Marvin Zelen

Marvin Zelen
Born (1927-06-21)June 21, 1927
New York, New York
Died November 15, 2014(2014-11-15) (aged 87)
Boston, Massachusetts
Nationality American
Fields Statistics, biostatistics
experimental design models
Institutions

Stevens Institute of Technology, 1951-1952
National Bureau of Standards (renamed National Institute of Standards & Technology), 1952-1961
University of Maryland, 1960-1961
National Cancer Institute, 1963-1967
State University of New York (Buffalo), 1967-1977
Frontier Science & Technology Research Foundation (Founmer)
Dana-Farber Cancer Institute, * 1977-??
Harvard School of Public Health, Harvard University, 1977–2007
University of California, Berkeley - visiting
University of Wisconsin - visiting
Imperial College of Science & Technology (London) - visiting
London School of Hygiene and Tropical Medicine (London) - visiting

Hebrew University - visiting
Alma mater

City College of New York, New York City, B.S., mathematics, 1949;
University of North Carolina at Chapel Hill, M.S., mathematical statistics, 1951;

American University, Ph.D., Statistics, 1957
Known for Zelen's randomized consent design (a.k.a. Zelen's design
study design

Marvin Zelen (June 21, 1927 – November 15, 2014) was Professor Emeritus of Biostatistics in the Department of Biostatistics at the Harvard T.H. Chan School of Public Health (HSPH), and Lemuel Shattuck Research Professor of Statistical Science (the first recipient).[1] During the 1980s, Zelen chaired HSPH’s Department of Biostatistics. Among colleagues in the field of statistics, he was widely known as a leader who shaped the discipline of biostatistics.[2] He "transformed clinical trial research into a statistically sophisticated branch of medical research."[3]

Zelen was noted for his developing some of the statistical methods and study designs still used in clinical cancer trials, in which experimental drugs are tested for toxicity, effectiveness, and proper dosage. He introduced measures to ensure that data gathered from human trials would be as free as possible of errors and biases - measures that are now standard practice. Zelen helped transform clinical trial research into a well-managed and statistically sophisticated branch of medical science. His work in this area led to significant medical advances, such as improved treatments for several different forms of cancer. His research also focused on improved early detection of cancer; on modeling the progression of cancer and its response to treatment; and on using statistical models to help determine optimal screening strategies for various common cancers, especially breast cancer. Ironically, he died after a prolonged battle with cancer.

One of those experimental design models for randomized clinical trials is known as Zelen's design or Zelen's randomized consent design,[4] in which patients are randomized to either the treatment or to the control group before they give their informed consent. Because the group to which any given patient is assigned is known at the time of consenting, the study patient's consent can be sought conditionally.

Education

Work History

Visiting faculty member:

Early life and career before Harvard

Marvin Zelen was born and reared in New York City, where he attended and in 1944 received a diploma from Evander Childs High School. Then, as a mathematics major at City College of New York, he discovered and developed his lifelong interest in statistics and probability. In 1949, he earned his bachelor's degree in mathematics there. After earning a master’s degree in mathematical statistics from the University of North Carolina at Chapel Hill in 1951, he worked for 10 years at the mathematics lab of the National Bureau of Standards in Washington, D.C. He was the only math lab employee without a doctorate, which he later earned in 1957 at American University.

In the early 1960s, Zelen spent two years (1961-1963) as a visiting professor at the University of Wisconsin’s Mathematics Research Center, where he first worked with cancer researchers, helping them address problems with study design. After that, for four years beginning in 1963, he led the National Cancer Institute’s applied mathematics and statistics section, where he delved further into cancer and clinical research. He spent a year in London as a Fulbright Scholar, and then he joined the biostatistics department at the State University of New York in Buffalo, now University at Buffalo.

During his 10 years in Buffalo, Zelen helped the Eastern Cooperative Oncology Group (ECOG) — one of several regional organizations established by the National Cancer Institute (NCI) to test experimental cancer treatments — with its studies. In an American University alumni magazine article in 2008, Zelen said those early studies were “terrible.” He said the studies were “poorly thought out; the data was wrong; they had poor quality control, not enough patients — everything you can think of that was antiscientific.” He urged biomedical researchers in charge of the studies to begin from scratch because they had learned relatively little because of study design flaws. They agreed with Zelen, and along with his longtime collaborator Paul Carbone, he established research standards and practice now used in clinical trials for many infectious diseases. During that period, Zelen formed the Statistical Laboratory at the University of Buffalo, which focused on overseeing and improving statistical aspects of large, complex drug trials. ECOG would later become one of the world's largest programs for testing and evaluating various cancer treatments.

