CIBMTR Center Reference Guide

CIBMTR CENTER REFERENCE GUIDE

OVERVIEW OF CIBMTR Stem Cell Therapeutic Outcomes Database (SCTOD) Levels of Participation • Transplant Essential Data (TED) Only Centers • Comprehensive Report Form (CRF) Centers • BMT CTN Participation o Reimbursement

CENTER MEMBERSHIP INFORMATION IRB Approvals EBMT Centers

CIBMTR ACCESS FormsNet™2.0 • SecurID® and Log‐in CIBMTR Portal • Data Back to Centers (DBtC) • FormsNet™ Center Volume Data

TRAINING AND RESOURCES Mentor Program Data Manager Education Tips from the Network Cibmtr.org website

STUDIES CIBMTR Observational Studies Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Resource for Clinical Investigations in Blood and Marrow Transplant (RCI BMT) Study of long‐term complications of Kepivance (KGF) Comparison of intravenous busulfan versus total body irradiation for pretransplant conditioning (Otsuka Study)

ATTACHMENTS A: CIBMTR Working Committees B: Glossary of Abbreviations C: New Center Information Sheet D: Center Change Form E: Forms Submission Process

ENCLOSURES CIBMTR Progress Report CD

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OVERVIEW OF CIBMTR

The Center for International Blood and Marrow Transplant Research (CIBMTR) collaborates with the global scientific community to advance hematopoietic cell transplantation (HCT) and cellular therapy research worldwide. A combined research program of the National Marrow Donor Program (NMDP) and the Medical College of Wisconsin (MCW), the CIBMTR facilitates critical, cutting‐edge clinical research that has led to increased survival and an enriched quality of life for thousands of patients. The research is accomplished through scientific and statistical expertise, a large network of transplant centers and clinical database of more than 300,000 transplant recipients.

CIBMTR is comprised of four main programs: observational research, clinical trials support, immunobiology and statistical methodology. In addition, the NMDP Network— now called the “Be the Match Registry”— has grown to more than 7 million donors and nearly 100,000 cord blood units, the largest and most racially and ethnically diverse registry of its kind in the world.

CIBMTR collects observational data for HCT recipients from approximately 450 centers around the world, who register about 15,000 new transplants each year. Nineteen Working Committees design and conduct studies that focus on specific diseases and complications. Research looking at biologic and genetic factors that may affect transplant outcomes (immunobiology) is also underway.

Large clinical trials testing new strategies in blood and marrow transplantation are coordinated with NMDP and the EMMES Corporation, and performed under the auspices of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Scientific and statistical support for small clinical trials is provided to researchers worldwide through the Resource for Clinical Investigation in Blood and Marrow Transplantation (RCI BMT).

More information about the CIBMTR and its programs can be found in several places. The CIBMTR Progress Report is published yearly and is available in print format, on CD or online at http://www.cibmtr.org/About/AnnualReports/index.html. The CD is included in this Reference Guide as an enclosure. CIBMTR also publishes a progress report on the BMT CTN annually, which can be found online at https://web.emmes.com/study/bmt2/BMT%20CTN%20Annual%20Report_July%202009.pdf. For those interested in a printed version of the RCI BMT report, please contact Sarah Mull at [email protected].

CIBMTR also publishes a semi‐annual newsletter summarizing activities and highlighting the research work of the Working Committees and other CIBMTR activities. The Summary Slides are an annual report on data submitted to the CIBMTR. Part 1 focuses on trends in the use of HCT according to donor type, graft sources, patient age and transplant regimes. Early outcomes such as mortality rates at day 100 post HCT and causes of death are also included this series. Part II focuses on survival outcomes by age, disease, transplant and donor type, and by conditioning regimen intensities.

Newsletters and Summary Slides are available at: http://www.cibmtr.org/ReferenceCenter/index.html

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Stem Cell Therapeutic Outcomes Database (SCTOD) The Stem Cell Therapeutic and Research Act of 2005 (Public Law 109‐129) established the C.W. Bill Young Cell Transplantation Program (the Program), which is overseen by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services. The C.W. Bill Young Cell Transplantation Program is an expansion of the National Bone Marrow Donor Registry (the Registry). The Registry was begun in 1987 through a grant from the Navy and formally established in 1990 as a responsibility of the Department of Health and Human Services. The first transplant under its auspices took place in 1987.

The four components of the C.W. Bill Young Cell Transplantation Program are: • Office of Patient Advocacy and Single Point of Access (OPA/SPA); • Bone Marrow Coordinating Center (BMCC); • Cord Blood Coordinating Center (CBCC); • Stem Cell Therapeutic Outcomes Database (SCTOD).

While some of the activities of the Program are similar to those of the preceding NMDP Registry, the current Program has the added responsibility of collecting, analyzing and reporting on outcomes for all allogeneic transplants and on other therapeutic uses of blood stem cells. The Program also has expanded what the National Bone Marrow Donor Registry was doing to increase the number of available marrow donors and cord blood units. Initial contracts were awarded to thirteen U.S. Cord Blood Banks for the NCBI. The BMCC, CBCC and OPA/SPA contracts were awarded to NMDP. The SCTOD Contract was awarded to the CIBMTR.

Congress has legislated that outcomes data must be collected on all allogeneic transplants, both related and unrelated, where either the donor or the recipient resides in the United States or on transplants performed elsewhere with products collected in the United States. The CIBMTR, as recipient of the SCTOD contract, is responsible for administration of this activity and for collection and analysis of the data.

The SCTOD required the following changes in practice and procedures at CIBMTR: • Development of new systems to collect data electronically; • Enhanced efforts to develop a standard dataset of clinical HCT data; • New requirements for U.S. centers to report outcomes data for all allogeneic transplantations; • Development of a related donor‐recipient research sample repository; • Systems to make more data publicly available; • Broadened reporting of U.S. transplant center‐specific survival rates to include outcome of related donor transplants; • Data collection on uses of hematopoietic stem cells for new therapeutic applications (e.g., regenerative medicine).

