Economic evaluaton of non-invasive investigation of static and dynamic liver function to assist...

ECONOMIC EVALUATON OF NON-INVASIVE INVESTIGATION OF STATIC AND DYNAMIC LIVER FUNCTION TO ASSIST CLINICAL DECISION MAKING IN HEPATOCELLULAR CARCINOMA

Martin HenrikssonDivision of Health Care Analysis, Department of Medical and Health Sciences, Linköping University, Sweden

Outline 2

• Background• Economic evaluation• Discussion

Background3

Liver Function Evaluation

5

Healthy liver Not so healthy liver

Fibrosis/cirrhosisHepatocellular carcinoma (HCC)

Primary liver cancer (HCC)6

• Most common type of liver cancer• Most cases are secondary to either a viral hepatitis infection

(hepatitis B or C) or cirrhosis (alcoholism being the most common cause)

• Treatments include:– Surgical resection

• Remove the tumor together with surrounding liver tissue while preserving enough liver remnant for normal body function

– Transplant– Radiofrequency ablation

• Imaging guidance to place a needle electrode into a liver tumor. High-frequency electrical currents are passed through the electrode, creating heat that destroys the cancer cells

– Trans catheter chemoembolization (TACE)• Delivering cancer treatment directly to a tumor through minimally-

invasive means

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Decision to perform surgery based on liver function and other parameters

Fibrosis/cirrhosisHepatocellular carcinoma (HCC)

In general there is limited information:

• Liver function (a series of lab values)

• ECOG (performance status)• Tumor burden (Staging)• Age

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How surgery is performed is also based on knowledge of liver function

The amount that can be resected depends on global and local liver function:

Limited knowledge less precision in surgery

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Better knowledge better precision in surgery

10




Better knowledge better precision in surgery

11CMIV flagship project 29 FEBRUARY 2016

The vision with the current research programme is to develop a comprehensive and non-invasive diagnostic MR-toolkit for investigating liver diseases

Inflammation SteatosisFibrosis

and cirrhosis Iron loading

Liver diseasee.g. NAFLD, NASH, PSC

Liver function

1229 FEBRUARY 2016CMIV flagship project

Inflammation SteatosisFibrosis

and cirrhosis Iron loading

Liver diseasee.g. NAFLD, NASH, PSC

Liver function

Multimodal MR• Fat content• Fat and muscle content and distribution • Fibrosis stage• Iron loading• Liver function• Energy levels, phosphorus metabolism• Liver blood flow• Inflammation grade• Conventional images for morphological investigation

Diagnosis & treatment

Blood panels

Our Group and Researchers Involved with our Projects

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MR Physics and Systems Biology• Professor Peter Lundberg (PhD)• Lektor Olof Dahlqvist Leinhard (PhD)• Lektor Gunnar Cedersund (PhD)• Lektor Petter Dyverfeldt (PhD)• Mikael Forsgren (PhD student)• Markus Karlsson (PhD student)• Thobias Romu (PhD student)Hepatology• Professor Stergios Kechagias (MD, PhD)• Docent Mattias Ekstedt (MD, PhD)• Patrik Nasr (MD, PhD student)Liver Surgery• Professor Per Sandström (MD, PhD)• Anna Lindhoff-Larsson (RN, PhD student)

Radiology• Lektor Nils Dahlström (MD, PhD)• Bengt Norén (MD, PhD)• Amir Razavi (MD, PhD)• Professor Örjan Smedby (MD, PhD; KTH)• Docent Torkel Brismar (MD, PhD; KS)Pathology• Professor Darren Treanor (MD, PhD; Leeds, UK)• Simone Ignatova (MD)• Post-doc Nazre Batool (PhD)Health Economics• Professor Lars-Åke Levin (PhD)• Lektor Martin Henriksson (PhD)Business Partners• AMRA AB• Wolfram MathCore AB

Our projects

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NILBn = 110

LIFE & 4LIFEn = 60

HiFin > 100

•fat•fibrosis•iron•inflammation

•OATPB1•OATPB3•MRP2•MRP3

digiNILBn > 150

Steatosis

Non-Alcoholic Steatohepatitis

(NASH)

Fibrosis

Cirrhosis & Cancer

SCAPISn = 400

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Diagnostic tool or demonstrator (4LIFE)

The technology would add:• Degree of

fibrosis/cirrhosis• Liver function• Iron concentration• Body fat

composition• The visualization

Multimodal MR-method that can replace standard biopsy plus measure liver function

Aim 16

• Overall aim is to provide an early assessment of the value of the diagnostic tool (demonstrator referred to as 4LIFE technology)

• With a focus on HCC in this particular application

• Generic consideration of early assessments of the diagnostic tool under development

Economic evaluation17

Decision problem18

• Liver function (lab tests)

• Tumor burden• ECOG• AgeHCC patients

candidates for operation

4LIFE strategy

Clinical practice

• 4LIFE technology • Clinical practice

Costs and outcomes?

