseases

Abdominal pain syndrome, Reflux syndrome, Indigestion syndrome, Diarrhoea syndrome, Constipation syndrome

15

Lower score-better QoL

Last week

Self-administered

10 min

PP

B,D

HADS

Signs and symptoms

Nervous System Diseases Mental Disorders

Anxiety, Depression

14

Lower score = better QoL

In the past week

Self-administered

2–5 min

E, PP

C

HHHQ

Diet

Dietary habits

Patient demographics, Education, Medical surgical history and environmental exposure including dietary habits

370 questions

Unknown

Unknown

Self-report

Unknown

Unknown

Unknown

IDS-SRS 30

Signs and symptoms

Psychiatry/Psychology/Behaviour

Vegetative features, Cognitive changes, Mood disturbance, Endogenous symptoms, Anxiety symptoms

30(28 initial version)

Higher score = higher severity

Past 7 days

Clinical-rated, interviewer-administered, self-administered

10–15 min

E, IVR, PP

C

IIEF

HRQOL

Erectile Dysfunction

Erectile function, Orgasmic function, Sexual desire, Intercourse satisfaction, Overall satisfaction

15

Higher score = better QoL. Scores by dimension

Past 4 weeks

Self-administered

15 min

PP

B,D

LDH

Alcohol consumption patterns

Intake assessment

Consumption levels (quantity), frequency of use, variability in consumption, types of beverages, drinking pattern, solitary versus social drinking, time of the day alcohol consumption

Unclear

Scored by hand or calculator

Unknown

Unknown

20 min

Unknown

Cost nominal (copyright)

LDQOL 1.0

HRQOL

Digestive System Diseases

- Generic core SF-36v2

- Disease-targeted scales:

Liver disease-related symptoms,

Effects of liver disease, Concentration/Memory, Health distress, Sleep, Loneliness, Hopelessness, Stigma of liver disease, Sexual functioning/problems

72

Higher score = Better HRQOL.

The past 4 weeks; Presently (for few items)

Self-administered

18 (+/− 9) min

PP

D

MFI

Signs and symptoms

Pathological conditions, signs and symptoms

General fatigue, Physical fatigue, reduced activity, Reduced motivation, Mental fatigue

20

Lower score = better QoL

Lately

Self-administered

5 min

PP

B

NIDDK-QA

HRQOL

Patients undergoing Liver transplant

Liver disease symptoms, physical functioning,

health satisfaction & overall well-being (OWB)

47

Higher scores indicate better QOL

Unknown

Unknown

Unknown

Unknown

Unknown

OS

Functional outcome

IPAA or IRA

Bowel movements, urgency, evacuation difficulties, soiling or seepage, perianal/stomal soreness, protective pad, dietary restrictions and social handicap

Unclear

best 0, worst 15

Unknown

Unknown

Unknown

Unknown

Unknown

PBC-27

HRQOL

Disease specific

Symptoms, Dryness,Itch, Fatigue, Cognitive, Emotional and Social

40

Higher scores = greater symptoms impact & poorerHRQOL.

Last four weeks

Self-completion

<  5 min

PP

Unknown

PBC-40

HRQOL

Disease specific

Other Symptoms domain, Itch, Fatigue, Cognitive, Social and Emotional

27

Higher scores = greater symptoms impact & poorerHRQOL.

Last four weeks

Self-completion

5 min

PP

Free access

PedsQL 4.0

HRQOL

Generic

Physical functioning, Emotional functioning, Social functioning,school functioning

21 to 23

Higher score = better QoL

Standard version: past one month. Acute version: past 7 days

Interviewer-administered

Proxy-rated

Self-administered

5 min

PP

A,B

PGWB

HRQOL

Generic

Anxiety, Depression mood, Positive well-being, Self-control, General health, Vitality

22

Higher score = better QoL

Standard version = past month/ acute version = last week/ last four weeks

Self-administered/Interviewer-administered

15 min

PP

 

PHQ-9

Depression

Severity of depression

Nine questions on symptoms

10

Depression severity:1–4: None; 5–9: Mild; 10–14: Moderate, 15–19: Moderately severe, 20 to 27: Severe

over past 2 weeks

Self-completion

2 to 5 min

PP

Unknown

Pruritus numerical rating scale

Pruritus

Severity of symptoms

Unknown

Unknown

Numerical rating scale 0–10 (0 for having no symptoms and 10 for having the worst imaginable pruritus)

