OHSRP Newsletter 2020 Q3

New Policy Implementation Guidance

September 15, 2020

Dear Research Community

Over the past 18 months, we have rewritten the HRPP policies to be compliant with the revised common rule and consistent with the reorganization of OHSRP and the NIH IRBs.  As these policies are all inter-related, with few exceptions we were not able to implement them as they were developed and cleared.  Now that they are complete, we are rolling them out in groups between now and years end.  We understand that releasing so many new policies rapidly is a little overwhelming.  Hopefully, as you become familiar with the new policies, you will see that in many cases there is not a lot of change in the actual policy requirements, and for those that there is change, it is for the better.

To guide you in the implementation of these new policies, please review the following:

• Each policy has a release date and an implementation date.  The release date is when we post it on the web and make it available.  The implementation date is when you should begin following the new policy requirement in your research.
• If a new policy impacts what is written in your consent or protocol, you do not need to immediately update the consent/protocol to be consistent with the revised policy.  In fact, we would prefer that you don’t, as this will lead to a surge in amendment submissions which would rapidly overwhelm the office.  You can update the documents with the next planned amendment to the IRB.  Even if you do not update the sections with an amendment, the IRB will not stipulate that you update the documents at this time.  At some point in early 2021, the IRB office will begin requiring that the relevant sections of the protocols/consents be updated.

For example, the new policy requires that the protocol and consent describe the compensation plan, even if the plan is that there will be no compensation.  Some protocols that are not compensating subjects are silent on this.  At this time, you do not need to amend your protocol to add a new section stating there is no compensation. With your next planned amendment you can change this.

• You should implement the new policies on their effective date, even if your protocol is not updated.  For example, the new policy on enrolling subjects who cannot consent for themselves (Policy 403) changes who can serve as the LAR for research in Category C research and specifies a new next of kin hierarchy.  You should follow the new policy as of the effective date of September 14, but you do not need to immediately amend your protocol.  You should change this section of your protocol only with your next planned amendment.  In this case, even though your protocol does not match your actions, you do NOT need to submit a Reportable Event Form (REF) for a protocol deviation.

OHSRP Education Series 2020: What You Need to Know About Single IRB Review: Principles and Practice (Part 1)

July 07, 2020 / Jeffrey Rollins and Shirley Rojas

Videocast

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OHSRP Newsletter 2020 Q2

Letter from the Director - 2020 Q2

We are approaching the 6-month mark for the consolidation of all the legacy IRBs into the new NIH Intramural IRB (NIH IRB).  I know that this has not been the easiest transition for the NIH community, and I thank you for your support and patience as we continue to build our new organization.  Our goal is to serve the intramural research community by providing optimal protections for our research subjects and facilitating the ethical conduct of the life-saving research conducted here at NIH.

Despite the challenges of an entirely remote workforce, the IRB continues to improve its metrics.  The IRB is receiving approximately 400 forms submitted each month.  The mean time to approval in May for new studies, amendments and continuing reviews reviewed by the full board were 40, 46 and 28 days respectively.  For forms approved by the expedited path, initial reviews were approved in 13 days, amendments in 14 days and continuing reviews in 11 days.  We continue to examine our processes to identify areas for increased efficiencies.

We have prioritized all COVID research, and the mean approval times for COVID related research were 4.5 days for initial reviews, 5.7 days for amendments, 2 days for NHSR determinations and 5.5 days for institutional approvals for multi-site research in which we are relying on an external IRB.  These truly amazing stats reflect the incredible hard work and dedication of the entire OHSRP staff that have dropped everything and worked many long hours to move these studies from submission to approval.  I can’t thank them enough for their dedication.

We have begun exploring the feasibility of replacing iRIS with a new electronic IRB system.  A steering committee made up of representatives from the ICs, the Assembly of Scientists and OHSRP have met once to discuss the process for evaluating the current landscape of systems.  While we cannot have a committee that has representation from every IC, rest assured that we will be soliciting direct input from the entire research community throughout the entire process.  Our goal is to find a system that serves our entire research community well, is forward looking and can grow as clinical research grows at the NIH.  I expect that this will be a long process, and in the meantime, we will continue to optimize iRIS.

