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The Lucentis-Avastin Trial for Age-related The Lucentis-Avastin Trial for Age-related Macular Degeneration –  A Non-Inferiority Macular Degeneration –  A Non-Inferiority Trial for which the Company Refuses to Trial for which the Company Refuses to

Pay for the New DrugPay for the New Drug

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Center for Clinical Trials Seminar SeriesJohns Hopkins University

Maureen G. Maguire, PhDDepartment of Ophthalmology

University of Pennsylvania

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DisclosuresDisclosures

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I have no relevant commercial entity relationships or financial interests to disclose.

I will discuss off-label use of Avastin

 

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Overview

Comparative effectiveness

Health Care and the American Recovery and Reinvestment Act

Robert Steinbrook, MDRobert Steinbrook, MD – NEJM, March 12, 2009

““studies that directly compare the risks and benefits of studies that directly compare the risks and benefits of different treatments for a particular condition are different treatments for a particular condition are essential for improving practice and slowing cost essential for improving practice and slowing cost escalation.”escalation.”

Case study on how one CE trial faredComparison of AMD Treatment Trials (CATT):

Lucentis-Avastin Trial

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Public Health Significance of Age-Related Macular Degeneration

(AMD)

Leading cause of blindness among adults in Leading cause of blindness among adults in US and most western countriesUS and most western countries

8.5 million affected in US – 20008.5 million affected in US – 2000

>6.6 million early AMD>6.6 million early AMD

>1.8 million late AMD>1.8 million late AMD

By 2020, these numbers will By 2020, these numbers will DOUBLEDOUBLE due to due to the aging US populationthe aging US population

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Early AMD

Early AMD or age-related maculopathy (ARM)

Drusen - yellowish deposits

Pigmentary change

Both eyes affected often

Normal

Early AMD

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Impact of Early AMD on Vision

Visual acuity usually Visual acuity usually good - often 20/20 good - often 20/20 rarely worse than 20/40rarely worse than 20/40

Some problems withSome problems with

Night visionNight vision

Color visionColor vision

Contrast sensitivityContrast sensitivity

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Late AMD

Choroidal neovascularization ~2/3 of late AMD is CNV~2/3 of late AMD is CNV ~90% of legal blindness ~90% of legal blindness

due to CNVdue to CNV

Geographic atrophy ~ 1/3 of late AMD is GA~ 1/3 of late AMD is GA ~ 10% of legal blindness ~ 10% of legal blindness

due to GAdue to GA

Fluorescein Angiogram

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Impact of Late AMD on Vision

http://www.nei.nih.gov/photo/sims/index.asp

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Age-Specific Prevalence of Late AMD in Whites

Eye Diseases Prevalence Research Group. Arch Ophthalmol 2004; 122:564-572

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Proportion of Adult Blindness by Race

0

10

20

30

40

50

60

White Black Hisp.

AMD

Cataract

Glaucoma

Diab. Ret.

Other

Eye Diseases Prevalence Research Group. Arch Ophthalmol 2004;122:477-485

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Established Risk Factors for AMD

Age and race

Genes

Complement Factor H

HTRA1

Others

Cigarette smoking

Diets low in specific nutrients

Beta-carotene, vitamins C & E, zinc

Lutein/zeaxanthin Omega-3 Fatty Acids

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Prevention

Age-Related Eye Disease Study (AREDS) – NEIAge-Related Eye Disease Study (AREDS) – NEI Daily, high dose anti-oxidant vitamins and zinc Daily, high dose anti-oxidant vitamins and zinc

Reduction of risk of progression to Late AMD and Reduction of risk of progression to Late AMD and vision loss by 25% over 5 years for patients with vision loss by 25% over 5 years for patients with large drusenlarge drusen

AREDS 2AREDS 2Supplementation with lutein and/or omega-3 fatty

acidsOngoing

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Treatment Efficacy for CNV at 1 Year- 2005

≤ 15 Letter ≥ 15 Letter Mean Change

Loss Gain ≥ 20/40 VA (letters)

No Rx 39% 2% 1% --

Laser 50% 1% --- --

PDT 67% 6% 5% - 10

Macugen 70% 6% --- - 7

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Next Clinical Trial for CNV Next Clinical Trial for CNV

Macugen – intravitreal injection every 6 wks, Macugen – intravitreal injection every 6 wks, $1000 per injection$1000 per injection

