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ANNUAL REPORT
2014
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Cancer Research And Biostatistics (CRAB) is a non-profit organization whose purpose is to help conquer cancer and other diseases through the application of biostatistical principles and innovative data management methods.
TABLE OF CONTENTS MESSAGE FROM THE PRESIDENT
4
LEADERSHIP & GOVERNANCE
5
SWOG
9
GENERATING BUZZ
11
LUNG
14
HEMATOLOGIC
16
PANCREATIC
18
PROSTATE & BREAST
20
FRIENDS & SUPPORT
21
COMMUNITY CONNECTIONS
22
FINANCIAL SUMMARY
25
ZELEN REMEMBERED
26
CRAB - Improving Cancer Patient Survival Cancer Research And Biostatistics (CRAB) leverages its experience in cancer clinical research to advance the standard of care for cancer patients. By expanding our participation in cancer research, we can have a broader impact on cancer prevention and treatment. Dedicated to cancer patients, our focus is on quality clinical trials that deliver results used to identify targeted treatment options, prevention strategies, and ultimately improve survival from cancer. Some 40 years since the War on Cancer was proclaimed, we strive to take cancer off the list for most common cause of death around the world.
Message from the President 4
MESSAGE FROM THE PRESIDENT John Crowley, President 2014
and industry support, matches patients with squamous cell carcinoma of the lung to a clinical trial appropriate to the particular genetic properties of their tumor. Each sub-study of Lung-MAP is being conducted in such a way that the results, if positive, will be reviewed by the Food and Drug Administration for possible market approval. Much praise is due to the many statisticians, data coordinators, forms designers, information technology staff, programmers, and testers in the SDMC who made this happen. A particularly noteworthy occurrence in 2014 was the acquisition by CRAB of the Pancreatic Cancer Research Team (PCRT). CRAB has participated in the work of this consortium of pancreatic cancer specialists since the inception of the PCRT in 2003, but as of August we are its
The year 2014 was a pivotal one in the short history
operational and fiscal home. With this added responsibility
of CRAB. I will highlight just a few of the many events
comes the opportunity to build on the work of the last
that contributed to our success last year, and that are
decade and continue the progress against this most deadly
indicators of a very bright 2015 and beyond.
of cancers.
In the previous Annual Report from 2013, I discussed the
This year also marked the culmination of five years
submission of two large grant proposals to support the
of transition and succession planning for the future of
work of the SWOG Statistical and Data Management
CRAB. William Charters was brought on as the Chief
Center (SDMC), a shared project between CRAB and the
Financial Officer, overlapping for much of the year with
Fred Hutchinson Cancer Research Center. This year I am
his predecessor, Cay Crowley, whose retirement from the
delighted to report that both grants, for SWOG participation
company she co-founded with me in 1997 became effective
in the National Clinical Trials Network and the NCI
on December 31. That day was also my last day as the
Community Oncology Research Program, received highly
leader of this wonderful organization. After an international
favorable reviews and were funded at levels above what
search, and with the committed involvement of the Board
we have received in the past. For the first time SWOG was
of Directors, Antje Hoering was promoted to President and
reviewed for merit and budget at the same time as other
Chief Executive Officer of CRAB as of the New Year. I will
competing Cooperative Groups and, as a result, for the
continue as Board Chair and will have a new day-to-day role
first time in over 30 years the SWOG SDMC has resources
as Chief of Strategic Alliances. As such I will be working with
comparable to the other Groups. We are busy hiring the
Antje on helping to bring new partnerships and opportunities
data coordinators and other specialists this funding permits
to CRAB. I am delighted to be turning over the reins to
and the work demands.
someone who has already devoted a decade of her career to making CRAB such a successful and special place, and
Another SWOG milestone was achieved midyear with the opening to accrual of the Lung Master Protocol, or LungMAP. This ambitious project, with government, foundation
look forward with confidence to CRAB’s luminous future.
5 Leadership & Governance
LEADERSHIP & GOVERNANCE
Antje Hoering Selected to Succeed John Crowley as President and CEO In 2015, CRAB will be under the leadership of a new Chief
biostatistics, encompassing areas such as the design and
Executive Officer. On May 21, Antje Hoering, Ph.D., accepted
analysis of oncology clinical trials, as well as the analysis
an offer from CRAB’s Board of Directors to become the
of a wide variety of correlative data. I have worked with
organization’s next President and CEO, effective January 1,
Antje for 10 years at CRAB, and am proud to hand over the
2015.
leadership reins to her.”
Dr. Hoering brings distinguished academic and scientific
Upon learning the news, Dr. Hoering said, “I am honored and
achievements, executive leadership and more than 15
humbled to be taking over the reins from our founder, John
years of experience to the role. Dr. Hoering, formerly Chief
Crowley. This is a very exciting time for oncology clinical
Scientific Officer at CRAB, will continue to serve as the
trials and CRAB. There have been great advances in the
lead statistician for the SWOG Myeloma Committee and is
treatment of cancer over the last few years and it is now
an active member of the Myeloma Steering Committee for
more important than ever to definitively test the efficacy
the National Clinical Trials Network. She also serves as the
and tolerability of these treatments in soundly-designed
Director of the Biostatistics Core for a Specialized Programs
clinical trials. CRAB offers an integrated, state-of-the-art
of Research Excellence (SPORE) grant funded through the
infrastructure including sophisticated statistics, secure
Sarcoma Alliance for Research Through Collaboration, and
electronic data capture as well as experienced data
is the Co-Director of the Biostatistics Core for a Program
management to lead such trials.”