As I said when I first arrived here, we can only succeed as a human research protection program (HRPP) if we work collaboratively with our investigator community.  I am grateful that the investigator community has been so willing to work with us and help us understand how best to serve their needs and those of our research participants.  The NIH can be a challenging place from an organizational standpoint.  I was asked recently, what do I know now that I wish I knew earlier.  My response was that when I arrived here, I thought the NIH was like a University with 27 different departments.  I now know it is more like 27 different Universities.

Policy Update - 2020 Q2

The revision of the human research protection program (HRPP) policies is ongoing. To date 22 HRPP policies have been approved, of which three (3) have been released and are implemented. The implemented policies are located on the Policy page on the newly updated OHSRP website. All other HRPP Standard Operating Procedures (SOPs) continue to apply until they are superseded by new policies. The active SOPs are also accessible on the Policy page. We will be implementing some of the approved policies in the very near future. Keep an eye out for announcements on these policy releases. To aid investigators and research teams in in understanding what has changed, these implemented policies will be accompanied by policy change documents. Investigators will be responsible for reviewing and complying with the newly implemented policies. The SOPs that have been superseded will continue to be available for historical purposes only, on the Policy Archive which is also located on the Policy page.

Accreditation Activities

In April 2020, the NIH Annual Report was submitted to the accrediting body, the Association for Accreditation of Human Research Protection Programs (AAHRPP). The report was accepted by AAHRPP with no changes. This year it took the NIH “Village” to prepare the report.  Thank you to the IC AAHRPP Liaisons and to ORSC for helping us with this year’s report.  This year, ORSC established a new QAQI database to help us collect information about IC QAQI activities. So, we want to give a special thank you to ORSC and the IC QAQI teams for piloting this new system. We got a little bit of a surprise in February, when AAHRPP asked us to pilot their new online submission system. On the upside, AAHRPP gave us till mid-April to submit the report, since we were willing to pilot their new system. However, they asked us for all the data we normally collect in preparation for re-accreditation, which is quite a bit more than what is normally requested in the annual report. With the help of our stellar IT team, we got the job done. It was a good dry run for our actual accreditation renewal which will be submitted in March 2021. That means we will have a site visit in early 2022!  Lastly, in May, we submitted a status report to AAHRPP to update the accrediting body on the status of the consolidation of the IC IRBs into the NIH Intramural IRB, and to provide an update regarding the streamlining of IRB operations. We were able to inform AAHRPP that we fully consolidated the IC IRBs into the NIH Intramural IRB in December 2019. We provided metrics which highlighted the increase in submission volume due to IRB consolidation, and the impact of COVID-19 on IRB operations. We also highlighted the changes to iRIS and the streamlining of forms. This report will be reviewed at the next AAHRPP Council.

What's New in iRIS?

Release Updates:

The iRIS team continues to streamline and make more efficient the iRIS workflow.  We thank all of the research community for their feedback in the development and testing of these improvements.  Below are some of the improvements made for you in the first half of this year:

New

Progress Report Form

New combined standalone form that allows users to submit:

• Continuing Reviews
• Study Closures
• Progress Reports 

Revised

Amendment Form

New combined standalone form that replaces the following extraneous forms:

• Investigator Brochure Submission Form
• KSP Changes Form
• Participant Recruitment Materials Form
• Miscellaneous Documents Submission Form
• Short Consent Approval Form
• DSMB or SMC Outcome Letter Submission
• Outside IRB documents for multi-institutional trials

NHSR Form

Roll out

Radiation Safety Review (all ICs are now submitting in iRIS)

Scientific Review (all ICs are now submitting in iRIS)

Training: “Making iRIS work for you”

Sue Tindall, our iRIS Team lead delivered by videocast the May 2020 OHSRP Education Series.  Thank you for the heavy attendance and interest in what we have been doing to make iRIS work better for the research community so that you can do what you do best.  You can view the recording on the NIH Employee Intranet here.

Compliance & Training Update - 2020 Q2

The OHSRP Education Series for 2020 continues, albeit virtually for now, and the archived presentations can be found here on the OHSRP webpage.  Once you click on the title of a specific session, a link to the videocast is also provided. The IRB Office Reliance and Single IRB team will be presenting a two-part education session in July and August. Part I will cover fundamental concepts and requirements relating to multi-site research and review by a single IRB. Part II will outline the responsibilities, and related processes, when an NIH study team plans to lead a multi-site research study and requests that the NIH IRB serve as the single IRB for all Participating Sites. It will also discuss requirements when NIH Investigators wish to rely on an external IRB.

