Economic Evaluation Journal Club:

PINT TrialDmitry Dukhovny, MD MPH

Instructor in Pediatrics, Harvard Medical SchoolNeonatologist, Beth Israel Deaconess Medical Center

Journal ClubFebruary 19, 2013

Conflicts of Interest

I have no conflicts of interest

Agenda

Why Economic Evaluations?

Brief overview of PINT Trial

PINT EE by Kamholz et al.

Objectives

1. To understand the key components of an economic evaluation

2. To identify sources to assist with critical appraisal of economic evaluations

3. To be able to critically assess an economic evaluation

Why do an economic evaluation?

SPR Workshop: Dollars and SPR Workshop: Dollars and Sense Sense

Framing: Type of Analysis

Costing Cost-minimization Cost-effectiveness Cost-utility Cost-benefit

“Incomplete” Economic Evaluations

“Complete” Economic Evaluations

© 2012 Dukhovny, Lorch, Profit, Kamholz, Zupancic© 2012 Dukhovny, Lorch, Profit, Kamholz, Zupancic

Framing: Study DesignFraming: Study Design

Frankenstein’s Monster?

Vampire of Trials?

O’Brien B. Med Care. 1996;34(12 Suppl):DS99-108

Decision Analysis Randomized Trial

Slide used with permission from J AF Zupancic

SPR Workshop: Dollars and SPR Workshop: Dollars and Sense Sense

Cost-Effectiveness Study

Cost-Effectiveness = Costs of Treatment A – Costs of Treatment B

Effects of Treatment A – Effects of Treatment B

© 2012 Dukhovny, Lorch, Profit, Kamholz, Zupancic© 2012 Dukhovny, Lorch, Profit, Kamholz, Zupancic

Health Expenditures as a Percentage of Gross Domestic Product (GDP) in Selected OECD Countries, 1960–2009.

Fineberg HV. N Engl J Med 2012;366:1020-1027.

How can we can Neonatology more efficient?

1. Decrease cost

2. Improve or not change quality

3. Don’t push anything off to someone else

David Cutler, BIDMC Epi confernece 2/7/2013

Overview of thePINT Trial

PICOT P ELBW (BW<1,000 g), GA<31 wks, <48 hrs old at enrollment

I transfusion algorithm

C higher vs. lower threshold (depends on DOL, respiratory support and type of sample)

O – Primary: Death before d/c home or survival with BPD, severe ROP (3-5), Brain

injury (PVL, ventriculomegally)– Secondary: Death or CP, Cognitive Delay (MDI<70), severe visual (<20/200 in 1

eye) or hearing impairment (amplification or cochlear implant)

T – Primary: Discharge Home– Secondary: 18 to 21 months’ corrected age

Figure 1 from Kirpalani et al. J Pediatr 2006;149:301-7.

Table 2 from Kirpalani et al. J Pediatr 2006;149:301-7.

Table 1 from Kirpalani et al. J Pediatr 2006;149:301-7.

How were these thresholds determined?

Figure 2 from Kirpalani et al. J Pediatr 2006;149:301-7.

Table 5 from Kirpalani et al. J Pediatr 2006;149:301-7.

Primary Outcome

Table 6 from Kirpalani et al. J Pediatr 2006;149:301-7.

Secondary Outcomes

Table 3 from Whyte RK, et al. Pediatrics 2009;123:207-13.

Follow Up Trial: n=430/451

If cut off is MDI<85, cognitive delay favors high threshold group: Adjusted OR 1.81 [1.12, 2.93] (p=0.016)

Conclusions Higher Hgb level resulted in more

transfusions, but little evidence of benefit at:– First discharge home– 18 to 21 months’ corrected age

If the outcome is equivalent, then how do you decide?

