BRPC FAQS

Contents

General 2

What is the BRPC?. 2

I would like to obtain frozen tissue/blood products/paraffin tissue from the bank of consented-patients within BRPC.  How do I proceed?  What is the approval process?  How much does it cost?. 2

I want to perform a study utilizing the BRPC. Do I need to add all of the BRPC staff as personnel on my IRB protocol?  3

I would like BRPC to provide tissue processing support services for my upcoming clinical trial.  What is the procedure for this?. 3

Samples. 3

What types of tissues/samples does the BRPC collect?. 3

What is FFPE?. 3

I need snap-frozen tissue for my research. Do you have snap-frozen tissue?. 4

Can you screen for very specific cancer patients and provide fresh tissue?. 4

I need DNA from a cohort of patients with [XYZ] and controls.  [XYZ] is really rare.  What are the options?  4

I need tissue samples that I’m unlikely to receive from surgery.  Can BRPC access organ tissues from autopsy patients for tissue types such as parathyroid, adrenal gland, testicle, coronary artery, etc.?. 4

Can BRPC staff extract RNA from the samples I am requesting? What type of samples can you extract RNA from?  4

Is the RNA from FFPE tissue usable for my downstream applications?. 5

Can I use BRPC-stored plasma for Cell-free DNA analyses?. 5

Can you collect materials for study of the microbiome?. 5

I just need some fresh normal (organ) tissue for pilot testing.  What’s the easiest way for me to proceed?  5

I would like to start regularly receiving fresh (organ) tissue for my research.  How should I proceed?. 5

The clinical trial I want to open requests original diagnostic slides/entire archival paraffin blocks.  Why won’t Duke Pathology and Clinical Laboratories release these?  What other options do I have?. 5

Consenting Patients to Biobanking. 6

I would like my research staff trained to consent patients to BRPC protocol so that their leftover clinical samples can be biobanked.  What should I do?. 6

I would like to recommend that Duke consent a patient for biobanking.  I have already spoken with the patient.  What should I do?. 6

Why doesn’t BRPC consent everyone for biobanking?. 6

Budget. 7

I have my own IRB-approved protocol.  Why does BRPC charge a fee for patient specimen release to my lab?  7

Are there one-time project start-up fees?  What do these cover?. 7

I have a protocol in pre-submission and we are performing a feasibility review.  Will you provide an estimate for XX?  8

I have already chosen the blocks I need cut for my archival paraffin study.  Why am I required to pay for the Pathologist Fee?. 8

Why do we need Path Review approval?. 8

Why do you charge for Full Reviews?. 9

My team has previously been provided samples through the Department of Pathology at no charge. Why did this change?. 9

Is there any way for my team to avoid these fees?. 9

Is there a way to avoid the BRPC’s “Pathologist Review Fee?”. 10

Is there a way to avoid the BRPC’s “Case Handling Fee?”. 10

What does a sample budget look like for cutting unstained slides from a clinical archival case?. 10

Is there any DCI-member discounted rate available for technical histology fees (unstained slide creation, H&E staining, scrolls, etc.)?. 10

Path Review Form.. 11

Why do you ask if the study tissues are obtained via the Brain Tumor Center or BRPC?. 11

General Tips for Path Review Completion. 11

General

What is the BRPC?

The Duke BioRepository & Precision Pathology Center (BRPC) is an official shared resource of the School of Medicine, offering broad-consent biobanking as well as protocol-specific tissue procurement and research support services on behalf of the Department of Pathology & DUHS Clinical Laboratories.

I would like to obtain frozen tissue/blood products/paraffin tissue from the bank of consented-patients within BRPC.  How do I proceed?  What is the approval process?  How much does it cost? 

Please submit your approved IRB protocol, lab manual, and the following protocol request form: https://pathology.duke.edu/sites/pathology.duke.edu/files/BRPCProtocolReviewForm.pdf, and send to Aubrey Coulas: aubrey.coulas@duke.edu. Please provide as much information in the tissue processing section as possible. For most studies, an IRB protocol should also be submitted.  BRPC will review the documents, and send back a scope of work and budget.  Once everyone is in agreeance, BRPC will create internal Standard Operating Procedures, and your study will be considered approved.  There are one time fees associated with protocol start up, which are covered in “Are there one-time project start-up fees?  What do these cover?

Additional details on pricing and budget are given below.