Costs and outcomes?

Evaluation considerations19

HCC patients candidates for

operation4LIFE

strategy

Clinical practice Diagnostic

information

Diagnostic information

Management decision

Management decision

implemented treatments

Implemented treatments

Patient outcomes Healthcare costs


Information available with each diagnostic strategy

Type of treatment chosen for patient based on diagnostic information

Clinical outcomes associated with chosen treatment strategies

Patient long-term health outcomes and healthcare costs associated with treatment strategies

Evaluation of management sequences



operation4LIFE

strategy


information


Management decision

Management decision












resection4LIFE

strategy


information


Management decision

Management decision










The decision-analytic model24

Patient candidates for operation

4LIFE strategy

Clinical practice

Resection

RF

Transplant

TACE

Resection

RF

Transplant

TACE

Long-term consequences of each treatment

• Costs

• Quality of life

• Survival

Alive

Dead

TACE: Transcatheter chemoembolization RF: Radiofrequency ablation

Data sources25


4LIFE strategy

Clinical practice

Resection

RF

Transplant

TACE

Resection

RF

Transplant

TACE


• Costs

• Quality of life

• Survival

Alive

Dead

Data from Swedish quality register


Data sources26


4LIFE strategy

Clinical practice

Resection

RF

Transplant

TACE

Resection

RF

Transplant

TACE


• Costs

• Quality of life

• Survival

Alive

Dead

Literature based


Data sources27


4LIFE strategy

Clinical practice

Resection

RF

Transplant

TACE

Resection

RF

Transplant

TACE


• Costs

• Quality of life

• Survival

Alive

Dead

Expert opinion


Data inputs28

Clinical practice* 4LIFE**

Counts Proportion Proportion

Ablation 252 0.255 0.217

Resection 324 0.328 0.406

Transplant 151 0.153 0.153

TACE 261 0,264 0.225

Total 988 1.000 1.000

Treatment decision

*Based on current clinical practice decision making**Based on estimates from experts that 15% of ablation and TACE patients will be subjected to resection

“Treatment effect” based on expert opinion

Data inputs29

Survival prognosis after treatment

Estimated survival from the Swedish registry of tumors in the liver and bile ducts.

Potential “treatment effect” due to improved surgery

Data inputs30

• Literature review ongoing – not much data available (conditional on treatment given)– Investigating the possibility to use registries– Assuming a QoL decrement of 30 % compared with

general population in the present analysis

Quality of life

Data inputs31

CostsParameter SEK Cost of 4LIFE diagnostic procedure 5000Cost of liver resection the year of resection with 4LIFE 150000Cost 2nd and subsequent years after liver resection with 4LIFE 20000Cost of liver resection the year of resection with clinical practice 150000Cost 2nd and subsequent years after liver resection with clinical practice 20000Cost of RFA the year of RFA with 4LIFE 50000Cost 2nd and subsequent years after RFA with 4LIFE 10000Cost of RFA the year of RFA with clinical practice 50000Cost 2nd and subsequent years after RFA with clinical practice 10000Cost of TACE the year of TACE with 4LIFE 45000Cost 2nd and subsequent years after TACE with 4LIFE 10000Cost of TACE the year of TACE with clinical practice 45000Cost 2nd and subsequent years after TACE with clinical practice 10000Cost of transplant the year of transplant with 4LIFE 800000Cost 2nd and subsequent years after transplant with 4LIFE 30000Cost of transplant the year of transplant with clinical practice 800000Cost 2nd and subsequent years after transplant with clinical practice 30000

Data inputs32

CostsParameter SEKCost of 4LIFE diagnostic procedure 5000Cost of liver resection the year of resection with 4LIFE 150000Cost 2nd and subsequent years after liver resection with 4LIFE 20000Cost of liver resection the year of resection with clinical practice 150000Cost 2nd and subsequent years after liver resection with clinical practice 20000Cost of RFA the year of RFA with 4LIFE 50000Cost 2nd and subsequent years after RFA with 4LIFE 10000Cost of RFA the year of RFA with clinical practice 50000Cost 2nd and subsequent years after RFA with clinical practice 10000Cost of TACE the year of TACE with 4LIFE 45000Cost 2nd and subsequent years after TACE with 4LIFE 10000Cost of TACE the year of TACE with clinical practice 45000Cost 2nd and subsequent years after TACE with clinical practice 10000Cost of transplant the year of transplant with 4LIFE 800000Cost 2nd and subsequent years after transplant with 4LIFE 30000Cost of transplant the year of transplant with clinical practice 800000Cost 2nd and subsequent years after transplant with clinical practice 30000

