Change Clinical Practice Matthew Menard, M.D. Brigham and Womens - - PowerPoint PPT Presentation

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Change Clinical Practice Matthew Menard, M.D. Brigham and Womens - - PowerPoint PPT Presentation

Sep 19, 2022 429 likes •1.05k views

How The BEST-CLI Trial Will Change Clinical Practice Matthew Menard, M.D. Brigham and Womens Hospital Boston, Massachusetts Disclosure Statement of Financial Interest I, Matthew Menard, DO have a financial interest/arrangement or

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How The BEST-CLI Trial Will Change Clinical Practice

Matthew Menard, M.D. Brigham and Women’s Hospital Boston, Massachusetts

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I, Matthew Menard, DO have a financial interest/arrangement

  • r affiliation with one or more organizations that could be

perceived as a real or apparent conflict of interest in the context

  • f the subject of this presentation.

Disclosure Statement of Financial Interest

  • BEST-CLI Trial Co-Chair

Supported by NHLBI: 1U01HL107407-01A1

  • Janssen (SAB)
  • Aralez (SAB)
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CLI: A Growing Worldwide Epidemic

Diabetes Obesity Metabolic Syndrome Elderly PAD/CLI

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  • Medicare expenditure on CLI > $4 billion

(CHF = $3.9B, Cerebrovascular disease = $3.7B)

– 90% inpatient care – $1,700 per patient (>2X avg beneficiary) – 3% of total Medicare budget (THR = 0.9%, TKR 1.7%)

An Expensive Problem

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Ambroise Pare (1510-1590)

“ …I decided to wait until I had seen what the other surgeons did. They…made the

  • il as hot as possible and dabbed it on the

wound…my oil ran out and I had to apply a healing salve. To my great surprise those…with salve felt little pain while the

  • nes on whom seething oil had been used

lay in fever and aches….I resolved never again to cruelly burn poor people who had suffered shot wounds.”

Haeger, K. The illustrated History of Surgery, 1988.

20 40 60 80 100 120 250 500 750 1000 1250 1500 1750 1950 2000

Advances TIMELINE

Cautery Devices

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1964

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Endovascular Therapy for CLI

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J Cardiovasc Surg (Torino). 2013 Dec;54(6):679-84. Endovascular first as "preliminary approach" for critical limb ischemia and diabetic foot. Setacci C1, Sirignano P, Galzerano G, Mazzitelli G, Sauro L, de Donato G, Benevento D, Cappelli A, Setacci F.

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Adapted from: N Engl J Med 2007;357:217-27.

COMPASS Trial PAD+CAD

>90% with CAD, large subgroup with Concomitant PAD 28% Reduction in MACE 70% Increase in Major Bleeding

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J Vasc Surg 2015; 62:965-73

Initial revascularization for CLI

  • Critisch Registry: 45% bypass
  • Recent VQI Data: 40% bypass

(N= 38,470)

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What Is “Value” in Health Care?

Porter ME, Olmsted Teisberg E. Redefining Health Care: Creating Value-Based Competition on Results. 1st edition. Boston: Harvard Business School Press, 2006.

Value = dollars spent per health-related outcome

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Which FIRST Revascularization Option in CLI Has the BEST Value? VS

Bypass Surgery (LEB) Endovascular Therapy (Endo)

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What is current state

  • f evidence
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Tunis et al.

15

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Randomized controlled trials represent the most internally valid forms of evidence

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A WELL-DESIGNED TRIAL IDENTIFIES THE OPTIMAL COURSE OF ACTION IN RESEARCH SETTINGS

SOURCE: Ho et al. Circulation 2008;118:1675

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Advantages and Disadvantages of Randomized Clinical Trial Design

James, S. et al. (2015) Registry-based randomized clinical trials—a new clinical trial paradigm

  • Nat. Rev. Cardiol. doi:10.1038/nrcardio.2015.33

Clinical Trial Design Advantages Disadvantages

Randomized Clinical Trial

  • eliminates confounding factors
  • minimizes treatment selection bias
  • reduces spurious causality
  • most reliable form of scientific

evidence

  • time intensive
  • expensive
  • generizability
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NOTE: TEXT AND IMAGES IN GRAY BORDER WILL NOT PRINT AND WILL NOT BE PROJECTED How Often Do We Know What to Do for the Patient?

