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Societal burden and impact on healthrelated quality of life (HRQoL) of non-small
cell lung cancer (NSCLC)
PRM47
Enstone A,1 Panter C,1 Manley Daumont M,2 Miles R1
Adelphi Values, Bollington, UK; 2Bristol-Myers Squibb, Paris, France
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1. Background
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Figure 2. Summary of domains captured by publications in the patient burden SLR
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers in Europe
and is associated with poor prognosis and substantial social, economic and humanistic burden.1,2
Approximately 968 people die from lung cancer in the European Union (EU) each day.2
Activities of
daily life
(N=7)
Records after duplicates removed (n=1,517)
Emotional and
psychological
functioning
(N=22)
These effects are paramount when considering the Quality of Survival (QoS), a conceptual
framework which encompasses four interconnected domains: Quality of Life (QoL), survival,
side effects, and economic impact (see P208 presented at the European Cancer Congress, Vienna,
September 2015).9
Full-text articles assessed for eligibility (n=71)
Full-text articles excluded, with reasons (n=47)
(N=27)
Studies included in qualitative synthesis (n=24)
Social
functioning
A number of new treatments for NSCLC are now available which have had a positive impact
on progression free survival (PFS) and overall survival (OS); a key domain of the QoS concept. However
survival improvements are modest compared to other cancers and a significant unmet need remains.10
(N=17)
Figure 4. Breakdown of characteristics of publications in societal burden SLR
Some articles reported on multiple domains, therefore the total number of articles detailed here is greater than the 59 included
within the patient burden SLR.
Overall HRQoL
To understand the patient burden and societal cost associated with NSCLC in Europe.
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Two systematic literature reviews (SLRs) were conducted to explore the patient burden of NSCLC
and the associated societal burden and associated costs across Europe.
Primary objective: Summarise the impact of NSCLC on patients’ HRQoL and understand the key
drivers and factors that underpin these impacts.
Additional records
identified through grey
literature search
(n=3)
Records excluded on the basis of title and abstract (n=1,446)
Patient burden SLR – the impact of NSCLC on patients’ HRQoL
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General HRQoL
(N=44)
Physical
functioning
3. Methods
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Records identified in Medline,
Embase, PsychINFO, EconLIT,
and NHS EED
(n=1,521)
(N=6)
Lung cancer is associated with a considerable cost burden in terms of direct healthcare costs and wider
indirect societal costs, including caregiver burden, lost productivity and absenteeism from work.7,8
2. Objectives
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Cognitive
functioning
NSCLC and current treatments are associated with detrimental effects on HRQoL, notably,
physical functioning and emotional well-being, with a significant number of patients reporting
depressive symptoms and anxiety.3,4,5,6
Figure 3. Societal burden SLR results – PRISMA diagram
Of the 59 publications included in this review, the majority of publications (n=44) reported data on
the impact on NSCLC on patients overall HRQoL.
— Larsson (2012) and Lee (2011) found that stage III-IV patients reported a significant
reduction in global or overall health, as defined by the EORTC QLQ-C30 and WHOQOLBREF respectively, when compared to the general population or healthy controls.11,12
— Iyer (2014) found that patients with a later disease stage reported a greater impact of diseaserelated symptoms on their HRQoL, as defined by the LCSS and EORTC-QLQ-C30; while Iyer
(2013) found that patients on first-line treatment scored significantly higher on the total score of
the FACT-L than those on later lines of treatment, indicating that overall HRQoL decreases with
each subsequent line of therapy. 13,14
Emotional and psychological functioning
Publications on emotional and psychological functioning (n=27), notably depression and anxiety,
indicated that patients experience varying levels of emotional impact due to their NSCLC, although
this was dependent on treatment type and specific PROs used to assess the impact.6
— Three observational studies ran exploratory regression models to determine predictors of
psychological or emotional components. Data were collected using PROs such as the EORTC
QLQ C30, Quality-of-Life scale (patient version) and SF-36.
Direct costs of
bone metastatic
disease
Direct costs
associated with
surgery
(N=1)
(N=4)
Overarching
direct costs*
(N=4)
Direct costs of
chemotherapy and
targeted therapies
Indirect costs
associated with a
specific treatment
(N=6)
(N=2)
Societal burden
and indirect costs
Indirect and
direct costs
(N=3)
(N=1)
Direct cost of
diagnosis and
staging
(N=3)
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Secondary objective: Understand how impacts on HRQoL vary across different NSCLC patient
subpopulations (squamous/non-squamous cell, smokers/non-smokers, PD-L1 positive/PD-L1
negative, advanced (2nd/ 3rd line therapy)/non-advanced (1st line therapy) NSCLC, (Tumour node
metastasis) TNM stage grouping IIIB and IV, patients with brain metastases associated with NSCLC).
