Costs, effectiveness and cost-effectiveness of hadron...

Costs, effectiveness and cost-effectiveness of hadron therapy

Madelon Pijls-Johannesma, PhDJanneke Grutters, PhD

2nd Workshop on Hadron Beam Therapy, Erice 2011

Some facts…

• RT is a relatively cheap treatment modality (5% of costs of global oncology budget, advanced photon RT ~ 8000 euros)

• Particle therapy is about 2.4 times more expensive than most sophisticated RT with photons (Goitein & Jermann 2003)2003)

• Investment costs PT facility about € 100-140 million• Potential advantages PT regarding superior dose

distributions are clear!• However clinical efficacy PT not EVB proven yet…• Once decided to build a PT facility it will take several

years before first patients can be treated

Costs

• Construction (capital)– project management, equipment, building, treatment

infrastructure (CT, TPS etc.)

• Operation costs (running cost)• Operation costs (running cost)– personnel, utilities, maintenance, business cost

• Unit cost of treatment/cost per fraction– depending on construction/operation costs and

reimbursement system (agreements government/health insurances: can be highly variable between countries/regions)

• # patients/year• # fractions/year• # treatment rooms• # operation time/day• # operation days/week

• equipment (scanning beam, gantry, horizontal beam etc)

• treatment time• irradiation time• downtime

Some factors of influence on costs..

• # operation days/week• time per fraction• reimbursement per treatment• preparation time per patient• Maintenance

• downtime• required personnel• repayment of loan• etc• ……

Combined protons + C-ions

Protons Photons

Working days 5 days week 5 days week 5 days week

Quality assurance and calibration 06:00-08:00 06:00-08:00 06:00-08:00Operating hours patient treatment 08:00-22:00 08:00-22:00 08:00-22:00Contingency / Research

22:00-24:00 + Sat. 22:00-24:00 + Sat. 22:00-24:00 + Sat.

Hours per day available for patient treatment 14,0 h. 14,0 h. 14,0 h.

Days of operation p.a.250 d. 250 d. 250 d.

Hours p.a. available for patient treatment 3.500 h. 3.500 h. 3.500 h.Minutes p.a. available for patient treatment 210.000 min. 210.000 min. 210.000 min.

Average time per fraction

Cost AnalysisOperational model: base case

Peeters A, Grutters JP, Pijls-Johannesma M, Reimoser S, et al. How costly is particle therapy? Cost analysis of external beam radiotherapy with carbon-ions, protons and photons.

Radiother Oncol. 2010 Apr;95(1):45-53.

Capital Cost 138.600.000 € 94.930.000 € 23.430.000 €Assumed lifecycle in years 30 30 30Running Cost p.a. 32.138.027 € 21.800.383 € 8.800.850 €Realistic Szenario: Total cost p.a. 36.758.027 € 24.964.716 € 9.581.850 € Total cost per fraction 1.128,07 € 742,69 € 232,80 €

Average time per fraction (slot)

18 min. 18 min. 10 min.

Maximum fractions p.a. per treatment room 11.667 fra. 11.667 fra. 21.000 fra.Chosen number of treatment rooms 3 rooms 3 rooms 2 roomsTreatment room utilisation 98% 98% 100%

Treatment room availability 95% 98% 98%Total number of fractions p.a. (realistic szenario)

32.585 fra. 33.614 fra. 41.160 fra.

Average number of fractions per patient 18 fra. 20 fra. 18 fra.Total number of patients p.a. 1810 1681 2287

Results: costs for initial treatment per patient (inoperable stage I NSCLC)

€ 15.000

€ 20.000

€ 0

€ 5.000

€ 10.000

CRT SBRT Protons C-ions (35 fractions,

10 min/fraction)(4 fractions,



40 min/fraction)

Evidence…..

The clinical efficacy of particle therapy as opposed to best available photon therapy (eg IMRT) is not proven (yet), mainly due to a lack of RCT’s and poor reporting of results.

1. Brada et al J Clin Oncol. 2007;25(8):965-70.2. Jereczek-Fossa et al Head Neck. 2006;28(8):750-603. Lodge et al Radiother Oncol. 2007;83(2):110-22.4. Schulz-Ertner et al J ClinOncol. 2007;25(8):953-645. Brada et al The Cancer Journal. 2009;15(4):319-24.

Results literature search 12 databases (Lodge et al 2007)

Number of relevant papers by topic, identified out of 5089 references retrieved by search strategy of the review

563500

600

restrictions:

- < 20 patients

5410

140

0

100

200

300

400

neutron proton ion economics

- FU < 2 years

Protons final results : 40 studies

Ions final results : 22 studies

Search results protons and ions

total number of patients included in studies per tumor sitecccc

1642

1343

1200

1400

1600

1800

2000

9114

Results protons and ions per indication

33

311

88

777

47 25 353696 73

205

405

57 31 00

200

400

600

800

1000

H&N

pros

tate

ocula

rga

stro

-inte

st. lung

CNS

sarc

omas

uter

ine ce

rvix

bladd

er

protons

ions


lodge et al, 2007: total number of patients included in studies for H&N, prostate and lung