The NIH Intramural Research Program is approaching the one-year anniversary mark for the initial implementation of Policy 801, Reporting Research Events and Policy 802, Non-Compliance in Human Subjects Research that occurred 7/1/2019.  As was the case in 2019 after policy implementation, we continue to see fewer reportable events being submitted in iRIS in an expedited manner predominantly because protocol deviations that are minor in nature may now be reported as part of a high-level summary at the time of continuing review.  Information regarding these polices as well as helpful guidance documents can be found on this IRBO webpage under the section labeled “800 Series.”

Likewise, we are at the one year anniversary of the implementation of Policy 201, Education Program, that defines training requirements for investigators on protocols overseen by the NIH Intramural IRB.  As investigators submit new actions in iRIS, the IRB will be checking to confirm that investigators listed on the protocol have completed the appropriate human subjects research (HSR) training as described in the current policy.  We urge all investigators to check and confirm that they are up to date on the required training and that this information is reflected in iRIS, so that review of the submission is not delayed pending documentation of training completion in iRIS as required for all protocol investigators.  To check to see if training records are correctly updated in iRIS, investigators can go to this page on the IRBO webpage,  and scroll down to the section labeled “Personal Training Records.”  If the investigator has not completed the required training as listed in Policy 201, investigators can go to this link, which provides information about how to register for a new NIH CITI account and take the required training. Alternatively, if they have completed the correct training but it is not reflected in iRIS, this same link also includes instructions as to how to check HSR training completion records via the NIH CITI Portal. Only CITI training records that exist via this portal are automatically downloaded into iRIS. If an NIH investigator completed the appropriate training via another portal at NIH or at a non-NIH site, and the training is current, those records can be transferred into the NIH CITI database once the investigator has registered via that portal.  Instructions for all steps include screenshots. Please note that NIH investigators were required to complete a CITI basic HSR training course after 1/21/2019 without the option of testing out because these modules contained important changes included in the Revised Common Rule.  Policy 201 also outlines requirements for GCP training for those investigators conducting non-exempt (requiring IRB review) HSR.  Note that if investigators completed or tested out of CITI GCP or completed NIAID GCP within the prior 3 years, they are still considered current.  When this GCP training expires or, if investigators have never completed this training, they must complete or test out of CITI GCP (US FDA Focus).

IRB Operations Update

After the news of the spread of COVID-19 in the United States, the majority of IRBO staff immediately began teleworking.  Thank goodness for technology like Skype, MS Teams and WebEx which has allowed IRB Chairs, members, and staff to communicate and work diligently to continue to review vital NIH research projects. On March 17, we began holding all IRB meetings via teleconference and have held approximately 40 meetings in this manner since then. While meeting remotely is not ideal, we are proud to see the strong show of commitment on everyone’s part in stepping up to meet these new challenges.  

In fact, as noted above, many IRBO staff saw their workload increase as investigators rushed to submit important new studies related to COVID-19.  The IRBO/IRB has now reviewed 26 initial reviews, 16 amendments, 1 exempt study and 13 not human subject research studies focused on new research on SARS-CoV–2/COVID-19 or amendments to modify data collection methods.  During this time, the IRBO has received many questions related to conducting remote research and providing extra protections for staff and subjects.

Considerations When Writing a Protocol During the COVID-19 Pandemic

With regard to conducting telehealth as a part of IRB-approved research, please be sure to consider the following:

• Use only telehealth platforms that are approved by NIH IT/your ISSO or the Clinical Center, if applicable
  • Your telehealth plan must be described in detail in the protocol and include, as applicable:
  • Whether it will involve new subjects or ongoing/existing subjects;
  • How you will conduct consent;
  • How and when you will communicate with subjects;
  • What procedures/treatments may be performed locally; and
  • How and when you will communicate with local MDs.
• If you plan to conduct telehealth only temporarily for a few subjects, you can submit your plan on a single patient planned deviation request form rather than having to amend the protocol. (Please note that if the protocol is under an IND, the plan needs to be approved by the IND sponsor prior to IRB submission). When writing your request, be sure to also address:
  • What procedures/treatments may be omitted; and
  • How omitting procedures/treatments might affect the safety of the subjects and the scientific integrity of the study.

