Article
Reference
Hepatitis C prevalence in the psychiatric setting: cost-effectiveness of scaling-up screening and direct-acting antiviral therapy
GIRARDIN, François, et al.
Abstract
Patients hospitalised because of mental illness often have risk factors for contracting HCV.
Scaling-up HCV screening for all psychiatric inpatients as a case-detection strategy for viral elimination is underexplored. This study aimed to evaluate the cost-effectiveness of scaling-up HCV screening and treatment for psychiatry hospital admissions in Switzerland vs. the current standard-of-care risk-based approach, where only those with a history of substance misuse disorder are offered testing.
GIRARDIN, François, et al. Hepatitis C prevalence in the psychiatric setting: cost-effectiveness of scaling-up screening and direct-acting antiviral therapy. JHEP Reports : Innovation in Hepatology, 2021, vol. 3, no. 3, p. 100279
DOI : 10.1016/j.jhepr.2021.100279 PMID : 34522875
Available at:
http://archive-ouverte.unige.ch/unige:151338
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Hepatitis C prevalence in the psychiatric setting: cost-effectiveness of scaling-up screening and direct-acting antiviral therapy
François Girardin, MD, Chris Painter, MSc, Natalie Hearmon, DPhil, Lucy Eddowes, DPhil, Stefan Kaiser, MD, Francesco Negro, MD, Nathalie Vernaz, PharmD
PII: S2589-5559(21)00055-0
DOI: https://doi.org/10.1016/j.jhepr.2021.100279 Reference: JHEPR 100279
To appear in: JHEP Reports Received Date: 11 December 2020 Revised Date: 1 March 2021 Accepted Date: 3 March 2021
Please cite this article as: Girardin F, Painter C, Hearmon N, Eddowes L, Kaiser S, Negro F, Vernaz N, Hepatitis C prevalence in the psychiatric setting: cost-effectiveness of scaling-up screening and direct- acting antiviral therapy, JHEP Reports (2021), doi: https://doi.org/10.1016/j.jhepr.2021.100279.
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© 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
Cohort decision tree screening model with a Swiss healthcare provider perspective using HCV prevalence from inpatient
admissions at a Swiss psychiatry department
• Incremental
cost-effectiveness ratio = $9,188 per quality-adjusted life-year gained
• Population-level net monetary benefit =
$435,156,348
• 917 additional patients per year detected and treated Psychiatric inpatient admissions
with a history of substance misuse screened for HCV
$2,122 per person detected and treated
screened for HCV
$3,294 per person detected and treated
Intervention:
generalised screening
Comparator:
current clinical practice
What is the
cost-effectiveness of generalised HCV screening of
psychiatric inpatient admissions, compared to current clinical
practice of screening those with a history of substance misuse?
VS
HCV prevalence = 10.8%
HCV prevalence = 25.7%
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Hepatitis C prevalence in the psychiatric setting: cost-
1
effectiveness of scaling-up screening and direct-acting
2
antiviral therapy
3
François Girardin MD,1,2 Chris Painter MSc,3 Natalie Hearmon DPhil,3 Lucy 4
Eddowes DPhil,3 Stefan Kaiser MD,4 Francesco Negro MD,5 Nathalie Vernaz 5
PharmD1 6
1Division of Clinical Pharmacology and Toxicology, Department of 7
Anaesthesiology, Clinical Pharmacology, Intensive Care and Emergency 8
Medicine, Geneva University Hospitals, Geneva, Switzerland; 2Service of 9
Clinical Pharmacology, Department of Laboratory Medicine and Pathology, 10
Lausanne University Hospital (CHUV), Lausanne, Switzerland andFaculty of 11
Biology and Medicine, University of Lausanne, Lausanne, Switzerland;
12
3Costello Medical, London, UK; 4Division of Adult Psychiatry, Geneva 13
University Hospitals, Geneva, Switzerland; 5Divisions of Gastroenterology and 14
Hepatology and of Clinical Pathology, Geneva University Hospitals, Geneva, 15
Switzerland;
16
Corresponding author: Prof François Girardin, Service of Clinical 17
Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne 18
University Hospital (CHUV), Lausanne, Switzerland. Email:
19
Francois.Girardin@chuv.ch. Telephone: +41 (0)21 314 42 76 20
Keywords: Hepatitis C Infection; Screening Strategy; Direct-Acting Antiviral 21
Agents; Cost-Effectiveness Model; Psychiatric Disorder 22
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Word count: 3,459 words 1
Number of figures/tables: 7 figures/tables 2
Conflicts of interest: François Girardin is the representative of Swiss 3
hospitals at the Federal Drug Commission (Federal Office of Public Health) 4
and expert for InnoSuisse - the Federal Agency for Innovation (section Life 5
Sciences). Stefan Kaiser has received honoraria for cognitive test and training 6
software from Schuhfried. Francesco Negro advises Gilead, Merck and AbbVie, 7
and has received a research grant from Gilead. Lucy Eddowes and Natalie 8
Hearmon are employees of Costello Medical, and Chris Painter was an 9
employee of Costello Medical at the time of the study.