Project through the Myeloma Institute for Research and Therapy.
Dr. Hoering will succeed Dr. Crowley, CRAB’s founder and CEO since 1997, who will stay on to focus on research
Following the Board’s decision, Dr. John Crowley, CEO and
and project activities and will continue to serve as CRAB’s
Board Chair, said, “Antje brings a unique and comprehensive
Chairman of the Board.
background in applied and methodological research in
Leadership & Governance 6
Co-founder Dr. Catherine Crowley Moves on to “Other Duties” CRAB co-founder Dr. Catherine Crowley has decided to pursue a new chapter in her life. After 16 years in leadership, Cay retired from CRAB at the end of December. She joined her husband, Dr. John Crowley, in founding CRAB in 1997 as the home of the data management component of the SWOG Statistical Center, with a mission to help conquer cancer and other diseases using biostatistical principles and innovative data management methods. Cay became the original employee when CRAB’s first office opened in the Crowley’s basement in 1999. Sixteen years later, CRAB is a well-known research organization with more than 80 employees. Over the years, Cay has served several administrative roles at CRAB. Having a doctorate in Developmental Psychology from the University of Washington served Cay well in taking on the many challenges that are a part of building an effective organization. After completing postdoctoral training in clinical psychology at University of Wisconsin, Cay practiced in Wisconsin before moving to Seattle where she co-founded Northwest Psychological Services. Cay says that her training and business experience provided her with many of the skills she has used at CRAB. Cay has served as Chief Administrative Officer, Chief Operations Officer, and Chief Financial Officer. She performed the usual tasks associated with the titles and many others that fall under “other duties, as assigned,” a phrase that was always included in her job descriptions. Cay led the development of sound administrative, financial, and human resources policies and procedures. Recently, Cay completed comprehensive revisions to CRAB policies and procedures, and was instrumental in the design of the SharePoint site where the documents are now stored. Chief Executive Officer Dr. John Crowley, making his own transition in 2015 to Chief of Strategic Alliances, said, “Cay’s many contributions have been vital to CRAB’s growth as an effective research organization. I wouldn’t have started CRAB if I wasn’t sure that I could trust Cay to do whatever was required for us to succeed as an organization.” As CRAB’s co-founder, Cay will continue to contribute through her legacy and support. Cay’s next job description isn’t written yet, but it’s sure to include new challenges and adventures and the quintessential other duties as assigned, with one important distinction. For her new job description, Cay said, “I’ll be the one assigning the other duties.”
Award for Excellence Named for CRAB Co-founder In 2014, CRAB’s leadership team under incoming CEO Dr. Antje Hoering established an award to be given annually to a CRAB employee who has gone above and beyond to provide excellence in support of CRAB’s mission and clients. In honor of the many contributions of CRAB co-founder Dr. Catherine “Cay” Crowley, and in recognition that she embodies the spirit of the award, this tribute has been named the Cay Crowley Award for Excellence with Cay becoming the first to be bestowed the award for 2015. Dr. Hoering praised Cay for her many contributions to CRAB: “All of our job descriptions include the phrase ‘other duties as assigned.’ This phrase has applied to no one more so than to Cay. Cay was always there to support CRAB and its mission no matter what was required. If she didn’t know how to accomplish a specific task, she trained herself. She always got the job done and she always did it well and always with a smile. It is very fitting that she is the first recipient of this award of excellence.” An annual presentation of the Cay Crowley Award for Excellence will be held each January. Dr. Crowley will participate in the 2016 ceremony when the award will be bestowed upon another CRAB employee.
7 Leadership & Governance
John Crowley, President and Chief Executive Officer
Tammy Buist, Chief Business Development Officer
William Charters, Chief Financial Officer
Keith Goodman, Chief Technology Officer
Antje Hoering, Chief Scientific Officer
Evonne Lackey, Chief Data Management Officer
Financial Leadership Transitions to William Charters William Charters, M.B.A., joined CRAB in March as Chief Financial Officer. Mr. Charters came to CRAB with 30 years of comprehensive experience in leadership and business operations developed within the contract research organization, Battelle, where he applied business management and analysis skills to research operations. At Battelle, Mr. Charters was the Finance Manager for the Battelle Health and Analytics business unit, a public health research organization where he lead center business activities that included implementing operational plans and budgets and monitoring financial metrics and key indicators to achieve financial objectives. Mr. Charters took over CFO duties from Dr. Catherine Crowley who transitioned to retirement at the end of the year. He earned his bachelor’s in Business Administration from Seattle University, and his master’s in Business Administration from Gonzaga University prior to joining Battelle in 1984.
Leadership & Governance 8
CRAB Welcomes Curt Malloy to the Board of Directors Curt Malloy, J.D., M.P.H., is the operational leader for the Fred Hutchinson Cancer Research Center’s Vaccine and Infectious Disease Division. Curt is a strong advocate for life sciences and product development, playing a role in strategies to reduce the global burden of disease. Curt is a founding member of the Pacific Northwest Life Sciences Executive Forum and a leader in the region’s non-profit community. Mr. Malloy’s education includes a bachelor’s degree in Chemistry and Computer Science from Pacific Lutheran University; a master’s degree in Public Health from Columbia University; and a Juris Doctor degree, with an emphasis in Intellectual Property, from the Seattle University School of Law.