Unknown

Unknown

Unknown

Unknown

Unknown

PSC PRO

HRQOL

Disease specific

PSC symptoms, Physical function, Activities of Daily Living, Work Productivity, Role Function, Emotional Impact, Social/Leisure Impact, Q uality of Life, Total Impact of Symptoms

42

Module 1: 0–10 scale; Module 2 has 7 four item domains: 1–5 scale, summed within dmains and domain mean summed to give overall impact score

Module 1–24 h recall

Self-administered

7–15 min

E, PP

Unknown

Rome ll modular questionnaire

Symptoms

Functional bowel disorder

Esophageal symptoms, Gastroduodenal symptoms, Bowel symptoms, Abdominal pain symptoms, Biliary symptoms and Anorectal symptoms

Unknown

Unknown

Unknown

Unknown

Unknown

Unknown

Unknown

SADS

Signs and symptoms

Depression

Depressive mood and ideation, Endogenous (ie. Melancholic, vital or vegetative) features, Depressive syndrome, Suicidal ideation and behaviour

30

Unknown

Past week only

Unknown

Unknown

Unknown

Unknown

SF-36

HRQOL

Generic

Physical Functioning,

Role-Physical, Bodily Pain, General Health,Vitality, Social Functioning, Role-Emotional,Mental Health

36

0 to 100, higher score = better health status

Standard version 4 weeks / Acute version 1 week

Self-administered/Interviewer-administered

5–10 min

E, C, IVR, T, PP

B

SF-6D

Utilities & Health states

Generic- preference based measure

Physical functioning, role limitation, social functioning, pain, mental health, vitality

Unknown

0.296-most severe problems 1.0-no problems

Unknown

Unknown

Unknown

Unknown

Unknown

SIBDQ

HRQOL

Digestive System Diseases

Bowel symptoms, systematic symptoms, Emotional function, Social function

10

1 to 7, higher score = better QOL

Last two weeks

Self-administered/Interviewer-administered

5 min

E, PP

D

VAS

Fatigue and Pruritus

Severity of symptoms

Fatigue, Energy, Pruritus

Pruritus: 10 cm line

Pruritus 0 -no pruritus / 10- worst pruritus imaginable

Right now

Self-administered

Vas: Fatigue < 2 min

PP

Free access

WHOQOL-BREF

HRQOL

Generic

Physical, Psychological, social relationship, Environment, +  2 overall QOL & general health status

26

Higher score = better QoL

Last 2 weeks

Interviewer-administered, self-administered

5 min self-administration, 15–20 min interviewer-administration

PP

D

15 D 15-dimensional health-related quality of life measure, 5-D Itch Five dimensions Itch, BDI: Beck Depression Inventory, CGQOL Cleveland global quality of life questionnaire, CLDQ Chronic liver disease questionnaire, COMPASS Composite Autonomic Symptom Scale, EQ. 5D EuroQol EQ. 5D, ESS Epworth Sleepiness Scale, FFSS Fisk Fatigue Severity Scale, FIS Fatigue Impact Scale, FSFI Female Sexual Satisfaction Index, GSRS Gastrointestinal Symptom Rating Scale, HADS Hospital anxiety and depression scale, HBI Harvey-Bradshaw Index, HHQ Health Habits and History Questionnaires, HRQOL Health-related quality of life, IBD Irritable Bowel Syndrome, IDS-SR30 30-item Inventory of Depressive Symptomatology-self report, IIEF International index of erectile function, LDH Lifetime drinking history, LDQOL Liver Disease Quality of Life Questionnaire, MFI Multidimensional Fatigue Inventory, NIDDK-QA National institute of diabetes and digestive and kidney disease liver transplant questionnaire, No. Number, OS Oresland Scale, PBC-40 Primary Biliary Cirrhosis, PF Pouch Function Questionnaire, PGWB Psychological general well-being index, PHQ-9 Patient Health Questionnaire, PSC PRO Primary Sclerosing Cholangitis patient-reported outcome, QoL Quality of Life, SADS Schedule for Affective Disorders and Schizophrenia, SF-36 Short form 36, SIBDQ Short Inflammatory Bowel Disease Questionnaire, UCAI UC Activity Index, VAS Visual Analogue Scale, WHOQOL-BREF World Health Organization Quality of Life assessment instrument

aPP: Paper & pen, E: E-version, IVR: Interactive Voice Response, T: Telephone, C: Computer

bA: Free access to academic/non-profitable research, B: Fees for commercial/pharmaceutical companies/academics, C: Free access to public domain, D: Contact author / licence / signature of a contract or agreement