10
Funding: This work was supported by Gilead and the University Hospitals of 11
Geneva. The development of the model was funded by Gilead. Individual 12
patient data acquisition from medical records was funded by the University 13
Hospitals of Geneva (Department of Anaesthesiology, Clinical Pharmacology, 14
Intensive Care, and Emergency Medicine). The funding sources did not have 15
a role in the collection, analysis and interpretation of data; in the writing of 16
the report; or in the decision to submit the article for publication.
17
Authors contributions:
18
François Girardin: conceptualisation, formal analysis, investigation, writing – 19
review & editing 20
Chris Painter: formal analysis, methodology, writing – review & editing 21
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Natalie Hearmon: formal analysis, methodology, writing – review & editing 1
Lucy Eddowes: formal analysis, methodology, writing – original draft, writing 2
– review & editing 3
Stefan Kaiser: writing – review & editing 4
Francesco Negro: formal analysis, writing – review & editing 5
Nathalie Vernaz: conceptualisation, formal analysis, investigation, writing – 6
review & editing 7
Clinical trial number: Not applicable 8
Data availability statement: The data that support the findings of this 9
study are available from the corresponding author upon reasonable request.
10
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ABSTRACT 1
Background & Aims: People hospitalised due to mental illness often have 2
risk factors for contracting hepatitis C virus (HCV). Scaling-up HCV screening 3
for all psychiatric inpatients as a case-detection strategy for viral elimination is 4
under-explored. This study aimed to evaluate the cost-effectiveness of 5
scaling-up HCV screening and treatment for psychiatry hospital admissions in 6
Switzerland versus the current standard-of-care risk-based approach, where 7
only those with a history of substance misuse disorder are offered testing.
8
Methods: HCV prevalence by history of substance misuse disorder was 9
analysed in medical records from inpatient admissions at a Swiss psychiatry 10
department. Cost-effectiveness was analysed from a healthcare provider 11
perspective through a decision-tree screening model, using this HCV 12
prevalence data. We assessed model and parameter uncertainty using 13
deterministic and probabilistic sensitivity analyses.
14
Results: Prevalence of HCV in psychiatry inpatients with a history of 15
substance misuse disorder (n=1,013) was 25.7%, compared with 3.49%
16
among the remaining inpatients (n=3,535). Scaling-up HCV screening and 17
treatment for all psychiatry admissions was cost-effective versus the risk- 18
based approach, with an incremental cost-effectiveness ratio of $9,188 per 19
quality-adjusted life-year gained. The incremental cost-effectiveness ratio 20
remained cost-effective considering HCV prevalence as low as 0.07%. The 21
population-level net monetary benefit of the generalised screening approach 22
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was $435,156,348, with 917 additional patients per year detected and treated 1
at a cost of $3,294 per person (versus $2,122 under the risk-based screening).
2
Conclusions: Scaling-up HCV screening and treatment at diagnosis with all- 3
oral, interferon-free regimens as a generalised approach for psychiatric 4
admissions was cost-effective and may support reaching World Health 5
Organization targets for HCV elimination by 2030.
6
LAY SUMMARY 7
People hospitalised due to mental illness often have risk factors for hepatitis C 8
virus (HCV). We found that testing all psychiatry patients in hospital for HCV 9
was cost-effective compared to testing only patients who have a history of 10
substance misuse. Scaling-up HCV testing and treatment may help to wipe 11
out HCV.
