Sponsored Research (June 2012)
Operations Manual - Part 10
This section describes policies and procedures for the administration of sponsored project agreements for human subjects research.
I. ROLE OF THE DIVISION OF RESEARCH DEVELOPMENT ADMINISTRATION
The Division for Research Development and Administration (DRDA) assists faculty and staff members in all aspects of externally funded research projects and other scholarly activities -- from the identification of a potential sponsor and the preparation of a proposal, through various administrative problems (related to budgets, personnel, space, sub-contracts, reporting and accountability, patents, negotiations with the sponsor) during the course of the project, to the submission of the documents required to close out the project.
II. AGREEMENTS WITH SPONSORS
DRDA submits sponsored research proposals to external agencies, negotiates the terms of those agreements consistent with the mission and goals of the HRPP, and arranges for the establishment of appropriate financial accounts when a project is awarded. DRDA uses a campus-wide application for electronic Routing and Proposal Management (eRPM) to solicit information about the proposed activity including whether a research proposal involves human research participants. No sponsored project involving human research participants is established without confirmation that IRB approval has been received and other regulatory requirements for the protection of human research participants have been met.
A. Human Research Protection Program
The University of Michigan does not deviate from human research protection requirements mandated by the FDA, DHHS, other federal regulatory agencies, and existing accreditation standards. The University's policies and procedures require assurance of protection for human research participants in all sponsored activity and the University imposes its policies and procedures on all sponsors. In addition to IRB mechanisms for ensuring human research participant protection, sponsored research agreements or the protocols contain language requiring the University to conduct the research in accordance with applicable law, and organizational and industry ethical standards. Sponsored agreements for clinical trials include reference to the written protocol and language allowing the sponsor and regulatory authorities such as the FDA the right to inspect the University's property and documents related to the performance of a trial to ensure it is being conducted in accordance with the protocol and applicable law. In non-clinical research agreements, the responsibility for human research protections is included in the work statement or the sponsored research agreement.
To assure human research participant protection, the University does not establish accounts for projects until IRB approval is obtained. The status of the IRB approval, either the number/date of approval or an indication of pending status, is required in the eRPM project information, which is signed by the Principal Investigator. eRPM verification of approval is required before the University can sign any research agreement.
B. Medical Care For Human Research Participants With A Research-Related Injury
Prior to the start of any clinical research involving human research participants, arrangements for medical care for research-related injuries are defined including, who will provide such care and who will be responsible for paying for the care. Various University personnel including the Principal Investigator, his/her administrator, the clinical coordinator, the clinical trials planning unit, or the DRDA Project Representative , may conduct discussions with the sponsor concerning this issue. Information specifying financial and medical responsibility for these injuries is clearly presented to the research participant in the informed consent and includes instructions concerning where medical treatment should be sought if injury occurs and whom to contact in the event of a research-related injury.
In addition to the informed consent, the contract generally sets forth information concerning research-related injuries consistent with the information provided to the research participant. All effort is taken to ensure that the informed consent and contract provisions are in agreement. Further, the department coordinates with the clinical trials planning unit to document appropriate billing procedures depending on who is paying for research-related care.
When contracting with sponsors, the University first attempts, when appropriate, to require the sponsor be responsible for the payment of medical care provided for a research-related injury, illness or adverse event. This requirement is based on a determination of whether the University's contractual obligation with insurance carriers, including Medicare, precludes billing for service provided pursuant to a research protocol or for non-standard-of-care services provided to research participants.
The University also adheres to sponsor requirements, either set forth in the protocol or research agreement, necessitating the reporting of any adverse event experienced by a research participant. In addition, any adverse event must be reported to the applicable University IRB though eResearch or on a designated reporting form.
C. Communication of Findings that May Affect the Safety of Human Research Participants or Their Willingness to Continue in the Research Study or Alter the IRBs' Approval of the Research
In clinical sponsored research settings, there is frequent communication between various University personnel and the sponsor about monitoring of the study and any issues that might affect the continuation of the study. Such discussions commonly occur between the Principal Investigator or his/her study coordinator and the sponsor but also may involve DRDA if related to the contract. In addition, the sponsor's written plan for the dissemination of findings that could impact the safety or participation of research participants must be contained in the protocol, which is considered an integral part of the research agreement.