Collaborative efforts have allowed CIBMTR and NMDP to meet the new challenges and requirements dictated by the SCTOD. The two campuses are strategically adjusting internal procedures to collect

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data on a harmonized paper form and electronic data collection system. The SCTOD is offering new research opportunities to the transplant community and streamlining data collection. Articles about the SCTOD and the C. W. Bill Young Program can be found in the December 2006 CIBMTR Newsletter and the November 1, 2006 ASBMT eNews. 2007 BMT Tandem Meeting SCTOD Web Presentations may be viewed online at http://www.asbmt.org/News/Outcomes.

Data from a transplant recipient are considered part of the SCTOD if they meet at least one of the following criteria: • Allogeneic HCT occurs at a U.S. transplant center • Stem cell collection is performed within the United States • Donor is obtained from within the United States

Recipient data are not considered part of the SCTOD if they meet one of the following criteria: • Recipient receives an autologous HCT • HCT does not occur in the United States and the stem cell donor resides outside of the United States • Cord blood unit is obtained from a cord blood bank outside of the United States and the transplant occurs outside of the United States

Levels of Participation The CIBMTR offers two levels of participation, as a Transplant Essential Data (TED level) Program or as a Comprehensive Report Form (CRF level) Program. Using each center’s designation of preferred reporting status, as described above, the CIBMTR applies a selection system that assigns recipients, as reported to CIBMTR, to the appropriate data reporting track:

Form selection algorithm: CIBMTR has developed an algorithm to determine which set of forms will be required for each HCT recipient. The goal of the algorithm is to randomly select an epidemiologic sample of recipients for whom a Comprehensive Report Form will be requested. The algorithm includes, but is not limited to, type of HCT, age of the recipient, disease, etc. The algorithm is periodically reviewed to assess the burden of data submission for transplant centers.

Transplant Essential Data (TED) only centers A transplant center designated as TED only is required to submit the following forms: • Unique ID Assignment (CRID) (Form 2804), due for recipient’s first HCT only • Pre‐TED (Form 2400) • Post‐TED (Form 2450) • The HCT Infusion Form (Form 2006) is required for some allogeneic recipients

See attachment F for more detail.

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Comprehensive Report Form (CRF) centers Comprehensive Report Form Centers are those that have agreed to complete either Post‐TED (Form 2450) forms or CRFs for their patients. Once a Pre‐TED (Form 2400) is submitted for the first transplant, a selection algorithm will decide on a follow‐up track for this patient.

When a center submits Comprehensive Report Forms, the following forms are included: • Unique ID Assignment (CRID) (Form 2804), due for the recipient’s first HCT only • Pre‐TED (Form 2400), due for the recipient’s first HCT only • HCT Infusion Form (Form 2006) • Infectious Disease Markers (non‐NMDP donors) Form 2004 • Confirmation of HLA Typing (recipient and non‐NMDP donors) Form 2005 • Baseline (Form 2000), Day +100 (Form 2100), 6 mo – 2 yrs (Form 2200), Annually >2 yrs (Form 2300) and appropriate disease inserts.

See attachment F for more detail.

BMT CTN Participation The BMT CTN (Clinical Trials Network) was established in October 2001 to conduct large, multi‐ institutional clinical trials addressing important issues in HCT. Sixteen Core Clinical Centers and more than 90 Affiliate Centers nationwide are working collaboratively to improve outcomes for transplant patients. Since opening its first trial, the BMT CTN has accrued more than 3,000 patients on 18 different studies that address important issues in hematopoietic stem cell transplantation.

Centers that participate in BMT CTN studies must be willing to submit CRFs for all patients enrolled on BMT CTN clinical trials. Centers that participate in BMT CTN must submit a minimum of TED level data on all transplant recipients at their center.

Reimbursement CIBMTR reimburses transplant centers for all completed CRFs, as listed on the following table. However, when a center submits CRFs that were not requested by CIBMTR, the forms may not be reimbursed. This is particularly applicable to centers that make arrangements with CIBMTR to submit CRFs for all HCT recipients in order to build a database for their own purposes. In these circumstances, the center will be reimbursed only for CRFs that are requested by the CIBMTR.

Reporting of TED level data is not reimbursed, with the exception of the Form 2006, when it is requested for data on transplant recipients who received a graft from an unrelated donor procured through the NMDP Coordinating Center (BMCC or CBCC). Once a form is designated as “error‐free” in FormsNet™2 (FormsNet™) the transplant center will be reimbursed. Forms are reimbursed at the rates on the following table:

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Transplant Center fee schedule Form Rate Form Title number 2000 Recipient Baseline Form with required disease form(s) 2004 Infectious Disease Markers (non‐NMDP donor or cord blood unit ) $135 2005 Confirmation of HLA Typing (recipient &non‐NMDP donor or cord blood unit) 2006 HCT Infusion (selected for Comprehensive Report Forms) $110 2100 100‐day post‐HCT with required disease form(s) $85 2200 Six‐month to two‐year post‐HCT with required disease forms() Yearly Follow‐up for greater than two years post‐HCT with required disease $65 2300 form(s) Unrelated HCT using U.S. donor (not selected for Comprehensive Report Form $25 2006 submission) $15 2900 Recipient Death Data

Data Transmission Agreement

Data Transmission Agreements (DTA) allow the exchange of data (and payment for data) between centers and the CIBMTR. Reimbursement for report forms submitted to CIBMTR is conditional upon receipt of a completed DTA. If you have further questions about DTA agreements please contact Nancy Poland ([email protected]) at 612‐362‐3401.

The CIBMTR cannot reimburse for Comprehensive Report Form submissions until it receives a signed Data Transmission Agreement (DTA). Centers should submit the DTA to the NMDP Contracts Department c/o Nancy Poland, National Marrow Donor Program, 3001 Broadway St. NE, Suite 110, Minneapolis, MN 55413‐1753; email [email protected]. Centers should continue operating under their current Data Use Agreement until they have submitted a new DTA. For additional information or questions, contact Nancy Poland at 612‐362‐3401.

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CENTER MEMBERSHIP INFORMATION

Following is an outline of the information centers need, and the forms they must submit to CIBMTR in order to become a member.

