Contracts and Clinical Research
Under Research Operations, the Contracts and Clinical Research (“CCR”) team is responsible for the review and negotiation, of all contracts and subcontracts for sponsored projects at Children’s Hospital Los Angeles.
This internal review process is necessary to ensure that all sponsored project documentation concurs with the mission of the CHLA and adheres to all applicable federal, state, sponsor and institutional policies and guidelines. The review process allows CCR to assure potential sponsors that time and cost commitments are appropriate and all compliance issues (e.g., human subjects, export controls, conflicts of interest) are adequately addressed.
CCR reviews and negotiates all sponsored projects contracts, including confidential disclosure agreements (sometimes called non-disclosure agreements), material transfer agreements, lab study agreements, clinical trial agreements, master research agreements, consortium agreements, service agreements, consulting agreements, collaboration agreements, amendments, subcontracts, and grant agreements.
Clinical Trial Process
- Confidential Disclosure Agreement
- Protocol, Investigator Brochure, Draft Informed Consent Form, Lab Manual, Intake Form, SC Checklist, Draft CTA, and Draft Budget
- MCA & Budget Negotiation
- Clinical Trial Agreement (CTA) Negotiation
- Execution and Account Setup
In order to evaluate the feasibility of a principal investigator’s (PI's) participation in a research project, sponsors may want to provide CHLA protocols, scopes of work, or other confidential information so the PI may evaluate the appropriateness of their involvement in the project. In these instances, the sponsor may require a confidentiality disclosure, or non-disclosure, agreement (CDA or NDA) in order to protect their confidential information.
CCR is responsible for the review, negotiation, acceptance, and execution of CDAs and NDAs when the confidential information belongs to a third party. The Office of Technology Commercialization (OTC) is responsible for the review, negotiation, acceptance, and execution of CDAs when the confidential information belongs to CHLA.
The CCR Research Contract Analyst will work directly with the sponsor to negotiate the terms of the CDA. Once the agreement is fully-executed, a CCR team member will forward the completed agreement to the PI and their designated departmental staff.
Once a CDA is in place, a sponsor will typically disclose the study protocol, investigator brochure, draft Informed Consent Form (ICF), Lab Manual (if applicable), draft Clinical Trial Agreement (CTA) and draft budget to the PI for review.
After reviewing the study protocol, if the PI is interested in participating in the study, the PI or the study coordinator would forward the following to firstname.lastname@example.org:
- Study Protocol
- Investigator Brochure
- Draft ICF
- Lab Manual (if applicable)
- Draft CTA
- Draft Budget
- Completed Intake Form
- Completed Study Coordinator Checklist (SC Checklist)
The Intake Form and SC Checklist allow the CCR team to gather information about the study to expedite the budget and contract negotiation process.
Before budget negotiations can begin, a Medicare Coverage Analysis (MCA) must be prepared to determine whether procedures in the protocol are considered standard of care (SOC or “routine”) or if they are research activities. This exercise allows CCR to ensure all research-related costs are included in the budget and is crucial to ensure appropriate billing of clinical trial procedures.
Once the MCA is complete, the CCR Clinical Research Financial Analyst will incorporate the information from the SC Checklist into the CHLA budget, and will ask the PI or study coordinator to complete any remaining the time and effort related parts in the budget and confirm the budget is acceptable.
Upon confirmation from the PI, the CCR Clinical Research Financial Analyst will begin budget negotiations with the sponsor on behalf of CHLA. Budget negotiations typically take 45 days to complete, but this timeline may vary depending on the complexity of the study protocol.
In parallel with budget negotiations, a CCR Research Contract Analyst will negotiate the contact terms in a Clinical Trial Agreement (CTA) with the sponsor.
CTAs govern the terms of research between CHLA and an industry sponsor, and are executed for trials following a sponsor- or investigator-initiated protocol.
Clinical trials, generally funded by pharmaceutical and medical device companies, are an important part of the Food and Drug Administration (FDA) approval process to ensure the safety and efficacy of the drug or device being brought to market.
Other sponsored research is generally funded by pharmaceutical and medical device companies, and are typically initiated after a PI has submitted a proposal to the sponsor.
The CCR team is responsible for the review negotiation, and execution of CTAs and sponsored research agreements.
Departments should forward all agreement drafts - and company contact information - to email@example.com for review and negotiation. CCR will work directly with the research sponsor to finalize these agreements.
Typical components of a CTA are as follows:
All CTAs are agreements between CHLA and the sponsor. The PI may be named as a faculty member of CHLA, but will not be a named party to the Agreement.
CHLA is accredited by the Association for the Accreditation of Human Research Protection Programs (AAHRPP). As such, all CTAs executed by CHLA must include standards which address AAHRPP’s overarching principles for protecting human research participants.
