Sundeep Khosla, MD Gordon Bernard, MD Nickie Bruce, BS (Mayo) Terri Edwards,RN (Vanderbilt) Libby Salberg, JD (Vanderbilt)
Topics of Discussion Project history Development of contract model Consortium structure models Rolling up our sleeves Negotiation of contract terms focusing on best compromise position for all parties Outreach CTSA/other groups Differences with prior efforts What s Next!
PROJECT INITIATION Purpose: develop efficient contract model(s) to accelerate contracting processes across the country Initial Focus: industry-sponsored multicenter clinical trials = ACTA and ACDA Subgroup of 25 institutions/legal staff Vision: Obtain agreement on all terms Draft best compromise position Identify required legal terms for clinical trial agreements Not site-specific or company-specific terms Non-negotiable model (legal terms) Only budget negotiation required
ACTA Contract Working Group Master Contract Working Group CTSA Institutions Cincinnati Children s Hospital Medical Center Tufts Medical Center Duke University Harvard Catalyst Johns Hopkins University Mayo Clinic Medical College of Wisconsin The Ohio State University Medical Center New York University Medical Center Northwestern University Oregon Health & Science University Stanford University Children s National Medical Center University of Alabama at Birmingham University of Arkansas for Medical Sciences University of California, San Francisco University of Iowa University of Massachusetts Medical School, Worcester University of Michigan University of North Carolina at Chapel Hill University of Rochester Vanderbilt University Medical Center Washington University, St. Louis University of Miami University of California, Office of the President
Consortium Models Option 1: Lead Site Liaison: Registers study in ContractShare Queries other sites interest Each site executes ACDA/ACTA templates Each site negotiates own budget Option 2 more standard consortium model: Site Coordinating Center (CC) CC negotiates budget on behalf of all sites Executes ACDA and ACTA with sponsor Subcontracts with participating sites
Expediting Contracting Harmonizing language across sites, starting with the most feasible components Easiest contract terms to negotiate (with CTSA sites and Industry Sponsors) hardest
Indemnification/Limitation of Liability Confidentiality Publication Intellectual Property Subject Injury Others.
Common position Institutions: Policies (or statutes) limiting amount of financial exposure Consider straight negligence too broad Preference: gross negligence level OR cap Common position Industry: Institutions should agree to all negligence on their part; should be managing study activities in a responsible manner
Institution agrees to indemnify for 3rd party claims directly caused by Institution s negligence in its conduct of the study No cap required Subject to limits under applicable law Neither party is liable for special, consequential damages Carving out both parties indemnification obligations
Common position Institutions: Usually require mutual confidentiality provision Policies limiting period of nondisclosure (3 years) Common position Industry: Broader definition protecting company s confidential information Extending period of nondisclosure
Language one-sided - protecting only confidential information from sponsor Requiring marking; however. Broadly protects information that by its nature a reasonable person would consider confidential Oral discussions require follow-up in writing Protection (both parties) regarding what was discussed/disclosed Period of non-disclosure identified as 5 years
Common position Institutions: Institutions require independent right to publish (tax-exempt status, AAHRPP compliance, internal policies) Policies usually require delay of no more than 12 months after study completion/termination Common position Industry: Publication of aggregate data may take longer than 12 months
Institutions retain right to independent publication; however: Institution will not publish site data until: Multicenter publication is published; or 18 months after conclusion, abandonment or termination of study at all sites; or Sponsor confirms in writing that no multicenter publication will occur Prior 30 day review by sponsor, with additional delays for sponsor to file patent applications
Common position Institutions: Position that IP is result of principal investigator s knowledge/expertise retain ownership Royalty-bearing license; royalties used to help support additional research efforts Common position Industry: Company-sponsored study; owns product Usually require assignment of any IP resulting from conduct of study
Protects both parties background IP Language assigns ownership to sponsor of any inventions that uses/incorporates sponsor s product Any other inventions determined by U.S. patent law If an other invention should occur, sponsor granted option to an exclusive, royalty-bearing license to Institution s rights in that invention