The New Center Information Sheet (Attachment C). This is the first form to submit to the CIBMTR in order to start the membership process. On it, provide all contact information for your center and key personnel. On page 2 of the form, designate what type of transplants your center does, and enter your EBMT team number, old NMDP number and old IBMTR team number (if applicable).

• CIBMTR center number (CCN). Once the CIBMTR New Center Information Sheet is completed and submitted, your center will be assigned a unique CIBMTR Center number. This is a very important number – it will link all of the data that your center submits back to your center.

• What is your EBMT number? If you are a member of the European Group for Blood and Marrow Transplantation, you must provide us with that number for our records. EBMT Teams submitting data via FormsNet™ should include their Center Identification Code number (CIC#) so that both center numbers can be cross‐referenced to ensure accuracy. For more information on European Centers and EBMT, please see the section entitled EBMT centers.

• A Center Liaison will be assigned once your CIBMTR New Center Information Sheet is submitted. This person will serve as your personal contact with CIBMTR, and will work with your Data Manager to help resolve any issues or answer any questions you may have.

• Who is your Primary Contact/Data Manager? A Primary Contact/Data Manager must be designated on the CIBMTR New Center Information online form. This person will serve as the primary contact for your center in our Global Contact Management database (GCM). The Primary Contact/Data Manager is the only person who can grant access permission to other personnel at your center, using the Center Personnel Change online form found at: http://www.cibmtr.org/DataManagement/AdminResources/Personnel/index.html

• Which campus are you assigned to? Your campus assignment will be made at the same time your Center Liaison is assigned. This campus (either Milwaukee, WI or Minneapolis, MN) is where you would submit paper forms to (if needed).

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Institutional Review Board (IRB) Approvals To be compliant with federal regulations for human research subject protection, transplant centers must obtain IRB‐approved informed consent from recipients before data submitted to the SCTOD can be used for research. Informed consent must also be obtained from recipients prior to submitting blood samples to the Research Sample Repository. International centers are also required to follow the applicable laws and regulations of their country for obtaining informed consent from their transplant recipients.

NMDP and the CIBMTR have written protocols and informed consent documents for the Research Database and Research Sample Repository. The NMDP and MCW IRBs have approved these protocols and consent forms. All centers must also have approval from their local IRB for the Research Database protocol. NMDP network member centers must also have local IRB approval for the Research Sample Repository protocol. Centers performing only related donor transplants and/or autologous transplants will not be submitting research samples and do not need to obtain local IRB approval for the repository protocol.

Under new federal legislation, U.S. centers are required to submit outcomes data on all allogeneic transplants, related and unrelated. Data submitted without informed consent from the recipient will only be used for federally required research such as the center‐specific outcomes analysis.

• The Database and Repository protocols and consent forms that need to be submitted to your IRB for approval are located on the CIBMTR website at: http://www.cibmtr.org/DataManagement/ProtocolConsent/index.html. Consent forms may be formatted according to each site’s requirements; however, the protocols must be submitted as written. The IRB approval letter and IRB‐approved consent forms should be sent to Christina Jobe each year. Failure to have current local IRB approval can affect a center’s Continuous Process Improvement (CPI). If you have any questions about the protocols or consents, please contact Christina Jobe ([email protected]) at 612‐627‐8164.

CIBMTR and NMDP have been designated as Public Health Authorities in their capacity of collection and use of data for the SCTOD, addressing HIPAA (Health Insurance Portability & Accountability Act) privacy regulations. The electronic systems that are used to collect and house protected health information (PHI) are very secure. The electronic systems used for acquisition and generation of unique ID numbers have undergone rigorous certification and authentication from HRSA’s Office of Information Technology, and comply with all federal regulations relevant to security of electronic data in federal databases. PHI data transmitted through the electronic system to the CIBMTR are stored in a tightly secured database that is separate from the outcomes database.

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EBMT Centers European Group for Blood and Marrow Transplantation (EBMT) centers have a different process for reporting data to the CIBMTR than U.S. centers. In the past, the EBMT data centers electronically forwarded MED‐A data (comparable to TED form data) to the CIBMTR from centers that had given their permission. Since December 2007 when the FormsNet™ application was implemented, CIBMTR has not been able to receive this electronic transfer of Med‐A data. As a result, MED‐A level data appear on the CIBMTR Forms Due report as being “overdue,” even though a center may have submitted these data to EBMT. These Med‐A “overdue” forms listed on the report can be ignored, as the data will be electronically transferred by the EBMT data center once electronic data transfer is re‐established. Data submitted on the following forms will be obtained from the EBMT at that time: • Form 2400 Pre‐TED • Form 2450 Post‐TED • Form 2455 Selective Post‐TED All other forms (2000, 2100, 2200, 2300, etc.) are Comprehensive Report Forms. These forms should be submitted directly to CIBMTR, either in FormsNet™ or on paper to your liaison.

CIBMTR is working to restore future electronic data transfer from EBMT, but such systems are not yet available. We realize it is a burden for centers to submit MED‐A level follow‐up data to both EBMT and CIBMTR. We will collect these follow‐up data from EBMT once the two systems are reconnected, and we encourage all centers to maintain timely follow‐up with the EBMT.

Because of large differences in data elements and format between MED‐B data and CIBMTR CRF data, there has never been an “electronic pathway” for these data to be transferred from EBMT to CIBMTR. Therefore, CIBMTR plans to continue to request follow‐up wherever possible for patients for whom it has CRF data. Follow‐up for these patients can be submitted to CIBMTR on paper forms or electronically via FormsNet™. These patients also appear on Forms Due reports, and CIBMTR would like you to respond to requests for follow‐up CRF data.

We understand that the current Forms Due report is not optimal for EBMT centers, and apologize for this inconvenience. We appreciate your patience as we work to restore smooth electronic data transmission between the EBMT and CIBMTR databases. Feel free to contact your CIBMTR Center Liaison if you have additional questions about the Forms Due reports.

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CIBMTR ACCESS

FormsNetTM2.0 FormsNet™ is the CIBMTR’s Web‐based application for submission of outcomes data. This system allows transplant centers to electronically submit TED Form or CRF data to CIBMTR. FormsNet™ includes real‐time error validation and override capabilities, and access to the Forms Due Report.