Curt is a strong advocate for life sciences and product development, playing a role in strategies to reduce the global burden of disease.
9 SWOG
SWOG Goodbye Cooperative Groups: Hello National Clinical Trials Network (NCTN) Partners! February 28, 2014 marked the end of the National Cancer Institute’s funding program for the nine cooperative cancer groups. The National Clinical Trials Network (NCTN) was born March 1st as part of an extensive review and implementation process to strengthen and unite clinical trial activities within the United States and Canada. The number of funded groups shrank from nine to six, with efficiencies and collaborations strongly encouraged across all funded organizations. SWOG, with whom CRAB has a longstanding relationship, received a top score well beyond the scores of its competition. CRAB functions primarily as the data management and information technology hub of the SWOG Statistical Center (now named the Statistical and Data Management Center). The new funding program provided SWOG opportunities for changes in membership, governance and research direction. CRAB staff has been involved in shaping the future of clinical trials as well as updating the SWOG database to reflect these many changes to membership categories, institutional performance management, and quality initiatives. NCTN funding is for five years, at which time all members will be required to re-compete for continued funding.
NCI Community Oncology Grant Application Approved Another popular program funded by the National Cancer Institute (NCI), the Community Clinical Oncology Program (CCOP) was also reassessed and renamed in 2014. This program, sponsored by the NCI’s Division of Cancer Prevention, began in 1982 with the goal of providing cancer clinical trials and research opportunities to local communities in addition to large academic and cancer centers. The CCOP program emphasized prevention in addition to participation in treatment trials. The newly formed NCI Community Oncology Research Program (NCORP) was initiated August 1, 2014. Just as with NCTN, membership and institutional partnerships were dissolved and reformed under this new funding program. CRAB’s contribution to the overall grant application was well received, primarily due to the leadership of William Barlow, Ph.D., and the strong data management and database infrastructure support CRAB provides to SWOG. CRAB can look forward to five years of funding from this program as we work in collaboration with Fred Hutchinson Cancer Research Center and other SWOG institutions to design and activate scientifically sound research focused on cancer care delivery, cancer control and prevention.
Data Management Conducts the SWOG Clinical Trials Training Course As part of the spring SWOG Group Meeting, CRAB staff along with individuals from the SWOG Operations Office and Group Chair’s Office, conduct a Clinical Trials Training Course (CTTC) for those new to clinical trials. This one-day course provides an overview of SWOG and covers topics such as SWOG policies and procedures, the science of clinical trials, motivation for Phase I, II and III trials, and ethics in research. A practicum round-table discussion provides clinical research associates with practice in forms completion, adverse event grading, response assessments, and calculating laboratory values. Approximately 110 participants attended the training course offered at the 2014 spring Group meeting in San Francisco. Training clinical research associates, nurses, administrators and others that work in research and clinic settings is important to CRAB’s mission. These people are the touch points for cancer patients. It is through their dedication and commitment to quality research that CRAB can review and analyze patient data with the goal of making every cancer patient count.
SWOG 10
CRAB Launches SWOG Lung-MAP Trial CRAB is pleased to be part of the SWOG S1400 Lung-MAP trial, a first-of-its-kind squamous cell lung cancer clinical trial that uses a multi-drug, targeted screening approach to match patients with sub-studies, testing investigational new treatments based on their unique tumor profiles. Approximately 25% of lung cancer diagnoses are squamous cell, with very few treatment choices available beyond surgery. This trial, launched in June 2014, uses genetic profiling to match patients to one of five different investigational treatments that are planned to target the genomic changes driving the growth of their cancer. It is hoped that this clinical trial model will improve recruitment, reduce infrastructure burden and provide an opportunity for patients to have access to promising new drugs. CRAB is proud to be a part of this study that holds promise to change and fast-track the way treatments, particularly investigational biomarker-defined treatments, are tested and approved. If successful, this “bucket” clinical trial model will be expanded to other kinds of cancer. Charles D. Blanke, M.D., Chair of SWOG, says, “Squamous cell lung cancer, like many other neoplasms, is increasingly recognized as consisting of a host of relatively rare genomic subsets, each of which may require treatment with a different targeted drug. The Lung-MAP S1400 trial models a way to efficiently study a large number of these rare subsets under one master protocol.” CRAB’s role in Lung-MAP includes overseeing the application development, data management, risk-based monitoring, data access and security, and database structure. In addition, CRAB employees working on Lung-MAP are responsible for conducting training sessions and meetings at national conferences to encourage participation and support this innovative approach to clinical testing.
Young Investigators Trained in Clinical Trials In September 2014, CRAB once again had the opportunity to host the SWOG Young Investigators Training Course. This unique training program is designed to intensively train selected young investigators in the SWOG system for protocol development, maintenance, and administration in order to develop a cadre of experts to quickly and efficiently develop priority studies. For the purposes of this training, young investigators are defined as oncology fellows in training or assistant professor equivalents affiliated with Group institutions or otherwise eligible for Group membership. This course is limited to six attendees. Biostatisticians and data coordinators interact with participants by sharing information about statistical design, data management processes, and study chair responsibilities.