Exploratory objective: Identify patient-reported outcomes (PROs) used in research to assess the
burden of NSCLC on HRQoL.
— Findings suggested that the decrease in emotional functioning was related to poor performance
status, later stage disease and subsequent line of treatment,15 as well as younger patients,
particularly with increased anxiety and mental health issues.16
— Another common finding was that patients who had received treatment reported less anxiety
and depressive symptoms compared to the newly diagnosed; however the difference in many
cases did not reach statistical significance.15,17
Societal burden SLR – the direct and indirect cost associated with NSCLC
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Primary objective: Define the key components of indirect social and direct healthcare costs
associated with NSCLC and to identify the key drivers of these costs across Europe.
Secondary objective: Understand how costs vary across different NSCLC patient subpopulations
(squamous/non-squamous cell, smokers/non-smokers, PD-L1 positive/PD-L1 negative, advanced
(2nd/ 3rd line therapy)/non-advanced (1st line therapy) NSCLC, TNM stage grouping IIIB and IV,
patients with brain metastases associated with NSCLC).
Exploratory objective: Distinguish between symptom cost burden and treatment cost burden.
Methodology
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Both SLRs were conducted in line with Cochrane Handbook for Systematic Reviews of Interventions
(CHSRI) guidelines.
Both SLRs were conducted using the OVID search engine and reviewed: Medline® in process (PubMed)
and Embase for the patient burden SLR and societal burden SLR, PsycINFO for the patient burden SLR
and EconLit (EBSCOhost) and NHS Economic Evaluation Database for the societal burden SLR.
Searches were limited to human studies, English language and the past 10 years (July 2004 to
June 2014 [patient burden SLR] and to July 2014 [societal burden SLR]).
Both search strategies utilised a combination of subject heading terms and free text searching, in
order to ensure that the most relevant literature was identified and reviewed.
Abstracts and full-text publications were systematically reviewed during both SLRs and screened
against inclusion and exclusion criteria.
For the patient burden SLR, additional inclusion and exclusion criteria were applied to focus the
full-text publications included within the final analysis.
For the societal burden SLR, full-text publications considered for inclusion were ranked 1, 2 or 3
according to strict criteria following systematic principles. Those publications marked as rank 1 were
prioritised for inclusion within the final analysis.
To augment the findings of both SLRs, additional pragmatic searches were conducted via Google.
In particular, oncology organisation websites and conference proceedings of the American Society of
Clinical Oncology (ASCO) Annual Meetings (2009–2014) were reviewed.
Social functioning
● Publications on social functioning (n=17) indicated that patients experience a negative impact
on social functioning as a result of their NSCLC. One study reported that patients rated social
functioning as the most important HRQoL domain.15
Other impacts
● Publications exploring the impact of NSCLC on daily activities (n=7) indicated that the ability
to carry out daily activities becomes progressively worse with each subsequent line of therapy
and with more advanced disease stages.
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Publications presenting data on cognitive functioning (n=6) were extremely heterogeneous in
terms of how cognitive functioning was measured and reported, therefore findings were inconclusive.
Secondary and exploratory objectives
● The data suggested that there are decrements in HRQoL with each subsequent line of therapy,
although this also depended on type of treatment.
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Four publications demonstrated that emotional well-being, physical functioning and overall HRQoL
are significantly lower in Stage III-IV patients compared to Stage I-II patients.
The most frequently used PROs were: EORTC QLQ-C30 (n=34), The EORTC Quality of Life
Questionnaire – Lung Cancer (EORTC QLQ-LC13; n=22), FACT-L; n=16 and LCSS; n=15.
Societal burden SLR
An overview of the results from the societal burden SLR is detailed in Figure 3. A breakdown of the
publications by cost characteristic is displayed in Figure 4.
4. Results
Patient burden SLR
An overview of the results from the patient burden SLR is detailed in the Preferred Reporting Items
for Systematic Reviews and Meta-Analyses (PRISMA) diagram in Figure 1. A breakdown by domain of
the final results is displayed in Figure 2.