CIBMTR takes security of electronic and paper medical information seriously. Substantial security procedures are in place to maintain the integrity and confidentiality of data submitted to CIBMTR. These security procedures apply to the FormsNet™ application. All users must obtain a SecurID® that helps maintain proof of identity for all system users.

Your center’s Primary Contact/Data Manager must log into FormsNet™ and activate other employee accounts before they will be able to use the application. Your transplant center’s primary contact can request new or replacement SecurID® cards online through the CIBMTR website by clicking on: http://www.cibmtr.org/DataManagement/AdminResources/Personnel/index.html.

After the request is completed, the Primary Contact/Data Manager will need to activate the new user in FormsNet™ under the Maintenance tab.

FormsNet™ training Training in the use of FormsNet™ is very important. The FormsNet™ training modules (Core Application, Data Entry & Primary Contact) on the CIBMTR website will be updated in the near future.

It is recommended that each user complete the appropriate training module(s) before attempting to log into the application. The training portion of the CIBMTR website is located at: http://www.cibmtr.org/DataManagement/TrainingReference/index.html.

All teams should continue to submit paper forms until their access to FormsNet™ is established. All revised CIBMTR forms are available for submission using FormsNet™.

Please contact the NMDP Help Desk at [email protected] with technical problems. Contact your Center Liaison with all other questions. Be prepared to provide your center’s five‐digit CCN number when making inquiries.

SecurID® and Log‐In The SecurID® system is one of the important security features built into FormsNet™, and is used as a second form of identity authentication. Your center’s Primary Contact/Data Manager can expect to receive SecurID® tokens via FedEx approximately six to eight weeks after your application is received.

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The NMDP help desk will contact your center’s primary contact under separate cover with the user’s SecurID® PIN number, FormsNet™ User ID and Password. A SecurID® card is a small physical token that displays a six digit number. This number changes every 60 seconds and is in sync with a server at NMDP. The user should log into FormsNet™ at least once every 30 days in order to keep the two in sync. If the token gets out of sync, contact the NMDP help desk and they can sync the token with the server while you are on the phone with them.

Initially, only a few people at your center may be assigned a SecurID® token for FormsNet™ access. These tokens must not be shared between individuals. They remain the property of NMDP. Lost or stolen cards must be reported to NMDP immediately at 612‐362‐3411 (1‐800‐526‐7809) or by e‐mail at [email protected]. Please return the tokens to the help desk if staff leaves your organization. The help desk address is:

National Marrow Donor Program 3001 Broadway St. N.E. Broadway Ridge, Suite 100 Minneapolis, MN 55413 ATTN: HELP DESK

CIBMTR Portal Site The CIBMTR Portal Site is a special password‐protected area of our website where centers can access information of importance to their data operations: • Data Back to Centers (DBtC): https://portal.cibmtr.org/dbtc2/default.aspx DBtC was created to help transplant centers retrieve the data they have submitted through FormsNet™ since December 3, 2007. The first release of DBtC was designed to respond to the most immediate data needs of transplant centers, and will be regularly updated to improve functionality and increase the number of forms from which it can retrieve data.

Some forms submitted to CIBMTR through FormsNet™ may not be available immediately through DBtC. Data must be processed and verified by CIBMTR before they are released back to centers. See the online Frequently Asked Question (FAQ) page for more information.

These data can be exported back to you in either comma‐separated value (CSV) or XML format. Future releases of DBtC will include other data formats, as well as pre‐specified data queries. The content of future releases will be driven by feedback from users. See the online FAQ section for information on how to provide feedback. The roadmap of milestones will be updated as these features are ready for launch.

A Data Dictionary Guide for Forms 2400 and 2450, as well as an FAQ manual are included with the DBtC application, to provide guidelines for data interpretation and DBtC in general. The current data dictionary is limited to Pre‐TED and Post‐TED forms, but will be updated as more forms are added to DBtC. For questions, comments, suggestions, or help with understanding the Data Dictionary Guide and its supporting materials, please e‐mail cibmtr‐ [email protected]. E‐mails will be forwarded to appropriate support staff, with application failure given the highest priority.

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Your center (and each potential DBtC user) needs to be on CIBMTR's contact list in order to access the DBtC application. If you have not received an invitation to register for DBtC, please ask your center’s Primary Contact/Data Manager to e‐mail us at cibmtr‐[email protected], to add you to our Global Contact Management list.

At the present, not all forms are available for return to the centers. The FAQ section of the site is located at https://portal.cibmtr.org/dbtc2/default.aspx.

• FormsNet™ Center Volume Data: https://portal.cibmtr.org/FN2Center/default.aspx Since the SCTOD was implemented, CIBMTR has worked to inform center directors and data staff about uses of the data they have submitted. By law, CIBMTR is obligated to publish the transplant center volumes data it has received. This information will be posted at http://bloodcell.transplant.hrsa.gov, which is maintained by HRSA. The data that are being made available on the this site will include total number of transplants performed, detailed tables regarding type of transplant, broad categories of disease status at HCT, cell sources, age, gender and racial groups.

The FAQ sections of both the DBtC and FormsNet™ Center Volume Reports Portal pages are good sources of information – you may find answers to your questions there. The FAQ section is on the left side of the Portal screen. If you have questions or suggestions that are not addressed in the FAQ, please e‐mail us at cibmtr‐[email protected]. This new e‐mail address replaces the one previously posted on the DBtC web portal. We will respond to your inquiry within 24‐48 hours.

When submitting a request for help, please include your CCN number and the basic issue in the subject line of the e‐mail message (e.g. “Center 10120 – Access denied” or “Data download error – CCN 10297”).

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TRAINING AND RESOURCES

During the past two years, substantial resources have been focused on education related to the revised data collection tools, the FormsNet™ application, data quality audit procedures and changed general processes on both campuses. A wide variety of training resources are now available to new centers, Center Directors, Primary Contacts, and Data Managers. A great way to receive in‐person instruction and talk with others is by attending educational sessions held twice per year: at the BMT Tandem Meetings in February and at the NMDP Council meetings in November.