There were seven generic measures including: the 15 Dimensional Health-Related Quality of Life Measure (15D ©) [30, 31]; SF-36® [6, 2729, 3243]; Short Form 6 health survey (SF-6D) [27]; Psychological General Well-being Index (PGWBI) [44]; Paediatric Quality of Life Inventory™ generic core scale (PedsQL™) [25]; EuroQOL (EQ. 5D) [37, 45, 46]; and the World Health Organization Quality of Life assessment instrument (WHOQOL-BREF) [37].

Ten disease-specific measures included: the Short form Liver Disease Quality of Life questionnaire (LDQOL 1.0) [32]; CLDQ [27, 29, 38, 39, 42, 43]; the NIDDK-QA [26, 28]; Rome II Modular Questionnaire; the Cleveland Global Quality of Life questionnaire (CGQOL) [34]; the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) [32, 47]; Oresland scale; PSC PRO; [43] PBC-27 [35, 40, 41]; and PBC-40 [32, 35, 40, 41, 43].

The 17 symptom-specific PROMs included: the FIS [29, 37, 44]; Gastrointestinal Symptom Rating Scale (GSRS) [44]; Fisk Fatigue Severity Scale (FFSS) [36, 42, 48]; Multidimensional Fatigue Inventory (MFI) [48]; VAS [4850]; the 5-Dimension Itch; [42, 43] the Pruritus numerical rating scale; [51] the Hospital Anxiety and Depression Scale (HADS) [29]; Beck Depression Inventory (BDI) [44, 52]; Inventory of Depressive Symptomatology (IDS) [50]; Patient Health Questionnaire (PHQ-9) [6, 32]; Schedule for Affective Disorders and Schizophrenia (SADS) [52]; the Female Sexual Functioning Index (FSFI) [34]; International Index of Erectile Function (IIEF) [34]; Epworth Sleepiness Scale (ESS); [21] and Composite Autonomic Symptom Scale 31 (COMPASS 31) [21].

Two other measures included: the Lifetime Drinking History (LDH) and Health Habits and History Questionnaires (HHHQ), which focused on alcohol consumption and dietary intake.

Content comparison of included PROMs

The most frequent health domains (n = 6) included across the measures were: fatigue, pain, physical functioning, emotion, anxiety and general health.

Generic PROMs measured symptoms such as pain, physical functioning, emotion, mental health and depression. The disease- and symptom-specific PROMs targeted aspects surrounding gastro intestinal symptoms, such as abdominal pain, or gastroduodenal symptoms, sexual problems, somatic symptoms, depression, mood disturbance, and vegetative features (Additional file 3).

Quality assessment

Only three studies investigated measurement properties for PROMs, two studies evaluated the NIDDK-QA [26, 28] and one study evaluated the PSC PRO [43].

For NIDDK-QA, one validation study [28] included 76 Primary Biliary Cirrhosis (PBC) and 17 PSC patients. A second study examined health status and QOL in patients with cholestatic disease before and after a liver transplant. In this study the NIDDK-QA questionnaire was administered to 65 Primary Biliary Cirrhosis and 92 PSC patients [26]. The PSC PRO validation study included 102 patients with PSC who completed the PSC PRO and four other questionnaires (SF-36, CLDQ, PBC-40 and 5-D Itch Scale) using an ePRO website [43]. The results of the validation studies are presented in Table 3 and summarised below.
Table 3

Results of measurement properties of NIDDK-QA

PROM (Author, Year)

Total sample size

PSC sample size

Domains

Test retest reliability (Pearson Correlation)

Internal consistency (Cronbach’s Alpha)

NIDDK-QA (Kim, 2000)