12
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INTRODUCTION 1
Neuropsychiatric disorders contribute an estimated 13% to the global burden 2
of disease and are associated with increased physical morbidity.(1) People 3
with mental illnesses (PMI), particularly “severe” disorders, are more likely to 4
engage in behaviours that are risk factors for communicable and non- 5
communicable disease, and may be underserved by healthcare services.(1) 6
Integrating services for mental and physical health can ensure more equitable 7
access to care and reduce health inequalities.(2) 8
In Switzerland, between 30–50% of people with severe mental illness are 9
estimated to have a substance misuse disorder, placing them at risk of drug- 10
related adverse events and communicable diseases like hepatitis C virus 11
(HCV).(3) Other factors associated with mental illness, such as risky sexual 12
behaviours and incarceration, could also increase the risk of HCV infection in 13
PMI.(4) This is reflected in global HCV prevalence estimates of 4.6–17.4% for 14
those with severe mental illness,(4) compared with approximately 0.5–2.3%
15
in the global population.(5) 16
In 2016, the World Health Organization (WHO) outlined Global Health Sector 17
Strategy targets to guide HCV elimination by 2030, where nation states are 18
required to diagnose 90% of prevalent cases and treat 80% of those 19
diagnosed.(6) A key development to support this goal is the increasing 20
availability of highly effective, all-oral, interferon-free, direct-acting antivirals 21
(DAAs) for HCV.(7) DAAs allow infection to be cured in most individuals who 22
engage with healthcare services and adhere to treatment.(7, 8) Although 23
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some countries are implementing one-time universal screening for HCV,(9) 1
not all countries are doing so, including high-income countries such as 2
Switzerland; in 2019 the Swiss Federal Office of Public Health decided to 3
continue to prioritise at-risk groups only.(10) Therefore, innovative case- 4
detection strategies targeting high-risk and underserved populations, such as 5
PMI, are still essential for driving viral elimination.(6)
6
By screening for HCV infection in people engaging with psychiatric health 7
services, high-risk individuals can be targeted, cases identified, and patients 8
linked to short duration DAA-based treatments that are recommended for 9
managing the physical health of PMI.(1, 4) However, it is common practice to 10
only offer HCV testing to individuals with known risk factors for infection (i.e.
11
a history of substance misuse disorder) on psychiatric hospital admission. The 12
epidemiology of HCV amongst PMI is also not well characterised, preventing 13
health authorities from accurately considering the relative costs and benefits 14
of different approaches to diagnosing infection amongst PMI. Consequently, 15
clinical and economic data are required to assess the available options and to 16
ensure the optimal use of healthcare resources.(4)
17
This study explored the prevalence of HCV infection in patients admitted to a 18
large psychiatric hospital department. Using real-world prevalence estimates 19
from individual patient data, the study assessed the cost-effectiveness of a 20
generalised screening approach, where all patients are offered an HCV test on 21
psychiatric hospital admission, compared with a risk-based screening 22
approach, where only those with a history of substance misuse disorder are 23
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offered a test. This risk-based approach is currently used in hospitals in many 1
countries.
2
PATIENTS AND METHODS 3
The methods used for the epidemiological component of this study are 4
discussed first, followed by the modelling approach. Data from the 5
epidemiological investigation provided inputs for the cost-effectiveness 6
evaluation.
7
Epidemiological study 8
Study design, population, and outcomes 9
Epidemiological data on HCV infection in patients admitted to a psychiatric 10
unit were acquired from a retrospective review of clinical records at the 11
University Hospitals of Geneva (HUG; Hôpitaux Universitaires de Genève), the 12
largest university hospital in Switzerland with specialised psychiatric inpatient 13
and outpatient facilities. Adult patients hospitalised at the HUG Psychiatry 14
Department from January 2016 until July 2019 who were screened from 1990 15
onwards, either for antibodies to HCV (anti-HCV) or for HCV RNA, and whose 16
admission was coded as a mental illness (according to the ICD-10, mental 17
and behavioural disorders [F] categories) were eligible.
18
Patients with a history of substance misuse disorder were identified using text 19
data mining by searching for terms such as ‘heroin’, ‘methadone’ or ‘cocaine’
20
in their electronic patient records. HCV prevalence was then calculated for: all 21
patients; patients without evidence of a substance misuse disorder in their 22
medical records; and those with a history of substance misuse disorder. For 23
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the prevalence estimates, patients were deemed to be HCV-positive if they 1
were either anti-HCV antibody positive and/or HCV RNA positive.
2
Ethics 3
This study was performed in accordance with the Declaration of Helsinki.
4
Ethical approval was granted by Commission cantonale d’éthique de la 5
recherche, formerly Commission d’éthique du département de psychiatrie - 6
approval: 09-180R. Adult participant consent was not required because 7
anonymised data were initially aggregated or came from national and 8
institutional registries.
9
Cost-effectiveness study 10
The cost-effectiveness of a comprehensive HCV screening program for all PMI 11
admitted to Swiss psychiatric units, in comparison with the current risk-based 12
approach, was assessed by adapting a previously published economic 13
model.(11, 12) Briefly, the model simulated the screening process in this 14
setting and used epidemiological inputs from the retrospective review of HUG 15
clinical records to ensure that the model was reflective of Swiss psychiatric 16
patients. The model provided estimates of the costs and effectiveness, in 17
terms of QALYs, such that cost-effectiveness measures could be calculated.
18
The model methodology is described further here.