Peripheral meetings held in conjunction with the BMT Tandem Meetings include the BMT CTN Steering Committee, Coordinator and Investigator Sessions, FACT Training Workshops, Clinical Research Professionals/Data Management Conference, BMT Center Administrative Directors Conference, BMT Pharmacists Conference, Transplant Nurses Conference and BMT Center Medical Directors Conference. Up‐to‐date information about the 2010 meetings can be found on the CIBMTR (www.cibmtr.org) and ASBMT (www.asbmt.org) Web sites.

Mentor Program Thanks to the efforts of many dedicated CIBMTR Clinical Research Professionals from transplant centers in several countries, there is a website devoted to issues faced by data managers in collecting and reporting data to the CIBMTR, and to improve their effectiveness. It may be found at www.datamanager.blogspot.com.

This site includes the following: • Answers to frequently (and not so frequently) asked questions about HCT and CIBMTR; • Opportunities for experienced professional mentors to assist new or inexperienced data managers with specific challenges; • Help for data managers preparing for audits with practical tips from the personal experiences of other data managers; • Many useful internal and external links to related Web sites, e.g. online medical dictionary and a helping‐hand guide for data managers.

Data Manager Education CIBMTR offers two Clinical Research Professional /Data Management meetings; one in conjunction with the BMT Tandem Meetings in February and one in conjunction with the NMDP Council meetings in November. Self‐study packets for new CRPs, Webcasts, conference calls and individual sessions are provided by data management staff.

CIBMTR newsletters (available on the CIBMTR website) include articles addressing data reporting issues. Key presentations at the CRP Data Management meetings are video‐recorded and made available on the CIBMTR website. Topics include descriptions of CIBMTR policy changes, procedures and data forms, reviews of the HCT process, pertinent diseases, HCT‐specific medical terminology,

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hematology, histocompatibility and immunology, and good clinical practices for documentation, time management and resource allocation.

All training modules available on the cibmtr.org website will be updated soon. Currently there is a pre‐TED manual and a TED manual, and others are being developed. Please check the website at www.cibmtr.org for updates.

Tips from the Network We asked several successful CRP’s in the network to tell us how they stay organized. Following are some of the suggestions they made. Some may work for you and some may not. Note that most of these suggestions are based on paper forms submission – if your center submits forms electronically, you may need to adapt them. • Put patient’s name on a calendar (electronic or paper) for the dates when each report is due. Choose the time point that works best for your team: o When the infusion is scheduled or when the patient is admitted; o When the monthly report comes out; o When the Continuous Process Improvement (CPI) trimester begins; When the calendar reminder pops up, complete everything that you can and then make note of what you still need and check for it regularly. For instance, when an infusion is scheduled, complete as much information as you already know on the Baseline form. This will help you get forms submitted with contact dates closest to the standard reporting periods (100‐day, 6‐ month, annual).

• An alternate suggestion is to keep a file for each patient and for each month and place the patient’s file in the month file when the next form is due.

• Pick a day each week to work on forms. Minimize distractions on that day.

• For transplant recipients who received a graft from an unrelated donor procured through the NMDP Coordinating Center, “Search Forms” will not show up in FormsNet™. They are part of a different CPI phase. When you are setting up your calendar or files for a patient, print out a Form 22, complete the key fields and give them to the search coordinators. Print 180/183/184 or mark it on your calendar. These have a narrow window of completion time, so timely submission is vital.

• Keep up on events with your inpatients and watch for re‐admissions. Print or note what information you can, so you will have it available when it is time to do the form.

• Play with the online tools that are provided. If they don’t work for you, make your own tracking system. A few hours of organizing can save significant time.

• Keep a list in a visible area and mark off forms when they are complete. Watching the list get shorter and looking at what you’ve already accomplished can be very motivating.

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• Have someone else on the team review your paper forms for mistakes (check boxes missed, values left blank) before you submit them. If you do not have anyone available, wait a day or two and then scan the form again yourself. FormsNet™ will perform this check for you if you are entering the data electronically, but you probably still should review the data to be sure it is keyed correctly before you submit the form.

• Sort by what works for you. For example, generate lists by form type (Baselines, 100‐days, etc.) and work on them that way.

• Don’t hesitate to call or e‐mail your liaison.

CIBMTR.ORG website Our newly designed website can be found at www.cibmtr.org. It includes many resources for helping the new data manager. Topics include: • Center Membership o How to Become a CIBMTR Center o How to Work with the CIBMTR o SCTOD Requirements • Administrative Resources o Electronic Data Submission o Data Back to Centers o Fee Schedule o Personnel Change and User Access Forms • Protocols and Consent Forms o Observational Database Protocol and Consent Forms o Research Sample Repository Protocol and Consent Forms • Data Collection Forms o Samples of All Forms o Retired Data Collection Forms • Training and Reference o Programs and Presentations ƒ Forms Training o Manuals ƒ Data Management Manual ƒ Supplemental Report Form Manuals ƒ Retired Forms Manuals o FormsNet ƒ FormsNet Training ƒ FormsNet Release Notes ƒ FormsNet Google Group o AGNIS ƒ AGNIS Training ƒ AGNIS Release Notes

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ƒ AGNIS Google Group o FAQs o Legacy Data and Backlog Resources ƒ Legacy Data Error Corrections ƒ Legacy Data Amnesty (PDF) o Cord Blood Resources • Contact a Liaison

Other helpful websites

Mentors and website goals: www.datamanager.blogspot.com NMDP: BeTheMatch.org FormsNet™ and Traxis applications: https://connect.nmdp.org Bone Marrow Donors Worldwide (registry codes): www.bmdw.org/index.php?id=addresses_members&no_cache=1 National Cancer Institute: www.cancer.gov Social Security Death Index: ssdi.rootsweb.ancestry.com Good Clinical Practices (GCPs): International ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. For more information (International Conference on Harmonization Document): www.fda.gov/cder/guidance/959fnl.pdf Lab Conversions: www.unit‐conversion.info/volume.html www.globalrph.com/conv_si.htm www.lymphomation.org/testsimmunoglobulins.htm www.unc.edu/~rowlett/units/scales/clinical_data.html

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STUDIES

CIBMTR Observational Studies

Observational research using the large clinical databases of CIBMTR is a core activity of the organization. These studies culminate in peer‐reviewed publications and move the field of hematopoietic stem cell transplantation towards safer and more effective procedures for those who need them. Since its inception in 1972, CIBMTR data and statistical support have resulted in more than 400 paper addressing HCT issues.