1200

1400

1600

1800

2000


0

200

400

600

800

1000

1200

H&N

pros

tate

ocula

rga

stro

-inte

st.

lung

CNS

sarc

omas

uter

ine

cerv

ix

blad

der

protons

ions


Update 2010/2022: total number of patients included in studies for H&N, prostate and lung

1200

1400

1600

1800

2000


H&N: proton 33�185ion 37�333

Prostate: proton 1042�2075ion 96 �903

0

200

400

600

800

1000

H&N

pros

tate

ocula

rga

stro-

intes

t.

lung

CNS

sarc

omas

uter

ine c

ervix

bladd

er

protons

ions

ion 96 �903Lung: proton 88 �203

ion 205 �231

Tumor location Protons Ions

result n studies /N result

Head&Neck No firm conclusion 2/65 Comparable to prot.

ACC (loc.adv.) - 1/29 Superior to photons84% vs

Tumor location Protons Ions

result result

Head&Neck No firm conclusion Comparable to prot.

ACC (loc.adv.) - Superior to photonsLC 84% vs

Clinical evidence: Meta-analyses

• Systematic reviews

• Stratification per tumor site/stage/histology

• Correction for confounders e.g % of medically inoperable patients

• Pooled estimates for toxicity, disease specific survival and overall survivalsurvival

Examples: - Inoperable stage I NSCLC (grutters et al 2010)- H&N cancer: Oropharyngeal ca. and Mucosal Melanoma

(Ramaekers et al, 2010)

CRT

(N=750)

SBRT

(N=895)

NSCLC stage I

Protons

(N=180)

C-ions

(N=210)

Results: Oropharyngeal cancer (2y DFS)Proton therapy vs IMRT

Yao 2006 (n=66)

Chao 2004 (n=31)

Chao (po) 2004 (n=43)

Huang 2003 (n=41)

Protons pooled*

Slater 2005 (n=29)Protons (N=29)

IMRT (N=502)

0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00

IMRT pooled

Daly 2010 (n=107)

Eisbruch 2009 (n=67)

Rusthoven 2008 (n=32)

Schoenfeld 2008 (n=64)

Garden 2007 (n=51)

2Y Disease free survival

(I2 = 49.9%)

Protons:81%(66 – 96%)IMRT :87% (81– 93%) P = NS

IMRT (N=502)

Results: Malignant Mucosal Melanomas (5y OS)Carbon-ion therapy vs Conventional photon therapy

Kingdom 1995 (n=10)

Shibuya 1993 (n=28)

Guzzo 1993 (n=48)

Andersen 1992 (n=26)

Gilligan 1991 (n=28)

Carbon ions pooled

Mizoe 2009 (n=100)

Mizoe (ct) 2009 (n=57)

C-ion (N=157)

0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00

Photons pooled

Meleti 2008 (n=42)

Nakashima 2008 (n=20)

Wagner 2008 (n=17)

Huang 2007 (n=15)

Krengli 2006 (n=74)

Bridger 2005 (n=27)

Temam 2005 (n=69)

Yii 2003 (n=89)

Owens 2003 (n=44)

Patel 2002 (n=59)

Loree 1999 (n=28)

Lund 1998 (n=58)

Manolidis 1997 (n=14)

5Y Overall survival

(I2 = 51.7%)

CRT (N=696)

C-ions : 44 %(32 –56%) CRT : 25% (21 –29%)P = 0.007

Particle therapy: ongoing discussion

How to proceed?

• Trade-off between costs and effectiveness– Cost-effectiveness analysis

• To inform decisions regarding– Whether or not to adopt the new technology– Whether or not to adopt the new technology– Whether or not to perform additional research

Cost-effectiveness analysis

= The comparative analysis of alternative courses of action in both their costs and consequences

Choice

Treatment B

CostsA

CostsB

Treatment AConsequencesA

ConsequencesB

Characteristics of cost-effectiveness analysis

Only consequences

Only costs Both costs & consequences

No comparison Outcome description Cost description Cost-outcome

Adapted from: Drummond et al. Methods for the economic evaluation of health care programmes, 2005

No comparison Outcome description Cost description Cost-outcome description

Comparison Efficacy / effectiveness evaluation

Cost analysis Full cost-effectiveness analysis

• Incremental analysis– Incremental effect on health

• iEffectiveness = EffectivenessA – EffectivenessB• E.g. iEffectiveness = 4 life years – 2 life years = 2 life years

Cost-effectiveness analysis

• E.g. iEffectiveness = 4 life years – 2 life years = 2 life years

– Incremental costs• iCosts = CostsA – CostsB• E.g. iCosts = €20.000 – €4.000 = €16.000

– Incremental cost-effectiveness ratio• ICER = iCosts / iEffectiveness• E.g. ICER = €16.000 / 2 life years = €8.000 / life year gained

Systematic literature review*:

– Only 14 potential papers were retrieved– 4 reported on cost-effectiveness 1-4

Cost-effectiveness particle therapy

1. Lundkvist J, Ekman M, Ericson SR, et al: Economic evaluation of proton radiation therapy in the treatment of breast cancer. Radiother Oncol 2005:179-185

2. Lundkvist J, Ekman M, Ericson SR, et al: Cost-effectiveness of proton radiation in the treatment of childhood medulloblastoma. Cancer 2005;103:793-801

3. Lundkvist J, Ekman M, Ericson SR, et al: Proton therapy of cancer:potential clinical advantages an cost-effectiveness. Acta oncol 2005;44:850-861

4. Jäkel O, Land B, Combs SE et al: On the cost-effectiveness of Carbon ion radiation therapy for skullbase chordoma. Radiother Oncol 2007: 83(2):133-8.