19
Model structure and perspective 20
A previously published cohort decision tree screening model was adapted to 21
analyse the cost-effectiveness of diagnosis and treatment, after scaling-up 22
HCV screening in PMI compared with current standard-of-care.(11, 12) The 23
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decision tree simulated the patient pathway from screening to diagnosis and 1
treatment initiation (Figure 1). The proportion of patients within each branch 2
of the decision tree was estimated using uptake and outcome probabilities, 3
representing the likelihood of attrition at each stage of the patient pathway.
4
Costs and quality-adjusted life-years (QALYs) were assigned to each pathway.
5
The model took the national healthcare provider’s perspective, based on 6
nationwide guidance from the Federal Office of Public Health.(13) The model 7
simulated one-off testing upon admission, whilst the costs and QALYs 8
associated with treatment took a lifetime time-horizon due to the lifelong 9
nature of chronic HCV. Regular annual screening over a longer time period 10
was not appropriate, given the closed nature of the inpatient population 11
where, based on point-of-care data from the HUG Psychiatry Department, 12
uptake of testing and of treatment is 89% and 84%, respectively. In addition, 13
the average length of stay in Swiss inpatient facilities is usually short, limiting 14
the potential for repeat testing; the most recent figures available for the HUG 15
show that the mean length of stay for psychiatric inpatients was 47 days in 16
2017 (median 15 days).(15) 17
Target population and screening strategies 18
The population size considered for the model was 60,378 individuals, the 19
number of patients hospitalised due to mental illness in Switzerland in 2018, 20
the most recent estimate available for Switzerland.(16) We assumed that the 21
eligible screening inpatient population was this entire PMI population, 22
irrespective of viraemic status or awareness of HCV status.
23
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The intervention explored was a comprehensive screening initiative to scale- 1
up HCV treatment for all inpatients in psychiatric units. This generalised 2
strategy was compared with the current standard-of-care risk-based approach 3
to HCV testing, implemented by psychiatric departments, whereby patients 4
with a history of substance misuse disorder are primarily offered testing. All 5
patients were assumed to receive a 20-minute appointment to be offered 6
screening, regardless of whether they accepted the offer. Patients who 7
accepted the test offer were assumed to receive a further 5-minute pre-test 8
discussion with a specialist. The costs associated with time spent 9
communicating the results of the test were also included, for patients who 10
collected their results (5 minutes for a HCV-negative result and 20 minutes for 11
a HCV-positive result). The standard test package (3rd generation ELISA and 12
quantitative HCV RNA test by RT-PCR) and a standard, all-oral, interferon-free 13
DAA regimen were assumed for the screening and treatment approaches.
14
Viral genotyping was not included in the test package as it is not an absolute 15
requirement for treatment, due to the availability of pan-genotypic regimens 16
and in line with European Association for the Study of the Liver (EASL) 17
guidelines.(17) 18
Based on point-of-care data from psychiatric inpatients at the HUG, we 19
assumed that 11% of patients would decline screening, testing would have a 20
combined sensitivity/specificity of 1, and those receiving a positive test result 21
would experience a negative impact on their quality-of-life (modelled as a 22
disutility).(11) 23
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The model also permitted patients diagnosed with chronic HCV infection to 1
decline HCV treatment. Those that accepted treatment received the costs and 2
QALYs associated with treatment, whilst those that did not receive treatment 3
were assigned costs and QALYs corresponding to natural HCV disease 4
progression.
5
Model inputs 6
The screening methods and model inputs were derived from individual 7
psychiatric inpatient data. The target population was assumed to align with 8
the demographic and epidemiological data acquired from the retrospective 9
review of records from the HUG Psychiatry Department. The number of 10
people admitted to psychiatric units in Switzerland was obtained from the 11
Swiss Health Observatory (ObSan, Federal Office of Statistics).(16) Model 12
inputs related to treatment effects and natural disease progression were 13
derived from a peer-reviewed cost-effectiveness model of an all-oral, 14
interferon-free DAA treatment regimen in people who inject intravenous 15
drugs.(18) The lifetime costs (including drug acquisition, resource use and 16
monitoring costs) per treated or untreated HCV-infected patient were also 17
sourced from the same model.(18) Further model inputs were derived from 18
targeted literature searches, publicly available databases, and discussion with 19
clinical experts. Model inputs are summarised in Table 1 and Table 2.
20
Since the model explored a single screening round, discounting of costs and 21
QALYs was not applied. The model from which the lifetime treatment costs 22
and QALYs were sourced applied 3% discounting to costs and QALYs.(18) 23
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Model outputs 1
The primary outputs from the screening model were combined with the 2
treatment model outputs to calculate the incremental cost-effectiveness ratio 3
(ICER) of generalised versus risk-based screening, with benefits given in 4
QALYs and costs in Swiss francs, assumed to be equivalent to US dollars (as 5
per exchange rates in November 2020). A willingness-to-pay (WTP) threshold, 6
which is the valuation of the health benefit in monetary terms, of 7
$100,000/QALY was chosen as it falls within the range of recommended WTP 8
thresholds for cost-effectiveness analyses for Switzerland.(19, 20) A lower 9
WTP threshold of $50,000 per QALY gained was also considered.