The research agenda of the CIBMTR is accomplished within the framework of 19 Working Committees (see attachment A) that are responsible for: • Designing and conducting observational studies relevant to their subject area and involving CIBMTR data, statistical resources, networks and/or centers. • Considering proposals to use CIBMTR data for studies pertinent to their subject area. • Periodically assessing and revising relevant sections of CIBMTR data collection forms. • Planning and conducting workshops at CIBMTR meetings. • Setting priorities for CIBMTR observational studies.

Blood and Marrow Transplant Clinical Trials Network (BMT CTN)

The BMT CTN was established in October 2001 to conduct large multi‐institutional clinical trials. The trials address important issues in HCT, thereby furthering understanding of the best possible treatment approaches. Participating investigators collaborate through an organization (BMT CTN) designed to maintain continuity of operations, facilitate effective communication and cooperation among participating transplant centers along with collaborators at NIH, and to offer trials participation to patients in all regions of the United States. The BMT CTN Web site can be found at: http://www.bmtctn.net

Resource for Clinical Investigation in Blood and Marrow Transplantation (RCI BMT)

Well planned and coordinated multi‐center phase I and II studies are critical for advancing the field of hematopoietic cell transplantation. To facilitate such studies, the CIBMTR has formed the RCI BMT to provide statistical expertise and data management services for smaller multi‐center phase I and II trials. While not a funding agency, the CIBMTR, through the RCI BMT, will partner with investigators to obtain necessary support for trial completion.

The goal of the RCI BMT is to bridge the gap between single‐center studies and the larger phase II and phase III studies conducted by the BMT CTN. For further questions, please contact us by e‐mail at [email protected], or by phone at 612‐884‐8600 (Becky Drexler).

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Study of long‐term complications of Kepivance (KGF)

In June 2006, as part of a Food and Drug Agency (FDA) post‐marketing commitment, Amgen Pharmaceutical contracted with CIBMTR to develop and implement a 10‐year prospective observational study to compare secondary, long‐term outcomes for patients receiving hematopoietic stem cell transplantation for hematologic malignancies with and without Kepivance (palifermin). In December 2008, Kepivance was sold by Amgen to the Swedish pharmaceutical company Biovitrum AB. At that time, the CIBMTR Kepivance study contract was transferred to Biovitrum AB.

The contract provides funding to facilitate the assembly of detailed, long‐term data on a cohort of 4,800 patients. Upon completion of accrual, the study population will contain 2,400 patients that were exposed to KGF and 2,400 unexposed patients. Due to the study size and duration, the cohort group created is expected to be valuable for use with other CIBMTR late effects studies.

During the fall of 2007, CIBMTR began the patient accrual process for the study, and patients from your center are eligible for inclusion. While the study will require an annual tracking form to be completed, we have made every effort to ensure that the study has minimal impact on data reporting for each enrolled subject. The study will provide additional reimbursement for all study reporting requirements. Every effort has been made to keep the study reporting requirements essentially the same as the standard reporting requirements for a CIBMTR research case. The study will provide additional reimbursement of $100 for each study subject upon receipt of each set of completed follow up forms.

If you have any questions or concerns regarding the study, please contact the CIBMTR Program Manager, Patricia Steinert, [email protected], 414‐805‐0648 or the Study Clinical Research Coordinator, Amy Prentice, [email protected], 414‐805‐0650.

Comparison of intravenous busulfan versus total body irradiation for pre‐ transplant conditioning (Otsuka)

A prospective study with Otsuka Pharmaceutical Development & Commercialization, Inc. as a collaborative and funding partner was begun in 2009. It is an observational cohort study using data reported to CIBMTR.

The study compares outcomes for patients receiving a first allogeneic transplant with myeloablative conditioning using intravenous busulfan in combination with other agents, versus patients receiving a first allogeneic transplant with myeloablative conditioning with total body irradiation in combination with other agents. The protocol was finalized in January 2009, and received IRB approval on March 8, 2009.

The patient accrual process began in March 2009. The study’s general design will assemble a cohort of patients from CIBMTR centers that are already submitting Comprehensive Report Form data. The study will provide $1,000 reimbursement per patient for all patients enrolled to the study that meet the

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eligibility criteria. The reimbursement will be distributed in addition to routine reimbursement for CIBMTR CRF forms.

CIBMTR has tried to minimize the additional burden of participation in this important study. Although the study may increase the number of patients selected for Comprehensive Report Forms at your center, we hope that the $1,000 reimbursement in addition to the regular CIBMTR reimbursement schedule will offset all costs associated with the study. Patients enrolled into the IV busulfan cohort will require a very short supplemental form be completed at the time of transplant.

If/when CIBMTR has identified patient(s) from your center that are eligible for inclusion to the study, your center will be contacted by the Program Coordinator.

If you have any questions or concerns regarding the study, please contact the CIBMTR Program Coordinator, Jeanne Burkart, at [email protected] or 414‐805‐0667.