I want to perform a study utilizing the BRPC. Do I need to add all of the BRPC staff as personnel on my IRB protocol?

No. BRPC activities (which often include access to Pathology-related PHI because of the nature of our work) are covered under our own IRB protocol Pro00035974. The language specifically states that the BRPC Shared Resource infrastructure will be “viewed as an extension of the specific study team’s capabilities” and therefore each person in the BRPC does not need to be on every IRB protocol that we support.

I would like BRPC to provide tissue processing support services for my upcoming clinical trial.  What is the procedure for this?

Please submit your approved IRB protocol, lab manual, and the following protocol request form: https://pathology.duke.edu/sites/pathology.duke.edu/files/BRPCProtocolReviewForm.pdf, and send to Aubrey Coulas: aubrey.coulas@duke.edu. Please provide as much information in the tissue processing section as possible. For most studies, an IRB protocol should also be submitted.  BRPC will review the documents, and send back a scope of work and budget.  Once everyone is in agreeance, BRPC will create internal Standard Operating Procedures, and your study will be considered approved.  There are one time fees associated with protocol start up, which are covered in “Are there one-time project start-up fees?  What do these cover?

Additional details on pricing and budget are given below.
 

Samples

What types of tissues/samples does the BRPC collect?

We are flexible as to tissue types collected, as we meet the standard of ‘fit for purpose’ rather than any arbitrary sample type.

We collect and distribute tissue “fresh” (hydrated, maintained at 4C, for PDX creation, cell culture creation, immune profiling via flow cytometry).

We collect and distribute tissue frozen in OCT and held at -80C (in order to create a ‘top slide’ for histologic quality assurance).

We collect and distribute tissue as formalin-fixed, paraffin-embedded (FFPE) blocks or their derivatives.

If you are interested in a sample type not listed here, we can work with you to develop a protocol.

What is FFPE?

Formalin-fixed, paraffin-embedded (FFPE) blocks are the standard used to make clinical diagnoses. Tissue from biopsy or resection specimens is processed, fixed in formalin, then embedded in paraffin blocks. These blocks are thinly sectioned to make slides for diagnosis, and can also be used for ancillary studies.

I need snap-frozen tissue for my research. Do you have snap-frozen tissue?

BRPC has frozen samples of tumors, diseased organs, and normal organs.  Most of our frozen samples have been embedded into water-soluble OCT medium prior to freezing. 

For research using downstream nucleic acid analysis, we do not use snap frozen tissue without embedding material into OCT because we cannot evaluate it histologically.  This is a CAP requirement – i.e., that all of our samples be qualified with % tumor nuclei and % necrosis.

However, research using downstream proteomics can be problematic using OCT-embedded samples.  For this reason we have created an SOP by which we can snap freeze tissue without OCT/embedding medium if we take a ‘mirror face’ for FFPE block.  This ‘mirror face’ allows us to quantitate % tumor nuclei and % necrosis. 

Please contact us about specific tissue types required.

Can you screen for very specific cancer patients and provide fresh tissue?

Yes, we can provide this service prospectively for investigators.

I need DNA from a cohort of patients with [XYZ] and controls.  [XYZ] is really rare.  What are the options?

For rare diseases, the options are to search in our FFPE archives, or other databases nationally like the NCI specimen locator, CHTN, etc. The BRPC can assist with these queries.

I need tissue samples that I’m unlikely to receive from surgery.  Can BRPC access organ tissues from autopsy patients for tissue types such as parathyroid, adrenal gland, testicle, coronary artery, etc.?

Yes. Please contact us about specific tissue types required.

Can BRPC staff extract RNA from the samples I am requesting? What type of samples can you extract RNA from?

Yes. We can extract RNA from fresh tissue, flash frozen tissue, tissue frozen in OCT, FFPE tissue, and whole blood buffy coat.

Is the RNA from FFPE tissue usable for my downstream applications?

It depends on your downstream applications. For RT-qPCR yes; but for sequencing purposes, no. Formalin impacts RNA quality in a way such that quality may not be sufficient for sequencing.

Can you collect materials for study of the microbiome?

Yes. For microbiome collections, the protocol will depend on types of tissue samples you want to collect and if there is any added value from histologic QC.  For example, if you are taking tissue samples of ‘normal’ colon it might be appropriate just to snap freeze these without histologic confirmation. However, if we are taking tissue samples of tumor, we may considering freezing a “mirror face” in OCT for histologic evaluation, if, for example, you want to know whether the organisms came from a region of viable tumor or necrosis.