The 2014 SWOG Young Investigators
11 Generating Buzz Karen Anderson and Monica Yee presenting poster at the annual ASPO meeting.
GENERATING BUZZ CRAB Data Management Staff Present at National Conferences Evonne Lackey, Karen Anderson, and Monica Yee were all
Evonne reported that both conferences were a successful
honored to have had abstract submissions accepted in
forum for CRAB. “We were fortunate to have connected with
the form of poster presentations at the annual American
some patient advocacy organizations and researchers to
Society of Preventive Oncology meeting held in Arlington,
inform them of CRAB’s efforts to make every cancer patient
Virginia in early March. Monica Yee presented “Research
count through our ongoing partnerships, collaborations, and
Opportunities from SELECT, a Long Term Prevention Study:
connections,” she said.
Biospecimens, Data and Participants.” Evonne and Karen
Jo Ann Hartline, who retired from CRAB in October 2014
also presented “Assessing Needs of Cancer Patients
after many years of service as the Director of Prevention
(Survivors) in Providing Follow-Up Cancer Information” at
Studies, gave an interesting talk regarding CRAB’s follow-up
the conference.
experience related to the Selenium and Vitamin E Cancer
Karen Anderson and Evonne Lackey also attended the
Prevention Trial (SELECT). Her presentation was given at
Biannual Cancer Survivorship Conference co-sponsored by
the Society for Clinical Trials meeting held in Philadelphia.
the National Cancer Institute’s Office of Survivorship and
The title of her presentation was “Mixed Mode Follow-up for
the American Cancer Society. This three-day conference
an Aging Study Population.”
was held in Atlanta, Georgia. Evonne and Karen’s poster was entitled “Meeting Cancer Survivor Needs: Survivor’s Perspective.”
Generating Buzz 12
Clinical Oncology Workshop Presented in Brussels John Crowley, Ph.D., and Antje Hoering, Ph.D., led the Statistics in Clinical Oncology workshop in Brussels from October 9-10, 2014. The event featured two day-long modules that covered topics in clinical trials, presenting real-world examples of SWOG and CRAB clinical trials and trial designs demonstrated with widely-recognized on-line statistical calculators (https://stattools.crab.org) that have been developed by SWOG and CRAB. The course reviewed concepts of oncology clinical trials including safety, efficacy and endpoint considerations. Phase I, II and III oncology clinical trial designs were discussed. The pros and cons of the different trial designs in various clinical settings were covered, including trial designs for cytostatic or targeted agents. “This was a great opportunity for us to showcase CRAB and SWOG tools, publications and expertise to an international audience,” Dr. Hoering said. The event strengthened CRAB’s relationships with the international clinical trials community. The third edition of the Handbook of Statistics in Clinical Oncology, edited by Drs. Crowley and Hoering, was used as a reference throughout the workshop.
Chief Scientist Presents at Biomarker and Drug Workshop Antje Hoering, Ph.D., was an invited keynote speaker at the Workshop on Statistical Issues in Biomarker and Drug Codevelopment. The workshop was held November 7 - 8 at the Fields Institute in Toronto and sponsored by CANSSI, the Canadian Statistical Sciences Institute. The title of her talk was “Statistical Designs of Phase III Clinical Trials in the Era of Targeted Agents.” The two-day workshop on biomarker and drug co-development aimed to educate researchers about emerging developments in statistical designs and analyses for clinical trials and translational research, as well as to identify open statistical problems for which attendees considered organizing research proposals. International experts provided an introduction to biomarker data and an overview of current design, analysis, and reporting principles with issues for research. Dr. Hoering, CRAB’s Chief Scientific Officer, said, “This workshop was a great opportunity to network and exchange ideas with fellow researchers in the field.”
Instructors at the workshop on Statistical Issues in Biomarker and Drug Co-development
13 Generating Buzz
Statistical Design Focus of AACR Presentation CRAB’s Chief Scientific Officer, Antje Hoering, Ph.D., gave an invited talk at one of the major methods workshops of the annual meeting of the American Association for Cancer Research (AACR) on April 5, 2014. Nearly 18,000 researchers, patient advocates, and other professionals in the field of cancer from around the world attended the AACR annual meeting. Dr. Hoering’s talk was titled “Statistical Designs of Complex Phase II Trials and Definitive Phase III Studies in the Era of Targeted Agents” and was part of the workshop entitled “Insights in the Era of Personalized Cancer Therapy and Targeted Therapies: Definitive Advanced Stage Clinical Trials.”
Biomarker Use in Oncology Clinical Trials Discussed Antje Hoering, Ph.D., organized an invited session at the 27th International Biometric Conference (IBC) in Florence, Italy. The session took place on Monday, July 7, 2014. The title of Dr. Hoering’s session was Biomarkers in Oncology Clinical Trials. Speakers in the session included Michael LeBlanc, Ph.D. of the Fred Hutchinson Cancer Research Center and SWOG Group Statistician; Shigeyuki Matsui of the Institute of Statistical Mathematics, Tokyo, and Donna Ankerst, Ph.D., of the Technische Universitaet Muenchen in Germany. John Crowley, Ph.D., CRAB’s Chief Executive Officer, served as the discussant. Session topics included the direction of subgroup modeling in Phase III clinical trial designs, maintenance of clinical risk calculators and statistical analysis plans in Phase III trials. The session reinforced CRAB’s international collaboration network in cancer clinical trials. “This was a wonderful opportunity to exchange research ideas with colleagues from afar while showcasing recent research advances from SWOG and CRAB,” said Dr. Hoering, CRAB’s Chief Scientific Officer.
