PREPARATION OF A SINGLE PROJECT ASSURANCE (SPA)
How should the SPA be prepared for submission?
What parts of an Agreement require special care during preparation?
Are there any other issues I should know about before submitting the Single Project Assurance (SPA)?
What is a Single Project Assurance (SPA)?
What should be done when additional performance sites will be involved in this research?
What does the term "certification" of IRB review mean?
My institution does not have an IRB. Does this mean my project can not be funded?
Where do I get information about setting up an IRB?
Can an investigator's research activity under an SPA be approved by expedited IRB review?
Do you have any tips on Informed Consent?
Can I use another Institution's IRB?
QUESTION: How should the SPA be prepared for submission?
ANSWER: The Assurance document must be on institutional letterhead (do not just type the name and address). The signatures that are required must be originals. Reproductions and photocopies are not acceptable for final approval. Please make certain that the date of IRB review and approval, and the next scheduled IRB review at the beginning of Part 3 are provided. This date of IRB review and approval must be within the last 12 months and must be the same date or precede the dates which correspond to signatures for the institutional official and IRB Chair. The institutional official must be a person who is authorized to enter into commitments on behalf of the institution (e.g., President, CEO, or Dean).
QUESTION: What parts of an Assurance require special care during preparation?
ANSWER: The following parts of a standard SPA should be prepared as follows:
| Face Page | Top | Pleaseprovide the exact legal name of the awardee orperformance site institution for which the Assurance isbeing prepared. The award could be a grant, contract, orcooperative agreement. |
| Part 2 Part 3 |
I. Top |
Be sure to insert (1) thefull name (title) of the research activity for which the SPA applies, (2) theproject award number assigned by DHHS, and (3) theoverall principal investigator (PI) for the project who may be located at anotherinstitution for multisite projects. |
| Part 3 | Top | Be sure to insert thedate of latest preaward full board review by the IRB ofrecord, and be sure to enter the projected date for theIRB's next full board review for this research activity(this date must be within twelve months of initial reviewor sooner if the IRB has determined that the degree ofrisk warrants more frequent intervals). |
| Part 3 | I. | The authorized officialof the institution named on page one of this Assurance isan administrator who is authorized to commit thisinstitution to legal agreements and is an employee ofthis institution. Be sure to provide (1) an originalsignature by the hand of the authorized official, (2) thedate signed, and (3) the typed name of the authorizedofficial, address, telephone and FAX numbers. Theinvestigator may not sign as the authorized officialunless approved by OPRR. |
| Part 3 | II. | A signature in thissection is not necessary if the institution named on pageone of this Assurance has its own IRB. However, if thisinstitution must use the IRB of another institution, theauthorized official of the institution with theIRB must sign in this section, and provide thedate signed, and the typed name, address, and telephoneand FAX numbers. |
| Part 3 | III. | Be sure to have theChairperson of the IRB sign this section by his/her hand,provide the typed name, date signed, and telephone andFAX numbers. If the institution with the IRB has aMultiple Project Assurance (MPA) approved by OPRR, pleaseprovide the OPRR assigned number of the MPA and suffixthat specifically identifies the MPA IRB. |
| Part 3 | IV. | Be sure to have theProject Investigator (PI) or Director sign in thissection by his/her hand, and provide the typed name,address, and telephone and FAX numbers. The PI shouldinspect this Assurance and make sure that copies of any IRB-approved Informed Consent Documents areattached unless the institution with the IRB has an MPA. |
| IRB List | All | Neither investigators, members of the research team, nor the signatory official should participate as voting members on the designated IRB for the research activity (or, if they are shown, a footnote is required that states they are to be absent from reviews in which they have a vested interest except as providedfor in the regulations [please see |
ANSWER: OPRR is obligated to enter into the negotiation of assurances of compliance with institutions (not investigators when at institutions) and, specifically, with an institutional official who is authorized to commit the institution to binding agreements. The institutional official must not be the investigator. The submitted Assurance document must bear original signatures (signature stamps are not acceptable and use of FAXed or photocopied signatures must receive prior approval of OPRR, when temporary expediency may be warranted, so long as the original page(s) are in transit to OPRR and received within a period of time specified by OPRR).