10
The model produced further standard cost-effectiveness outputs, such as the 11
net monetary benefit (NMB). The NMB is defined as the incremental effects 12
multiplied by the WTP threshold of $100 000/QALY, minus the incremental 13
costs. Thus, a positive NMB indicates that the intervention (generalised 14
screening) is cost-effective at each given WTP threshold. Further outputs 15
included separate clinical- and cost-focused results, such as the cost of 16
diagnosis per HCV patient identified (both completing the diagnosis process 17
and initiating treatment).
18
Analyses 19
A deterministic sensitivity analysis was performed to identify which inputs 20
influenced the ICER most, in which each input was varied by 20% above and 21
below the base-case value. Parameters were ranked hierarchically by their 22
impact on the ICER.
23
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A probabilistic sensitivity analysis (PSA) was performed from 1,000 Monte- 1
Carlo simulations, to test the robustness of model outputs. A standard 2
deviation of 20% of the mean was used to derive the probability distributions 3
for the PSA. The PSA results were assessed on the cost-effectiveness plane 4
using a scatter plot of incremental costs versus incremental QALYs for the 5
generalised HCV screening approach versus the current risk-based strategy.
6
The probability of cost-effectiveness of the generalised screening approach 7
was tested at a range of WTP thresholds to generate a cost-effectiveness 8
acceptability curve. This provided an overall probability of cost-effectiveness 9
at the chosen WTP threshold of $100,000/QALY.
10
Data availability 11
The data that support the findings of this study are available from the 12
corresponding author upon reasonable request.
13
RESULTS 14
Prevalence estimates 15
The HCV prevalence study comprised 5,420 inpatients, of which 4,548 were 16
eligible for inclusion. Patients were excluded if they were a paediatric 17
admission (n=581), lacked a relevant ICD-10 diagnostic code (n=279) or 18
were the child of an admitted patient (n=12). During the four-year period 19
(2016–2020), 32% of inpatients were re-hospitalised in the psychiatric 20
department.
21
The proportion of males in the cohort was 51.4% (males aged 18–96;
22
females aged 16–100) and the average age of the cohort was 46.5 years.
23
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According to the ICD-10 codes, the most common diagnoses were mood 1
(affective) disorders (n=1,649), schizophrenia, schizotypal and delusional 2
disorders (n=1,079), neurotic, stress-related and somatoform disorders 3
(n=679), personality disorders (n= 570), and disorders due to active 4
psychoactive substance use (n=511). Of the inpatients, 1,013 (22%) had a 5
history of substance misuse disorder and their mean age was 39 years 6
(female: 41 years [age: 16–89]; male: 38 years [18–88]). A history of 7
cirrhosis was evident in 5.8% of inpatients with a history of substance misuse 8
disorder compared with 2.4% of those without.
9
HCV screening was performed in 55.1% of inpatients with a history of 10
substance misuse disorder compared with 31.8% of those without (Figure 2).
11
HCV prevalence in inpatients with a history of substance misuse disorder 12
(positive for anti-HCV antibodies or HCV RNA) was 25.7% (117/155 patients 13
were viraemic). For those patients without a history of substance misuse 14
disorder, HCV prevalence was 3.49% (28/43 patients were viraemic), 15
resulting in an overall prevalence of 10.8% for all admissions.
16
Base-case 17
Generalised screening of all admitted PMI was cost-effective compared to 18
risk-based screening, with a base-case ICER of $9,188 per QALY (Table 3), 19
much lower than the WTP thresholds of $50,000 and $100,000 per QALY 20
gained.(19, 20) At the population level, generalised screening was associated 21
with a greater overall cost (incremental costs: $44,028,136) and more QALYs 22
(incremental QALY gain: 4,792), equivalent to $729 per person and 0.08 23
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QALYs per person. The NMB of generalised screening was $435,156,348 for 1
the whole target population.
2
The total cost of screening per person completing the diagnosis pathway was 3
lower for generalised screening than the current risk-based approach ($330 4
versus $455). The total cost of screening per HCV-positive person initiating 5
treatment with DAAs was $2,122 and $3,294 in the current risk-based 6
approach and the generalised screening approach, respectively.