PDT ~ 3 treatments per year, $5000-$7500 PDT ~ 3 treatments per year, $5000-$7500 Can treatment frequency be reduced with Can treatment frequency be reduced with

combination therapy?combination therapy? May 2005 – submit grant June 1 for trial of :May 2005 – submit grant June 1 for trial of :

MacugenMacugenPDT + MacugenPDT + MacugenPDT + triamcinolonePDT + triamcinolone

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History - Lucentis Arrives History - Lucentis Arrives

May 23, 2005 – News releaseMay 23, 2005 – News release Phase III trial MARINA by GenentechPhase III trial MARINA by Genentech

Intravitreal Lucentis 0.3mg every 28 daysIntravitreal Lucentis 0.3mg every 28 daysIntravitreal Lucentis 0.5 mg every 28 daysIntravitreal Lucentis 0.5 mg every 28 daysSham injection every 28 daysSham injection every 28 days

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21.4 letter difference*

20.3 letter difference*

+7.2

+6.5

-10.4

2 4 6 8 10 12 14 16 18 20 22 24

Month-15

-10

-5

0

5

10

ET

DR

S le

tters

-14.9

+5.4+6.6

MARINA: 2 Doses of Lucentis vs Sham RxMean Change in Visual Acuity Over Time

Note: Vertical bars are ± one standard error of the mean.

*P<0.0001(Rounded values)

Sham (n=238) Ranibizumab 0.5 mg (n=240)Ranibizumab 0.3 mg (n=238)

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Treatment Efficacy at One Year

≤ 3 Line ≥ 3 lines Mean Change

Loss Gain ≥ 20/40 VA (letters)

No Rx 39% 2% 1% --Laser 50% 1% --- --PDT 67% 6% 5% - 10Macugen 70% 6% --- - 7Lucentis MARINA 95% 34% 40% + 7 ANCHOR 95% 40% 39% + 11

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Planned Trial Planned Trial

May 2005 – grant to be submitted for trial of :May 2005 – grant to be submitted for trial of :MacugenMacugenPDT + MacugenPDT + MacugenPDT + triamcinolonePDT + triamcinolone

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History – Avastin Arrives History – Avastin Arrives

July 18 2005 – ASRS meetingJuly 18 2005 – ASRS meeting MARINA results presented MARINA results presented Report of a Report of a 1 pt1 pt treated with intravitreal Avastin treated with intravitreal Avastin

Avastin – anti-VEGF agent, FDA approved for colon CA, Avastin – anti-VEGF agent, FDA approved for colon CA, intravenous administrationintravenous administration

Derived from the same molecule as Lucentis, but largerDerived from the same molecule as Lucentis, but larger Believed not to penetrate the retina from the vitreousBelieved not to penetrate the retina from the vitreous Previous case series with intravenous Avastin – showed Previous case series with intravenous Avastin – showed

promise but concern over systemic side effectspromise but concern over systemic side effects

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Avastin Quickly Adopted by Many Avastin Quickly Adopted by Many

August – December 2005August – December 2005 Lucentis not generally availableLucentis not generally available Salvage cases only Salvage cases only first line therapy first line therapy

– Chemically similar to Lucentis– Dramatic results in the short term– Inexpensive (~$50 per injection) if 4 ml vial divided– Medicare and insurance carriers started covering Avastin and

the injection procedure (no National Coverage Decision)– Off-label use– Unknown safety– No controlled trials of short- or long-term efficacy

Widespread debate on ethics of off-label useWidespread debate on ethics of off-label use

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CATT History CATT History

January 2006 – grant submitted to NEI for January 2006 – grant submitted to NEI for Lucentis-Avastin trial; expedited reviewLucentis-Avastin trial; expedited review

June 2006 – NEI will fund clinical and resource June 2006 – NEI will fund clinical and resource centers - $16 million over 4 yearscenters - $16 million over 4 years

June 2006 – Lucentis receives FDA approval for June 2006 – Lucentis receives FDA approval for treatment of CNV – price ~ $2000 per dosetreatment of CNV – price ~ $2000 per dose

February 2008 – First patient enrolledFebruary 2008 – First patient enrolled What took so long???What took so long???

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Centers for Medicare and Medicaid Services (CMS)

2006 - Not positioned to support comparative effectiveness studies

95% of AMD CNV patients covered by Medicare/Medicaid

Drug cost to CMS (80% of total) if 1200 patients receive:

Lucentis similar to Genentech trials $50 Million

Treatments as in CATT $25 Million

Savings to CMS during study $25 Million

CMS estimates total cost reduction (AMD claims data) is $1 to $3 Billion dollars each year

Talks between CATT and CMS began Nov 2005 – involvement contingent on NIH approval of design

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Centers for Medicare and Medicaid Services (CMS)

July 13, 2006 Meeting at CMS Headquarters with CMS (OCSQ) and NEI leaders

Funding100% payment for Lucentis?Avastin? Drug distribution costs?