Biomarkers in Oncology Clinical Trials speakers, from left to right, included Donna Ankerst, Shigeyuki Matsui, Antje Hoering, and Michael LeBlanc. Discussant John Crowley is on the far right.
Lung 14
LUNG Safety Studied in Dose Escalation
Lung Cancer Consortia Works to Improve Outcomes
A clinical trial in the Lung Cancer Research Team (LCRT) consortium that investigated safety in patients receiving a
The Lung Cancer Research Team (LCRT) is a multi-
combination of agents has concluded. The study, known as
disciplinary group of preeminent researchers dedicated to
Phase I Dose Escalation Study of Everolimus, Pemetrexed,
organizing and accelerating the clinical development of
Carboplatin, and Bevacizumab in Stage IV Non-Squamous
new agents for the treatment of patients with lung cancer.
Non-Small Cell Lung Cancer, opened in October, 2010
The mission of the LCRT is to create a focused, world-wide
with an objective to discover the maximum tolerated dose
cancer clinical trials group that will centralize, prioritize and
for this treatment combination. The trial was closed by
accelerate the clinical development of the most promising
the sponsor before this objective could be achieved. Ten
agents for patients with lung cancer with the ultimate goal
patients were screened with six patients enrolled between
of improving survival and quality of life for patients with this
October 8, 2010 and October 31, 2014 when the trial was
devastating disease. The LCRT provides a central resource
closed by the sponsor. The lowest dose level was evaluated
for Clinical Investigators wishing to explore and become
successfully without any occurrence of dose limiting toxicity.
involved with the clinical development of novel interventions
The next higher planned dose level did not reach its accrual
and Biopharmaceutical companies seeking a cohesive
goal prior to study closure. One patient had a confirmed
network of clinicians to expedite development of promising
partial response while on treatment, and another patient
novel agents.
had stable disease.
Statisticians Interpret Lung Cancer Data for Staging The analysis of a retrospective database of the International Association for the Study of Lung Cancer (IASLC) consisting of more than 77,000 evaluable patients diagnosed with non-small cell lung cancer between 1999 and 2010 is almost complete. The analyses of this comprehensive data will be used to produce recommendations for the eighth edition of the IASLC tumor, node and metastasis (TNM) classification of lung cancer. The TNM staging process is used to describe the growth and spread of the disease and is used to determine the best option for treating a patient. Analyses are spearheaded by CRAB statisticians and are based on data from established databases or submitted via an electronic data capture (EDC) system set up by CRAB programmers. The database has been extensively analyzed by CRAB statisticians using sophisticated statistical methods based on established TNM components. Results and recommendations from these analyses will be the basis for the latest edition of the IASLC classification of lung cancer that is scheduled to be published in 2016.
Logo designed by Jo Jarvis, the Art Institute of Seattle
15 Lung
Lung Cancer Dose Escalation Study Completes First Phase Enrollment The Lung Cancer Research Team (LCRT) consortium completed enrollment for the first phase of a study examining dose toxicity. The study is known as: Phase 1b/II Trial of Carfilzomib with Irinotecan in Irinotecan-Sensitive Malignancies (Phase Ib) and Small Cell Lung Cancer Subjects (Phase II) Who Have Progressed on Prior Platinum-based Chemotherapy. For the first phase of this study, a total of 22 patients were screened with 16 being enrolled. No dose-limiting toxicities (DLTs) were observed at the lowest dose level. Two patients experienced DLTs at a higher dose level. Another cohort at a medium dose level included 6 patients, with one patient experiencing a DLT. The MTD (maximum tolerated dose) was established at the medium dose level (20/36 mg/m2). This is the dose that will be investigated in the second phase of this study which will enroll 80 patients with relapsed small cell lung cancer and treat them with this combination therapy.
CDISC Medical Research Data Standards Being Implemented at CRAB In the last days of 2014, the Food and Drug Administration (FDA) released final guidance documents that established a future requirement for sponsors submitting electronic data for review by the FDA to conform to specific CDISC Foundational Standards. CDISC (Clinical Data Interchange Standards Consortium) is a multi-disciplinary organization formed in 1997 to develop global standards for data used in medical research. Many organizations, including CRAB, have been ahead of the curve pursuing CDISC compliance ahead of a federal requirement. CRAB has focused on training and involvement within the CDISC community in addition to working with the Study Data Tabulation Model (SDTM) and Analysis Data Model (ADaM) standards. Three staff members have been certified following CDISC training on SDTM and ADaM standards. This year, two statisticians from CRAB gained further perspective on data standards and implementation when they attended the PharmaSUG (Pharmaceutical Industry SAS™ Users Group ) 2014 conference.
Hematologic 16
HEMATOLOGIC
Leadership Transition in Place at the UAMS Myeloma Institute The Myeloma Institute at the University of Arkansas for Medical Sciences (UAMS), one of the largest and most renowned US centers for the treatment of multiple myeloma, had a major transition last year. Dr. Gareth Morgan from the UK took over the reigns as director of the institute from the founder, Dr. Bart Barlogie. CRAB has been the Biostatistics Core supporting their efforts for over ten years. CRAB statisticians in collaboration with UAMS Myeloma Institute investigators have been working on a competitive renewal of the program project grant consisting of four scientific projects. The grant will be submitted during the second quarter of 2015 and CRAB will serve as the Biostatistics Core. Several manuscripts, including one entitled “Curing myeloma at last: defining criteria and providing evidence,� were published in 2014 as part of this ongoing collaboration.