7
The number of individuals treated increased from 4,191 to 5,108 with the 8
generalised screening program, with 1,099 additional HCV-positive patients 9
linked to care and 917 additional HCV-positive patients initiating treatment in 10
the generalised approach. The number of patients needed to screen to link 11
one HCV-positive person to HCV care was higher for the generalised approach 12
compared with the current risk-based approach (10.0 versus 4.7 people 13
tested per HCV-positive diagnosis), given the lower HCV prevalence in the 14
overall patient population as compared with those with a history of substance 15
misuse disorder.
16
Sensitivity analyses and scenario analyses 17
The deterministic sensitivity analysis identified the inputs with the greatest 18
influence on the ICER (the key drivers of cost-effectiveness) as: QALYs gained 19
from treatment/no treatment; cost of treatment/no treatment; probability of 20
initiating treatment; and HCV prevalence in the subgroup of patients not 21
currently offered screening (Figure 3A). All resulting ICERs were well below 22
the WTP threshold of $100,000/QALY.
23
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The results of the PSA showed that 98.2% of simulations predicted 1
generalised screening of patients admitted to psychiatric units to be cost- 2
effective (WTP threshold of $100,000/QALY; Figure 3B). The probability of 3
generalised screening being cost-effective compared to current risk-based 4
HCV screening remained stable on the cost-effectiveness acceptability curve 5
when the WTP threshold was varied (Figure 3C).
6
The most recent estimate of the prevalence of HCV from the Swiss Federal 7
Office of Public Health suggests a prevalence of 0.45%–0.54% in the Swiss 8
population.(21) Assuming a target population prevalence of 0.5% in the 9
model, the ICER increased to $19,026 per QALY, suggesting that a 10
generalised approach to screening and treating is cost-effective, regardless of 11
whether HCV prevalence in those not currently offered screening on 12
admission to a psychiatry department approaches that of the general 13
population in Switzerland (Figure 4).
14
At a WTP threshold of $100,000/QALY, the NMB remained positive with a 15
target population prevalence as low as 0.07% (population NMB: $1,002,650;
16
data not shown), indicating that scaling up screening was cost-effective 17
compared to the current approach over a broad range of HCV prevalence.
18
DISCUSSION 19
As countries progress towards viral elimination by using DAAs to treat HCV 20
infection, screening programs focused on underserved communities will 21
become increasingly important.(22) Psychiatric hospitals represent an 22
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overlooked setting, where high-risk individuals can be diagnosed and treated 1
in a controlled environment.(1, 4) 2
Results from this analysis demonstrated that generalised screening of all 3
patients admitted to psychiatric hospital units, combined with treatment using 4
oral interferon-free DAA regimens, is likely to be cost-effective compared with 5
the current risk-based screening strategy at a range of WTP thresholds. This 6
result is consistent with WHO guidelines for the management of physical 7
health conditions in people with severe mental illness, which recommend 8
screening for HCV in this population and emphasise the use of interferon-free 9
DAA regimens due to the severe psychological side-effects of interferon-based 10
treatments (depression, mental confusion, anxiety, psychosis).(1, 23) Further, 11
drug-drug interaction between opioids, illicit substances or psychotropic 12
medications and DAA regimens are limited, making DAA regimens suited to 13
treating this population.(24) 14
In Switzerland, disease elimination models suggest that 1,500 patients need 15
to be diagnosed annually, beginning in 2020, if Global Health Sector Strategy 16
targets are to be achieved.(25) With 60,378 individuals treated as inpatients 17
for mental illness in Switzerland per year and an estimated HCV prevalence of 18
10.8%, diagnosing and treating the 6,521 HCV-infected PMI using psychiatric 19
hospitals and outpatient units would play a key role in meeting this target.
20
However, with inpatient treatment being increasingly substituted by intensive 21
outpatient care, considering the generalisability of results of this study is 22
important. It will be important to evaluate whether HCV screening can be 23
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comparably cost-effective in the outpatient setting, where linkage to care and 1
treatment initiation rates may be lower.(26) In addition, different countries 2
have different clinical thresholds for hospitalisation due to mental illness, and 3
a lower proportion of patients may be hospitalised for their mental illness in 4
some countries.
5
Furthermore, the HCV prevalence estimates used in this study, acquired from 6
the HUG Psychiatry Department, may not be representative of the true HCV 7
prevalence of psychiatric inpatients in Switzerland or in other countries.
8
Nevertheless, our analysis accounted for variation in these parameters and 9
generalised screening remained cost-effective at a WTP threshold of 10
$100,000/QALY down to an HCV prevalence of 0·07%. A similar HCV 11
prevalence threshold for cost-effectiveness was recently reported for universal 12
HCV screening in pregnant women in the US,(27) suggesting that screening 13
and treatment programs can be cost-effective at low prevalence.