We are currently working on some guidance on conducting informed consent during the COVID-19 pandemic. In the interim, we want to share some key points, although most of this information is relevant for human subjects research in general:

1. The IRB is only allowed to approve a waiver of consent, an alteration of consent, or a waiver of documentation of informed consent when the research meets the criteria described in 45 CFR 46 (pre-2018 Common Rule; 2018 Common Rule). When requesting a waiver or alteration, the PI must address all of the regulatory criteria along with a justification in the protocol.
   1. A Waiver of Consent refers to a waiver from obtaining consent from subjects before conducting research.
   2. An Alteration of Consent refers to a consent procedure which omits or alters some or all of the elements of consent in the consent language.
   3. A Waiver of Documentation refers to a waiver of obtaining a signature on a written or electronic informed consent form as part of the consent procedure.
2. Generally speaking, when a research project involves interacting with subjects to conduct research procedures on site, the IRB will not approve a waiver of documentation. The IRB will consider approving a waiver of documentation for minimal risk, in person research in which the subject is known or is likely to be infected with SARS-CoV–2.
3. If subjects will never come to the NIH, and the consent process will occur remotely, e.g. over the telephone, the protocol should include a plan to send the consent form to the subject and return of a signed consent document. See NIH HRPP SOP 12 for more information about the requirements associated with telephone consent.
4. Electronic Informed Consent (eConsent) refers to using a consent document that includes all the elements of consent in an electronic format. It involves obtaining the subjects’ electronic signature with a time stamp. The use of eConsent for FDA-regulated research must meet additional regulatory requirements. Currently there is no eConsent technology that has been approved for use as part of NIH IRB-approved research. When research will be conducted remotely and entirely online, e.g. completion of an online survey only, it is likely that the IRB would approve a process in which the subject reviews an on-line consent form along a waiver of documentation of informed consent. This is different from what is referred to as eConsent.
5. Under the Privacy Act, all subjects, about whom the investigator is collecting identifiers, have to receive the notice in writing.  If you intend to conduct an oral consent process and request a waiver of documentation, please note that you will still need to provide a written notice about privacy to your research subjects. Be sure to describe how you will be providing this written notice to subjects in the consent section of your protocol. If your subjects will not be registered as Clinical Center patients, you must consult with your IC Privacy Officer to find out the appropriate language that must be shared. 
6. In addition, for all protocols involving personal identifiers, all consent forms/scripts must include the approved language about Certificates of Confidentiality (CoCs).
7. Please note that if your protocol involves the use of a drug, biologic, diagnostic, device, or vaccine used to treat, diagnose (e.g. testing), cure, prevent, or mitigate COVID–19 or the transmission of SARS-CoV–2, your consent form must include the PREP Act language.

Amending Studies

We want to remind investigators that if you wish to pursue a new research question or conduct a new sub-study, in most cases this would require submission of a new protocol.  A research protocol should only be amended, if the planned research is covered under the current specific aims in the IRB-approved protocol. If you have questions about whether you should submit a new study or amendment a previously approved study, please contact the IRBO at IRB@od.nih.gov.

New Protocols

When designing a new study, please utilize the protocol templates on the IRBO website.  We now have templates to cover interventional drug and device studies, natural history/observational studies, secondary research studies (identifiable specimens or data), repositories (for new collection or storage of identifiable specimens or data), and exempt human subject research studies.  The process for IRB review and approval is always more efficient, when the appropriate NIH protocol template has been utilized and all of the required content is included.

Continuing Reviews/Progress Reports for Studies Reviewed on or after January 21, 2019

If your initial protocol was reviewed and approved by the full board on or after Jan. 21, 2019 and determined to be minimal risk, you will need to submit a Continuing Review annually.  The Continuing Review will be able to be reviewed through an expedited pathway.

If your initial protocol was reviewed and approved by an expedited reviewer on or after Jan. 21, 2019, you will need to submit a Progress Report annually.  The Progress Report will collect certain data that is required at NIH to meet other reporting requirements.

If your study was reviewed and determined to be exempt and involves the collection of inclusion enrollment data, as long as you are enrolling new subjects, you will need to submit a Progress Report annually in iRIS to provide this data.

You should receive a reminder to submit Continuing Review and Progress Reports. If you are confused about when your review/report is due, what to submit or think you have received inaccurate information, please contact the IRBO at IRB@od.nih.gov.

