The Premarket Assessment of the Cost-effectiveness of a Predictive Technology StraticyteTM

for the Early Detection of Oral Cancer

Khoudigian S1, Blackhouse G1,2, Tsoi B1, Levine M1,2,3, Thabane L1,3, O’Reilly D1, 2,3

 

1 Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada;

2 PATH Research Institute and St Joseph’s Healthcare, Hamilton, ON, Canada;3 Research Institute of St. Joseph’s, Hamilton, ON, Canada

CADTH Symposium 2016Ottawa

April 12th, 2016

Outline

1. Background/ Research Objective2. Methods3. Results4. Strengths/ Limitations5. Conclusions

Disclosure

I have no actual or potential conflict of interest in relation to this topic or presentation.

Oral Cancer: Epidemiology & Diagnosis Oral cancer (i.e., lip, oral cavity or oropharynx) accounts for 3% of

all cancers worldwide and was responsible for 1,100 deaths in 2013 in Canada

Currently, the SOC for diagnosing oral cancer is the histopathologic assessment of a tissue biopsy of the suspicious lesion.

The presence and the degree of epithelial dysplasia (i.e., mild, moderate, severe) assesses the malignant risk of oral pre-malignant lesions

Prognostic Tool for Oral Cancer: StraticyteTM

Novel technology determines the risk of an oral lesion becoming cancerous

Classified as Laboratory Developed Test (LDT)

Objectively and more accurately ID patients at high risk for developing oral cancer

Potential to save lives, reduce morbidity with less traumatic surgeries, increase the duration of productive work lives, and save healthcare costs

The “Histopathology” Vs. “StarticyteTM + Histopathology” Diagnostic Algorithms

“Histopathology” Algorithm

“StraticyteTM + Histopathology”

Algorithm

Pre-cancerous Lesion

MILD dysplasi

a

MODERATE dysplasia

SEVERE dysplasi

a

HIGH risk

MEDIUM risk

LOW risk

HIGH risk

MEDIUM risk

LOW risk

HIGH risk

MEDIUM risk

LOW risk

Research Objective

To determine the cost-effectiveness of StraticyteTM + Histopathology compared to Histopathology alone (i.e. SOC) for the diagnosis of oral lesions in Canada in adult patients with suspected oral cancer, who had already undergone biopsy.

Cost-Effectiveness Analysis (CEA) METHODS

Perspectives: Patients’ and private payers

Patient population: Individuals (≥35 years) with suspected oral cancer, who had already undergone biopsy

Outcome: Cancer cases

Time horizon: 5 years

Discounting: 5% (based on CADTH guidelines)

Sensitivity analysis: Deterministic (one-way) and Probabilistic (1000 Monte Carlo simulation)

1

2

3

4

5

6

Severe

Moderate

Mild

SOC

Cancer

No Cancer

Cancer

No Cancer

Cancer

No Cancer

M

M

M

M

M

M

Patients with Dysplasia

“Histopathology” Algorithm

Decide which diagnostic test to use

“Histopathology + StraticyteTM” Algorithm

Patients with Dysplasia

000

SOC +

StraticyteTM

High Risk

Medium Risk

Low Risk

High Risk

Medium Risk

Low Risk

High Risk

Medium Risk

Low Risk

Cancer

No Cancer

Cancer

No Cancer

Cancer

No Cancer

Cancer

No Cancer

Cancer

No Cancer

Cancer

No Cancer

Cancer

No Cancer

Cancer

No Cancer

Cancer

No Cancer

M

M

M

M

M

M

M

M

M

M

M

M

M

M

M

M

M

M

Decide which diagnostic test to use

Additional Scenarios

Scenario #1(Assesses only 2

categories)Moderate

Mild

Scenario #2(Assesses only 1

category)Mild

Base Case Analysis (Assesses all 3 categories)

SevereModerate

Mild

Model Details and Assumptions

Decision tree POPULATED based on the retrospective

study

Relative Risk of MTR given treatment mortality was

OBTAINED from SRDecision treeDEVELOPED

ASSUMPTION

MTR reflects the natural disease

progression

Experts interview CONDUCTED to determine change in clinical practice given StarticyteTM