96

17

Liver symptoms men women

0.94

Men = 0.94, women =0.87

   

Physical function

0.99

0.88

   

Health satisfaction

0.82

NR

   

Overall well being

0.83

0.91

    

Time interval of 2 weeks

 

NIDDK-QA (Gross, 1999)

157

92

Symptoms

NR

0.81 & 0.85

   

Functioning

NR

0.82 & 0.88

   

Index of General Affect (IGA)

NR

0.91 & 0.93

PSC PROM (Younossi, 2017)

102

Test retest n = 53 Internal consistency n = 155

PSC Symptoms

0.84

0.89

   

Physical Function

0.83

0.91

   

Activities of Daily Living

0.85

0.86

   

Work Productivity

0.7

0.93

   

Role Function

0.83

0.91

   

Emotional Impact

0.82

0.91

   

Social/Leisure Impact

0.8

0.93

   

Quality of Life

0.79

0.94

   

Total Impact of Symptoms

0.88

 

NIDDK-QA National institute of diabetes and digestive and kidney disease liver transplant questionnaire, PSC PRO Primary Sclerosing Cholangitis Patient Reported Outcome

Internal consistency

All the validation studies, appropriately calculated Cronbach’s alpha to estimate reliability and internal consistency. Reported Cronbach’s Alpha ranged from 0.87 to 0.94 for the NIDDK-QA and 0.86 to 0.94 for the PSC PRO which suggests good internal consistency. Criteria defined by the COSMIN tool meant that for the NIDDK-QA the measurement properties were evaluated as ‘poor’ in methodological quality in both studies primarily because of small sample sizes and a lack of information regarding the proportion of missing items and how missing items were managed. The PSC PRO was rated as ‘fair’ due to the lack of explicit reporting of missing items and sample size for unidemensionality analysis.

Reliability

Kim et al. (2000) [28] assessed test-retest reliability of the NIDDK-QA by administering the measure on two separate occasions approximately 2 weeks apart in 19 patients. Although Pearson’s correlation was high at 0.80 (range 0.82 to 0.94), this measurement property was evaluated as ‘poor’ methodological quality due to the small sample size. For the PSC PRO, 53 patients completed the PSC PRO a second time within 3 months and correlations between administrations was high (range 0.70–0.88). The reliability of the PSC PRO was rated as ‘fair’ due to this length of time between administrations.

Validity

Kim et al. (2000) [28] assessed concurrent validity, by investigating the correlation between the NIDDK-QA and SF-36. The authors postulated that observed correlations between theoretically related domains such as physical function and health satisfaction (r = 0.86 and 0.72 respectively) demonstrated concurrent validity of the tool. However, this measurement property was also evaluated with ‘poor’ methodological quality owing to the absence of details regarding the measurement properties of the comparator scale (SF-36) in this population, and issues with sample size and missing data.

Kim et al. (2000) [28] also measured discriminant validity and information on the significant differences in the item and domain level scores of NIDDK-QA reported. Again, this property was evaluated with ‘poor’ methodological quality, secondary to issues regarding sample size, proportion and handling of missing data.

For the PSC PRO, 26 PSC patients enrolled in cognitive interviews for assessment of content validity, which was rated as ‘excellent’ according to the COSMIN checklist. An external validation cohort of 102 patients completed the PSC PRO along with SF-36, CLDQ, PBC-40 and 5-D Itch Scale; all correlations were statistically significant. The structural validity measurement property was rated as ‘fair’ due to the sample size in relation to the number of items.

Evidence synthesis

Both NIDDK-QA studies reported limited information regarding internal consistency, reliability and validity (concurrent and discriminant). Using the COSMIN guidance these properties were rated as indeterminate due to the poor methodological ratings of both studies (Tables 4 and 5) (Additional file 4) [23]. The PSC PRO study [43] had higher methodological quality compared to the NIDDK-QA studies; however, as there was only one study the level of evidence is limited.
Table 4

Methodological quality of each study per measurement property and PROM

Author (Year)

PROM

Internal consistency

Test-retest reliability

Measurement error

Content validity

Structural validity

Hypothesis testing

Criterion validity

Cross structural validity

  

Discriminant validity

Concurrent validity

 

Kim (2000)