ResponseCMS is enthusiastic about the trialCMS pays bills conduct CMS does not conduct research

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Centers for Medicare and Medicaid Services (CMS)

July 13, 2006 Meeting at CMS Headquarters with CMS (OCSQ) and NEI leaders

Funding100% payment for Lucentis?Avastin? Drug distribution costs?

ResponseCMS is enthusiastic about the trialCMS pays bills conduct CMS does not conduct researchCurrent CMS policy appears to prohibit payment of

Lucentis in CATT

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2000 Clinton Clinical Trial Policy

Intent: to open participation in clinical trials to Medicare beneficiaries

Language focused on by CMS lawyers“Medicare covers the routine costs of qualifying

clinical trials …except: the investigational item or service, itself”

Other language not cited“Routine costs in clinical trials include: Items or

services that are typically provided absent a clinical trial (e.g., conventional care);”

Scheduled for revision in Summer 2007 to explicitly allow coverage of treatments otherwise covered by Medicare

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CMS Options for CATT

Wait a year to allow Lucentis to be covered (80%) CMS Payment Demonstration Project

Intended for exploring alternative payment mechanisms

Very few had ever been approved by CMS/DHHS lawyers

An Act of Congress

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Comparative Effectiveness Comparative Effectiveness

Major needs for CATTMajor needs for CATTSupply of drugsSupply of drugsPayment for Lucentis and Avastin Payment for Lucentis and Avastin Masking Masking

Needs pertain to most comparative effectiveness trialsNeeds pertain to most comparative effectiveness trials Comparative effectiveness is not embraced by industryComparative effectiveness is not embraced by industry “… “… some are concerned that the government or some are concerned that the government or

insurers may use the results to mandate specific insurers may use the results to mandate specific approaches to treatment or to deny coverage. “approaches to treatment or to deny coverage. “

NEJM, Steinbrook, March 12, 2009NEJM, Steinbrook, March 12, 2009

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Demonstration Projects Demonstration Projects

Major needs (even with coverage of Lucentis)Major needs (even with coverage of Lucentis) Central supply of both drugs for clinical centersCentral supply of both drugs for clinical centers Payment for Lucentis co-payPayment for Lucentis co-pay Masking (Medicare EOB names drug)Masking (Medicare EOB names drug)

ManyMany plans, ultimately not feasible or deemed plans, ultimately not feasible or deemed illegalillegal CMS Acting Director Leslie NorwalkCMS Acting Director Leslie Norwalk NIH Director ZerhouniNIH Director Zerhouni Ophthalmology professional organizationsOphthalmology professional organizations Congressmen and senatorsCongressmen and senators High level contacts in White HouseHigh level contacts in White House

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Plan Proposed by CATT Group Plan Proposed by CATT Group

CMS provides funds to purchase drug supply (both, CMS provides funds to purchase drug supply (both, 100% of cost) - $24 million100% of cost) - $24 million

Avastin repackaged into vials identical to LucentisAvastin repackaged into vials identical to Lucentis CATT accounts for all drug used (Medicare CATT accounts for all drug used (Medicare

beneficiaries only)beneficiaries only) Pay back any unused funds to CMS at end of trial Pay back any unused funds to CMS at end of trial Favorable featuresFavorable features

Drug cost (no cost) identical to patients in all Drug cost (no cost) identical to patients in all groupsgroups

No billing expenses for Penn, clinical centersNo billing expenses for Penn, clinical centers No EOB with drug nameNo EOB with drug name Allows complete maskingAllows complete masking

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CMS “G” Code Plan CMS “G” Code Plan

Penn/NEI buys supplies of both drugsPenn/NEI buys supplies of both drugs Avastin repackaged into vials identical to LucentisAvastin repackaged into vials identical to Lucentis CATT supplies and bills clinical centersCATT supplies and bills clinical centers Centers treat pts, bill “CATT Drug” using a “G” Centers treat pts, bill “CATT Drug” using a “G”

code, receive Medicare payments, and pay back code, receive Medicare payments, and pay back CATTCATT Amount equal to 80%/ 100% of the average costAmount equal to 80%/ 100% of the average cost Use weighted average based on predicting ratio Use weighted average based on predicting ratio

of Lucentis:Avastin injectionsof Lucentis:Avastin injections Use weighted average with allowance for Use weighted average with allowance for

breakagebreakage

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CMS “G” Code Plan CMS “G” Code Plan