PRO Less transfusions

– Blood product exposure– Medical Errors– Less IVs– COST

CON Trends towards slightly

worse outcomes– NEC/Bowel Perforation– Length of Stay– Death or Impairment at 18-

21 months’ corrected

Kamholz et al. Archives of disease in childhood Fetal and neonatal edition 2012;97:F93-8

Big Picture

RCT: – Generalizability– In what directions do the issues in the trial

bias the result? EE:

– Generalizability– Stakeholder– Policy

Framing of EE

Type of Study

DesignPerspectiveTime Horizon

Cost-Effectiveness Analysis

Alongside RCTThird Party Payer18-21 months’

CGA

Costs 2008 Canadian Dollars Discount Rate 3% (a dollar in your hand

right now is worth more then the same dollar in 1 hour or 1 month)

Used case report forms from RCT– Per diem costs (based on respiratory support)

Adjusted for nurse to patient ratio

– Transfusion Costs– Surgery– Physician fees– Re-hospitalization post discharge home

Table 1 from Kamholz et al. Archives of disease in childhood Fetal and neonatal edition 2012;97:F93-8

SPR Workshop: Dollars and SPR Workshop: Dollars and Sense Sense

Types of Resource CostsHealth Care Related Costs

– Direct Medical Costs Variable: Drugs, personnel, tests Fixed: Land, equipment

Non-Health Care Related Costs– Direct Non-Medical Costs

Child care, parking, meals, gym membership

Productivity Costs – “Absenteesim”

Work absence of family or patient due to illness

– “Presenteeism” Decreased productivity of family or patient due to illness

– Employment choices due to condition (eg CP)© 2012 Dukhovny, Lorch, Profit, Kamholz, Zupancic© 2012 Dukhovny, Lorch, Profit, Kamholz, Zupancic

Effectiveness

Survivor without BPD (at 1st discharge home)

Survivor without NDI (at 18-21 months’)

Trial Author Year

Perspective

Time Horizon

Measure of Effectiveness

Surfactant Rescue

Backhouse

1994

3rd party payer

1 year Survivor w/o impairment

iNO for PPHN

Lorch 2004

Societal Discharge home

Per life year gained; QALY

ECMO Petrou 2006

3rd Party Payer

7 years Per life year gained

TIPP Zupancic 2006

3rd party payer

18 months CGA

Survivor w/o impairment

NO CLD Zupancic 2009

3rd party payer

D/C home Survivor w/o BPD

SOD McBride 2009

3rd party payer

D/C home;1 year of age

Survivor w/o BPD; Chronic Respiratory morbidity averted

ET ROP Kamholz 2009

3rd party payer

9 months Cost per eye with severe visual impairment averted

PINT Kamholz Draft

3rd party payer

18 to 21 months

Survivor w/o impairment

Analysis

SPR Workshop: Dollars and SPR Workshop: Dollars and Sense Sense

Cost-Effectiveness Study

Cost-Effectiveness = Costs of Treatment A – Costs of Treatment B

Effects of Treatment A – Effects of Treatment B

© 2012 Dukhovny, Lorch, Profit, Kamholz, Zupancic© 2012 Dukhovny, Lorch, Profit, Kamholz, Zupancic

Table 2 from Kamholz et al. Archives of disease in childhood Fetal and neonatal edition 2012;97:F93-8

Uncertainty/Sensitivity Analyses

Deterministic Probabilistic

Supplement Table from Kamholz et al. Archives of disease in childhood Fetal and neonatal edition 2012;97:F93-8

iCER Plot

Figure 1 from Kamholz et al. Archives of disease in childhood Fetal and neonatal edition 2012;97:F93-8

Cost-Effectiveness Acceptability Curve

Figure 2 from Kamholz et al. Archives of disease in childhood Fetal and neonatal edition 2012;97:F93-8

Limitations

International Trial, but only used Canadian Costs

Time horizon at 2 years Quality of Life Data Societal Perspective (would taking family

expenses move the estimate in one direction or another?)

Summary

PINT trial showed similar outcomes at discharge and 18-21 months’ corrected age for different transfusion thresholds– Trends for better in higher threshold group

The cost estimate appears favorable towards the higher threshold group, but a wide confidence interval around it

Take Home Points

If clinical equivalence between 2 treatment options, must consider a “risk-benefits” calculus

Systematically look at Economic Evaluations just like you do at RCTs

References for Critical Appraisal of Economic Evaluations

Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party. BMJ 1996;313(7052):275-83.

– British Medical Journal has a checklist that is required to be filled out along with the paper submission:

http://resources.bmj.com/bmj/authors/checklists-forms/health-economics

Ungar WJ, Santos MT. The Pediatric Quality Appraisal Questionnaire: an instrument for evaluation of the pediatric health economics literature. Value Health 2003;6(5):584-94.