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Identifying the Role of Funded Research in Pivotal Cancer Research Advances

Identifying the Role of Funded Research in Pivotal Cancer Research Advances. AEA 2011 Brian Zuckerman (IDA Science and Technology Policy Institute ) Co-authors: James Corrigan (NIH); Seth Jonas (STPI); Lawrence Solomon (NIH). Project Origins.

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Identifying the Role of Funded Research in Pivotal Cancer Research Advances

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  1. Identifying the Role of Funded Research in Pivotal Cancer Research Advances AEA 2011 Brian Zuckerman (IDA Science and Technology Policy Institute) Co-authors: James Corrigan (NIH); Seth Jonas (STPI); Lawrence Solomon (NIH)

  2. Project Origins • NCI exploring potential approaches to assessing impact/return on research investments • Sought complement to econometric studies (e.g., Manton et al 2009, Sun et al 2009) that correlate changes in cancer mortality with R&D spending • Sought to build on independent statements regarding value of research

  3. Two Linked Studies Conducted • Analysis of “Clinical Cancer Advances” series of the Journal of Clinical Oncology (JCO) 2005-20010 • Analysis of 2006 Nature special article, “Milestones in Cancer”

  4. JCO analysis

  5. JCO Clinical Cancer Advances Methodology • Relies on expert judgment to identify the key advances and key publications either reporting or relevant to the selected advances • Each article identifies “Major Advances” and “Notable Research Advances” accomplished in the previous year. • “Major advances” denote those likely to affect mortality

  6. Examples of Major Advances • Trastuzumab (Herceptin) Cuts Breast Cancer Recurrence in Half, Increases Survival • Childhood Cancer Survivors Face Increased Risk of Heart Disease • Researchers Create Genetic Test to Predict Lung Cancer Prognosis • Sorafenib Improves Survival in Liver Cancer • Shortage of Oncologists Forecasted by 2020 • Two Large Trials Find Routine PSA Testing Has a Small, If Any, Effect on Reducing Prostate Cancer Mortality • FDA Approves Bevacizumab for Glioblastoma

  7. Definition of “Support” • Advances where one or more publications: • Acknowledge an NCI award to a U.S. institution • Include an NCI intramural scientist as an author • Make use of materials collected in the course of NCI-funded research (e.g., human tissue used for biomarker/correlative studies collected from an NCI-funded clinical trial)

  8. Methodology for Analyzing Sources of Support for Advances • Collect papers and presentations underlying both major advances and notable research advances • Collect acknowledgements of funding sources for those papers and presentations • Analyze sources of funding at the level of single advances and disease areas • Summarize results by funder (e.g., industry, NCI)

  9. Finding: NCI Support for Half of Advances

  10. Finding: More than Half of NCI-Supported Advances Also Had Non-NCI Support

  11. Finding: NCI Support Varied by Area

  12. Finding: NCI Support Varied by Area (continued) • Variation in extent of NCI support within both disease specific advances and other categories • Genitourinary less than 20% versus pediatric 86% • Survivorship higher than cancer prevention and quality of life, higher than access to care

  13. Finding: Diverse Set of NCI Programs Supports Advances Cooperative Groups were acknowledged on 57% of the NCI-supported major advances

  14. Finding: Non-NCI Sources of Support Are Diverse • Nearly half of advances acknowledge industry support • 56% of major advances • 38% of notable research • Many other sources (e.g., non-NCI U.S. government, U.S. foundations) provide support for 10-20% of advances

  15. Nature Milestones Analysis

  16. Nature Milestones Cancer Study Source Data • 2006 Nature special article identifies 24 milestones in cancer research in order to, “highlight the most influential discoveries in the field of cancer over the past century.” Each milestone description includes: • Listing of one or more papers describing the initial advance as well as later papers • Listing of other papers that extended and deepened the initial finding • “Milestones” are pivotal basic research discoveries - first discovery milestone traces back to 1889

  17. Nature Milestones Cancer Study Analysis Methodology • Analysis identifies funding sources and NIH intramural authors of articles • Discovery milestone considered to have NCI support for “initial discovery” if any publications within one year of first publication were NCI-funded • Discovery milestone considered “NCI-supported” if any publications were NCI-funded as determined from analysis of acknowledgements • Analysis focuses on 14 discovery milestones where the initial discovery was post-1970 because of the difficulty of identifying pre-1970 funding sources • Seven during the 1970s • Three during the 1980s • Three during the 1990s • One after 2000

  18. Examples of Discovery Milestones (Year) • Milestone 1: (1889) Seed and soil hypothesis • Milestone 2: (1890) Cancer as a genetic disease • Milestone 5: (1915) Hormones and cancer • Milestone 6: (1937) Cancer stem cells • Milestone 12: (1972) Apoptosis and cancer • Milestone 13: (1975) Tumor microenvironment • Milestone 20: (1989) Cell cycle and DNA damage checkpoints • Milestone 21: (1990) Genetic basis for cancer predisposition • Milestone 22: (1990) Mechanisms of genetic instability in cancer • Milestone 23: (1999) Cancer profiling • Milestone 24: (2001) Targeted cancer therapy

  19. Findings • NCI funding associated with at least one publication for all 14 of the discovery milestones • NCI funding associated with the initial discovery for 10 of the 14 discovery milestones • Non-NCI NIH support for at least one publication associated with eight of the 14 milestones supported by NCI, including for three of the initial discoveries

  20. More Detail: NCI Programs and non-NCI ICs • NCI programs: R01s, Cancer Centers, P01s most often acknowledged • Non-NCI Institutes: 10 other Institutes involved with at least one discovery milestone (NIGMS, NICHD 5 each)

  21. Methodological Implications • Use of acknowledgements to identify sources of funding of set of external expert-identified advances is feasible • Methodological difficulties arise when attempting to trace antecedents of those advances • Interpretation of results of such a study is complex and requires careful attention to caveats and limitations

  22. Acknowledgments • NCI/OSPA • Larry Solomon • Elizabeth Hsu • Karl Poonai • Sudha Sivaram • NCI/CTEP • Sherry Ansher • Malcolm Smith • Jamie Zwiebel • Jeff Abrams • IDA STPI • Seth Jonas • Rashida Nek • Judith Hautala • John Taggart • Cara O’Donnell • Ashley Brenner • Mary Beth Hughes • Ritu Chaturvedi • Marta Kowalczyk

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