As an academic medical institution, CHLA strives to create a vibrant academic environment. As such, CHLA cannot accept language which seeks to make raw source data or documentation, including the results of the study, confidential.
Timely publication and dissemination of the results of research performed by faculty are important principles behind CHLA’s mission as an academic medical institution. Research sponsors are afforded a period of time to review and comment upon on the content of such publications, to protect intellectual property, and to ensure their confidential information is not improperly published, but CHLA does not accept terms that restrict faculty from freely publishing the results of their research.
Indemnification is addressed in all clinical trial agreements, and the terms may differ depending on the entity developing the protocol or providing the funding.
Sponsor-Initiated Protocols: CHLA faculty members conducting a sponsor-designed clinical trial protocol are following the sponsor’s instructions. Therefore, CHLA cannot be held responsible for any injury or damages resulting from work performed during a clinical trial, or from a sponsor’s use of CHLA’s results of the study.
For Investigator-Initiated Protocols: When the protocol is developed by the investigator, the sponsor is generally not required to provide indemnification. However, if the industry-sponsor is providing funding source may provide limited indemnification. The industry sponsor generally expects indemnification from CHLA.
CHLA encourages the development of intellectual property to enhance research, scholarship, teaching, and discovery for the best interest of the public, the creator, and the research sponsor.
For Sponsor-Initiated Protocols: Patent rights for inventions made in the direct performance of a sponsor-developed clinical trial protocol, involving little or no PI involvement in the conception or development of the protocol, are generally granted to the sponsor. However, CHLA reviews patent terms on a case-by-case basis.
For Investigator-Initiated Protocols: When the protocol is developed and the work is performed by the investigator, CHLA and PI will maintain ownership of the study documentation and data.
For Sponsor-Initiated Protocols: Except in cases of rare cases, all research-related subject injuries resulting directly from study drug or device administration, or procedures carried out in accordance with the sponsor-designed protocol are the financial obligation of the sponsor.
For Investigator-Initiated Protocols: Generally, industry sponsors will not be responsible for any study-related subject injuries. However, injury liabilities will be examined on a case-by-case basis for investigator-initiated protocols, and will be dependent upon the specifics of the work being performed and the drugs or devices provided by the sponsor.
To support the indemnification detailed in this section, including subject injury liabilities, the sponsor must maintain a sufficient level of insurance. CHLA will maintain in force adequate insurance to cover its indemnification obligations.
CHLA is California non-profit public benefit corporation and contracts accepted by CHLA also will be interpreted under California law. CHLA will also consider contractual silence regarding this issue, but generally will not subject itself to the laws of any other jurisdiction.
Generally, clinical trial budgets are based on a fixed price-per-subject amount with a payment schedule. Such schedules usually provide for regular payments upon the completion of milestones (e.g., enrollment of a certain percentage of subjects, submission of a certain number of case report forms, etc.). These payments should include all applicable indirect costs.
When the contract and budget negotiations have concluded, a finalized agreement will be sent to CHLA from the sponsor to route for signatures.
When CHLA receives the finalized agreement, CHLA’s PI will be the first to sign the agreement and will only sign the agreement as “Read and Understood” or “Read and Acknowledged,” and will not a party to the agreement. In turn, the agreement will be signed by CHLA’s official signatory in Research Operations. In turn, the partially executed agreement will be sent by Research Operations to the sponsor for the sponsor to sign.
Once the agreement is fully executed, a PeopleSoft account number will be setup for the project and a congratulatory email will be sent to the PI. The congratulatory email will include a copy of the fully executed agreement, an award summary (study account number, title of the project, and invoicing instructions) and will notify the PI that the start-up invoice for the project will be sent to the sponsor within two (2) weeks.
- Material/Data Transfer Agreements
- Laboratory Services Agreements
- Master Agreements
- Consortiums at CHLA & Consortium Agreements
- Service Agreements
- Consulting Agreements
- Collaboration Agreements
- Grant Agreements
A Material Transfer Agreement (MTA) or Data Use Agreement (DUA) is a contract that establishes terms and conditions governing the transfer of research-related materials or data between CHLA and another institution or company. An MTA or DUA between a providing entity and a receiving entity should be fully-executed before any materials or data are sent or received.
MTAs/DUAs IN (RECEIVING MATERIALS/DATA)
An MTA or DUA must be completed when a CHLA PI has requested materials or data from another entity. Typically, the providing entity will provide its own MTA/DUA template for CHLA’s review and execution.
All MTAs or DUAs should be forwarded to the CCR team for review. For each MTA/DUA, the PI must submit a MTA-DUA Intake Form detailing the specifics of the transfer. Following negotiation of the terms and conditions of the MTA/DUA, if necessary, the Research Contract Analyst will obtain signature or email approval from the PI. Following the execution of the MTA/DUA, which includes the signature of an authorized institutional signatory, the Research Contract Analyst will notify the PI so that the PI can follow up with the providing entity regarding specific transfer arrangements.
