THE EVOLVING BUSINESS MODEL FOR

CHRIS BEARDMORE

CHIEF EXECUTIVE OFFICER

6100 CENTER DRIVE, SUITE 600 LOS ANGELES, CA 90045

(424) 208-8866 [email protected] WWW.TRMLLC.COM

T

HE

E

VOLVING

B

USINESS

M

ODEL

FOR

Personalized Medicine

Translational Research

MOVING BASIC RESEARCH FINDINGS INTO CLINICAL PRACTICE

Promotion of concept implies that

research is conducted within a

learning system.

•

Integrated Into Clinical Care

•

Multi-disciplinary

•

Data Cloud Based

(shared clinical

data for public good)

National Cancer Institute

ANNUAL PLAN AND BUDGET FOR THE NATIONAL CANCER PROGRAM



2013 – 75

Anniversary of the NCI



NCI Budget for FY 2013 was $4.8 Billion



Additional Cancer Research Funded by NIH, the CDCP and the DoD

IOM Report 15APR2010 – Restructuring of Cooperative Group System

Biopharmaceutical Companies

THE MARKET



Top 20 Capitalized at Over 1.3 Trillion



2013 Global R&D Spending $135.9 Billion (projected)



Oncology Leading Market Segment Accounting for 23.9 Billion

R&D Costs and Delays Threaten Shareholder Returns

Study Conduct Process

Study Conduct Process

The Federal Approach

A ROBUST STANDING CANCER CLINICAL TRIALS NETWORK IS ESSENTIAL



Reconfigure/Consolidate Cooperative Groups (speed and efficiency)

 Alliance for Clinical Trials in Oncology (CALGB, NCCTG, ACOSOG)  Children’s Oncology Group (was POG and CCG)

 ECOG-ACRIN Cancer Research Group (ACRIN and ECOG)  NRG Oncology Group (NSABP, RTOG, GOG)



Incorporate Innovative Science

 Biorepositories / Novel Designs / Standards for New Technologies



Improve Prioritization/Selection/Support/Completion of Clinical Trials

 More Process Driven Phase IIs  Fewer Large Phase IIIs



Incentivize Participation

TransCelerate Biopharma, Inc.

THE MARKET



Risk Based Monitoring

 Common Tools and Triggers to Identify Risk

 Categorization Criteria for Low, Medium and High Risk Trials



Site Qualification and Training

 Common Criteria and Recognition of GCP-Training

 Common Forms to Collect Generic Information About Study Sites



Clinical Data Standards

 Acceleration of Standards Development – CDISC Partnership



Comparator Drugs

 New Model – Permits Direct Shipment Between Companies  Master Service Agreements

Association of Community Cancer Centers

ANNUAL SURVEY REVEALS MISALIGNED INCENTIVES

“…community oncologists are being marginalized…despite

the expectation that these same community providers will

enthusiastically support, contribute to, and ultimately

implement these programs.”

Michael A. Kolodziej, M.D. Medical Director – US Oncology J National Comprehensive Cancer Network 2011; 9:345-347

84% Unaware of Clinical Trials

Only 2-4% Participate in Clinical Trials

• Spending/Marketing Does Not Help

Participation Improves Outcomes (Phase I)

• 17.8% Objective Response Rate

• 34.1% Stable Disease or < Partial Response •Toxic Death Rate .54%

Focus on Value Add Activities

ADDRESS CHALLENGES BY BEING A PART OF THE SOLUTION



Local Efforts

 Establish Proper Payer Mix - Federal vs. Industry

 Match Studies to Patient Population/Treatment Standards  Bill for Routine Patient Care Costs

 Prepare Flexible and Reusable Administrative Infrastructure  Commit to More Flexible Use of Central IRBs

 Prepare Flexible and Reusable Clinical Infrastructure  Fight Regulatory Fundamentalism



Collaborative Efforts

 Clinical Trial Agreement Language  Preparing for Just-In-Time Accrual

Determining Payer Mix

PROGRAM FINANCIAL HEALTH HELPS PATIENTS

Cooperative Group Trials



$2,000 per-case

Industry Sponsored Trials



$16,499 per-case

(oncology)



Phase I - $19,282

Phase II - $12,962

Phase III - $11,649

Selecting Studies

MATCHING STUDIES IN THE ERA OF PERSONALIZED MEDICINE



Build Base of Studies Open to Larger Number of Patients

 Enroll 15 or More Patients Per Year

 Gravitate Toward Multiple Populations in Inclusion/Exclusion  HER2, HRG, TGF-β2 in Multiple Disease Types

 Focus on Earlier Phase Studies (Phase I, IB or II)



Add Studies Focused on Certain Lines of Therapy

 Enroll 5 or More Patients Per Year

 Understand Patient Population/Treatment Standards



Accept Studies of Novel/Exciting Compounds

 Enroll 2 or 3 Patients Per Year



Participate in Cooperative Group and Site Management

Routine Patient Care Costs

REDUCES COSTS FOR SPONSORS AND INCREASES RETURNS FOR SITES

Source: http://www.cancer.gov/clinicaltrials/ctlaws-home1



Current State Laws Require Insurance Companies to Pay for Routine

Patient Care Costs for Patients Participating in Cancer Clinical Trials

(highlighted in blue)



Patient Protection and Affordable Care Act (HR3590, Section 2709)

Requires All Insurance Companies to Pay for Routine Patient Care Costs

in Approved Clinical Trials.

Affordable Care Act Coverage

FOR HEALTH PLANS NEWLY ISSUED OR RENEWED AFTER JANUARY 1, 2014



Approved Clinical Trial

“…means a phase I, phase II, phase III or phase IV clinical trial that is conducted in relation to the prevention, detection, or treatment of cancer or other

life-threatening disease or condition and is described in any of the following subparagraphs:”

 Federally Funded Trials (NIH, CDC, AHCRQ, CMMS, Cooperative Group,

DOD/DVA)

 Conducted Under Investigational New Drug Application Reviewed by the FDA.



