Clinical trials, which are funded by a cooperative agreement or individual grant or contract award, often utilize one or more investigational agents which are proprietary to a pharmaceutical and/or a biotech company (hereinafter, Collaborator). In this circumstance, the NCI has negotiated and executed a collaborative agreement, either a Cooperative Research and Development Agreement (CRADA) or a Clinical Trials Agreement (CTA), for the clinical co-development of the agent. The CRADA is a statutorily based mechanism created under the Federal Technology Transfer Act of 1986 for the purpose of facilitating Government-Industry collaboration and technology transfer. The CTA is an NCI-initiated mechanism for the clinical co-development of an agent.
Each CTA or CRADA defines certain obligations for the government and the Collaborator. Generally, these obligations focus on intellectual property and data rights, which may arise pursuant to these studies. Under federal funding agreement guidelines and the agreements in place between the Cooperative Groups and the NCI, certain obligations and guidelines apply to the Cooperative Groups. Compliance with any of the guidelines (in particular, publication review, data access, and intellectual property licensing) is mandatory for the Cooperative Group. Although these guidelines have been written to address NCI Cooperative Group-Industry interactions, much of the material contained in this document is also applicable to individual cancer centers and clinical investigators.
In accordance with the following obligations and guidelines, each approved protocol contains the NCI standard language for protocols, stating the existence of relevant agreement(s). A summary of these obligations and guidelines follows:
1. Proprietary Agent(s): Often, the agent provided under a protocol sponsored by the NCI is proprietary. The agent has been provided either by the NCI or by the Collaborator for the sole purpose of the studies specified by the protocol. Neither the NCI nor the Cooperative Group may use the agent outside the scope of the protocol, nor can the agent be transferred or licensed to any party not participating in the studies under the protocol.
2. Confidentiality: In the course of any clinical study which is subject to a CTA or a CRADA, the NCI is required to maintain Collaborator information relating to the agent as proprietary and confidential. The duration of the confidentiality generally shall be a minimum of three years and is extendable until the NCI and the Collaborator agree that the data no longer remains confidential. Confidential information that is made available to any Cooperative Group by the Collaborator and the NCI shall be labeled "CONFIDENTIAL." The Cooperative Group shall either be required to maintain the confidentiality of the material or, at its option, decline acceptance to any confidential materials. All protocol documents, including Investigator's Brochures, for studies utilizing investigational agents under a collaborative agreement are also confidential and must not be shared or distributed without the permission of the NCI.
As part of the NCI review and audit of records, the FDA, the NCI, and the Collaborator will have access to medical records that identify patients. Such records are confidential, and no information which identifies a patient will be released without authorization.
3. Indemnification / Liability: The government is prohibited by statute from indemnifying any party without specific legislative authority and consultation with the United States Department of Justice. Government liability for its own actions is usually limited by the Federal Tort Claims Act.
4. Intellectual Property and Extramural Inventions: Under the Bayh-Dole Act (see 35 U.S.C. 201 et seq.) and 37 Code of Federal Regulations Part 401, Cooperative Groups or member institutions have the right to elect title to any invention they discover in the performance of a study under NCI sponsorship, provided that neither the NCI nor the Collaborator shares ownership of the invention by virtue of co-inventorship. The Cooperative Group's institutions agree to grant Collaborators a paid-up nonexclusive, nontransferable, royalty-free, world-wide license to all inventions for research purposes only; and a time-limited first option to negotiate an exclusive, world-wide royalty-bearing license for all commercial purposes, including the right to grant sub-licenses, to all inventions on terms to be negotiated in good faith by Collaborator and the Cooperative Group. The Collaborator has to notify the Cooperative Group, in writing, of its interest in obtaining an exclusive license to any Cooperative Group's invention within six (6) months of Collaborator's receipt of notice of such invention(s).
Clinical investigators are required to report any inventions relating to studies under an NCI-funded protocol to: National Institutes of Health, Division of Extramural Inventions and Technology Resources, 6705 Rockledge, Drive Room 1136 MSC 7980, Bethesda, MD 20892-7980 Attn: Dr. George Stone, Special Assistant to the Deputy Director. The report should be in sufficient detail so as to enable the government to evaluate any potential contributions in the technological advances by NCI scientists. To allow more effective evaluation, the NCI requests that the clinical investigator send an additional copy of the invention report to: Regulatory Affairs Branch, Cancer Therapy Evaluation Program, DCTD, NCI, Executive Plaza North, Suite 7111, Bethesda, MD 20892.
5. Exclusive Access to Proprietary Data: Under a collaborative clinical development agreement, the NCI agrees to make all data in the NCI's possession and control available exclusively to the Collaborator for the commercialization of the agent. In the case of Cooperative Groups, clinical data and results and raw data will be provided exclusively to the NCI, the Collaborator, and the FDA, as appropriate. This provision does not affect the investigator's right to publish or present as described in the standard protocol language. This statement ensures that data generated using an investigational agent proprietary to a Collaborator will be kept confidential and shared only with the NCI, the FDA, and the Collaborator. Furthermore, this addresses the needs of the Collaborator to have access to the patient records and raw data; it has no effect on the investigator's right to publish. The Collaborator has the opportunity to contact the Cooperative Group or Cooperative Group's institution (subject to the terms of Articles 6 and 7, below) in order to negotiate and secure rights to the data and intellectual property generated by that Cooperative Group or member institution(s) of the Cooperative Group. The Cooperative Group and/or the member institution(s) are then free to negotiate terms.