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Attachment A CIBMTR Working Committees

ACUTE LEUKEMIA INFECTION AND IMMUNE RECONSTITUTION Chairs: Steven Devine, MD ; John DiPersio; Chairs: Michael Boeckh, ARND Donald Bunjes, MD Juan Gea‐Banacloche, MD; Paul Szabolcs, MD Scientific Director: Daniel Weisdorf, MD Scientific Director: Marcie Tomblyn, MD, MS Statisticians: Waleska Pérez, MPH; Mei‐Jie Zhang, PhD Statisticians: Min Chen, MS; Kwang Woo Ahn, PhD

AUTOIMMUNE DISEASE LATE EFFECTS AND QUALITY OF LIFE Chairs: Steven Pavletic, MD, FACP; Chairs: Christine Duncan, MD Paolo Muraro, MD, PhD David Jacobsohn, MD; Mohammed Sorror, MD Scientific Director: Marcelo Pasquini, MD, MS Scientific Director: J. Douglas Rizzo, MD, MS; Statisticians: Manza Agovi, MPH; Kwang Woo Ahn, PhD; Navneet Majhail, MD, MS Statisticians: Zhiwei (Jerry) Wang, MS; Ruta Bajorunaite, PhD

CHRONIC LEUKEMIA Chairs: Matt Kalaycio, MD; Jorge Cortes, MD; LYMPHOMA Richard Maziarz, MD Chairs: David Maloney, MD; Ginna Laport, MD; Scientific Director: Mukta Arora, MD, MS Silvia Montoto, MD Statisticians: Eric Iverson, MS; Kwang Woo Ahn, PhD Scientific Director: Parameswaran Hari, MD, MS Statisticians: Jeanette Carreras, MPH; Mei‐Jie Zhang, PhD

DONOR HEALTH AND SAFETY Chairs: Michael Lankiewicz, MD NON‐MALIGNANT MARROW DISORDERS David Stroncek, MD; Steven Goldstein, MD Chairs: Shalini Shenoy, MD; Mouhab Ayas, MD; Scientific Director: Dennis Confer, MD Joachim Deeg, MD Statisticians: Tanya Pedersen; Brent Logan, PhD Scientific Director: Mary Eapen, MD, MS Statisticians: Jeanette Carreras, MPH; Jennifer Le‐Rademacher, PhD GRAFT SOURCES AND MANIPULATION Chairs: Daniel Fowler, MD; Mary Laughlin, MD; Richard Champlin, MD PEDIATRIC CANCER Scientific Director: Mary Eapen, MD, MS Chairs: Carrie Kitko, MD; Paul Carpenter, MD; Statisticians: Fiona Kan, MS, MA; Mei‐Jie Zhang, PhD Adriana Seber, MD Scientific Director: Mary Eapen, MD, MS Statisticians: Vincent He, MS; Mei‐Jie Zhang, PhD GRAFT‐vs‐HOST DISEASE Chairs: Corey Cutler, MD, MPH, FRCPC Mary Flowers, MD; Alvaro Urbano Ispizua, MD REGIMEN‐RELATED TOXICITY/SUPPORTIVE CARE Scientific Directors: Mukta Arora, MD, MS; Chairs: Philip McCarthy, MD Stephen Spellman, MS Vincent Ho, MD; Kenneth Cooke, MD Statisticians: Erik Iverson, MS; Tao Wang, PhD Scientific Director: Marcelo Pasquini, MD, MS Statisticians: Manza Agovi, MPH; Brent Logan, PhD

IMMUNE DEFICIENCIES/INBORN ERRORS Chairs: Harry Malech, MD; Paul Veys, MD; SOLID TUMORS Ed Horwitz, MD, PhD Chairs: Michael Bishop, MD Scientific Director: Mary Eapen, MD, MS Edward Stadtmauer, MD; Naoto Ueno, MD Statisticians: Anna Hassebroek, MPH; Scientific Director: Mukta Arora, MD, MS Jennifer Le‐Rademacher, PhD Statisticians: TBD; Kwang Woo Ahn, PhD

IMMUNOBIOLOGY Chairs: Carlheinz Mϋller, MD; David Miklos, MD; Marcelo Fernandez‐Vina, PhD Scientific Directors: Stephen Spellman, MS; Stephanie J. Lee, MD, MPH Statisticians: Michael Haagenson, MS; Fiona Kan, MS, MA; John P. Klein, PhD; Tao Wang, PhD

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Attachment B Glossary of Glossary of Abbreviations Abbreviations

AE Adverse Event DCC Data and Coordinating Center AGNIS A Growable Network Information System DFS Disease Free Survival aGVHD Acute Graft Versus Host Disease DLBCL Diffuse Large B‐cell Lymphoma AID Autoimmune Disease DLI Donor Leukocyte Infusion ALL Acute Lymphoblastic Leukemia DM Data Management AML Acute Myelogenous Leukemia DSA Donor‐Directed Specific Allo‐Antibodies AP Accelerated Phase DSS Durie‐Salmon Scoring System APC Antigen‐Presenting cells DUA Data Use Agreement APL Acute Promyelocytic Leukemia American Society for Blood and Marrow European Group for Blood and Marrow ASBMT EBMT Transplantation Transplantation ATG Antilymphocyte Globulin EDSS Extended Disability Severity Score ESRD End Stage Renal Disease BM Bone Marrow BMI Body Mass Index FA Fanconi Anemia Foundation for the Accreditation of Cellular BMT Blood and Marrow Transplant FACT Therapy Blood and Marrow Transplant Clinical Trials BMT CTN FL Follicular Lymphoma Network BO Bronchiolitis Obliterans GVHD Graft‐Versus‐Host Disease BP Blast Phase GVL Graft‐Versus‐Leukemia Bu Busulfan GVT Graft‐Versus‐Tumor BuCy Busulfan/Cytoxan HBV Hepatitis B Virus CAC Consumer Advocacy Committee HCT Hematopoietic Stem Cell Transplantation caDSR Cancer Data Standards Registry HCV Hepatitis C Virus CDE Common Data Elements HIPAA Health Insurance Portability & Accountability Act cGVHD Chronic Graft versus Host Disease HL, HD Hodgkin Lymphoma, Hodgkin Disease CI Confidence Interval HLA Human Leukocyte Antigen Center for International Blood and Marrow CIBMTR HLA‐C Human Leukocyte Antigen‐C Transplant Research CIT CIBMTR Information Technology HLH Hemophagocytic Lymphogistiocytosis CLL Chronic Lymphocytic Leukemia HRSA Health Resources and Service Administration CML Chronic Myelogenous Leukemia CMV Cytomegalovirus IATO Interim Authority to Operate CNS Central Nervous System IBMTR International Bone Marrow Transplant Registry COG Children’s Oncology Group IHWG International Histocompatibility Working Group CP Chronic Phase IM Imatinib Mesylate CPI Continued Process Improvement IPSS International Prognostic Scoring System CR1 First Complete Remission IRB Institutional Review Board CR2 Second Complete Remission IRG Immune Response Gene CR3 Third Complete Remission ISS International Staging System CRC Clinical Research Coordinator IV Intravenous CRF Comprehensive Report Form CRID CIBMTR Recipient Identification Number JACIE Joint Accreditation Committee‐ISCT & EBMT CRP Clinical Research Professional CSA Cyclosporine KIR Killer‐cell Immunoglobulin‐like Receptors CTAC Clinical Trials Advisory Committee KPS Karnofsky Performance Score CY Cyclophosphamide