14
Integration of psychiatric inpatient and outpatient facilities into the wider 15
network of HCV services will also be necessary to ensure reliable progression 16
from diagnosis to cure for patients, particularly as most patients spend too 17
short a duration in hospital to receive a complete course of treatment 18
(typically 12 weeks); the most recent estimates from the HUG show the 19
proportion of patients staying for more than 100 days was approximately 20
7.2%.(15) Training of psychiatric staff to ensure effective implementation of 21
HCV services will increase costs.(4) However, this study showed that 22
generalised screening would likely remain cost-effective, despite additional 23
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implementation costs, whilst integrating mental and physical healthcare may 1
bring wider operational benefits for healthcare services and clinical benefits 2
for patients.
3
Our results are most relevant to countries with similar HCV epidemiology, 4
existing screening programs and treatment availability. A systematic review 5
and meta-analysis investigating HCV in patients with severe mental illness 6
(out- and inpatients), reported a prevalence of 4.9% (95% CI: 3.0–7.9%) in 7
Europe, 17.4% (95% CI: 13.2–22.6) in North America and 3.1% (95% CI:
8
1.0–9.3) in Oceania.(4) However, these values were based on a small number 9
of studies, where viral prevalence varied considerably (Europe: 0.7–10.7%;
10
North America: 2.7–38%; Oceania: 3.1%), as compared to 10.8% estimated 11
in hospitalised PMI in this study.(4) Although further research is needed to 12
better characterise the epidemiology of infection within different PMI 13
populations, our analyses suggest that expanded screening of inpatients at 14
psychiatric departments represents a clinically beneficial and cost-effective 15
approach for other high-income countries with similar healthcare systems.
16
Overall, this study supports the scaling-up of screening and treatment 17
programs designed to eliminate HCV.(6) Offering DAAs at the point of 18
diagnosis is an effective method of containing disease progression in groups 19
with a high prevalence of HCV infection, such as PMI, people living in 20
detention, or people who inject drugs.(4, 11, 12) Worldwide projections also 21
indicate that outreach screening and DAA provision at the point of diagnosis 22
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are more efficient at reducing HCV-related mortality than current infection 1
control and harm reduction measures for people who inject drugs.(28) 2
As health authorities look to target HCV screening initiatives at underserved 3
and high-burden populations, in order to achieve the WHO incidence 4
reduction target of 80% by 2030, this study provides further evidence 5
suggesting PMI are a high-risk group and that psychiatric facilities are a 6
crucial location in which to diagnose and treat HCV infection.(6) Although 7
further efforts are required to characterise viral epidemiology amongst PMI in 8
many countries, results from this study support a generalised HCV screening 9
approach in psychiatric hospitals.
10
ABBREVIATIONS 11
DAA Direct-acting antiviral 12
HCV Hepatitis C virus 13
ICER Incremental cost-effectiveness ratio 14
PCR Polymerase chain reaction 15
PMI People with mental illnesses 16
QALY Quality-adjusted life-year 17
RNA Ribonucleic acid 18
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ACKNOWLEDGEMENTS 1
The authors acknowledge Anita Schnyder PhD and Corinna Oberle PhD 2
(Gilead) for their editorial contributions to the manuscript, Seth Francis- 3
Graham, Costello Medical (UK), for writing and editorial assistance, and 4
Daniela Schuler, Alexandre Touch (both from the Swiss Health Observatory 5
[ObSan]), and Pascal Maradan, from the Swiss Federal Office of Statistics in 6
Neuchâtel, Switzerland, for providing the national estimates on psychiatric 7
inpatient diagnoses and characteristics.
8
Manuscript preparation: Costello Medical, funded by Gilead, provided 9
assistance in preparing and editing the manuscript in accordance with Good 10
Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
11
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TABLES 1
Table 1. Population and clinical model inputs 2
Input Value Source
Population
Eligible population size 60,378 Unpublished 2018 data from Swiss Health Observatory
Male proportion 51.4% HUG Psychiatry Department
Average age (years) 46.54 HUG Psychiatry Department HCV prevalence (population
currently tested) 25.70% HUG Psychiatry Department HCV prevalence (population
not currently tested) 3.49% HUG Psychiatry Department Proportion who present for
testing (current screening) 38.3% HUG Psychiatry Department Screening and Diagnosis
RNA PCR sensitivity 1 Assumed
RNA PCR specificity 1 Assumed
Proportion of tests in which a confirmation of diagnosis is requested
3.4% HUG audit on the quality of laboratory results
Proportion of patients who receive an antibody test as part of the test package
39.0% HUG audit on the quality of laboratory results
Proportion of patients who receive an RNA test as part of the test package
94.9% HUG audit on the quality of laboratory results
Probably of accepting invitation to
screening/testing
89% Point of care, HUG Psychiatry Department
Probably of collecting test
results 95% Point of care, HUG Psychiatry
Department Probably of initiating
treatment 84% Point of care, HUG Psychiatry
Department Disutility of HCV-positive
result 0.02
Based on estimate by Singer and Younossi. 2001(29) (from Rodger 1999)(30)
Treatment
Lifetime QALYs per infected person (no antiviral
treatment)
16.45 Scott et al. 2016(18)
Lifetime QALYs per infected person (early treatment)
21.70 Scott et al. 2016(18) HCV, hepatitis C virus; HUG, University Hospitals of Geneva; PCR, polymerase chain reaction; QALY, quality-adjusted life-year; RNA, ribonucleic acid.