APPLICATION

RR where appropriate given

the interview outcome

Decision tree RE-POPULATED based on the SR and Experts

interview

Analysis/ Results

Step #1

Step #4

Step #3

Step #5

Step #2

Results – Base Case Analysis

Histopathology Histopathology+ StraticyteTM

Total Cost $ 3,962.76 $ 3,723.02

Total cancer cases 0.30 0.24

Incremental cost $ -239.74

DOMINATESCancer cases avoided

0.06

Results – Scenario Analyses

Scenario #1 (Moderate and Mild Cases)Histopathology Histopathology+ StraticyteTM

Total Cost $2,885.79 $2,578.30Total cancer cases 0.23 0.16Incremental cost $-307.49

DOMINATESCancer cases avoided 0.06

Scenario #2 (Mild cases)

Histopathology Histopathology+ StraticyteTM

Total Cost $577.71 $1,078.32

Total cancer cases 0.14 0.08

Incremental cost $500.61

IS DOMINATED by HISTOPATHOLOGY

Cancer cases avoided 0.06

ICER $7,854.09/ cancer case avoided

ICUR Plane – Base Case Analysis

-0.04 -0.02 0 0.02 0.04 0.06 0.08

-7000

-5000

-3000

-1000

1000

3000

5000

7000

Cancer cases avoided

Δ C

ost

Base case

NENW

SW SE

New treatment DOMINATES

New treatment Is

DOMINATED

Scenario #1

Scenario #2

Probabilistic Sensitivity Analysis

-0.15 -0.10 -0.05 0.00 0.05 0.10 0.15 0.20 0.25

-1000.00

-800.00

-600.00

-400.00

-200.00

0.00

200.00

400.00

600.00

Cancer cases avoided

Δ C

ost

69%Of the time Dominates

23%Of the time

Expensive & More Effective

6%Of the time

Cheaper & Less Effective

3%Of the time

Expensive & Less Effective

Strengths and Limitations of this Study Strengths:

First to assess the cost-effectiveness of StraticyteTM

Helps prepare for its licensing and the adoption

Supports internal investment decisions in order to prioritize potential products to take forward

Helps avoid investing in technologies that are unlikely to be cost-effective

It allows the investigation of its potential downstream impact

Limitations: First to market- No clinical and economic evidence in literature

Classified as Laboratory Developed Test (LDT)

• Pre-market review and other applicable FDA requirements are not required for LDT

Easy to introduce into the market but hard to seek reimbursement

CONCLUSIONS The “StraticyteTM and Histopathology” diagnostic algorithm

would be less expensive and results in less cancer cases than “Histopathology” alone

Scenario #1: “StraticyteTM and Histopathology” dominant strategy

Scenario #2: “StraticyteTM and Histopathology” dominated by “Histopathology” alone

Probabilistic sensitivity analysis demonstrates:• The “StraticyteTM and Histopathology” diagnostic algorithm would

be cost-effective over a wide range of WTP values

THANK YOU!

Shoghag Khoudigian, H.BScPhD. Candidate

Department of Clinical Epidemiology and Biostatistics, McMaster University

Programs for Assessment of Technology in Health (PATH) Research Institute, St Joseph’s Healthcare

Hamilton Telephone: (905) 523-7284 ext. 5275Fax: (905) 522-0568Email: khoudisv@mcmaster.ca

25 Main Street West20th floor, Suite 2000

Hamilton, ON L8P 1H1

BACK UP

ICUR plane:

New treatment more effective

New treatment less

effective

New treatment

more costly

New treatment less costly

Existing treatment

dominates

New treatment more effective but more costly

New treatment less costly but less

effective

New treatment dominates

Maximum Acceptable ICUR

North East

North West

South West

South East

Model ParametersTransition Probabilities

Retrospective study 1 study (n=107) from Mt Sinai

Hospital 5 year follow-up No treatment information

RR of Malignant Transformation

Comprehensive SR 5 retrospective studies reported

the development of cancer given treatment modality (i.e. excision vs. no-excision)