Figure 1. Patient burden SLR results – PRISMA diagram
Records identified
through database
searching and screened
(n=1,388)
Physical functioning
● Publications on physical functioning (n=22) demonstrated inconclusive findings, although results
indicated that NSCLC does impact negatively on patients’ physical functioning.
— Some studies found that physical functioning decreased as a result of treatment whereas others
reported an increase in physical functioning with treatment.
— Better physical functioning was found to be associated with newly diagnosed patients and
patients in the earlier stages of treatment.
— Poorer physical functioning was found to be significantly associated with pain.
Additional records
identified through
google search
(n=50)
Additional records identified
through conference searches NSCLC AND QOL
NSCLC AND patient burden
(n=46)
Indirect costs of NSCLC
● Publications on societal burden and indirect costs were scarce (n=6), and those which were found
reported heterogeneous data in terms of the costs reported and analysis/evaluation methods.
The societal/indirect costs reported in the literature reviewed included:
— One-year, three-year and five-year mortality estimates.
— Productivity loss (measured by days off work using the human capital approach [loss of
productivity = non-working days * labour cost]).
— Informal caregiver costs (costs that would be incurred if informal caregivers were paid for
e.g. feeding, housework, administrative tasks) and formal caregiver costs (e.g. from healthcare
professionals such as nurses).
— Sick leave benefits, disability pensions, disability living allowance, home care benefits.
Direct costs of NSCLC
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Total number of abstracts screened (n=1,504)
Excluded (n=1,445)
Included (n=59)
• 28 observational
• 7 randomised trials
• 21 reviews
• 3 observational studies
Publications on direct costs (n=18) were highly variable in terms of how costs were measured,
evaluated/analysed and reported. The direct/healthcare costs reported in the literature reviewed
included the following:
— Direct costs of diagnosis and staging.
— Direct costs associated with surgery.
— Direct costs of chemotherapy and targeted therapies.
— Overarching direct costs (e.g. publications including more than one of the above listed direct
costs/reported on mean direct costs).
— Direct costs of bone metastases.
*Overarching direct costs capture publications including more than one of the following direct costs: direct costs of diagnosis and staging,
direct costs associated with surgery, direct costs of chemotherapy and targeted therapies, or publications reporting mean direct costs.
Secondary and exploratory objectives
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One specified sub-group was fully reported within the literature reviewed – TNM staging. However,
the data presented were too heterogeneous to provide conclusive evidence for how costs varied
across these disease stages.
A small amount of data on NSCLC patients with brain and/or bone metastases were identified,
demonstrating that these patients incur greater direct costs and higher associated caregiver burden.
None of the literature reviewed distinguished results between disease symptom burden and
treatment burden.
No data relevant to the other specified sub-groups of interest were identified.
5. Conclusions
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Overall HRQoL, and specific domains of HRQoL including, emotional functioning and physical
functioning were adversely affected by NSCLC. However, the degree to which disease impacts
patients depends on treatment type, stage of disease and demographic characteristics.
The impact of NSCLC on daily activities, work, cognitive function and social functioning was less
commonly reported than overall HRQoL, emotional functioning and physical functioning.
Although currently none of the PRO instruments identified would be suitable for gaining a
labelling claim with the FDA, the EORTC QLQ-C30 and EORTC QLQ-LC13 have been included in
European label claims. There is a need for more validated PRO measures to be included within in
clinical trials.
Data from the societal burden SLR suggest the burden of NSCLC is substantial; however paucity of
data and heterogeneity in study designs, reporting and evaluation methods limit cost comparisons.18
In addition, with the development of new and novel treatments patients are living longer and there is
an increasing need to assess their QoS (domains: QoL, survival, side effects, and economic impact),
to understand patient experiences, inform treatment decisions and optimise oncology care. In this
capacity, further research to explore particular HRQoL domains and to quantify the societal burden of
NSCLC is ongoing.
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Conflict of interest
This study was sponsored by Bristol Myers-Squibb.
The authors take full responsibility for the content of the poster. Adelphi Values received funding from Bristol-Myers Squibb for
conducting the study on which this poster is based.
Presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 18th Annual European Congress,
Milan, Italy (7–11th November 2015)
Copies of this poster obtained through Quick Response Code are for personal use only and may not be
reproduced without permission from Bristol Myers-Squibb and the authors of this poster.