NIDDK-QA

Poor

Poor

NR

NR

NR

Poor

Poor

NR

Gross (1999)

NIDDK-QA

Poor

NR

NR

NR

NR

NR

NR

NR

Younossi, (2017)

PSC PROM

Fair

Fair

NR

Excellent

Fair

NR

NR

NR

NIDDK-QA National institute of diabetes and digestive and kidney disease liver transplant questionnaire; PSC PRO: Primary Sclerosing Cholangitis Patient Reported Outcome

Table 5

Quality of measurement properties

PROM

Internal consistency

Test-retest reliability

Measurement error

Content validity

Structural validity

Hypothesis testing

Criterion validity

Responsiveness

      

Discriminant validity

Concurrent validity

 

NIDDK-QA

?

?

NR

NR

NR

?

?

NR

PSC PROM

+

+

NR

+

+

NR

NR

NR

Level of evidence (COSMIN): +++ or --- ‘Strong’ Consistent findings in multiple studies of good methodological quality, ++ or – ‘Moderate’ Consistent findings in multiple studies is fair, + or – ‘Limited’ One study of fair methodological quality, +/− ‘Conflicting’ Findings are conflicting,? ‘Unknown’ Studies of poor methodological quality. NIDDK-QA National institute of diabetes and digestive and kidney disease liver transplant questionnaire, PSC PRO Primary Sclerosing Cholangitis Patient Reported Outcome

Discussion

This review identified a total of 37 studies assessing 36 different PROMs used in patients with PSC; however, only one of these tools was specifically developed for the PSC population in accordance with FDA guidelines. The rationale for PROM utilization in the included studies varied. Most studies sought to measure the burden of the disease using constructs such as HRQOL and symptom severity; however, some studies examined the effectiveness of treatment, cost effectiveness and health utility. No studies researched the use of real-time monitoring of PROMs to directly inform PSC patient care in a routine clinical setting. Only three studies evaluated the measurement properties of PROMs in PSC patients: two studies evaluated the NIDDK-QA [26, 28] and one study evaluated the PSC PRO [43]. Currently, due to weakness in the methodological quality, there is limited evidence to support the use of these PROMs in the PSC population; however the PSC PRO is a promising new measure designed with patient input which requires further validation.

Clinicians or researchers wishing to use PROMs in PSC patients may consider use of both generic and disease specific measures. Choice of measurement selection should be informed through consideration on psychometric properties and patient input [53]. Generic measures such as the SF-36, although not formally validated in PSC patients, are widely used and allow comparison of the burden of PSC with other chronic disease, whilst the EQ-5D and SF-6D may be used to provide estimates of health utility to inform cost-effectiveness analysis [54]. Use of the PSC PRO will provide a more detailed assessment of symptoms and impact of symptoms relevant to PSC patients and help identify patients with varying disease severity [43, 55].

Although the PSC PRO has been developed with input from patients with and without IBD, questions focused on IBD symptoms appear fairly limited. This is important to note since 70–80% of PSC patients have co-existent IBD, most frequently ulcerative colitis [3]. This is a long term comorbidity and can occur even after a liver transplant [56]. The clinical course for patients with PSC and concomitant IBD can be different when compared to IBD or PSC alone [57]. PSC-IBD patients have higher incidence of rectal sparing, colorectal neoplasia, pouchitis following ileal pouch anal anastomosis (IPAA), pancolitis, and an overall poorer prognosis when compared to patients with IBD alone [57, 58]. Thus, PSC-IBD patients have additional symptoms and burdens that impact on activities of daily living with the consequential impact on HRQOL [59]. Additional use of an IBD measure such as the IBS-QOL may therefore be warranted [60].

Following further validation, the PSC PRO has potential for use in a number of ways to inform PSC patient care. The PRO may be used in clinical trials to assess the impact of new treatments or be used at the individual patient level in routine clinical practice to facilitate shared decision making and tailor care to individual patient needs. This approach has been highly successful in other settings such as cancer where routine monitoring using ePROs reduced emergency room admissions by 7%, hospital admissions by 4%, helped patients stay on treatment longer, improved patient quality of life by 31% and increased survival on average by 5 months at low cost [61, 62].