The University's IRB informed consent template for clinical projects includes the requirement, if applicable, to provide the human research participant information concerning any new findings that develop during the course of the research which may relate to the human research participant's willingness to continue participation. In addition, the informed consent must provide human research participants with information about the risks and benefits involved, including how risks will be monitored and reduced and what steps will be taken if adverse events occur. The informed consent also indicates that the researcher has the right to remove the human research participant from the study despite the human research participant's desire to continue participation. Such situations may occur when the sponsor has communicated to the University the existence of adverse events, safety concerns, or the suspension or cancellation of the study. While sponsor-initiated trials commonly require use of sponsor-created informed consents, the University's IRB reviews those documents to ensure that the consent is consistent with the protocol and that the human research participant is adequately informed of all aspects of the study.
Clinical research agreements explicitly incorporate compliance with the protocol into the contractual obligations of the sponsor. Therefore, the written plan for reporting issues that affect safety of subjects and subject participation continuation, as contained in the protocol and reflected in the informed consent, are integrated into and become part of the research agreement. The agreement also addresses matters relating to the continuation of the study in the event of adverse event reporting, the need for IRB approval for any protocol or informed consent changes, other issues that may influence the conduct of the study or alter the IRB's approval to continue the study, and the right of the sponsor to terminate the agreement when, in the opinion of the sponsor and/or investigator, human research participant safety concerns make continuation impossible or medically unwise. For projects requiring a Data Safety and Monitoring Plan (DSMP) when the sponsor has the responsibility to conduct data safety and monitoring, the protocol must address provisions for monitoring the data to ensure the safety of participants and for providing data and safety monitoring reports to the University and must specify the time frame for providing routine and urgent data and safety monitoring reports to the University. Clinical research agreements include compliance with sponsor obligations as articulated in the protocol.
In the informed consent investigators tell the research participants what the participants may expect to happen or hear about during the clinical trial. A specific statement within the informed consent tells the participant that they will be told of any new information or knowledge obtained during the course of the trial that could change the participant's willingness to stay in the study. Further, the informed consent ensures that human research participants know how to obtain reports and obtain medical care for any adverse events that necessitate communication with the University. In addition, the legal right of the University to terminate the study due to human research participant safety concerns reinforces an investigator's ability to inform the participants about the risks or adverse events that may require study cancellation. The protocol may contain language regarding the reporting of results to participants in addition to reporting to the sponsor, and becomes part of the contractual communication obligations assumed by the University. In addition, the protocol must describe the steps followed to communicate findings from a closed research study to the investigator or the University when those findings affect subject safety. The protocol must specify the time frame after closure of the study during which the sponsor will communicate such findings (e.g., two years).
University policy requires freedom to disseminate all research results. This policy includes the freedom to communicate information to research participants. On occasions when participants request information concerning the results of a completed trial, they are provided a copy of a transcript, if available. In addition, if adverse events are experienced at the University or have occurred at other sites involved in the trial and are made known to the University via broadcasting of such instances from the sponsor or other sites, the University will revise the informed consent to include notice of any safety issues and actually may require re-consent of the research participants. Further in its research agreements, the University reserves the right to use results, data, information, etc. for, among other things, patient care purposes.
D. Finder's Fees and Bonus Payments
Research sponsors typically provide financial support commensurate with the work required to do the study. Although research sponsors may from time to time offer to pay investigators or study personnel an additional finder's fee or bonus payment to encourage participant recruitment efforts, University policy prohibits these types of payments. This policy is not intended to prohibit renegotiation of contract fees when recruitment is progressing much more slowly than anticipated such that additional time and effort are required for recruitment activities than initially anticipated. (This policy does not address payments to research subjects, which are addressed in Part 7(III) of this Operations Manual.)
"Finder's fee" is defined here as compensation of any type (e.g. cash, cash equivalent, office or medical supplies, educational stipends, gift certificates, travel cost in excess of normal reimbursement costs, or anything else of value) to an individual made in exchange for referral or recruitment of a participant to a research study. Such payments, generally, are made to study team members who are in a position to identify potential participants who might qualify for enrollment into a study. The finder's fee is paid to the study team member for each participant they recruit who actually enrolls in the study. It is not permissible to pay or accept "finder's fees" at U-M. Additionally, it is not permissible for U-M employees or students to accept personal payments from sponsors or others in exchange for accelerated recruitment or referrals of patients.