UAMS Myeloma Institute Mission Statement: Since 1989, our mission has been guided by one enduring principle: CURE. UAMS Myeloma Institute is a world leader in multiple myeloma research and treatment. Our team of dynamic scientists and clinicians translates advances from the laboratory into novel clinical treatments, continually expanding the boundaries of myeloma research and therapy toward cure for all patients. (http://myeloma.uams.edu/)
17 Hematologic
Statisticians Work Illuminates Long Term Follow-Up of Myeloma Patients CRAB statisticians have been analyzing data from myeloma patients treated on trials in eight different countries and followed for at least five years to shed light on the main factors that allow patients to live progression-free for many years. This is a very rich and unique data set. Dr. Antje Hoering, CRAB’s Chief Scientific Officer and incoming Chief Executive Officer, presented initial findings at the International Myeloma Working Group (IMWG) meeting at the annual meeting of the American Society of Hematology (ASH) in December 2014. There were well over one hundred myeloma doctors in the audience.
AML Registration Trial for Leading Edge Therapies CRAB’s first registration trial in secondary acute myeloid leukemia (AML) closed to accrual in December 2014, slightly earlier than anticipated. Patients are still being treated and followed. A second trial investigating the same agent and focusing on specific toxicities as part of a submission to the Federal Drug Administration (FDA) is well underway. The study team has been busy preparing Data Safety Monitoring Board (DSMB) reports, creating annotated electronic case report forms, data sets and analysis code that is compliant with complex and rigorous FDA standards. Data managers at CRAB are posting and following up with over a thousand data queries asking clinical research associates at participating sites to complete or confirm data for over 300 patients and well over 30 forms.
Pancreatic 18
PANCREATIC Pancreatic Cancer Research Team Moves to CRAB CRAB expanded its network of research investigators in 2014 with the acquisition of the Pancreatic Cancer Research Team (PCRT). This acquisition added 45 clinical sites and 10 active projects to the CRAB Clinical Trials Consortium (CTC). The PCRT sites joined the original 28 sites of the CRAB Lung Cancer Research Team (LCRT) . Alignment of the LCRT and PCRT under the CRAB CTC will give pharmaceutical companies broad access to expertise and clinical sites in these two important areas of oncology research. CRAB’s consortium experience now ranges over sponsored Phase I-II clinical trials, Investigator-Initiated Phase I-II trials, and site acquisition management services for registration trials.
Purple Friday Art Show Raises Funds for Pancreatic Cancer Research Pancreatic cancer research received a boost from a Northwest artist, during a “Purple Friday” weekend gift show in the days following Thanksgiving. Valerie Coxon, RN, Ph.D., bead artist and owner of AnnieAlta, sold two purple-themed necklaces that she created to support CRAB’s research efforts. Valerie, a long-time friend of CRAB, donated $207 in proceeds from the necklaces she made by drawing on glass beads in the melting heat of a 900 degree propane- and oxygen-fed flame. Purple Friday Weekend was held Nov. 28 to 30 at a Kirkland gallery, Ryan James Fine Arts. Valerie decided to create the necklaces as a way to help CRAB when she learned that a friend of the gallery had recently lost her brother to pancreatic cancer. “The ribbon color for pancreatic cancer is purple and the event is Purple Friday Weekend,” she said. “And CRAB is now a home for crucial pancreatic cancer research. This feels like a message from heaven.”
Pancreatic Cancer Studies Make Progress When CRAB acquired the Pancreatic Cancer Research Team (PCRT) in 2014, it brought two specific studies fully inhouse.. Both studies have been ongoing for a few years, and will be completed in 2015. These studies were funded using philanthropic dollars and are investigating new combinations of chemotherapy treatment for advanced pancreatic cancer patients, capitalizing on the recent FDA approval in 2013 of the chemotherapy combination of Abraxane plus gemcitabine. One study has enrolled 60 patients over the past 3 years and is looking at which sequential treatments may work best for advanced pancreatic patients, combining Abraxane/gemcitabine with FOLFIRINOX (or FOLFIRI), for a total of 12 month chemotherapy treatment, followed by molecular profiling of the patient’s tumor at the end of the chemotherapy treatment to determine the next possible treatment. The second study is combining Cisplatin with Abraxane/gemcitabine to use possibly as an induction regimen to significantly reduce the tumor size and the metastasis quickly before going onto another treatment. This study is in its initial stages, with only a small number of patients treated in 2014. There will be additional patients to enroll into this study before the PCRT team can determine how effective this possible triplet combination of chemotherapy agents can be for advanced pancreatic cancer patients.
