21st Edition - January 15, 2020

The Office of Research Compliance is kicking off its Joint Public Lecture Series – the Office of Research Compliance collaborates with Indiana CTSI to host Heather Pierce, J.D., M.P.H. in Indianapolis at Hine Hall March 3^rd from 4-5:30pm. We invite you to attend this inaugural lecture event titled, Reducing Burden for Researchers and Advancing Research Ethics: Is It A Tradeoff?

Heather Pierce, Regulatory Counsel for the Association of American Medical Colleges, where she is the subject matter expert for issues related to the regulation of science and research, as well as interactions between industry, academia, and government. In a public lecture, she will discuss whether recent welcome efforts to reduce burden for researchers may be in conflict with a growing emphasis on transparency, research integrity, and research security. From headline reports on researchers' failure to disclose financial interests to concerns about the integrity and reproducibility of research, animal welfare, and human subject protection, external pressures on universities and researchers seem to be increasing. In this tension between a national commitment to decreasing burden and calls for more reporting, more transparency, and more accountability, where does that leave the academic research enterprise?

A little more information on the Joint Lecture Series - The Office of Research Compliance, in collaboration with academic units throughout IU, hosts this lecture series on key topics in research compliance. Twice a year – in the spring in Indianapolis and the fall in Bloomington – ORC brings in an internationally/nationally known speaker for 1.5 to 2 day visit including a public lecture and a series of meetings with relevant key stakeholders. Please join us. If you would like to collaborate with ORC on co-sponsoring such a visit, contact Becca Hopson at rhopson@iu.edu

The Human Research Protections Program (HRPP) has completed evaluation and begun implementation of Kuali Protocols, an electronic IRB submission system that will replace KC IRB.  We expect Kuali Protocols to go live in late 2020 or early 2021.  The new system will feature an improved user interface and an improved pre-review process, among other changes.  We are carefully planning the implementation to minimize the impact on researchers.  All active studies in the KC IRB system will be transitioned into Kuali Protocols; therefore, some updates may be requested by HSO staff in preparation for the transition.  No other actions are required on your part to prepare for the transition at this time.  Additional information and training opportunities will be provided throughout 2020.  Contact Beth Johnson at bwinnie@iu.edu with any questions at this time regarding the implementation.

The Indiana CTSI will host a Research Conflict of Interest Workshop in partnership with the Office of Research Compliance. This moderated panel will be a nuts and bolts discussion to foster best practices for clinical research staff when navigating research conflict of interest issues. Stephanie Jones, Associate Director of the Office of Research Compliance, will moderate and present with this panel to discuss 4 content areas with case study examples explored by the diverse stakeholders:

1. Big Picture Perspective: What it is and what it is not
2. Industry Thought Process: Differences between IU and Industry
3. IU COI: Key areas of a management plan – what are the current trends/themes the Committee is looking for in establishing a management plan
4. COI Responsibilities with IRB Submission

Moderator Stephanie Jones is currently the Associate Director within the Office of Research Compliance at IU where she has been managing conflicts of interest, radiation and biosafety. She has 12 years of experience at IU facilitating the research conflict of interest staff and operations, the coordination of the committee and management plans. Prior to IU, Stephanie worked at Cook Inc. managing national and international clinical trials and regulatory submissions.

Panelists Include:

• Stephanie Jones, Associate Director, IU Office of Research Compliance
• Mark Kelley, MS, PhD, Betty and Earl Herr Professor of Pediatric Oncology Research, IU School of Medicine
• Kris Parmelee, Consultant, Parmelee Consulting Group

The Clinical Competencies addressed in this workshop include Ethical and Participant Safety Considerations, Clinical Trials Operations, and Study and Site Management. Join us for this clinical research staff education panel February 3^rd, 2020 at the Regenstrief Social Hub 9am-11am. Contact rceducat@iupui.edu for more information.

Please note that KC IRB is not a HIPAA-compliant environment.  Thus, documents containing PHI should not be uploaded to the system.   If you need to upload a document that contains PHI, please redact the PHI before uploading to KC IRB.

If you find that you have uploaded a document that contains PHI to KC IRB, please email hsosys@iupui.edu for assistance in getting that document removed.  In the email, please include the protocol number, document type and document name.

Unless the IRB grants a waiver of documentation of informed consent, adult subjects must sign the consent document prior to participation in research.  In everyday life, other people may be permitted to sign legal documents on behalf of another competent adult; however, research consent is not one of those scenarios.  Instead, mentally competent adult participants must sign the consent on their own behalf unless a physical disability completely prevents them from doing so.  Subject preferences to have another individual sign on their behalf are not considered to be appropriate justification for not signing the document personally. 