DisadvantagesDisadvantages $ Millions in “up front” costs$ Millions in “up front” costs Dependent on efficient billing from clinical Dependent on efficient billing from clinical

center and payment to Penn center and payment to Penn Huge loss if weighting ratio incorrectHuge loss if weighting ratio incorrect

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CMS Capitated Plan CMS Capitated Plan

Penn/NEI buys supplies of both drugsPenn/NEI buys supplies of both drugs Avastin repackaged into vials identical to LucentisAvastin repackaged into vials identical to Lucentis CATT supplies clinical centersCATT supplies clinical centers Clinical centers enroll patients in CATT and receive Clinical centers enroll patients in CATT and receive

capitated payments for all CATT care, regardless of capitated payments for all CATT care, regardless of actual treatments, pay CATT a portion to cover drugsactual treatments, pay CATT a portion to cover drugs Payment 100% anticipated costsPayment 100% anticipated costs Only need 1 request to start the flow of paymentsOnly need 1 request to start the flow of payments

DisadvantagesDisadvantages $ Millions in “up front” costs$ Millions in “up front” costs Dependent on clinical center paying Penn Dependent on clinical center paying Penn

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CMS “Dr Fine Treats All” Plan CMS “Dr Fine Treats All” Plan

Penn/NEI buys supplies of both drugsPenn/NEI buys supplies of both drugs Avastin repackaged into vials identical to LucentisAvastin repackaged into vials identical to Lucentis CATT supplies clinical centersCATT supplies clinical centers Clinical centers enroll patients in CATT and send Clinical centers enroll patients in CATT and send

billing information to CATT Coordinating Center billing information to CATT Coordinating Center Coordinating Center generates bills based on data Coordinating Center generates bills based on data

collected on treatmentscollected on treatments UPHS bills their Medicare carrier with “Stuart Fine, UPHS bills their Medicare carrier with “Stuart Fine,

MD” as the treating physicianMD” as the treating physician UPHS Medicare carrier reprograms computers so UPHS Medicare carrier reprograms computers so

that EOB does not list drug namethat EOB does not list drug name

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Genentech Offers DrugGenentech Offers Drug

May 2007 ARVO meetingMay 2007 ARVO meeting Genentech leaders contact CATT leadersGenentech leaders contact CATT leaders Some believe helping CATT is bestSome believe helping CATT is best Will supply both drugs, masked vials Will supply both drugs, masked vials Planning date of drug fill, distribution of suppliesPlanning date of drug fill, distribution of supplies

June 2007 – DSMC approves trial plansJune 2007 – DSMC approves trial plans Training meeting set for end of SeptemberTraining meeting set for end of September July 2007 – Genentech board decides to not supply July 2007 – Genentech board decides to not supply

drugdrug

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Moving ForwardMoving Forward

July 2007 – Revised Medicare Clinical Trials Policy July 2007 – Revised Medicare Clinical Trials Policy explicitly allows payment for drugs under study if explicitly allows payment for drugs under study if otherwise availableotherwise available

CMS/NIH leaders re-interpret Medicare laws to CMS/NIH leaders re-interpret Medicare laws to allow another government entity to pay the co-payallow another government entity to pay the co-pay

NEI agrees to pay the Lucentis co-pay (15% of NEI agrees to pay the Lucentis co-pay (15% of patients without supplemental insurance)patients without supplemental insurance)

NEI says do the best you can, start trialNEI says do the best you can, start trial Early September, DSMC approves revised planEarly September, DSMC approves revised plan Late September – Investigator’s MeetingLate September – Investigator’s Meeting

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CATT Resource CentersCATT Resource Centers

Daniel F. Martin MD Daniel F. Martin MD Study Chair (Emory) Study Chair (Emory) Stuart L. Fine MDStuart L. Fine MD Study Vice-Chair (Penn) Study Vice-Chair (Penn) Maureen Maguire PhDMaureen Maguire PhD Coordinating Center Coordinating Center

(Penn)(Penn) Glenn J. Jaffe MDGlenn J. Jaffe MD OCT Reading Center (Duke) OCT Reading Center (Duke) Juan Grunwald MDJuan Grunwald MD Fundus Photograph Fundus Photograph

Reading Center (Penn)Reading Center (Penn)

Supported by Grants from the National Eye InstituteSupported by Grants from the National Eye Institute

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Primary Study QuestionsPrimary Study Questions

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Is Avastin as safe and effective as Lucentis?