LAD Leukocyte Adhesion Deficiency QOL Quality of Life Attachment B LCH Langerhans Cell Histiocytosis Glossary of LEL Low Expression Loci RCC Renal Cell Cancer Abbreviations Resource for Clinical Investigations LFS Leukemia Free Survival RCI BMT in Blood and Marrow Transplantation LTA Lymphotoxin Alpha RF Report Form RFI Request for Information MA Myeloablative RI Reduced Intensity MCW Medical College of Wisconsin RIC Reduced Intensity Conditioning MDS Myelodysplastic Syndrome RR Relative Risk mHAg Minor Histocompatibility Antigens RTX Rituximab MM Multiple Myeloma RUCA Rural Urban Commuting Area mmRD Mismatched Related Donor MS Multiple Sclerosis SAA Severe Aplastic Anemia MSDs Matched Sibling Donors SCD Sickle Cell Disease MSP Minneapolis SCID Severe Combined Immunodeficiency MTX Methotrexate SCTOD Stem Cell Therapeutic Outcomes Database SEER Surveillance Epidemiology and End Results NCBI National Cord Blood Institute SES Socioeconomic‐Status NCI National Cancer Institute SLL Small Lymphocytic Leukemia NHL Non‐Hodgkin Lymphoma SM Secretory Myeloma NHLBI National Heart, Lung and Blood Institute SNPs Single Nucleotide Polymorphisms NIAID National Institute of Allergy and Infectious Disease t‐AML Transformed‐Acute Myeloid Leukemia NIH National Institutes of Health TBI Total Body Irradiation NIMA Non‐Inherited Maternal Antigens TCED T‐cell Epitope Disparate NK Natural Killer TCR T‐cell Receptor NMA Non‐Myeloablative TED Transplant Essential Data NMDP National Marrow Donor Program TGFB1 Transforming Growth Factor beta 1 Non‐SCC Non‐Squamous Cell Carcinoma t‐MDS Transformed Myelodysplastic Syndrome NSM Non‐Secretory Myeloma TNF Tumor Necrosis Factor TRM Transplant Related Mortality OIT Office of Information Technology UCBT Umbilical Cord Blood Transplantation OPA Office of Patient Advocacy UML Unified Modeling Language OS Overall Survival URD Unrelated Donor

PB Peripheral blood VOD Veno‐Occlusive Disease Pediatric Blood and Marrow Transplant VRE Vancomycin Resistant Enterococcus PBMTC Consortium PBPC Peripheral Blood Progenitor Cells PBSC Peripheral Blood Stem Cells WBC White Blood Count PFS Progression Free Survival WMDA World Marrow Donor Association PHA Public Health Authority PI Principal Investigator PLL Prolymphocytic Leukemia PTLD Post‐Transplant Lymphoproliferative Disorder

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SAMPLE NEW CENTER INFORMATION SHEET Attachment C New Center Info Sheet

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Attachment C New Center Info Sheet

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Attachment C New Center Info Sheet

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Attachment C New Center Info Sheet

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Attachment D SAMPLE CENTER CHANGE FORM Center Change Form

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Attachment E Forms Submission CIBMTR Forms Submission Process Process • Center submits CRID Assignment Form (Form 2804) • CRID generated o If autologous recipient declines consent for research participation, stop here1 • Pre‐TED (Form 2400) is added to Forms Due list • Center completes and submits Pre‐TED • CRF Track: Pre‐TED data is processed through the selection algorithm resulting in CRF or TED track. Follow appropriate track below • TED Track: Follow TED track below

CRF Track2 TED Track • Forms 2004 and 2005 due for each non‐ • Forms 2004 and 2005 will be added if NMDP allogeneic donor participating in related specimen repository 1 • Form 2005 due for each non‐NMDP • Form 2006 due for all NMDP products and all allogeneic recipient cord blood units • Form 2006 added for all products Baseline and Follow‐up Forms added to Forms Post‐TED Follow‐up Form 2450 added to Forms Due 2 Due list list Center completes Baseline form after infusion Center completes Post‐TED Forms at appropriate 3 time points3 Center completes CRF Follow‐up Forms at Is recipient alive? If yes, go to Step 5. If no, go to 4 appropriate time points3 Recipient Death Table Did recipient have a subsequent transplant? If yes, Follow‐up Form entered 5 go to Step 6. If no, go to Step 3 Is recipient alive? If yes, go to Step 7. If no, go Contact your Center Liaison with date of 6 to Recipient Death Table subsequent transplant Did recipient have subsequent transplant? If Center completes and submits Pre‐TED (Form 2400) 7 yes, go to Step 8. If no, continue reporting at for subsequent transplant. Go to Step 2. next time point (Step 4). Future time points will be deleted for prior Future time points will be deleted for prior transplant from FormsNet when the form transplant from FormsNet when the form reporting 8 reporting the subsequent transplant is error the subsequent transplant is error free. free. Go to Step 2 for subsequent transplant Recipient Death Table

Death Form 2900 is completed to report the recipient’s death.* If a follow‐up form is received and reports the The recipient’s death is reported on the Post TED. recipient’s death, and a form 2900 has not been submitted, one will be made due on the Forms Due list.

* Complete the Death Form 2900 even if autopsy is pending. Another Death Form will be requested to confirm Cause of Death if autopsy was pending.

1 If your center has chosen to submit autologous forms without consent, follow the TED track. 2 Recipient has the option to withdraw consent at any time. If this happens, your Center Liaison can move this transplant record to the TED Track. 3 100 days, 6 months, annually

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