Data inputs33

CostsParameter SEK Cost of 4LIFE diagnostic procedure 5000Cost of liver resection the year of resection with 4LIFE 150000Cost 2nd and subsequent years after liver resection with 4LIFE 20000Cost of liver resection the year of resection with clinical practice 150000Cost 2nd and subsequent years after liver resection with clinical practice 20000Cost of RFA the year of RFA with 4LIFE 50000Cost 2nd and subsequent years after RFA with 4LIFE 10000Cost of RFA the year of RFA with clinical practice 50000Cost 2nd and subsequent years after RFA with clinical practice 10000Cost of TACE the year of TACE with 4LIFE 45000Cost 2nd and subsequent years after TACE with 4LIFE 10000Cost of TACE the year of TACE with clinical practice 45000Cost 2nd and subsequent years after TACE with clinical practice 10000Cost of transplant the year of transplant with 4LIFE 800000Cost 2nd and subsequent years after transplant with 4LIFE 30000Cost of transplant the year of transplant with clinical practice 800000Cost 2nd and subsequent years after transplant with clinical practice 30000

Model settings in base case34

• Model a 65 year old with HCC• Cost and outcomes discounted at 3%• “Treatment effect” incorporated through

changed decision making (not on outcome of surgery)

Results (preliminary)35

Strategy 4LIFE evaluation Clinical practice Incremental Cost (SEK) 284055 266192 17863Life years 5.104 4.952 0.152QALYs 2.932 2.846 0.087 Cost/Life year 117371Cost/QALY 206011

Sensitivity scenarios (general investigation of parameter importance)

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Incremental

costsIncremental

QALYs ICERBase case 17863 0.087 206011 “Treatment effect” on resection (mortality HR 0.80) 24407 0.258 94679Importance of long-term costs (0 from year 2) 15327 0.087 176764Importance of long-term costs (x2 from year 2) 22932 0.087 264506Survival prognosis (20% increase in mortality risk) 17257 0,087 214676General QoL 0.5 17863 0.062 288416Cost of 4LIFE diagnostic (x2) 22863 0.087 263676

Sensitivity scenarios (treatment effect parameters)37

HR Incr cost Incr QALY ICER1.00 17862 0.087 2060110.95 19342 0.125 1545180.90 20918 0.166 1257870,85 22601 0.210 1074340.80 24407 0.258 946790.75 26350 0.309 852850.70 28450 0.364 78068

0.6 0.65 0.7 0.75 0.8 0.85 0.9 0.95 10

50000

100000

150000

200000

250000

HR survival

ICER

Survival post resection

Proportion resected

Proportion Incr cost Incr QALY ICER0 5000 0 NA5 9288 0.029 321342

10 13475 0.058 23484415 17863 0.087 20601120 22150 0.116 191595

0 5 10 15 20 25 300

50000

100000

150000

200000

250000

300000

350000

Proportion of TACE/RP patients shifted to resection

ICER

Conclusion early evaluation38

• Many and large uncertainties (no surprise given the early evaluation approach)

• A structure do define what we need to look for in order to assess the technology appropriately

– How do treatment decisions change– Long-term prognosis of patients

• Based on cost-effectiveness there may still be a case for this technology in clinical practice

• Need to resolve many of the uncertainties• Where do we go from here?

Discussion 39

The full value of the technology?40

• Liver surgery (resection in HCC)• Liver transplantation• Early onset of liver disease• Liver donation

Our first attempt to assess value in terms of cost-effectiveness is partial in the sense that there are many potential applications.

Research councils (and developers) are interested in the overall value. Unclear to me to address this broader question. Is our partial evaluation a small piece in a larger puzzle?

41Incorporation in clinical practice and treatment effect

• Do we need to be more explicit about treatment effect (proportion that go to resection and outcome of resection)?

– Much focus is not on getting an understanding of baseline values, thresholds for abnormality etc in developing the diagnostic tool

– Imply we can more “accurately” distribute patients (according to thresholds) to different treatments

– Incorporating the post-resection MR scan for prediction?

– Moving from our endpoint driven epidemiological type of models to organ level models (systems biology)

MR scan Surgery MR scan

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Sum up

• Indication of cost-effectiveness and which parameters that may be worth researching

• Bridge from basic research to clinical practice to policy decision• Should we do partial cost-effectiveness analyses early on or should

other assessments of value be considered (PET-scans, PCI etc)

Economic evaluaton of non-invasive investigation of static and dynamic liver function to assist...

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