Does “as needed” dosing of either drug compromise long term visual outcome relative to fixed dosing?

Is Avastin as safe and effective as Lucentis?

Does “as needed” dosing of either drug compromise long term visual outcome relative to fixed dosing?

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ObjectiveObjective

To evaluate the relative efficacy and safety of To evaluate the relative efficacy and safety of treatment of subfoveal, neovascular AMD withtreatment of subfoveal, neovascular AMD with

1) 1) LucentisLucentis®® on a on a fixedfixed schedule (every 4 weeks) schedule (every 4 weeks)

2) 2) AvastinAvastin®® on a on a fixedfixed schedule (every 4 weeks) schedule (every 4 weeks)

3) 3) LucentisLucentis®® on a on a variable*variable* dosing schedule dosing schedule

4) 4) AvastinAvastin®® on a on a variable*variable* dosing schedule dosing schedule

* Depending on lesion activity* Depending on lesion activity

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Major Eligibility CriteriaMajor Eligibility Criteria

Choroidal neovascularization (CNV) or sequelae Choroidal neovascularization (CNV) or sequelae subfovealsubfoveal

Fibrosis < 50% of lesionFibrosis < 50% of lesion Visual acuity (VA) 20/25-20/320Visual acuity (VA) 20/25-20/320 Age > 50 yrsAge > 50 yrs >1 drusen (>63μ) in either eye or late AMD in fellow eye>1 drusen (>63μ) in either eye or late AMD in fellow eye No previous treatment for CNV in study eyeNo previous treatment for CNV in study eye No other progressive retinal disease likely to affect VANo other progressive retinal disease likely to affect VA No contraindications to injections with LucentisNo contraindications to injections with Lucentis®® or or

AvastinAvastin®®

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Goal: Be as inclusive and simple as Goal: Be as inclusive and simple as possible possible

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RandomizationRandomization

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Informed Consent

VariableAvastin®

VariableLucentis®

FixedAvastin®

FixedLucentis®

Randomization

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Randomized Treatment AssignmentRandomized Treatment Assignment

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TimeTime

1 yr1 yr

Lucentis Lucentis FixedFixed

Avastin Avastin FixedFixed

Lucentis Lucentis VariableVariable

Avastin Avastin VariableVariable

FixedFixed Vari-Vari-ableable

FixedFixed Vari-Vari-ableable

LucentisLucentis VariableVariable

AvastinAvastin VariableVariable

Eligible Eligible PatientsPatients

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CATT Study DrugsCATT Study Drugs

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Ranibizumab (Lucentis ®) 0.5 mg (0.05 mL) Supplied same as outside the study Billed to primary and supplemental

insurance, residual paid by study (NEI)

Bevacizumab (Avastin®)

1.25 mg (0.05 mL) Supplied by the study No charge

Ranibizumab (Lucentis ®) 0.5 mg (0.05 mL) Supplied same as outside the study Billed to primary and supplemental

insurance, residual paid by study (NEI)

Bevacizumab (Avastin®)

1.25 mg (0.05 mL) Supplied by the study No charge

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Treatment GuidelinesTreatment Guidelines

ALL patients treated immediately after randomization

Patients assigned to FIXED schedule treated at each visit

Patients assigned to VARIABLE schedule treated if

Fluid on OCT

OR

One or more of the following New subretinal or intraretinal hemorrhage Decreased VA (relative to last visit) w/o explanation Lesion growth on FA Leakage on FA

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MaskingMasking

Masked to drug and schedule

Visual acuity examiner

OCT and photograph graders

Masked to drug

Ophthalmologist

Patient initially, billing statements may unmask

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CATT Treatment Masking Procedure

Decides to treat Obtains drug

Syringe filled and labeled

Prepares the eye

Injects

OphthalmologistOphthalmologist

Observes

Clinic CoordinatorClinic Coordinator

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Maintaining Masking (CATT Training Mtg) Patients will not be told the identity of the drug by clinical center staff.

Patients will be told that they may learn the identity of their drug from

billing and insurance statements. They will not be told that patients receiving Avastin® will not be billed.

Patients will be asked not to discuss the name of their anti-VEGF drug with anyone but the clinic coordinator if they learn which drug they are on.