Zelen was also prominent in President Richard Nixon’s “war on cancer” during the early 1970s. He was chair of a committee responsible for designing and organizing the new program. Lee-Jen Wei, HSPH biostatistics professor, called Zelen's involvement in the early war on cancer “tremendous and lasting.”

Academic career at Harvard

In the mid-1970s, Zelen’s pioneering work in Buffalo brought him to the attention of HSPH’s then-biostatistics chair, Frederick Mosteller. Zelen insisted that he would only come to Harvard if he could bring the biostatistics team which he had built in Buffalo, since he wanted to build the world's greatest biostatistics department wherever he went. Thus, in 1977, 27 faculty, researchers, and other staff members moved from Buffalo to Boston, along with their DEC-20 computer and their research projects, the ECOG trials — 150 cancer trials involving several thousand patients. Zelen’s lab was established at the Dana-Farber Cancer Institute, where, simultaneously with his tenure at HSPH, he built the Dana-Farber Cancer Institute’s Department of Biostatistics and Computational Biology.

Zelen’s colleague and successor (as Department Chair), biostatistics professor Nan Laird, recalled that “those first few years of integrating twelve new faculty members from Buffalo with half as many from Harvard were part of Marvin’s grand plan to make Harvard the nation's leading biostatistics department — which it is and has been for quite some time. It was an enormously exciting time when we were united in working towards a common goal. Marvin’s genius was that he got all of us involved, then stepped back and gave us all the credit.”

He served for a decade in the 1980s (1981-1990) as chair of the Harvard School of Public Health's Department of Biostatistics, where he has been credited with transforming HSPH’s biostatistics department into the best biostatistics department in the United States. He was also a member of the Faculty of Arts and Sciences at Harvard University, in the FAS Department of Statistics in Harvard Square, and voted to remain an Emeritus Professor there, also, until his death in late 2014.

In 2007, Prof. Zelen became the first holder of the newly named (by Harvard President Derek Bok) Lemuel Shattuck Research Professor of Statistical Science at HSPH.[6]

Prof. Zelen was known for developing the statistical methods and study designs that are used in clinical cancer trials, in which experimental drugs are tested for toxicity, effectiveness, and proper dosage. He also introduced measures to ensure that data from the trials are as free as possible of errors and biases—measures that are now standard practice. Prof. Zelen helped transform clinical trial research into a well-managed and statistically sophisticated branch of medical science. His work in this area has led to significant medical advances, such as improved treatments for several different forms of cancer. His research also focused on improved early detection of cancer; on modeling the progression of cancer and its response to treatment; and on using statistical models to help determine optimal screening strategies for various common cancers, especially breast cancer.

Dr. Mitchell H. Gail, senior investigator in the biostatistics branch of NCI’s Division of Cancer Epidemiology and Genetics, commented:

Marvin had a lot of guts and a vision for what was important. He finagled NCI into supporting the use of DEC-10 (PDP-10) computers in clinical trials, long before the study section supported it. He inspired the clinical trials community of statisticians.

On a more personal level, his colleague and successor Laird said that

[Prof. Zelen was] a tremendous force in my personal and professional life. He was always in and out of my office, asking how things were going. Even as he was trying to convince me to do something I absolutely did not want to do, I always felt his intentions for me were the best. Marvin was always honest and unpretentious.

In 1981, Prof. Zelen succeeded Frederick Mosteller as Biostatistics Chair. He continued working on the ECOG trials, helped lay the groundwork for the department’s pre-eminence in AIDS clinical trials, and improved the biostatistics curriculum. As its chair, he helped propel the department to its position as a leading center for biostatistical research.

Prof. Zelen also achieved another level of fame in the early 1980s when he and his late colleague (died 2009) in the biostatistics department, Stephen Lagakos, launched a study of a possible connection between a cluster of childhood leukemia cases in Woburn and the town’s water supply. Known as the Harvard Health Study, the investigation showed, for the first time, a connection between Woburn’s contaminated water and a variety of adverse health effects, including leukemia. The matter made headlines, wound up in court, and was chronicled in the book A Civil Action, which was later made into a movie. As the book notes, when Prof. Zelen announced the study’s results in the basement of a Woburn church in February 1984, someone in the audience called out, “Thank God for Marvin Zelen,” and the crowd burst into applause.