3
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Table 2. Cost model inputs 1
Input Value Source
Screening
Test offer and voluntary counselling cost (regardless of uptake); 20 minute consultation
CHF 62.53
Tarmed Suisse. Tariff version:
1.09, from Jan 1st 2018. TARMED CT00.0010 + CT00.0020 + CT00.0030
Pre-test discussion cost; 5-
minute consultation CHF 17.86
Tarmed Suisse. Tariff version:
1.09, from Jan 1st 2018. TARMED CT00.0050
Cost of communicating results, HCV viraemia- negative; 5-minute consultation
CHF 17.86
Tarmed Suisse. Tariff version:
1.09, from Jan 1st 2018. TARMED CT00.0050
Cost of communicating results, HCV viraemia- positive; 20-minute consultation
CHF 62.53
Tarmed Suisse. Tariff version:
1.09, from Jan 1st 2018. TARMED CT00.0010 + CT00.0020 + CT00.0030
Cost of antibody test CHF 66.00
Tarmed Suisse. Tariff version:
1.09, from Jan 1st 2018. TARMED CA3070.00 (Hepatitis C virus, Ig or IgG, test)
Cost of RNA test
(quantitative PCR for HCV) CHF 180.00
Tarmed Suisse. Tariff version:
1.09, from Jan 1st 2018. TARMED CA3073.00 (Hepatitis C virus, RNA amplification)
Cost of FibroScan (including
consultation) CHF 183.55
Tarmed Suisse. Tariff version:
1.09, from Jan 1st 2018. TARMED CT00.0056 + CT00.0161 + CT39.3515 + CT39.3660 + CT00.2285
Confirmation of diagnosis if
HCV positive CHF 180.00
Tarmed Suisse. Tariff version:
1.09, from Jan 1st 2018. TARMED CA3073.00
Treatment, including drug acquisition, monitoring and resource use Lifetime cost per infected
person (no antiviral treatment)
CHF 15,970 Scott et al. 2016(3) Lifetime cost per infected
person (early treatment) CHF 55,336 Scott et al. 2016(3)
CHF, Swiss francs; HCV, hepatitis C virus; HUG, University Hospitals of Geneva; RNA, ribonucleic acid.
2
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Table 3. Summary of model results 1
Generalised screening approach
Current risk-based screening approach No. patients initiating
treatment 5,108 4,191
Total costs $333,593,535 $289,565,399
Total QALYs 1,213,151 1,208,359
Cost per person $5,525 $4,796
QALYs per person 3.07 2.99
Incremental cost of generalised screening approach
$44,028,136 Incremental QALYs
gained from generalised screening approach
4,792 Incremental cost of
generalised screening approach per person
$729 Incremental QALYs
gained from generalised screening approach per person
0.08
ICER $9,188 per QALY
ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.
2
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FIGURE LEGENDS 1
Figure 1. Decision tree structure of the model 2
Figure 2. Patient flow diagram of retrospective study eligibility and HCV 3
screening status 4
Figure 3. Model sensitivity analyses results. (A) Tornado plot of the 5
deterministic sensitivity analysis. (B) Scatter plot of the probabilistic sensitivity 6
analysis. (C) Cost-effectiveness acceptability curve 7
Figure 4. Impact of target population prevalence on the ICER 8
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FIGURES 1
Figure 1 2
3
HCV, hepatitis C virus; RNA, ribonucleic acid.
4
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Figure 2 1
2
HCV, hepatitis C virus; RNA, ribonucleic acid.
3
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Figure 3 1
2
HCV, hepatitis C virus; QALY, quality-adjusted life year; RNA, ribonucleic acid. Light grey dots: individual simulations. Dark purple dot: mean of all simulations.
3
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Figure 4 1
2
ICER, incremental cost-effectiveness ratio
3
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HIGHLIGHTS 1
• Screening all psychiatry admissions for HCV was cost-effective vs 2
standard-of-care 3
• Generalised HCV screening enabled 917 extra patients to be treated 4
per year 5
• Scaling-up HCV testing to all psychiatry admissions would support HCV 6
elimination 7