Common position Institutions: Policies require sponsor to pay for medically necessary services related to study injuries Cannot first seek reimbursement from Medicare/ commercial payers (policies will not allow discrimination based on insurance status) Common position Industry: Requirement to include broader carve-outs limiting obligations
Broader carve-outs than institutions usually agree to: Sponsor agrees to pay for reasonable expenses, but only to the extent expenses not attributable to: Institution s negligence/willful misconduct or The natural progression of an underlying or preexisting condition or events
Site visits eliminated need for specific timeframe requirements Termination removed requirement for site to terminate with/without cause Limited to patient safety reasons, material breach, if principal investigator unavailable Biospecimens subject to patient s informed consent form Governing law intentionally omitted
Organizations: TransCelerate-very supportive; discussing internally; awaiting final University/Industry Demonstration Project (UIDP) (willing to help nationalize the ACTA and post the agreement on UIDP website, documenting buy-in from institutions and industry) AAHRPP-very supportive; language within compliance of domains Industry: Pfizer (received comments/incorporated revisions) Epizyme (received comments/incorporated revisions) Shire (received comments/incorporated revisions) Eli Lilly (received comments/incorporated revisions) Johnson & Johnson (supportive; didn t provide any revisions to the agreement)
WHY USE THIS MODEL? Use of standard templates eliminates contract negotiation delays (legal terms): CTA = Previously 71.2 days (mean) CDA = Previously 15 days (mean) Study initiation/patient enrollment considerably earlier than non-model processes permit 61 member sites can sign ACTA without further legal negotiation/time-delays required
DIFFERENCES WITH PRIOR EFFORTS Drafted contract vs. term library Final agreement based on terms both parties usually end up agreeing to Buy-in by academic medical centers Discussions with/support by industry partners Flexibility in model application Standard consortium model (coordinating center) One-on-one capability Significant and organized promotion
61 Institutions who have accepted the ACTA (57 are CTSA or affiliated) Albert Einstein College of Medicine Stanford University University of Michigan Boston University Tufts Medical Center University of Minnesota Children s National Medical Center University of Illinois, Chicago University of New Mexico Health Sciences Center Cincinnati Children s Hospital Medical University of Alabama at Birmingham University of North Carolina at Chapel Hill Center Dartmouth College University of Arkansas for Medical Sciences University of Pennsylvania Duke University University of California, Davis University of Pittsburgh/University of Pittsburgh Medical Center (UPMC) Georgia Regents University University of California, Irvine University of Rochester The Ohio State University University of California, Los Angeles University of Southern California Indiana University School of Medicine University of California, Riverside University of Texas-Austin Johns Hopkins University University of California, San Diego University of Texas-Houston Mayo Clinic University of California, San Francisco University of Texas-Medical Branch Medical College of Wisconsin University of Chicago University of Texas, San Antonio Mount Sinai School of Medicine University of Florida Georgetown University New York University School of Medicine University of Iowa University of Texas-Southwestern Dallas Northwestern University University of Kansas Medical Center University of Utah Oregon Health & Science University University of Kentucky Research University of Wisconsin Madison Foundations Penn State Milton S. Hershey Medical Center University of Louisville Vanderbilt University Medical Center Rockefeller University University of Massachusetts Medical School, Washington University, St. Louis Worcester Scripps Health University of Miami Yale University Case Western University University Hospitals Case Medical Center University of Kansas Rush University Medical Center 22
NOW IN PLACE Accelerated Clinical Trial Agreement (ACTA) Company-sponsored, multicenter clinical trials Option 1 model (site/sponsor) Web Portal https://www.ara4us.org/ List of institutions/companies agreeing to terms House latest version of ACTA The terms reflect a best compromise position
What is next? Continue outreach to Industry and other sites (CTSA and non-ctsa groups): Pfizer, Eli Lilly, Celgene, Merck, Genentech (and others ) Model Agreements & Guidelines International (MAGI), WIRB/Copernicus group Patient-Centered Outcomes Research Inst. (PCORI) Assoc. for Clinical & Translational Science (ACTS) Website registration/list of participating entities Initiate pilots with Industry Infraredx, Inc. Novadaq Technologies Currently in other discussions. Revise ACTA as needed for sustainability
Coming soon! Future agreements planned: CDA (incorporating ACTA terms) ACTA for CRO arrangements PI-Initiated version of the ACTA Prime template with subcontracts (Option 2 model) Others
Questions?