Another of Prof. Zelen’s achievements was his establishment, in 1975, of the Frontier Science and Technology Research Foundation in Boston, a nonprofit devoted to advancing the use of statistical science and practice and data management techniques in science, health care, and education. Prof. Zelen served as president, and his wife Thelma was chief administrative officer. Several of his other close friends and Harvard colleagues were also directly involved. Richard D. Gelber, professor of biostatistics of HSPH and at DFCI,[7] and winner of the 2008 Komen Brinker Award for Scientific Distinction, noted:

This is another excellent example of how Marvin established an environment within which others could flourish. Thelma’s contributions to Marvin’s success cannot be overlooked. Their partnership is a role model of working together, and she has been a major force in the formation and administrative leadership of Frontier Science as its chief operating officer for almost 40 years.

and, adding his voice of praise for Prof. Zelen's mentorship and generosity

During the past 39 years, Marvin taught me much about the importance of collaborative research, and how progress is fueled by statistical and clinical scientists working together as partners.

Fellow biostatisticians from around the country—people like Jack Kalbfleisch from the University of Michigan, Ross Prentice from the Fred Hutchinson Cancer Research Center, and Norman Breslow from the University of Washington - have all spoken of Prof. Zelen’s huge influence. Said Kalbfleisch, “Marvin was a tremendous force in the profession and a great mentor to so many of his colleagues and students.” Prentice said Prof. Zelen “did much to define the biostatistical profession.” Breslow said he was “greatly influenced by Marvin and his work.”

Again, Mitchell H. Gail of National Cancer Institute recalled:

So many people were helped by Marvin, whether they needed assistance with starting a company, with a personal matter, or with ideas and guidance in academic statistics. That is truly a legacy to be proud of.

Prof. Zelen is survived by his wife, Thelma Geier Zelen, and their two daughters, Deborah and Sandy Zelen, and by two grandsons, Matthew and Toby Mues.[8]

Honors and awards

Awardees:[11]
  • 2014 - Xiao-Li Meng, PhD, Dean of the Graduate School of Arts & Sciences and Whipple V.N. Jones Professor of Statistics at Harvard University, "Personalized Treatment: Sounds heavenly, but where on Earth did they find the right guinea pig for me?"[12][13][14]
  • 2013 - John J. Crowley, PhD, President and CEO of Cancer Research And Biostatistics (CRAB), “A Brief History of Survival Analysis”[15]
  • 2012 - Nicholas P. Jewell, Professor, Division of Biostatistics, School of Public Health; Professor, Department of Statistics, University of California, Berkeley, “Counting Civilian Casualties”[16]
  • 2011 - J. Richard Landis, “Methods for Investigating Agreement & Concordance: with Applications in the Biomedical Sciences”
  • 2010 - Ingram Olkin, Professor and Chair Emeritus of statistics and education at Stanford University and the Stanford Graduate School of Education, for developing statistical analysis for evaluating policies, particularly in education, and for his contributions to meta-analysis, statistics education, multivariate analysis, and majorization theory, “Measures of Heterogeneity. Diversity and Inequality”
  • 2009 - David L. DeMets, “Challenges in Clinical Trials; Some Old and Some New”
  • 2008 - Norman E. Breslow, for developing and popularizing case-control matched sample research designs, with co-author Nicholas Day, in their two-volume work Statistical Methods in Cancer Research, “The Case-Control Study: Origins, Modern Conception and Newly Available Methods of Analysis”
  • 2007 - Scott L. Zeger, cofounder of journal Biostatistics, “The Symbiosis of Statistical Science and Biomedicine: Past and Future”
  • 2006 - Mitchell H. Gail, Past President (1995), American Statistical Association, “Absolute Risk: Clinical Applications and Controversies”
  • 2005 - Ross L. Prentice, “Chronic Disease Prevention: Research Strategies and Needs”
  • 2004 - Robert C. Elston, “The Analysis of Case-Control Data to Detect Candidate Genes”
  • 2003 - Wayne Fuller, “Analytic Studies with Complex Survey Data”
  • 2002 - Robert O’Neill, “A Perspective on the Development and Future on Statistics at the FDA”
  • 2001 - Niels Keiding, “Event Histories and Their Analysis”
  • 2000 - Lincoln E. Moses, “Deciding Whether Large Clinical Trials and Meta-analyses (deceased) Agree or Not”
  • 1999 - John W. Tuke,y “A Smorgasbord of Handy Techniques That Can Help in (deceased) Analyzing Data”
  • 1998 - Sir David Roxbee Cox, “Graphical Models in Statistics: A Review”
  • 1997 - Frederick Mosteller, (former) Chair, Department of Biostatistics, Harvard School of Public Health, “The Importance of Clinical Trials in Education” (deceased)