MTAs/DUAs OUT (PROVIDING MATERIALS/DATA)
An MTA or DUA must be completed when a CHLA PI desires to send materials or data to a researcher at another entity. In these instances, a CHLA MTA/DUA template will be sent to the receiving entity for review and execution. CHLA may choose to utilize its MTA/DUA template or, for material transfers, it may choose to utilize a Uniform Biological Materials Transfer Agreement (UBMTA), if appropriate. For each MTA/DUA, the PI must submit a MTA-DUA Intake Form detailing the specifics of the transfer.
Lab Study Agreements (LSA) are typically used when a sponsor wants an investigator to analyze samples and provide them with results or other scientific information related to the samples. This work may result in new intellectual property which is defined in the agreement.
Lab Testing Agreements (LTA) are used when a sponsor requests an investigator to run routine tests on the samples and give the results back to them without analysis. There is no new intellectual property involved in this type of Agreement.
CCR is responsible for review, negotiation, and execution of LSAs and LTAs. The department is responsible for completing the Intake Form and submitting the required documents to the appropriate review boards (Institutional Review Board, Animal Welfare Committee, etc.).
Once the Agreement is fully-executed, the Research Contract Analyst will forward the completed agreement to another CCR team member for account setup.
CHLA has negotiated universal and master agreements with several private research sponsors. Master agreements streamline the contract negotiating process since contract terms have already been agreed upon by the sponsor and CHLA.
CHLA has master agreements with the following sponsors:
- Allergan Sales, LLC
- Almac Clinical Services
- Amgen Inc.
- Astellas Pharma Global Development, Inc.
- Baxalta US Inc
- Bayer HealthCare Pharmaceuticals Inc.
- Becton, Dickinson and Company (BD)
- Biogen Idec Hemophilia Inc.
- Celgene Corporation
- COG (The Children’s Oncology Group)
- Eleison Pharmaceuticals LLC
- Genzyme Corporation
- H. Lee Moffitt Cancer Center and Research Institute Hospital, Inc.
- Nellcor Puritan Bennett Incorporated
- NERI (New England Research Institutes, Inc.)
- NMDP (National Marrow Donor Program)
- Novartis Pharmaceuticals Corporation
- Novo Nordisk, Inc.
- Purdue Pharma LP
- Sanofi US Services Inc
- Siemens Medical Solutions USA, Inc.
- Shire Pharmaceutical Development Limited
- St. Jude’s Children’s Research Hospital, Inc.
- Sucampo Pharma Americas, LLC
- UCB Biosciences
- Unitio, Inc.
NANT, TACL, and PBMTC
There are currently three (3) active consortiums coordinated through CHLA. This includes the New Approaches to the Neuroblastoma Therapy (NANT) consortium, the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) consortium, and the Pediatric Blood and Marrow Transplant Consortium (PBMTC).
CCR reviews and negotiates all consortium agreements, whether the consortium is centered at CHLA or at another institution.
A Service Agreement is a contract that establishes terms and conditions governing the delivery of research related health care services. CCR is able to construct and negotiate Service Agreements with other parties when the services provided are related to a research project.
A Consulting Agreement is a contract that establishes terms and conditions governing the delivery of research related consulting services. CCR will only review and negotiate a consulting agreement if the PI confirms the consulting services will be conducted during his/her time at CHLA and a net benefit exists to CHLA to further its research activities. Consulting agreements for services performed by a CHLA faculty or staff member are handled through Academic Affairs.
A Collaboration Agreement is a contract that establishes terms and conditions governing for a distinctive arrangement, where other standard agreement types may not be suitable. CCR is able to construct and negotiate research Collaboration Agreements with other parties.
An amendment is a formal or official change made to a contract or other legal document. CCR is able to construct and negotiate amendments to existing agreements with other parties.
Subcontracts and subawards are contract mechanisms used when the intent is to have another institution or party carry out an integral portion of a project’s scope of work. The sub is a formalized agreement that spells out the fiscal arrangements, defines the scope of work to be performed by the subcontractor, and flows down the appropriate terms and conditions of the prime award to the subrecipient.
Review of Grant Agreements
CCR reviews all research related grant agreements to ensure compliance with CHLA guidelines and all applicable laws. CCR reviews grant agreements funded by the following sponsor types:
CCR provides invoicing services for all clinical research studies.
- To invoice a sponsor, please complete the following steps:
- A study coordinator shall complete the invoice template with the items that require invoicing, and submit it to firstname.lastname@example.org.
- A CCR Clinical Research Financial Analyst will review the by comparing it to the allowable costs in the contract. If the invoice is acceptable, the CCR Clinical Research Financial Analyst will submit the invoice to the sponsor.
- A CCR Clinical Research Financial Analyst will follow-up with the sponsor until the invoice is paid.