* Pijls-Johannesma M, Pommier P, Lievens Y. Cost-effectiveness of particle therapy: current evidence and future needs. Radiother Oncol. 2008 Nov;89(2):127-34.Update currently in process

Update 2011:Konski, 2007Grutters, 2010Mobaraki, 2010

Some results….

• Analysis based on decision model for breast, prostate, head and neck, and medulloblastoma (Lundkvist et al, 2005) :– Average cost per quality adjusted life year – Average cost per quality adjusted life year ≈ € 10.130

• Skull base chordoma (Jäkel et al, 2007) :– € 7.692 per life year gained

• Both studies high level of uncertainty: many assumptions, suboptimal methodology

Conclusion review on cost-effectiveness

• Only little evidence based on available data• Lack of calculations of the cost per QALY• No firm conclusion could be drawn

…. therefore cost-effectiveness studies were initiated for:

• Lung cancer• Prostate cancer• Head&Neck cancer

Example: lung cancer

• Cost-effectiveness of particle therapy in the treatment of lung cancer– Grutters JPC, Pijls-Johannesma M, De Ruysscher D,

Peeters A, et al. The cost-effectiveness of particle Peeters A, et al. The cost-effectiveness of particle therapy in non-small cell lung cancer: Exploring decision uncertainty and areas for future research. Cancer Treat Rev 2010; 36(6):468-76.

Research question

• Which of the following treatment modalities is the most cost-effective for stage I inoperable non-small cell lung cancer (NSCLC)?– Conventional radiotherapy (CRT)– Conventional radiotherapy (CRT)– Stereotactic body radiotherapy (SBRT)– Proton therapy – Carbon-ion therapy

Method

• Systematic review, meta-analysis (Grutters et al, R&O 2010)• Cost-analysis (Peeters et al, R&O 2010)• Decision-analytic model (Markov)

– Health care perspective– Total expected costs and outcome (QALYs) per patient

over a 5 year period– Probabilistic sensitivity analysis to examine existing

uncertainty– Additional sensitivity analysis only of recent studies

Results: Meta-analysis

• For stage I inoperable NSCLC• 23 studies included• Corrected for % of medically inoperable patients • Pooled estimates for toxicity, disease specific

survival and overall survival

SBRT

(N=895)

CRT

(N=750)

Grutters JP, Kessels AG, Pijls-Johannesma M, et al. Comparison of the effectiveness of radiotherapy with photons, protons and carbon-ions for non-small cell lung cancer: a meta-analysis. Radiother Oncol. 2010 Apr;95(1):32-40 .

Protons

(N=180)

C-ions

(N=210)

Costs for initial treatment per patient

€ 15.000

€ 20.000

€ 0

€ 5.000

€ 10.000

CRT SBRT Protons C-ions (35 fractions,




40 min/fraction)

€ 30.000

€ 35.000

€ 40.000

Exp

ecte

d c

ost

s p

er p

atie

nt o

ver

5 ye

ars

Results: cost-effectiveness (all studies)

CRT less effective and more

expensive than all other treatments

protons slightly less effective and more

expensive than c-ions and SBRT

c-ions slightly more effective and more

expensive than SBRT: cost-effectiveness ratio

€ 67.257 per extra QALY

€ 0

€ 5.000

€ 10.000

€ 15.000

€ 20.000

€ 25.000

0,0 1,0 2,0 3,0 4,0 5,0

Expected QALYs per patient over 5 years

CRT

SBRT

Protons

Carbon-ions

Exp

ecte

d c

ost

s p

er p

atie

nt o

ver

5 ye

ars

€ 67.257 per extra QALY

Results: cost-effectiveness (all studies)

high level of uncertainty!

€ 25.000

€ 30.000

€ 35.000

€ 40.000

CRT

Exp

ecte

d c

ost

s p

er p

atie

nt

ove

r 5

year

sResults: cost-effectiveness (excluding studies

Conclusion

• Cost-effectiveness results highly uncertain / dependent on included studies

• For stage I inoperable NSCLC unable to conclude that particle therapy is cost-effective conclude that particle therapy is cost-effective compared to SBRT

• More evidence needed to reduce uncertainty– Wait for new evidence? Sunk costs versus costs of delay– Evidence of toxicity (international particle therapy registry)– Particle therapy may be more beneficial in other indications

Summary

• Cost-effectiveness is more than just cost issues• Cost as well as effectiveness are taken into

account• At least two alternatives have to be compared• At least two alternatives have to be compared• Model-based economic evaluations can give

‘quick’ recommendation for medical decision-making

Costs, effectiveness and cost-effectiveness of hadron...

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