Symposia

Boards, Chairmanship, and Professional Service

Collegial praise

Current HSPH biostatistics chair Victor de Gruttola said

Scientists from around the world have benefited from Dr. Zelen’s innovative ideas and transformative effect on biomedical research, but those of us associated with the Harvard Department of Biostatistics are particularly grateful for Dr. Zelen’s commitment to educating students and advancing the careers of junior scientists.

Bibliography

Marvin Zelen has had work published in more than 150 publications. The most complete list published in one place is on his profile page in the Harvard Catalyst.

Obituaries

Dr. Zelen died on November 15, 2014, at 87, after a battle with histiocytic sarcoma. Prof. Zelen is survived by his wife Thelma Geier Zelen and two daughters, Deborah and Sandy Zelen, and two grandsons, Matthew and Toby Mues.

See also

References

  1. ↑ Awarded newly-established Lemuel Shattuck Research Professorship in Statistical Science, established and named by Harvard President Derek Bok, effective September 1, 2007
  2. ↑ HSPH Biostatistics Department Zelen Award page
  3. ↑ Lagakos Symposium profile for Marvin Zelen
  4. ↑ Joy Adamson & Sarah Cockayne & David J. Torgerson, Zelen's randomized consent design, Encyclopedia of Research Design, Neil J. Salkind, Ed., 2010, DOI: http://dx.doi.org/10.4135/9781412961288, Print ISBN 9781412961271; Online ISBN 9781412961288
  5. ↑ 'About' page, Frontier Science & Technology Research Foundation website
  6. ↑ Awarded newly-established Lemuel Shattuck Research Professorship in Statistical Science, established and named by Harvard President Derek Bok, effective September 1, 2007
  7. ↑ Dana-Farber/Harvard Center Center profile page for Richard D. Gelber
  8. ↑ Legacy.com local obituary for Marvin Zelen, published in the Boston Globe Friday, November 17, 2014
  9. ↑ 1996 announcement of the establishment of the Marvin Zelen Leadership Award in Statistical Science
  10. ↑ Awards and Lectureships of the HSPH Department of Biostatistics
  11. ↑ Awardees of the annual Marvin Zelen Leadership Award in Statistical Science
  12. ↑ HSPH Biostatistics Department announcement of 2014 Zelen Award
  13. ↑ CV for Dr. Xiao-Li Meng
  14. ↑ Esha Senchaudhuri, 2014 Zelen Award Honors Statistician and Educator, 2014, accessed 11/21/2014
  15. ↑ "John Crowley honored with Zelen Leadership Award", SWOG announcement of Crowley's award, April 20-13, accessed 11/21/2014
  16. ↑ Minibio of Jewell, The Third Joint Biostatistics Symposium, Chengdu, Sichuan, China, June 25-28, 2014Accessed 11/21/2014
  17. ↑ COPSS, TABLE 1.4 Recipients of the R.A. Fisher Lectureship (cont’d), Past, Present, and Future of Statistical Science, CRC Press, page 15 (middle)
  18. ↑ Parzen Prize Lecture to Feature World-Renowned Statisticians, May 12, 2008, Accessed 11/21/2014
  19. ↑ Announcement of Parzen Prize
  20. ↑ Conference Information, , David W. Warne (Editor), International Society for Clinical Biostatistics, 2006 (December), Number 42, page 36 (top left corner of page)
  21. ↑ Frontier Science Foundation-Hellas (FSF-H) website announcement of the Lagakos Symposium, Athens
  22. ↑ DFCI site for "Play the Winner" Symposium
  23. ↑ Esha Senchaudhuri, 2014 Zelen Award Honors Statistician and Educator, 2014, accessed 11/21/2014
  24. ↑ Joy Adamson & Sarah Cockayne & David J. Torgerson, Zelen's randomized consent design, Encyclopedia of Research Design, Neil J. Salkind, Ed., 2010, DOI: http://dx.doi.org/10.4135/9781412961288, Print ISBN 9781412961271 | Online ISBN 9781412961288

External links

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