I just need some fresh normal (organ) tissue for pilot testing.  What’s the easiest way for me to proceed?

The simplest approach for a one-time request is via anonymous tissue release. This means that the tissue is deidentified and all links to additional patient information are broken. BRPC can anonymize the tissue and release as fee-for-service under our own IRB protocol, with no need for additional IRB approval.

I would like to start regularly receiving fresh (organ) tissue for my research.  How should I proceed?

Submit an IRB protocol to the Duke IRB indicating that you wish to receive either (1) anonymized leftover clinical samples and/or (2) leftover clinical samples labelled with BRPC ID only where the patient has signed BRPC broad consent for tissue donation.

The clinical trial I want to open requests original diagnostic slides/entire archival paraffin blocks.  Why won’t Duke Pathology and Clinical Laboratories release these?  What other options do I have?

The United States Federal Government enforces CLIA law requiring pathology labs to maintain original diagnostic material. Duke strictly follows CLIA regulations as enforced through our CAP inspection process. That said, Duke offers a flexible array of options for the above.

For original diagnostic slides, alternative options are:

                -Whole Slide Images (WSI)

                -recut sections

For archival paraffin blocks, we are extremely flexible with options short of sending an entire diagnostic block:

                - core tumor with re-embedding in new paraffin block

- scrolls of tissue from blocks

-unstained sections from blocks

-special exemption from the Directors of Surgical Pathology and Duke Clinical Laboratories – this is required in less than 5% of clinical trials.
 

Consenting Patients to Biobanking

I would like my research staff trained to consent patients to BRPC protocol so that their leftover clinical samples can be biobanked.  What should I do?

The BRPC conducts training sessions for a fee on consenting to the BRPC protocol. Please contact the BRPC shared inbox: brpc@duke.edu and Aubrey Coulas: Aubrey.coulas@duke.edu to submit a consent training request for your staff members.

 

I would like to recommend that Duke consent a patient for biobanking.  I have already spoken with the patient.  What should I do?

Please contact the BRPC shared inbox at brpc@duke.edu with the following information: patient name, patient MRN, date of clinic visit if known, date of surgery if known, type of consent request (excess tissue for resections or additional tissue for biopsy procedures), and confirmation whether the patient has been introduced to biobanking research or not.

Why doesn’t BRPC consent everyone for biobanking?

The Duke BioRepository & Precision Pathology Center (BRPC) is an official shared resource of the School of Medicine and the Duke Cancer Institute (DCI). As such, our primary responsibility is to support research groups and efforts of the SoM and DCI. The consent process is time-consuming and requires dedicated and trained personnel. The BRPC works closely with disease groups, and in addition to BRPC staff, different disease working group staff members are trained to serve as consenters to the BRPC protocol. While we all work together to ensure that many patients (approximately 5,000 to date) can be consented, the logistics and time involved preclude us from consenting every patient who is seen at Duke.
 

Budget

I have my own IRB-approved protocol.  Why does BRPC charge a fee for patient specimen release to my lab?

Every patient specimen (blood for CBC, biopsy tissue sample, surgically-resected organ, and organs procured at the time of medical autopsy) is ultimately the responsibility of DUHS Clinical Laboratories which are directed by faculty members of the Department of Pathology.  It is our responsibility to ensure that the intended purpose of the specimen procurement (diagnosis, surgical pathology report, autopsy report, etc) is met.

Often, additional sample is available for research, but the decision of how much sample and when it can be made available is the responsibility of the attending pathologist.  The BRPC coordinates this approval through creation, approval and documentation of procurement protocols and arranging real-time dissection to be performed or overseen by an attending pathologist when necessary.

DUHS Clinical Laboratories and the Department of Pathology also have a responsibility to verify the investigator’s IRB protocol approval and track the release of all samples (anonymous, coded or identified) to ensure compliance with the protocol specifications.  The BRPC utilizes Duke School of Medicine and Duke Office of Clinical Research-sanctioned software (OnCore and LabVantage) to create ‘release’ accounts that track the transfer of specimens to investigators under open IRB protocols.