Strengths and limitations

This study is the first to undertake a systematic review of PROMs used in PSC, in accordance with the PRISMA [63] and COSMIN guidelines [64]. The use of COSMIN criteria has permitted a structured and comprehensive evaluation of the identified measures. However, the NIDDK QA studies evaluated in this review were carried out before the COSMIN guidance was available and at the time of publication the level and detail of reporting may have been deemed acceptable at that time. Another important consideration for research studies or clinical trials in rare diseases such as PSC are the small study populations. When guidelines such as COSMIN judge the quality of the methodology on sample sizes, it can make it more difficult to demonstrate sound methodological quality when there are only small numbers of patients available for recruitment and validation of PROs [65]. The use of international multi-centred studies may be one approach to overcome the small numbers available in studies that aim to evaluate and develop PROs for use in PSC in future studies.

Conclusion

In conclusion, a wide variety of PROMs are used to assess HRQOL and symptom burden in patients with PSC, but none have undergone comprehensive and extensive validation in this patient group. The PSC PRO is a promising new measure to assess symptoms and symptom impact in PSC patients; however further validation work is required. Collection of PROs in PSC patients can provide valuable information in a research setting and routine clinical practice to improve PSC patient care.

Abbreviations

15D: 

15 Dimensional health-related quality of life measure

5-D Itch: 

Five dimensional itch

BDI: 

Beck depression inventory

CGQOL: 

Cleveland global quality of life questionnaire

CLDQ: 

Chronic liver disease questionnaire

COMPASS 31: 

Composite autonomic symptom scale 31

COSMIN: 

Consensus-based standards for selection of health measurement instruments

EQ 5D : 

EuroQOL

ESS: 

Epworth sleepiness scale

FDA: 

Food and Drug Administration

FFSS: 

Fisk fatigue severity scale

FIS: 

Fatigue impact scale

FSFI: 

Female sexual functioning index

GSRS: 

Gastrointestinal symptom rating scale

HADS: 

Hospital anxiety and depression scale

HHHQ: 

Health habits and history questionnaires

HRQOL: 

Health-related quality of life

IBD: 

Inflammatory bowel disease

IDS: 

Inventory of depressive symptomatology

IIEF: 

International index of erectile function

LDH: 

Lifetime drinking history

LDQOL 1.0: 

Short form liver disease quality of life questionnaire

MFI: 

Multidimensional fatigue inventory

NIDDK-QA: 

National Institute of Diabetes Digestive and Kidney Diseases Liver Transplant

PBC-27: 

Primary biliary cirrhosis

PBC-40: 

Primary biliary cirrhosis

PedsQL: 

Paediatric Quality of Life Inventory generic core scale

PGWBI: 

Psychological General Well-being Index

PHQ-9: 

Patient Health Questionnaire

PROMs: 

Patient-reported outcome measures

PSC PRO: 

Primary sclerosing cholangitis patient reported outcome

PSC: 

Primary sclerosing cholangitis

SADS: 

Schedule for affective disorders and schizophrenia

SF-36: 

Short Form 36 health survey

SF-6D: 

Short Form 6 health survey

SIBDQ: 

Short inflammatory bowel disease questionnaire

VAS: 

Visual analogue scale

WHOQOL-BREF: 

World Health Organization Quality of Life assessment instrument

Declarations

Funding

This project was funded by the Metchley Park Medical Society. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Authors’ contributions

FI, DK, AS, TP, LK, TK, JF and MC contributed to the study conception and design. FI and GK conducted the searches, FI, GT and GK completed the screening titles and abstracts; identifying eligible full text papers; data extraction and quality assessment. FI drafted the manuscript and GT, GK, DK, AS, TP, LK, TK, JF and MC provided feedback. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Public Health England, 5 St Philips Place, Birmingham, B3 2PW, UK
(2)
Centre for Patient Reported Outcomes Research (CPROR), Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
(3)
NIHR Birmingham Biomedical Research Centre, Birmingham, B15 2TT, UK
(4)
University Hospital Birmingham, Birmingham, B15 2TH, UK
(5)
Birmingham Children’s Hospital, Birmingham, B4 6NH, UK
(6)
PAREXEL International, Evergreen House North, 160 Euston Road, London, NW1 2DX, UK

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