Subjects who have experienced events such as a stroke, an upper extremity injury, or a neurodegenerative disease process may be able, or may have accommodations that allow them, to provide a signature.  Importantly, any mark by the subject intended to act as a signature can satisfy the signature requirement.  In the exceedingly rare situation where a subject is unable to make a mark of any kind on the consent document, a witness must (1) observe the consent documentation process, (2) observe the subject’s verbal agreement to participate, and (3) must sign and date the consent document as a witness.  Rather than allowing the witness to sign “as the subject,” the witness should sign as a witness.  A witness signature line can be drawn onto the consent document when the need arises.  You should document in the study files the circumstances related to assessing a subject’s physical impairment and/or including a witness to the consent process, as well as any reason why the subject may have been unable to provide the date that should accompany their signature/mark.

If the subject does not have physical limitations to prevent signing or making a mark on the consent document, but declines to sign on his or her own behalf, the consent process must be discontinued, and the subject cannot be enrolled, until the IRB reviews and approves an amendment requesting permission to either enroll the subject without obtaining a signature or to permit the signing of documents by another individual, despite the participant’s cognitive and physical abilities to sign for themselves. 

Of note, while the witness process is permitted in very limited circumstances to document research consent signatures, the accommodation does not extend to research authorization.  If a subject is physically unable to sign the authorization form or make a mark, the authorization process must be discontinued pending submission and IRB review and approval of an amendment to waive the signature requirement for this specific case.

A subject might provide their consent to participate in research either verbally (if approved by the IRB) or in writing, by signing a consent document.  In either case, the study records may require additional documentation about the consent process that occurred.  The consent process must include the following elements:

• subjects must be provided with ample time to read the document (or, for non-readers, the documents must be read aloud to them);
• subjects must be provided an opportunity to ask questions and have those questions answered to their satisfaction prior to providing their consent;
• subjects’ consent must be obtained prior to the conduct of study procedures;
• a copy of the consent document must be provided to the subject to keep.

For FDA-regulated studies, the FDA expects the study records to include not only the signed consent document, but also documentation of the consent process outlined above.  Therefore, study teams should document the consent process for every subject and for each consent occurrence, including the initial consent process and any reconsent processes that may occur during the subject’s participation.  Using a template document – either an EMR template note or a paper form template – may help to ensure that none of the conducted steps are inadvertently missing from the documentation.  Care should be taken to customize the template for each study to ensure the process is accurately described. While a template is recommended for most consent procedures, when the consent process for an individual subject substantially deviates from the norm, a narrative note should be used in place of the template.  The process documentation should be authored, signed and dated by the person who conducted the consent process and should be completed promptly following the consent process (while the details of the process can still be recalled).  Best practice would be to complete the documentation either immediately following the consent process or at the conclusion of the consent visit. 

Even for non-FDA-regulated studies, study teams should consider documenting the consent process as described above.  Such efforts will assist external reviewers, such as auditors, in quickly determining that institutional policies – including those pertaining to informed consent – were followed.  Several example templates can be found on the IU HRPP website, along with other clinical research management templates.  The templates should be modified to fit the study’s needs and to accommodate the anticipated subject population(s).  Contact the Quality Improvement Office with any questions regarding use of the templates.

In the recent revisions to GCP E6 (R2), the GCP expectations for site record keeping were updated to include specific requirements:

• The investigator/institution should maintain adequate and accurate source documents and trial records that include all pertinent observations on each of the site's trial subjects. Source data should be attributable, legible, contemporaneous, original, accurate, and complete. Changes to source data should be traceable, should not obscure the original entry, and should be explained if necessary (e.g., via an audit trail).

The IU HRPP Policy on Research Data Management further supports good documentation practices by requiring all observations/data recorded on paper documents to be recorded in ink, all fields to be completed, and errors to be corrected with a single line-through accompanied by the editor’s initials and the date of revision.

The above GCP documentation principles are well known as they apply to data and observations recorded by research personnel, but how does this apply to source data recorded by the subjects themselves?   During a recent FDA inspection, the auditor explained the FDA’s interpretation that this principle applies to all source data – including that documented by the subjects – and provided some advice for consideration:

• If the study’s source data includes information to be documented by the subjects (questionnaires, diaries, consent signatures, etc.), subjects should be instructed to record the data in ink (rather than in pencil) and should be educated about the appropriate way to correct any errors that they may make in data recording.
• Upon completion and return of the source materials, the study team should review the materials to identify any GCP issues that may still need to be addressed. Changes made by the subject prior to returning the materials can be addressed at that time if necessary, by asking the subject to initial and date the corrections at the time of study team discovery.  Neither study teams nor subjects should ever be encouraged or permitted to back date corrections or signatures.  As needed, the subject should be re-educated on GCP expectations.
• If subject materials are completed and returned in pencil, the study team should retain them as the original source, but are also encouraged to make a photocopy of the document(s) for the study file, as pencil can fade or smear over time. The additional photocopy, if signed and dated by the study team as an exact copy of the original, can then be used as a certified copy of the original should the need arise in a future inspection or audit.
• A note to file about the study visit can then be used to document the action of reviewing the materials for needed GCP documentation revisions, to explain any “late” corrections made by the subject upon return of the materials, to justify the need to make a certified photocopy, and to document the subject’s re-education, if any, on GCP expectations.