Logo designed by Jo Jarvis, the Art Institute of Seattle
19 Pancreatic
Clinical Trial Consortia Active in Pancreatic and Lung Cancer Research With CRAB’s two clinical consortia dedicated to lung cancer and pancreatic cancer research, CRAB is able to collaborate easily with the pharmaceutical companies working on the most recent and exciting therapies for both of these lifethreatening diseases. With clinical experts from around the world in both lung cancer and pancreatic cancer research in the two consortia, CRAB can advise which treatments are most effective and which ones should be pursued for further research. As part of CRAB’s full ranges of clinical trial services, the Lung Cancer Research Team (LCRT) and the Pancreatic Cancer Research Team (PCRT) consortia can operate as a site management organization (SMO) in clinical trials to provide our partnered pharmaceutical companies with specific premiere sites and researchers to enable the clinical trials to progress faster and more efficiently. SMO services in both LCRT and PCRT included new collaborations in both consortia. In 2014, LCRT began work on two lung cancer studies—one for non-small cell lung cancer patients, and one for small cell lung cancer patients. Also during the year, the PCRT began work on three new front-line studies for advanced pancreatic cancer patients, one study for those patients who qualify for surgery, and two studies for second-and third-line treatments.
Prostate & Breast 20
PROSTATE & BREAST Grant Awarded to Study Survival in Prostate Cancer CRAB was awarded a grant sub-contract to support a prospective randomized study comparing treatment with testosterone versus treatment with enzalutamide in men with metastatic castrate-resistant prostate cancer. For the study, known as the Transformer Trial, CRAB will be responsible for data coordinating center activities, statistical support, data management support, and development of the electronic data capture system. The trial, supported by a grant from the Department of Defense, is a collaboration between CRAB and the Johns Hopkins University. Data from 180 men will be collected to assess whether testosterone improves progression free survival (time to disease relapse or death).
Understanding of Circulating Tumor Cells Helps Patients and Physicians In 2005, Dr. Jeffrey Smerage proposed a Phase III clinical trial as part of his training as a SWOG Young Investigator. He worked with mentor Dr. Dan Hayes and CRAB biostatistician Dr. Bill Barlow to design a test of a new diagnostic tool to measure the number of circulating tumor cells found in the blood of women with metastatic breast cancer. It was believed that higher concentrations of these cells would spread the disease to other parts of the body. Chemotherapy often reduces the number of these cells even after one cycle (3 weeks) of therapy. The SWOG team proposed that a patient’s prognosis depended on the number of cells before treatment and after one cycle of therapy. Furthermore, if patients did not show a reduction in cells after 3 weeks of treatment, patients were randomized to change to a different chemotherapy or remain on the same treatment. After 9 years of accrual and follow-up, the definitive results of the study were published in the Journal of Clinical Oncology (June 2014). The trial showed that a simple switch of therapy did not help patients survive longer. However, the trial showed that the number of cells before treatment and after one cycle of chemotherapy is very predictive of how a patient will do. Thus, this simple test will help patients and physicians know what to expect in the future even if we cannot yet extend the patient’s horizon.
21 Friends & Supporters
FRIENDS & SUPPORTERS Our Donors Make Every Cancer Patient Count We are sincerely grateful for the generosity of our donors whose commitment and support help make our work possible. Your gift has the power to save lives. With your contributions, CRAB can: •
Fund tumor scans for tracking treatment effectiveness
•
Match an individual patient to a potentially life-saving clinical trial
•
Pay for laboratory tests that direct the best patient treatment choices
•
Fund cancer patients to participate in clinical trials
In Recognition of our 2014 Donors Cynthia Adkins
David Gray
Michael LeBlanc
Jeffrey Ross
Alex Arslan
John Hall
Diane Liggett
Nancy Salts
Jean Barce
Rachel Harpel
Rimi Louis
Matt Scott
Tammy Buist
Jason Harris-Talley
Terry Lynch
Lynn Shemanski
William Charters
Jo Ann Hartline
Curt Malloy
Craig Silva
Wesley Burns
Louise Highleyman
Dona Marrah
Angela Smith
Teresa Chern
Antje Hoering
Christine McLeod
Iris Syquia
Chris Cook
Jeri Jardine
Alan Mitchell
Roxanne Topacio
Valerie Coxon
Amy Johnson
Caryn Munkers
Patricia Ware
Cay Crowley
Yoong Kim
James Muldoon
Hongwei Wei
John Crowley
Laura Kingsbury
Alex Nelson
Daniel Wisebrauner
Steve Dong Lee
Beth Kirlin
Taylor Philips
Jane Xie
Frank Curci
Evonne Lackey
Yoko Rivers
Susan Finneran
Mike Lackey
Jim Rockwell
Keith Goodman
Dave Law
Adam Rosenthal
WE THANK YOU FOR YOUR CONTINUING PARTNERSHIP AND GENEROSITY
Community Connections 22
COMMUNITY CONNECTIONS 2014 VOLUNTEER SPOTLIGHT Thank you to all our volunteers and intern who generously shared their time and talents in support of our work. CRAB values their many contributions and is very grateful to all who helped us in our efforts and supported our mission throughout the year.
LARISSA HO: “Interning at CRAB was an eye opening experience as I got the opportunity to get the taste of the real world.”
HUIYIN LU: “It was a great opportunity for me to understand how the statisticians apply the biostatistics method into the reallife research.”
MAKENA YEE: “Ever since I was little, I’ve always wanted to study in the medical field. I loved volunteering there...I would most definitely come back to CRAB to volunteer more.”
YSABELL MULLARKY: “Being at CRAB showed me how crucial to the process of drug development and cancer treatment statistical analysis can be.”