Clinic Coordinators and ophthalmologists should use terminology such as “study drug” or “anti-VEGF drug” or “VEGF drug” when they talk to patients rather than the names of the two drugs.

For many conversations about side effects, mode of action, time course for visual improvement, etc, the same explanations apply to both drugs.

The goal is to minimize opportunities for the patient to volunteer which drug they are taking, if they become aware of it.

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Maintaining Masking (CATT Training Mtg)

Patients Not told the identity of the drug Told that they may learn the identity of their drug from

billing and insurance statementsNot told that Avastin® will not be billedTold not to discuss the name of their anti-VEGF drug

CATT Clinic staff - use “study drug” or “anti-VEGF drug” or “VEGF drug” when talking to patients

Most side effects, time course for visual improvement, etc, the same

The goal is to minimize opportunities for the patient to volunteer which drug they are taking, if they become aware of it.

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Would Our Central Masking Have Worked?

Over-labeling Change to double vented

stopper

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Remove Plastic Caps

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Foil Wrap to Cover the Tattoo

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Vial Shape Different!

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Outcome MeasuresOutcome Measures

Primary Mean change in VA at 1 year

Secondary Number of treatments 3-line change in VA (15 letters on ETDRS chart) Change in fluid on optical coherence tomography Change in lesion size on fluorescein angiography Incidence of endophthalmitis, retinal detachment,

cataract, uveitis Incidence of other adverse events Cost

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Follow-upFollow-up

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Every 4 weeks for 2 years

Data collection

History Each visit

Refraction Every 3 months

Visual Acuity Each visit

Eye examination Each visit

OCT Fixed: Months 1,2,3,6,12,18,24

Variable: Each visit

Photography Months 12 and 24

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Sample SizeSample Size

Non-inferiority limit = 5 letters (>5 is inferior)

Confidence limits will be used

All pairwise comparisons accommodated

Loss to follow-up (death, missed visits) = 8%

300 (292) patients per treatment group

1200 (1168) patients total study

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Is 5 Letters Close Enough?Is 5 Letters Close Enough?

CATT Non-inferiority limit is 1.0 line (5 letters)

%%

Time Mean (VA Letters) 15-letter LossMean (VA Letters) 15-letter Loss

Trial/Treatment (Yrs) Rx Control Difference DifferenceTrial/Treatment (Yrs) Rx Control Difference Difference

MPS / Laser 2 MPS / Laser 2 -15 -15 -22 7 -22 7 20%20%

TAP/PDT 1 TAP/PDT 1 -11 -17.5 6.5 -11 -17.5 6.5 15%15%

TAP/PDTTAP/PDT 2 2 -13.5 -19.5 6 -13.5 -19.5 6 15%15%

VIP/PDTVIP/PDT 2 2 -19 -25.5 6.5 12% -19 -25.5 6.5 12%

Eye001/Macugen 1 Eye001/Macugen 1 - 8 - 15 7 15% - 8 - 15 7 15%

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Interpretation of CATTInterpretation of CATTNot A Strict Non-Inferiority TrialNot A Strict Non-Inferiority Trial

http://bmc.ub.uni-potsdam.de/1468-6708-5-8/1468-6708-5-8-1.jpg

Avastin - LucentisAvastin

Fixed

Lucentis Fixed

5 5Difference

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Status April 2009 Status April 2009

43 Clinical centers, 50+ sites43 Clinical centers, 50+ sites 200 ophthalmologists certified200 ophthalmologists certified 700 patients enrolled700 patients enrolled Recruitment targeted for completion Nov 2009Recruitment targeted for completion Nov 2009 1-year results due early 20111-year results due early 2011

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Medicare Act of 2008

SEC. 184. COST-SHARING FOR CLINICAL TRIALS. “The Secretary may develop alternative methods of payment for

items and services provided under clinical trials and comparative effectiveness studies sponsored or supported by an agency of DHHS … to the extent such alternative methods are necessary to preserve the scientific validity of such trials or studies, such as in the case where masking the identity of interventions from patients and investigators is necessary to comply with the particular trial or study design. ”

Due in large part to the work of Sen. Herb Kohl (D-Wisc)

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Medicare and Clinical Trials 2009

Could 100% of Lucentis be paid for?

Could the Avastin be paid for?

Could CATT be paid “up front” to allow central distribution?

No response from CMS

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Summary

CATT – before revised Clinical Trial Policy and Kohl amendment

Comparative effectiveness trials still face challenges in implementation

Financing and study design are intertwined Methods for communicating between CMS and

researchers need to be developed

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