ANSWER: Any IRB-approved informed consent document that has been requested by OPRR must accompany the SPA. The IRB should be sure that all appropriate elements of informed consent are present before it approves the research. Additional elements of consent (45 CFR 46.116[b]) also should be considered as mandatory until found not to be appropriate. If special populations are involved, additional regulatory requirements apply that may influence informed consent and its approval by the IRB (please see Subparts B, C and, D of the regulations). If vulnerable populations are regularly involved, IRB membership must be appropriately composed to represent their welfare (please see 45 CFR 46.107). This requirement is intended to encourage adequate insight and consultation on issues such as risk assessment and consent language. Informed consent documents that do not meet regulatory requirements are a frequent cause for delay in the approval of Assurances.
QUESTION: What is an Assurance?
ANSWER: An Assurance is a document that formally acknowledges an organization's intent to comply with the Department of Health and Human Services (DHHS) regulations for the protection of human subjects (45 CFR 46). A list of Institutional Review Board (IRB) members is part of the Assurance document.
QUESTION: What is a Single Project Assurance (SPA)?
ANSWER: A Single Project Assurance (SPA) acknowledges an understanding of and intent to comply with DHHS human research subject regulations in the conduct of a specific research activity. Some institutions have a Multiple Project Assurance (MPA) that does not require separate Assurance documents for individual projects. Most institutions neither have nor qualify for a Multiple Project Assurance (MPA) and therefore they need to submit an SPA for each specific DHHS-supported research activity.
ANSWER: Yes, as a DHHS awardee on a project including research with human subjects, your institution must submit an Assurance and have it approved by OPRR regardless of whether human subjects are involved at your institution or not. If human subjects are not involved at the awardee institution, but are involved at one or more performance sites including independent investigators, each such performance site or independent investigator also needs to submit an Assurance for the protection for human subjects.
ANSWER: All performance sites not owned and operated by the applicant institution must independently assure OPRR of the intent to comply with 45 CFR 46 if materially involved in proposed research that is to be funded or conducted by DHHS and involves human subjects. For example, such involvement may consist of direct intervention with subjects or indirect involvement through the management of personally identifiable data, documents, or specimens obtained from living subjects. An assurance of compliance must be approved by OPRR for each site or independent investigator prior to initiation of research activities that involve human subjects at that site unless agreed to by OPRR.
QUESTION: What should be done when additional performance sites will be involved in this research?
ANSWER: Each applicant institution must ensure that all such sites assure OPRR of compliance with 45 CFR 46 prior to initiation of research activities that involve human subjects at each site. The principal investigator is responsible for alerting the funding authority and, upon request by or other arrangement with OPRR, provide a copy of the initial OPRR request letter to each new site for solicitation of required documents.
QUESTION: What does the term "certification" of IRB review mean?
ANSWER: "Certification" means the official notification by an institution to the sponsoring DHHS Agency, in accordance with the requirements of 45 CFR 46, that a research activity involving human subjects has been reviewed by the appropriate OPRR-approved IRB cited in the respective Assurance on file with OPRR. When an institution does not qualify for and possess a Multiple Project Assurance (MPA), certification of initial IRB review is incorporated into the text of each SPA which is then forwarded to OPRR. Exact requirements are specified in each request for an SPA. Subsequent certification of continuing IRB review is accomplished by filing an Optional Form 310 (formerly an HHS 596 Form) or an equivalent (letter) with the funding agency, not OPRR.
ANSWER: The regulations require both an assurance of compliance and certification of IRB review for all DHHS-supported activities involving research with human subjects.
QUESTION: My institution does not have an IRB. Does this mean my project can not be funded?
ANSWER: Neither an applicable Assurance nor an IRB needs to be in existence as a condition for applying to DHHS for an award. Upon receipt of a request to provide an Assurance, an institution must set up its own IRB, share one, or rely on another institution's IRB with OPRR's advance concurrence and provide an Assurance to OPRR before funding can occur.
If your institution does not have an IRB but, for example, one of the performance sites that will involve human subjects has an MPA, the MPA institution may be willing to extend access to its IRB. If so, you may be able to complete a Single Project Assurance for your institution and use the MPA's IRB as the designated IRB for your institution. If direct interaction or intervention will occur with subjects, prior consultation with OPRR is advisd. The IRB Chairperson and the official legally responsible for the MPA institution must also sign the assurance for your institution. Similar reliance upon an IRB at an SPA performance site for the research activity also is possible. The voting membership of the IRB upon which your institution relies must be properly composed or complemented by consultant input or other acceptable means to satisfy all requirements of 45 CFR 46 on behalf of the subjects at your institution.
QUESTION: Where do I get information about setting up an IRB?
ANSWER: The regulations contain the requirements for IRB membership and procedural requirements (45 CFR 46.107). Often, another local institution which conducts human subject research and has received OPRR approvals for Assurances in the past would be willing to offer operational advice for the benefit of a new IRB at another institution.