None used the StraticyteTM

Biomarker

Clinical Practice by O&M Surgeons

Brief Eliciting method Experts interview (n=4) on

treatment given a dysplasia grading and how the introduction of StraticyteTM might change their practice

Common prescribed medications to patients after excision

Average number of days off work after excision

Costs and Resources

Direct & In-Direct costs ODA suggested fee for services Mount Sinai Hospital & Laboratory

Medicine StraticyteTM cost based on

Proteocyte Diagnostics Inc. Statistics Canada and Canada

Revenue Agency

Model Input Parameters- Probabilities

To determine the relative risk of developing oral cancer in patients who had local excision (surgery)

MEDLINE and EMBASE databases were used

Keywords: • “dysplasia”, “oral or epithelial or mouth”, “progress”, “follow-up”, “treat”, “monitor”,

and “risk reduction”

No limits on year and language were applied

Inclusion criteria:• RCTs, comparative observational studies• Comparing outcomes of patients who had surgery vs. who were

solely monitored for at least 5 years

Model Input Parameters- RR of Malignant Transformation

PRISMA Diagram

EMBASE(n = 1480)

2669 Total Records

1036 duplicates excluded1633 Records

(title and abstract) screened

1573 Records excluded

60 Full-text articles assessed

for eligibility

55 Studies excluded:

Not RCT or OB (n=21)

No comparator (n= 25)

Wrong outcome (n=5)

Not English (n=4)

 

 

5 Studies included in synthesis

Iden

tific

atio

nS

cree

ning

Elig

ibili

ty

MEDLINE (n = 1189)

Incl

uded

1 grey literature • The following data were abstracted

from 5 included studies:

1. Authors2. Year3. Type and setting of the study4. Mean age5. Mean follow-up time6. Number of patients in each

arm7. Malignant transformation rate

Study Characteristics

First author/ year

Country Methodology/setting

Date of enrollment

Mean age

# of cancer cases/ total #

of surgically treated

patients

# of cancer cases/ total # of

non-surgically treated patients

Saito,2001

Japan Retrospective/ Hospital

1976-1997 54 1/48 3/34

Banoczy,1976

Hungary Retrospective/ Hospital

NR NR 1/45 8/23

Arduino,2009

Italy Retrospective/ Hospital

1991-2007 63.58 7/133 3/74

Arnaoutakis,2013

USA Retrospective/ Hospital

1990-2011 59.2 14/75 17/38

Holmstrup,2006

Denmark Retrospective/ Pathology laboratory

1977-1997 60.8 8/67 2/21

The Forest Plot

Model Input Parameters- Clinical Practice by Oral Surgeons

Treatment Follow-up

Histopathology

Severe Dysplasia Excision Every 6 months for 5 years

Moderate Dysplasia Excision Every 3 months for 5 years

Mild Dysplasia Monitor -

Histopathology + StraticyteTM

Severe + High Risk Excision Every 6 months for 5 years

Severe + Medium Risk Excision Every 6 months for 5 years

Severe + Low Risk Excision Every 6 months for 5 years

Moderate + High Risk Excision Every 6 months for 5 years

Moderate + Medium Risk Excision Every 6 months for 5 years

Moderate + Low Risk Excision Every 3 months for 5 years

Mild + High Risk Excision Every 6 months for 5 years

Mild + Medium Risk Excision Every 6 months for 5 years

Mild + Low Risk Monitor Every 6 months for 2 years

Interview Results

Deterministic Sensitivity Analysis

SOC +StraticyteTM Algorithm vs. SOC AlgorithmConservative Values Optimistic Values

Inc.Cost

Cancer cases avoided

ICER ($/cancer case avoided)

Inc. Cost

Cancer cases avoided

ICER ($/cancer case avoided)

Visits every 6 months per year $-714.29 0.06 -11,206.67 $326.98 0.06 5,130.08

DOMINATES DOES NOT DOMINATE

RR of malignant transformation given excision

$-193.66 0.09 -2,242.55 $-193.66 0.01 -15,697.86

DOMINATES DOMINATES

Visits every 3 months per year $206.75 0.06 3,243.74 $-594.06 0.06 -9,320.33

DOES NOT DOMINATE DOMINATES