IRB Member Considerations When Evaluating Reported Events as Possible Unanticipated Problems

June 15, 2020

The OHSRP Education Series 2020: Understanding the NIH IRB Review Processes to Improve Submissions

June 02, 2020 / Tiffany Gommel

Videocast

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IRB Member Considerations when Reviewing Criteria for IRB Approval of Research Protocols: Minimizing Risk and the Risk vs. Benefit Assessment

June 01, 2020

The OHSRP Education Series 2020: Making iRIS Work for YOU

May 5, 2020 / Sue Tindall

Videocast (NIH only)

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IRB and RSC Review of Research Protocols Using Radiation and Radiation Dosimetry Calculations for NIH protocols

May 15, 2020

Protocols will require RSC review (or RDRC if applicable) if it meets any of the following criteria: (this will be provided as a checklist in iRIS).

• Uses a radioactive research drug(s) regulated under the FDA requirements for review by the Radioactive Drug Research Committee (RDRC)
• Involves the use of any radiation in pediatric participants (<18 years old) with an annual effective dose >0.5 rem or healthy pediatric volunteers (any dose level)
• Uses any radiation in healthy adult volunteers, excluding DEXA and chest X-Ray
• Uses therapeutic administration of radioactive materials (Examples include therapeutic use of I-131, Lu-177, Y-90, Th-227, Ra-223, or Ir-192 permanent seed implants. The following would be excluded from required RSC review: Use of linear accelerator such as total body irradiation or high dose-rate afterloader such as brachytherapy for breast or prostate cancer.)
• Involves novel uses of radiation, including any radioactive Investigational New Drugs (IND) and radiation-producing investigational devices
• The radiation itself is the research agent being studied in the protocol (For example: the protocol compares the effectiveness of 2 different doses of radiation therapy; comparison of the effectiveness of drug X vs drug X + radiation therapy; study of the uptake and biodistribution of a novel radioactive tracer)

Protocols that fall into one of these categories will continue to be reviewed by the RSC as they are now, but submission of the required forms will be via iRIS. The RSC may determine at the time of review that continuing review by the RSC is not necessary.  As noted above, RSC will be calculating total effective dose (ED) based on all radiation listed in the protocol.

Note:  At the time of IRB review, the IRB may refer any protocol to the RSC for review if it deems RSC expertise is required.

For protocols that no longer require RSC review:

Investigators should calculate the total ED for all radiation in the protocol prior to IRB submission using the tools available on the RSC webpage.  A dose library and totals worksheet will be provided.  Using these resources, investigators should enter the scans, doses, and frequency of each specific scan will be conducted within a one-year period in the online spreadsheet.  This spreadsheet will be used to calculate the total annual ED for the protocol as well as the comparable risk assessments that need to be inserted into versions B and C of the informed consent language, and it should be retained in the study’s regulatory binder. It does not need to be included in the IRB submission.

Once the investigator has calculated the total annual ED, this information must be added to the protocol and consent documents along with specific approved language regarding associated risk based on the dose range in which the total calculated ED falls (< 0.3 rem vs. > 0.3 rem and < 5 rem for adults vs. > 5 rem for adults with different approved language for pediatric participants)  Investigators are responsible for ensuring that the appropriate radiation risk language is included in the consent. Consent language can be found within our consent library on the IRBO website.

These changes apply to all initial reviews submitted to the NIH IRB after May 15, 2020 unless the protocol has already been submitted for RSC review prior to that date. For protocols that are currently approved by the NIH IRB, the PI should update the protocol and the risk language in the consent at the time of the next planned amendment to include the total ED for all radiation.

For any questions regarding calculation of ED and associated consent language, please contact the RSC Executive Secretary, Teresa Fisher, at 301-496-2253 or RSCExecSec@nih.gov.  For IRB related questions, please contact the IRBO at 301-402-3713 or irb@od.nih.gov.   

How to Receive Email Updates About FDA Drug Label Changes

Step one

Click on this link to subscribe or manage subscriptions to FDA email updates.  You will see the screen for the FDA Subscription Management Center.   Enter and confirm your email address as instructed.

Step two

You will now see a list of all the possible FDA email update subscriptions.  The subscription that sends out changes in approved drug labels is titled “CDER Drug Safety Labeling Changes”.  You may choose any additional FDA updates that you may be interested in receiving.  You can always change this later. 

Step three

Save your changes and then you are done.