ANSWER: No, not use expedited IRB review unless the designated IRB is in an MPA institution and the project meets the qualifications specified in the regulations. Otherwise, all research activity under an SPA must be subject to full board review by the convened IRB for initial review. Use of expedited review for subsequent continuing reviews is governed by the terms and conditions cited in the Federal Register.
ANSWER: The regulations require that the awardee of a contract, grant, or cooperative agreement must have an OPRR-approved Assurance. The institution with the IRB must obtain an OPRR-approved SPA if it does not have an MPA, and is directly involved in the research project (more than just providing the IRB review) unless it already has an SPA. However, if the institution with the IRB provides only the IRB review and key investigators are not employed by this institution as full time or part time employees or paid consultants, it does not need an SPA.
QUESTION: Do you have any tips on Informed Consent?
ANSWER:
TIPS ON INFORMED CONSENT
The process of obtaining informed consent must comply with the requirements of 45 CFR 46.116. The documentation of informed consent must comply with 45 CFR 46.117. The following comments may help in the development of an approach and proposed language by investigators for obtaining consent and its approval by IRBs:
* Informed consent is a process, not just aform. Information must be presented to enable persons tovoluntarily decide whether or not to participate as aresearch subject. It is a fundamental mechanism to ensurerespect for persons through provision of thoughtful consentfor a voluntary act. The procedures used in obtaininginformed consent should be designed to educate the subjectpopulation in terms that they can understand. Therefore,informed consent language and its documentation (especiallyexplanation of the study's purpose, duration, experimentalprocedures, alternatives, risks, and benefits) must bewritten in "lay language", (i.e. understandable tothe people being asked to participate). The writtenpresentation of information is used to document the basis forconsent and for the subjects' future reference. The consentdocument should be revised when deficiencies are noted orwhen additional information will improve the consent process.
* Use of the first person (e.g., "Iunderstand that ...") can be interpreted as suggestive,may be relied upon as a substitute for sufficient factualinformation, and can constitute coercive influence over asubject. Use of scientific jargon and legalese is notappropriate. Think of the document primarily as a teachingtool not as a legal instrument.
* Describe the overall experience that willbe encountered. Explain the research activity, how it isexperimental (e.g., a new drug, extra tests, separateresearch records, or nonstandard means of management, such asflipping a coin for random assignment or other designissues). Inform the human subjects of the reasonablyforeseeable harms, discomforts, inconvenience and risks thatare associated with the research activity. If additionalrisks are identified during the course of the research, theconsent process and documentation will require revisions toinform subjects as they are recontacted or newly contacted.
* Describe the benefits that subjects mayreasonably expect to encounter. There may be none other thana sense of helping the public at large. If payment is givento defray the incurred expense for participation, it must notbe coercive in amount or method of distribution.
* Describe any alternatives toparticipating in the research project. For example, in drugstudies the medication(s) may be available through theirfamily doctor or clinic without the need to volunteer for theresearch activity.
* The regulations insist that the subjectsbe told the extent to which their personally identifiableprivate information will be held in confidence. For example,some studies require disclosure of information to otherparties. Some studies inherently are in need of a Certificateof Confidentiality which protects the investigator frominvoluntary release (e.g.,subpoena) of the names or otheridentifying characteristics of research subjects. The IRBwill determine the level of adequate requirements forconfidentiality in light of its mandate to ensureminimization of risk and determination that the residualrisks warrant involvement of subjects.
* If research-related injury (i.e.physical, psychological, social, financial, or otherwise) ispossible in research that is more than minimal risk (see 45 CFR 46.102[g]), an explanation must be given of whatevervoluntary compensation and treatment will be provided. Notethat the regulations do not limit injury to "physicalinjury". This is a common misinterpretation.
The regulations prohibit waiving or appearing to waive any legal rights of subjects. Therefore, for example, consent language must be carefully selected that deals with what the institution is voluntarily willing to do under circumstances, such as providing for compensation beyond the provision of immediate or therapeutic intervention in response to a research-related injury. In short, subjects should not be given the impression that they have agreed to and are without recourse to seek satisfaction beyond the institution's voluntarily chosen limits.
* The regulations provide for theidentification of contact persons who would be knowledgeableto answer questions of subjects about the research, rightsas a research subject, and research-related injuries.These three areas must be explicitly stated and addressed inthe consent process and documentation. Furthermore, a singleperson is not likely to be appropriate to answer questions inall areas. This is because of potential conflicts of interestor the appearance of such. Questions about the research arefrequently best answered by the investigator(s). However,questions about the rights of research subjects orresearch-related injuries (where applicable) may best bereferred to those not on the research team. These questionscould be addressed to the IRB, an ombudsman, an ethicscommittee, or other informed administrative body. Therefore,each consent document can be expected to have at least twonames with local telephone numbers for contacts to answerquestions in these specified areas.