In addition, the logistics of tracking the procedure (blood collection, biopsy, surgery, autopsy) and the logistics of acquiring excess sample and transferring it to the investigator require effort of DUHS Clinical Laboratories and Department of Pathology staff.  The BRPC has the ability to monitor blood draws, biopsy procedures, surgical procedures and autopsy procedures through EPIC and/or internal Pathology resources to facilitate sample procurement events.

The BRPC therefore charges FY2019 research sample procurement fees as follows:

Are there one-time project start-up fees?  What do these cover?

Yes.  The following fees are associated with “Pathology Review” in the IRB approval workflow.  See the Pathology Review Form for details, but some studies qualify for automatic approval and other studies require full review.  In general, full review is required if the project has the potential to interfere with the rendering of a diagnosis on the samples in question.  The full review fee will be waived if a faculty pathologist (member of your team) takes responsibility for all of the regulatory, logistic, and specimen release oversight requirements as indicated below in “Is there any way for my team to avoid these fees?”

The following fees are associated with the BRPC building a scope of work, budget, and standard operating procedure for your study.  Also, there is a fee to cover the building of your study in LabVantage (this allows the LabVantage software to monitor that all sample releases are occurring under an open, approved IRB protocol).

I have a protocol in pre-submission and we are performing a feasibility review.  Will you provide an estimate for XX?     

BRPC will provide a broad estimate for our services, based on information you provide about the proposed study.  Please complete the BRPC Request for Protocol Support form https://pathology.duke.edu/sites/pathology.duke.edu/files/BRPCProtocolReviewForm.pdf, and mention this is for a feasibility review only, and send to Aubrey Coulas: aubrey.coulas@duke.edu. Please provide as much information in the tissue processing section as possible.

I have already chosen the blocks I need cut for my archival paraffin study.  Why am I required to pay for the Pathologist Fee?

BRPC facilitates archival paraffin requests under the Duke Clinical Laboratories SOP for usage of paraffin materials in research (LTR77616), which states “All of the slides and paraffin blocks… must be reviewed by a DUMC pathologist… to verify that recuts will not deplete the paraffin block and that sufficient material remains for further diagnostic work if it should become required.” This step is required to ensure patient care will not be impacted by research use of patient materials.

 Why do we need Path Review approval?

Pathology slides, blocks and tissue retention are mandated by the US Federal Law (CFR493.1105).  At Duke, when these materials are utilized for clinical research purposes, compliance is ensured through the Path Review system according to CLIA/CAP guidelines as well as through policies of the DUHS Clinical Laboratories. Patient materials are also maintained for potential future studies that may be required for patient care. The path review process is in place to minimize impact on patient care from research use of patient materials.

Why do you charge for Full Reviews?

This is a safety requirement for the Duke IRB. Increased volume/demands as well as increasing complexity of protocols (some are 200+ pages or have a dedicated lab/tissue handling manual) mandated that Pathology begin to recover effort.  The fees are a way to recover the pathologist effort and staff record-keeping/administrative time.

My team has previously been provided samples through the Department of Pathology at no charge. Why did this change?

  1. As the years have progressed, almost every part of the School of Medicine and the Health System has come under greater regulatory scrutiny.  There is an ever-increasing focus, not only on compliance with IRB-approved protocols and departmental policies, but on documentation of these efforts. 
  2. During the same time period, the clinical and administrative demands of the Department of Pathology and DUHS Clinical Laboratories faculty and staff has increased, often with concomitant decreases in revenue for common clinical activities.  In short, we have entered a time in which all faculty and staff effort must be accounted.

Is there any way for my team to avoid these fees?

It depends.  The effort and tasks mentioned above must be performed, but you may be able to get support for them in different ways.

  1. As you can see, there is Duke Cancer Institute subvention for tissue procurement associated with BRPC-broadly-consented cancer or pre-cancer patients.  There may be additional Duke Cancer Institute support available for sample procurement activities if your project is part of one of the DCI’s ten Disease Working Groups:   
  2. Apply for a Duke School of Medicine “voucher” – these are grants of up to $10,000 offered twice per year that can be used to cover Duke Shared Resource fees.
  3. Work with the BRPC and Pathology leadership to make a case to the School of Medicine that dedicated funding support be provided to cover these activities. 
  4. The final option is for your team to work directly with a faculty pathologist for project support.  However, keep in mind that the faculty pathologist you work with must be:
    1. A board-certified MD, practicing anatomic or clinical pathology at Duke
    2. Identified in your IRB protocol and specifically on the IRB’s “Pathology Approval Form.”
    3. Included as a co-investigator and co-author on the research
    4. Willing to perform all of the regulatory documentation, procedure tracking, dissection and sample transfer logistics themselves.