Cardiovascular Treatment Guidelines

COMPANY CONFIDENTIAL | FOR INTERNAL USE ONLY | DO NOT COPY

Scientific Evidence Underlying the ACC/AHA Clinical Practice Guidelines

  • JAMA. 2009;301(8):831-841

PCI, Stents Peripheral Artery Disease CABG Secondary Prevention Unstable Angina Heart Failure Atrial Fib Echocardiography Pacemakers Radionuclide Imaging Supravent arrhythmias Stable Angina Sudden Death ST Elevated MI Exercise Testing Valvular Heart Disease

16 High impact cardiovascular guidelines used to power healthcare

decisions by payers, healthcare providers and consumers

2,711 Recommendations within these guidelines 11% Were based upon enough evidence to warrant the recommendation.

The vast majority were based upon a single trial and expert opinion

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Large RCT’s for Vascular Disease

  • Carotid Endarterectomy
  • NASCET, ACAS, ACST,

VA Trial, ECST,GALA

  • CEA vs Carotid Stent
  • ACT I, CREST,

CASANOVA,EVA 3s, ICSS, SAPPHIRE, SPACE, CAVATAS

  • AAA
  • ADAM, UK Small AAA
  • AAA vs EVAR
  • DREAM I and II, EVAR I

and II, OVER, Numerous IDE studies.

  • CLI: Bypass vs Endo
  • BASIL
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…There is paucity of high-quality data available to guide clinical decision making….

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Variation in Amputation Rates Among Patients with CLI

Dartmouth Atlas of Cardiovascular and Thoracic Healthcare Care. Manning Selvage & Lee; 1998

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Variation in LE Revascularization

Goodney P et al. Circ Cardiovasc Qual Outcomes. 2012;5:94-102

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0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

All VQI Centers Mean = 31%

Critical Limb Ischemia: % Treated by Bypass (vs. PVI)

0% Bypass 100% Bypass

Procedure Selection Variation

VQI Centers

Equipoise

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Limitations of Current Data

  • Retrospective
  • Poorly controlled
  • Suboptimal endpoints
  • Amputation free survival
  • Target lesion revascularization
  • Target vessel revascularization
  • Patency
  • Sponsor bias
  • Operator bias
  • Inclusion of claudicants
  • Short or incomplete follow up
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The Exponential Rise in Health Care Expenditures

Pear R. Administration Offers Health Care Cuts as Part of Budget Negotiations. New York Times, July 4th, 2011.

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We can’t afford every health intervention that is effective

NATIONAL HEALTH EXPENDITURES AS A SHARE OF GDP, 1987-2016

26 SOURCE: CMS

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The mandate for better evidence is compelling

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BEST-CLI Trial: Overview

  • NIH-funded, prospective, randomized, multicenter,

multispecialty, pragmatic, open-label superiority trial

  • 2100 patients at 160 clinical sites

Goal: to assess clinical outcomes, quality of

life, cost and value in patients who are candidates for both vascular surgery and endovascular therapy

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BEST-CLI Trial Design: Two Cohorts

  • Cohort #1 Patients with adequate single segment great

saphenous vein (SSGSV) N=1620

Open surgery vs. Endovascular treatment

  • Cohort #2 Patients without adequate SSGSV (if

randomized to OPEN conduit may include arm vein, short saphenous vein, composite vein, cryopreserved vein, and prosthetic conduit) N=480

Open surgery vs. Endovascular treatment

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Why Is BEST-CLI Important?

Uniquely positioned to provide level I data for CLI

  • Well-powered and designed
  • Real-world pragmatic trial
  • BASIL: n = 452
  • PREVENT III: n = 1405
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MALE defined as:

  • Above ankle amputation or
  • Major re-intervention
  • new bypass graft
  • jump/interposition graft revision
  • thrombectomy/thrombolysis

Novel Primary Endpoint

Major Adverse Limb Event (MALE) – free survival

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````````````````````

Additional Secondary Endpoints

  • Freedom from hemodynamic failure
  • Freedom from clinical failure
  • Freedom from critical limb ischemia
  • Number of re-interventions per limb salvaged
  • Freedom from re-interventions (major and minor)

in index limb

Key Secondary Endpoints

  • Re-intervention and Amputation-free Survival (RAS)
  • Amputation-free Survival
  • MALE-POD
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Optimal Medical Therapy

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SVS Lower Extremity Threatened Limb Classification - WIfI Index