* The statement regarding voluntaryparticipation and the right to withdraw at any time can betaken almost verbatim from the regulations (45 CFR 46.116[a][8]). It is important not to overlook the need to pointout that no penalty or loss of benefits will occur as aresult of both not participating or withdrawing at anytime. It is equally important to alert potential subjects toany foreseeable consequences to them should they unilaterallywithdraw while dependent on some intervention to maintainnormal function.
* Don't forget to ensure provision forappropriate additional requirements which concern consent.Some of these requirements can be found in sections 46.116(b), 46.205(a)(2), 46.207(b), 46.208(b), 46.209(d), 46.305(a)(5-6),46.408(c), and 46.409(b). The IRB may impose additional requirements thatare not specifically listed in the regulations to ensure thatadequate information is presented in accordance withinstitutional policy and local law.
QUESTION: Can I use another Institution's IRB?
ANSWER:
GENERAL GUIDANCE ON THE USE OF ANOTHER INSTITUTION'S IRB
Each approved Single Project Assurance designates an Institutional Review Board (IRB) which is authorized to review protocol(s). However, although it may be permissible under 45 CFR 46.114 for an institution to rely on an IRB of another OPRR-approved institution for protocol review, institutions planning such an arrangement should seek prior guidance from OPRR to avoid unnecessary delays. It is in the best interests of institutions to appreciate that review by another's qualified and OPRR-approved IRB raises questions about membership qualifications that would likely be inherently satisfied when reviews are confined to protocols conducted in the IRB's own institution. Local laws, institutional policies and constraints, professional and community standards, and population differences are examples of pertinent local factors that can influence the setting of research (see 46.103(d), 107(a), and 111(a)(3)). For example, the considered opinion of an IRB of one institution may be blind to information that would alter its decision for another where:
- institutions draw from culturallydissimilar patient populations;
- institutions are located in different states or othergeographical subdivisions with varied legal or regulatoryconstraints;
- institutions are not accustomed to each other's operationalpolicies, constraints, procedures, or commitments; or
- there is uncertain satisfaction of drug controlresponsibilities, or other FDA requirements.
Apparent efficiencies of such review to avoid perceived duplication of effort may be shortsighted if detached from concomitant review of the setting in which such protocols are to be conducted. Accordingly, reliance on another IRB should not be considered lightly. In spite of a joint willingness between institutions, OPRR may not approve a proposed arrangement if there are circumstances that are not appropriate. Therefore, such plans should include consultation with OPRR to avoid delays.
Several options for IRB arrangements are available which OPRR has found to comply with the letter and intent of both 45 CFR 46.114 and the regulations as a whole.
Institutional sites that are geographically close enough to comfortably contribute membership to a common IRB can share in bearing the costs of operation while simultaneously providing reviews for protocols that may be used by physicians at some or all of the sites. This approach results in one IRB that can be equally cited as their own IRB of record by all sites that contribute to its membership.
A second approach is for one IRB with unique expertise, a legal or administrative preference for involvement, or otherwise to host reviews for other nearby institutional sites with consultant representation from each site present for all initial and continuing reviews of protocols jointly used by these sites. In this approach only the hosting institution has its own IRB. The other sites rely on another's IRB but in such a way as not to defeat the intent of 45 CFR 46.
The most obvious way to comply fully with the regulations is for each site to host its own IRB. An institution that has a standing IRB which is qualified to perform reviews for a specified research activity would be expected to do so, or justify not doing so, before approval would be considered for other options. If a local institution exists with an applicable OPRR-approved Assurance for the research in question, a second institution may seek permission to rely upon such an IRB when justified. OPRR understands the propriety of considering and approving reliance on another's IRB when a plausible case is made apparent. For example, an IRB with a suitably diversified membership might exist at one site to host IRB reviews for another site due to: (1) the cosmopolitan nature of the host site; (2) a wide catchment area from which patients and subjects are referred to it, (3) or reasons as may otherwise be of a compelling and pertinent nature. However, institutional constraints are less easily accounted for between institutions when there is little or no intimate understanding of each other's staff, equipment, policy, practices, and legal issues. Each case deserves individual consideration.
See IRB Knowledge of Local Research Context
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Updated June 23, 2000