Inclusions -

 All Items and Services Typically Provided for Individuals Not in a Clinical Trial.



Exclusions

 Investigational Item , Device or Service Itself.

 Items and Services Provided Solely for Data Collection and Analysis Needs  Services Clearly Inconsistent with Accepted/Established Standards of Care.

Administrative Infrastructure

ACCOUNT FOR STUDY COMPLEXITY

Phase II, III and IV Clinical Trials

Community Physicians  Program Design

 Ancillary Service Agreements

 Study Identification

 Site Qualification

 Contract/Budget Negotiation

 Site Initiation

 Regulatory

 Research Billing/Collection

Phase I/II and Utilization of Ancillary Support Services Clinical Trials and Support Services Research Department

Example Administrative Pitfall

EVOLUTION IN INSTITUTIONAL REVIEW BOARD SYSTEM



Local Institutional Review Board

 Strength – Local Context and Oversight  Weakness – Speed and Efficiency



National Cancer Institute – Central Institutional Review Board

 Strength – Reduces Administrative Burden

 Weakness – Loss of Local Context and Oversight



Deferring to an Independent IRB

 Strength – Reduces Administrative Burden

 Weakness – Loss of Local Context and Oversight  Improvement – Defer to Accredited Central IRBs

Clinical Infrastructure

ACCESS TO PATIENTS AND FLEXIBILITY FOR PAYERS

Industry Sponsor Pharmacy Laboratory Interventional Cardiology Ophthalmology 1 1 1 1 1 2 3 4 Hub Facilities

Conflicting Expectations/Demands

ITS NOT THE REGULATIONS ITS HOW WE PREPARE FOR COMPLIANCE

Regulatory Fundamentalists

Individuals who demand strict adherence to regulatory requirements.

Characterized by unwavering attachment to a set of irreducible beliefs.

Faultless in their actions because they fully complied with and enforced all

regulations.

Regulatory Rationalists

Individuals who exercise judgment in aiming to fulfill the intent of regulations

while attempting to facilitate progress. Actions characterized by an

understanding of law/regulation, guidance and policies/procedures.

Stewart, D., 2010, Equipoise Lost: Ethics, Costs and the Regulation of Cancer Clinical Trials, Journal of Clinical Oncology, v. 28, pp. 2925-2935.

Example #1

1572 FORM - FDA STATEMENT OF INVESTIGATOR

Form has two purposes:

1. To provide the sponsor with information about the investigator’s

qualifications and the clinical site that will enable the sponsor to

establish and document that the investigator is qualified and the

site is an appropriate location at which to conduct the clinical

investigation, and

2. To inform the investigator of his/her obligations and obtain the

investigator’s commitment to follow pertinent FDA regulations.

Example #1

1572 FORM - FDA STATEMENT OF INVESTIGATOR

Information Sheet Guidance for Sponsors, Clinical Investigators and IRBs –

May 2010

Example #1

1572 FORM - FDA STATEMENT OF INVESTIGATOR

The Problem

– Guidance document expands the definition of clinical

laboratories engaged in research to include Ancillary Service Providers

(regardless of whether they are engaged in the conduct of research or not).

 Laboratories

 Cardiology

 Radiology

 Interventional Radiology/Surgery Centers,

 Ophthalmology

Note

- Facilities could be used a single time for a single patient.

Example #1

1572 FORM - FDA STATEMENT OF INVESTIGATOR

Regulatory Conflict

- FDA Information Sheets previously stated that

institutions whose employees or agents perform commercial or other

services for investigators are not engaged in the conduct of a clinical trial if

all of the following conditions are met:

 The services performed do not merit professional recognition or publication privileges;

 The services performed are typically performed by those institutions for non-research purposes; and

 The institution’s employees or agents do not administer any study intervention being tested or evaluated under the protocol.

Example #1

1572 FORM - FDA STATEMENT OF INVESTIGATOR

Solution

- Limit inclusion of Ancillary Service Providers in Box # 4 of FDA

1572 Form to clinical laboratories testing biological specimens collected

during the conduct of a clinical trial.

Justification for Action:

 Addition of other Ancillary Service Providers will not make research participation safer for patients or improve data quality.

Need for Site Collaboration

CHANGE THROUGH AGREEMENT



Society of Clinical Research Sites – Founded in 2012

 Advocate  Connect  Educate  Mentor

 White Paper – Better Payment Terms for Sites



Change Through Networking

 Certified Sites

 Master Clinical Trial Agreements

 Consistent Budget and Payment Terms

 Improving Compliance Through Common Order Sets  Change Through Networking

Just-In-Time

IMPROVE ACCRUAL AND REDUCE COST/WORK



Patient Centric Approach to Clinical Research

 No Pre-Study/Site Qualification Visits  Master Clinical Trial Agreement/Budget

 Central Site (Site Survey, Data Use Agreements, Investigator

Background Form, etc.) and Investigator Essential Documents (CV, Medical License, Training Certificates, etc.)

 Central Infrastructure and CRO/Sponsor Negotiate Essential

Document Requirements (e.g., core labs on FDA 1572 form)

 Routing of Essential Documents When Patient Identified

 Use of Common Systems (EDC, Core Imaging, Core Laboratory)  Workload Reduction on Sites

 Sponsor Directed to Active/Interested Sites with Patient Population.

Thank You!

CHRIS BEARDMORE

CHIEF EXECUTIVE OFFICER

6100 CENTER DRIVE, SUITE 600 LOS ANGELES, CA 90045

(424) 208-8866 [email protected] WWW.TRMLLC.COM