  • Wound: extent and

depth

  • Ischemia:

perfusion/flow

  • foot Infection:

presence and extent

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Risk of Amputation Benefit of Revascularization

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Swim with (the) TIDE

TIDE Ancillary Study Update

Sponsored by the National Heart Lung and Blood Institute

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TIDE: Trial Update

An NHLBI Substudy of BEST-CLI

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BEST-CLI in North America

130 Active Sites

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BEST-CLI Global Footprint

New Zealand (3) Finland (1)

4 Active Sites

Germany Italy

Europe New Zealand

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930 Investigators

 114 Interventional Cardiologists  111 Interventional Radiologists  3 Vascular Medicine Specialists  690 Vascular Surgeons  12 Other

41

Site Investigators

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Enrollment Update

As of 9/22/2018

  • 1,456 subjects randomized
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VALUE IN HEALTHCARE

Christopher J. White, MD, M-SCAI, FACC, FAHA, FESC, FACP

Right Treatment Right Patient Right Time

PERSPECTIVE

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Clinical outcomes

A typical trial

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CEA alongside a prospective study

$$ $ $ $$$ $$ $ $ $ $ $ $ $ $ $

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Cost-effectiveness analysis considers the cost of an intervention and its downstream consequences

Downstream costs

  • Reinterventions avoided
  • Complications

Upstream costs

  • Procedure
  • Hospitalization

46

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The approach we’re taking in BEST

$$ $ $ $$$ $$ $ $ $ $ $ $ $ $ $ $$ $ $ $$$ $$ $ $ $ $ $ $ $ $ $ MEASUREMENT MODELING

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Incremental cost-effectiveness ratio (ICER)

ICER = COSTTREATMENT A – COSTTREATMENT B EFFECTTREATMENT A – EFFECTTREATMENT

B

= ΔCOST ΔEFFECT

“HEALTH EFFECT” is often measured in quality adjusted life years (QALYs), a measure that incorporates both length and health-related quality of life

48

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Quality Adjusted Life Years (QALYs)

  • Quality Adjusted Life Years (QALYs) will be calculated based on area under the curve of

quality of life for each patient. The average QALYs in two intervention arms then will be compared as outcomes.

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1 3 12 24 36 48 Quality of Life (e.g.EQ-5D) Follow-up month

Quality of Life

Open Endo 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1 3 12 24 36 48 EQ-5D Follow-up month

Quality Adjusted Life Years

Open Endo

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Interpreting Cost-effectiveness analysis

Adopt new treatment? Improved Outcomes Worse Outcomes Saves money YES (“dominant strategy”) PROBABLY NOT Costs money MAYBE (usually if <$50- 100K/QALY) NO (“dominated strategy”)

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What could we possibly see in BEST?

WHICH TREATMENT REPRESENTS BETTER VALUE?

HYPOTHETICAL

OUTCOMES TREATMENT A TREATMENT B M.A.L.E. SUPERIOR COMPLICATIONS SUPERIOR QUALITY OF LIFE SUPERIOR COSTS LESS EXPENSIVE

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Collaboration and CLI teams

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  • Vascular Surgeons
  • Interventional Cardiologists
  • Interventional Radiologists
  • Vascular Medicine Specialists

Collaboration within BEST-CLI

Inclusive of everyone who treats CLI:

If our trial is going to define practice it has to involve everyone.

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CLI Teams in Action

  • George Adams
  • Sahil Parikh
  • Carlos Mena
  • Steve Henao
  • Ehrin Armstrong
  • Niten Singh
  • Mehdi Shishehbor
  • Peter Soukas
  • Rob Lookstein

Collaboration is the antidote to bias

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Case Review

62 yo f with nonhealing toe amputation site, good GSV

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Case Review

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Summary

  • Interdisciplinary collaboration and

awareness-raising

  • Everybody wins – especially our patients
  • Raise the bar of CLI care
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Conclusions

  • There is an exceptional knowledge deficit in CLI management cf other areas of clinical therapy.
  • Technical success is necessary, but Value in CLI care is far more complex
  • Systematic data regarding outcomes will be necessary in order to change behaviors and practice

patterns, and reduce cost

  • RCTs are imperfect … but are the best tool we have!
  • BEST CLI, in synergy with BASIL-2 and BASIL-3, will provide powerful, Level I data that

will help to shape a much-needed evidence based approach to CLI.

  • And set the stage for the next generation of investigations.