23 Community Connections
A Shared Challenge: CRAB’s Community Partners and Sponsors CRAB is fortunate to partner with many Pacific Northwest businesses and government agencies that believe it is important to give back and support non-profit organizations in the community. CRAB is sincerely grateful to the generosity of our philanthropic partners and sponsors whose investment and commitment to our mission is helping us to enable efficient and successful clinical trials and to pioneer methods that clearly show which new cancer treatments work. Through corporate philanthropy, retail rewards programs, employee giving, in-kind donations, pro bono services, and event sponsorship— our partners enable us to keep fighting cancer, one clinical trial a time.
A SPECIAL THANK YOU TO OUR 2014 PHILANTHROPIC PARTNERS AND SPONSORS
Community Connections 24
CRAB in the Community In 2013, when CRAB launched CRABCares – an employee-led program that promotes staff participation in events that align with the CRAB mission to prevent and cure cancer – the primary objective was to build collaboration within CRAB and to raise awareness of cancer. Since its inception, CRAB employees have walked and run more than 60 miles in support of pancreatic and lung cancers, climbed 4,000 grueling stair-steps to call attention to lymphoma and leukemia, and served numerous meals to Seattle’s homeless youth. In 2014, more than 50 CRAB employees, plus friends and family, stepped forward to lend their time, energy and money with a unified focus to raise awareness of cancer and draw attention to the importance of cancer research.
WE APPLAUD THE GENEROUS AND TIRELESS OUTREACH EFFORTS OF CRAB’S CARING EMPLOYEES. TOGETHER, WE MAKE A DIFFERENCE.
25 Financial Summary
2014 Audit and Financial Summary $12 Million $10 Million
Investment
$8 Million
Contributions
$6 Million
Workshop Patient/Site
$4 Million
Contract
$2 Million
Grant
$0
2014
2013
2012
2011
2010
2014 CRAB Revenue Sources Over the Past Five Years
The impact of the financial crisis and federal sequestration that affected 2013 eased in 2014. Our total revenue increased to above 2012 levels, almost equaling that of 2011. The gain in revenue was a result of continued increases in federal and private funded activity. Revenue from all SWOG grant sources grew from a low of $5,435,678 in 2013 to $6,009,941 in 2014. Revenue in our Clinical Research and Statistical Research Programs also increased, including growing Clinical Trial Consortia pass-through Patient and Site revenue/expenditures not relevant to prior years. Most notably, the reorganization of funding for the NCI national cooperative groups increased SWOG and thus CRAB’s federal funding in 2014, augmented by new SWOG Clinical Trial Initiative projects being supported by pharmaceutical companies. The prior trend in revenue has reversed and early indication of 2015 looks to be promising for CRAB. We are cautiously optimistic that non SWOG revenues will remain steady and SWOG funding will remain a strong foundation for CRAB in 2015.
Support & Revenue 2014
2013
2012
2011
2010
Investment
20,681
(5,182)
–
–
–
Contributions
35,716
16,329
46,101
18,773
15,441
Workshop
34,104
26,088
32,318
16,513
17,949
156,489
12,450
–
–
–
Contract
4,196,323
4,058,478
3,552,971
3,070,709
3,340,806
Grant
5,635,271
5,415,172
6,158,620
7,015,304
6,866,894
9,790,010
$ 10,121,299
$ 10,241,090
Patient/Site
$ 10,078,584
$
9,523,335
$
Operating Expenses 2014
2013
2012
2011
2010
Research
7,412,587
7,469,156
7,485,583
7,677,869
7,450,747
Workshop
29,105
20,764
32,318
16,513
17,950
2,496,891
2,903,616
2,821,290
2,818,364
2,805,096
9,938,583
$ 10,393,536
$ 10,339,191
$ 10,512,746
$ 10,273,793
Administration $
Zelen Remembered 26
ZELEN REMEMBERED Professor Marvin Zelen Remembered for His Impact on CRAB A long-time mentor to CRAB, Marvin Zelen, Ph.D., internationally renowned for his biostatistical expertise, is remembered for his inspirational support for CRAB’s mission. Dr. Zelen, who died on Nov. 15, at the age of 87 after a battle with cancer, is remembered for the sage advice and support he gave to John Crowley, Ph.D., before founding CRAB with his wife Catherine Crowley, Ph.D., in 1997. A faculty member and former Chair of the Department of Biostatistics for both the Harvard School of Public Health and the Dana-Farber Cancer Institute, Professor Zelen founded the Frontier Science & Technology Research Foundation in 1975, a non-profit research foundation to advance the application of statistical science and practice and data management techniques in science, health care, and education. When he sought input from Professor Zelen, Dr. Crowley found a mentor who would inspire him to start Cancer Research And Biostatistics with a non-profit focus similar to Frontier Science. “Marvin was an inspiration to me in many ways,” said Dr. Crowley. “His early work on survival analysis was groundbreaking. He made the work of the Eastern Cooperative Oncology Group Statistical Center an intellectual success, much more than just a service, and I tried to follow this example in SWOG. He and his wife Thelma took the time to advise Cay and me on how to get CRAB off to a good start.” Professor Zelen’s contributions to the field of biostatistics are honored through the annual Marvin Zelen Leadership Award in Statistical Science which was begun by the Department of Biostatistics at the Harvard School of Public Health in 1997. The award, bestowed to Dr. John Crowley in 2013, recognizes an individual in government, industry, or academia, who by virtue of his/her outstanding leadership, has greatly impacted the theory and practice of statistical science.
Marvin Zelen and John Crowley
“Wherever he went in his career he created an environment that helped others flourish, and that is perhaps his greatest legacy.”
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