When a clinical protocol involves either an agent, which is proprietary to another company, or involves another NCI collaborative effort, the NCI, the Collaborator, and all other Collaborators will jointly determine a reasonable and appropriate mechanism for data access and sharing prior to initiation of the clinical trial.
6. Procedures Under Which the Collaborator May Contact Cooperative Groups, Member Institutions or Individual Clinical Investigator(s): As the study sponsor, the NCI provides the initial notice to Cooperative Groups regarding all protocol issues, as well as issues related to rights to data and intellectual property created under a CRADA or a CTA. Without prior authorization from the Regulatory Affairs Branch (RAB) of CTEP, the Collaborator is not permitted to contact Cooperative Groups or member institution(s) directly to obtain protocol information, to arrange on-site data audits, or to discuss any other protocol or amendment matters. The NCI will contact the Cooperative Group to discuss the nature of the request prior to authorizing the Collaborator to contact the Cooperative Group. If a Cooperative Group is contacted directly by the Collaborator and that Cooperative Group has not had prior notice of the nature of the contact from the NCI, the Cooperative Group should refer the Collaborator to RAB, NCI, at (301) 496-7912. After subsequent discussions with the Collaborator, RAB will then provide notice to the Cooperative Group of the nature of the Collaborator's request and provide authorization, if appropriate, to the Collaborator to contact the Cooperative Group.
Contact of Cooperative Groups by the NCI: In accordance with the provisions delineated above, the NCI requests that the Cooperative Groups make the data generated in the trial fully available for review by the Collaborator, the FDA, and the NCI as specified in the protocol informed consent form. The NCI will notify the Cooperative Group Chair that the Collaborator may contact him/her to secure rights to data and inventions which may arise pursuant to the trials. Subject to the restrictions noted above, the Collaborator will then have the opportunity to contact the Cooperative Group directly in order to secure rights to data or inventions owned by the clinical investigator or clinical investigator's institution and developed in conjunction with the NCI-sponsored trials.
7. Nature and Form of Information Supplied to the Collaborator: The Collaborator may make only reasonable requests for access to Cooperative Group data. The information shall be provided according to a mutually agreed upon plan between the NCI, the Collaborator, and the Cooperative Group. The information provided will be in accordance with the guidelines and policies of the responsible Data Monitoring Committee as described by the NCI Cooperative Group Data Monitoring Committee policy. A Cooperative Group should be reasonably compensated for costs associated with satisfying the request, such as a request that the data be provided to Collaborator in a format which is different than that of the Cooperative Group. In addition, Collaborators may make arrangements directly with the NCI contractors for updates on NCI-sponsored studies.
8. Cooperative Group - Collaborator Agreements: If a Cooperative Group is entering into a discreet agreement with a Collaborator, without the direct involvement of the NCI, the Cooperative Group is responsible for notifying the potential Collaborator of the existence of a collaborative agreement with the NCI. RAB has authority to review any such Cooperative Group-Collaborator agreement for potential conflicts prior to the agreement's execution; however, the Cooperative Groups are in no way obligated to submit a draft to RAB for review or comment. However, CTEP must be assured by the Cooperative Group that the Cooperative Group-Collaborator agreement does not conflict with any provisions of the NCI CTAs or CRADAs.
9. Publications: The Cooperative Groups maintain full rights to present and publish the data from any protocol sponsored by the NCI. However, the Collaborator will be provided manuscripts from the trials for advisory review and comment prior to submission for publication. Under NCI Industry agreements, the Collaborator is not permitted to edit or require changes except that information proprietary to the Collaborator may be redacted.
Any manuscripts reporting the results of a clinical trial should be provided to CTEP for immediate delivery to Collaborator for advisory review and comment prior to submission for publication. Collaborator will have 30 days from the date of receipt for review. An additional 30 days may be requested in order to ensure that confidential and proprietary data, in addition to the company's intellectual property rights, are protected. Abstracts presented by investigators will be sent to CTEP for forwarding to the Collaborator for courtesy review as soon as they are received, preferably prior to submission, but prior to presentation or publication. Before submitting a paper for publication or otherwise publicly disclosing information concerning an agent under an NCI collaborative agreement, the Cooperative Groups are requested to send any such disclosure, marked CONFIDENTIAL, to the Coordinator, Research & Development Agreements, Regulatory Affairs Branch, Cancer Therapy Evaluation Program, National Cancer Institute, NIH, 6130 Executive Boulevard, Suite 7111, Rockville, MD 20852. RAB will coordinate and expedite the Collaborator's review.
10. Financial Disclosure: NCI will collect financial disclosure information to assist Collaborators in complying with the FDA regulations. This information will be collected on an annual basis when Form FDA1572 is updated.