As you can imagine, the pathologist you approach may appropriately request some salary support for performing all these functions.  If they are willing to provide some, but not all of the functions, the functions still being performed by Duke Pathology and DUHS Clinical Laboratories Staff will be charged cost-recovery at the approved rates.  For example, the approved rate for specialized technical service in FY2019 is $74 per hour.

 

Is there a way to avoid the BRPC’s “Pathologist Review Fee?” 

The Pathologist Review step accomplishes two goals.  First, the pathologist reviews the entire surgical pathology case and selects the best block for research (typically the block with the highest percentage of viable tumor cells).  Second, the pathologist reviews the overall request for compliance with DUHS Clinical Laboratory Policy which includes non-exhaustion of limited biopsy samples for waived research studies.  Therefore, if an investigator contracts directly with a Duke Surgical Pathologist to perform these two functions, the request for “10 unstained slides from block B5” can be routed directly to the technical laboratory and by pass the Pathologist Review Fee.

Is there a way to avoid the BRPC’s “Case Handling Fee?” 

If you are working with a pathologist who will be performing the two ‘pathologist review’ functions, that pathologist has the option of asking their staff assistant to pull slides and print pathology reports for them OR asking the BRPC to pull slides and print pathology reports.  If the faculty member’s staff assistant pulls the slides and prints the pathology reports in preparation for the Pathologist Review, the BRPC “Case Handling Fee” would not apply. 

What does a sample budget look like for cutting unstained slides from a clinical archival case?

 

As an example budget, cutting 10 unstained slides and one H&E from a clinical archival case is:

$16.25 to pull case

$32.00 for Pathologist to review

$6.75 to cut/face & first slide

$39.50 for 10 unstained slides

$5.95 for H&E

Total per block: $100.45

 

Is there any DCI-member discounted rate available for technical histology fees (unstained slide creation, H&E staining, scrolls, etc.)?

There is only a single rate sheet covering the technical research histology lab services.  No DCI-member discounts are available for these services.  Currently, DCI “CCSG” grant support funds are used to subsidize general consenting and biobanking activity on behalf of the disease working groups of the DCI.
 

Path Review Form

Why do you ask if the study tissues are obtained via the Brain Tumor Center or BRPC? 

Because pathology oversight automatically occurs with tissue that moves through these biorepositories (ie. mitigating the risk that tissue is exhausted for research and there is none left for future clinical/diagnostic purposes).  Please note:  If you answer “Yes” that you are using a biorepository, the study will be moved to the appropriate biorepository automatically for feasibility, planning and/or budgeting purposes.

General Tips for Path Review Completion

“Does your study also require collection of new or non-clinical archival tissue specimens?”

Another way to ask this question is “Does your study also require “fresh tissue specimens”? 

 “Is all of the tissue for this study on the Surgical Pathology Tissue and Medical Devices Exceptions List? [See appendix or DUHS intranet, DUH Policies & Procedures, Tissue and Medical Devices Exceptions List,   Search “pathology: at URL https://egrc.duhs.duke.edu]

If your tissue isn’t specifically listed on the Exceptions List, answer “No” (please note:  for oncology studies, the answer to this question is almost always “No”).  

 

Is (or was) all of the tissue obtained solely for research purposes?   

(All criteria a-e must be true to answer “yes”.   If any criterion is not met, or if you are unsure if it meets criteria, answer “no”)

a)                   The biopsy or surgery is an additional procedure performed for the sole purpose of collecting tissue for the study.

b)                   The patient will have an established diagnosis at the time of the additional biopsy.

c)                   No routine pathologic evaluation of the tissue from the biopsy will be performed at Duke.

d)                   No routine (non-experimental) clinical care will be determined by evaluation of the research tissue.

e)                   Patients will be consented to the additional biopsy including the lack of any pathologic evaluation of the tissue

The key to this question is that all study tissue (excluding archival blocks) must have been obtained for research purposes only (no diagnostics/clinical care is based on tissue nor any path evaluations performed either at Duke or by a central pathologist). 

Basically, if a pathologist is required to review/evaluate any of the tissue as part of study, then this answer should be “No”.