"Bonus payment" is defined here as compensation tied to the rate or timing of recruitment or performance or other aspects of a clinical study. Examples of bonus payments include the following: the sponsor announces that the highest enrolling site in the nation will receive a $10,000 bonus; the sponsor offers to pay an additional $10,000 beyond the budgeted study costs to any site than enrolls five participants within a week; the sponsor offers to pay an additional $10,000 beyond the budgeted study costs to any site that fulfills its recruitment target by the end of the month; the sponsor offers to pay an additional $1,000 beyond the budgeted study costs for any subject who agrees to enroll within one day of initial contact. Is not permissible to accept bonus payments at U-M.
It is acceptable to receive compensation for recruitment and screening related activities that are unrelated to whether the participant ultimately enrolls in or completes the research study (such as advertising, administrative and personnel costs). It is also acceptable to receive compensation for the cost of services provided to those individuals who do ultimately enroll. Investigators should be sure to determine a reasonable budget amount that is directly related to the value of the services provided to the study, and to document how that amount was determined. For example, the budget might include a portion of the salary of individuals that is related to the time spent recruiting and screening potential research participants (regardless of whether they are successful in recruiting those participants), and time spent for subsequent study visits, survey administration, and so forth. Staff may not be paid a fee for every successful recruitment (e.g., $10 for every participant who signs the consent document to participate in the study). Further, any payments to University for personnel must be reflected in the study budget and in the written agreement that is reviewed by DRDA.
III. DISSEMINATION OF FINDINGS FROM THE RESEARCH
The Regents of the University of Michigan adopted a policy that requires freedom to disseminate results of research conducted by University employees, i.e., the Regents' Policy Concerning Research Grants, Contracts and Agreements. This policy states that the University does not normally accept any research agreements that place restrictions on the publication or other dissemination of research results. Exceptions to the policy exist but require justification and approval of the principal investigator whose work may be affected by the restriction. Even with such exceptions, as discussed in greater detail below, sponsor approval of publication or disclosure of research findings are never accepted absent written authorization from relevant chair and dean and the University's Office of the Vice President for Research (OVPR).
University policy permits a sponsor a reasonable period to review and comment on proposed publication of study results. In instances where the investigator wishes to disclose the results in a format other than submission to a journal, i.e., slides, posters, conference, etc., negotiation with the sponsor typically provides for a reduced review period. University policy allows for a review period of up to 180 days, with investigator concurrence, and requires anything over 120 days to be reported to the OVPR. In ensuring a reasonable time period is contained in the contract, DRDA considers both the review period and the potential delay involved with the protection of intellectual property (IP) contained in the publication or other disclosure.
In sponsored research involving human participants where the University is the only site participating (this more typically occurs with an investigator-initiated trial), the publication provisions in the research agreement are straightforward. The provisions will include the review/comment period/potential delay for IP protection, and the right for the sponsor to require the removal of confidential information prior to the disclosure, which is consistent with the Regents policy.
Clinical trials are often designed as multi-center studies, where numerous sites are participating in the trial. In such instances, the sponsor may require the pooling of the information from all the trials and an initial publication based on the data from the various sites. Regental policy takes into consideration that, for assuring the integrity of these trial results, multi-site publication would prove the most effective and allows for a reasonable and determinate time delay for publication by the University of its site results following the initial multi-site publication or after the sponsor indicates that such publication will not take place. The usual period of delay for the University to publish in such instances is 12 months from the termination or cancellation of the study at all sites. After this time, the University investigator can present the results from his/her study to the sponsor for the review and comment period. The sponsor is required to provide notice to the University when the study is completed to allow the University to compute the publication delay period.
IV. ADDITIONAL INFORMATION
In addition to the links provided, there are numerous applicable and helpful University Web sites that provide information concerning University policies, Regental bylaws, and contracting procedures and requirements. Provided below are just a few of the links to such resources:
General Contracting Principles http://www.drda.umich.edu/contacts/overview/working_with_sponsors_ind.html