As the FDA inspector explained, without any evidence as to who changed or revised the source data, the revision can just as easily be attributed to the study team as to the study subject.  To protect the study team from any suspicion of having revised the source data upon receipt of the materials, study subjects should be asked and encouraged to comply with GCP expectations.  Although compliance with GCP is not required by the current FDA regulations, it should be considered best practice that will be noted and discussed by the FDA representative during an inspection.

While the bulk of the changes in the new Common Rule went into effect in January 2019, implementation of the single IRB (sIRB) requirement was delayed.  However, the final compliance date has arrived, and effective this month, all new cooperative human subjects research projects funded by a federal agency which has adopted the Common Rule must be reviewed by a single IRB.  Because the NIH sIRB Policy has been in effect since 2018, most federally funded research is already in compliance with this requirement. 

Researchers with funding from other federal agencies, including the Department of Defense, Department of Education, Department of Veterans Affairs, and National Science Foundation, will now need to comply with the single IRB requirement.  Note that the Department of Justice and Food and Drug Administration have not yet signed onto the revised Common Rule.  Therefore, studies funded by DOJ, NIJ, and FDA do not yet require use of a single IRB.

Please contact the HRPP Reliance team at irb@iu.edu as soon as you are aware of a multi-site federal grant proposal for which IU is the lead site and/or if you would like to use the IU IRB as the single IRB.  We will assist you in planning and appropriately budgeting to serve in this capacity in compliance with the federal requirements.

All research conducted at any Eskenazi Health facility, enrolling Eskenazi Health patients, or using Eskenazi Health patient data must have Eskenazi Health Research Committee approval prior to starting at Eskenazi Health.

Eskenazi Health is happy to announce the launch of the NEW Eskenazi Health Research Approval Application. The new approval application officially launched the week of January 13, 2020. This application is accessible through the Indiana University REDCap web-based platform at https://is.gd/EH_Research.

The new user friendly approval application will walk the applicant through the questions that are required for their specific project and divert the applicant around the questions that are not necessary. Requiring the applicant to only answer the necessary questions will decrease the time it will take for the applicant to complete and submit the application.

In addition to gathering information necessary for Eskenazi Health Research Committee approval, the new application contains information, instructions, and forms that the applicant may need related to Research Billing, Grants, Research Epic Training, Research Credentialing, and Investigational Drug Services.

Prior to completing the NEW Eskenazi Health Research Approval Application, the project must first have IU IRB approval or confirmation that IRB review is not needed (i.e., Letter of Approval, Notice of Exemption, Notice of Determination-Administratively Reviewed, or Notice of Reliance).

Documents you will need to complete the application:

1. IU IRB determination letter (e.g. Initial Approval Letter, most recent Renewal Approval Letter, Notice of Exemption Letter, Notice of Determination Letter – Administratively Reviewed, Notice of Reliance Letter). The determination letter must be on IU IRB letterhead and will include an approval signature.
2. Project Protocol (formal protocol). If this study does not have a formal protocol, provide a copy of the IRB application or KC IRB questionnaires.
   • To Print these in the KC IRB go to Protocol Summary Tab > Print > Questionnaires > Select all > Print selected.

OLD Eskenazi Health Research Application (Request to Conduct Research at Eskenazi Health)

The OLD Eskenazi Health Research Application will be disabled when the NEW application launches. All applications entered into the OLD application prior to the application being disabled will be processed via the OLD application. You do NOT have to resubmit these projects in the NEW application. Projects submitted in the OLD application will continue to live in the OLD application until they are completed and/or closed with the IU IRB.

Projects Completed and/or Closed with the IU IRB

Eskenazi Health MUST to be notified when projects (IRB Approved, Notice of Exemption, Administratively Reviewed, Notice of Reliance) approved by the Eskenazi Health Research Committee are completed and/or closed with the IU IRB. This includes projects submitted in both the NEW and OLD approval applications. 

Please notify Patricia Noblet patricia.noblet@eskenazihealth.edu and/or research1@eskenazihealth.edu when a project approved by the Eskenazi Health Research Committee has been completed and/or closed with the IU IRB.

Questions can be directed to:

General Eskenazi Health Research Questions: patricia.noblet@eskenazihealth.edu or research1@eskenazihealth.edu

Research Billing: Research.Billing@eskenazihealth.edu

Eskenazi Health Grants: EHGrants@eskenazihealth.edu

Research Training for Epic: researchtraining@eskenazihealth.edu

Medical Staff Affairs/Research Credentialing: ResearchCredentialing@eskenazihealth.edu

Investigational Drug Services: investigationaldrugs@eskenazihealth.edu