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Review article
peer-reviewed

A Model for Accelerating Identification and Regulatory Approval of Effective Investigational Agents



Abstract

A path for accelerated regulatory review of new drug and biomarker combinations is badly needed to transform the current clinical drug development process into an efficient, effective system that meets current and future healthcare needs. However, this type of radical transformation will not occur by layering regulatory change on existing clinical practice patterns. Here, we summarize a May 2011 I-SPY 2 TRIAL (Investigating Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular AnaLysis) workshop that included key leaders from the Food and Drug Administration (FDA), academia, industry, advocacy, and clinical trial-focused foundations that addressed this critical need. The workshop identified key aspects of the organization, trial design, and regulatory and industry alignment required to rapidly move successful agents from trial to clinical care. The workshop specifically focused on providing input for the development of a new evidence-based regulatory path for review of drugs and biomarkers that derive from neoadjuvant, modular, adaptive phase 2 screening trials achieved through precompetitive collaborations. The workshop participants agreed that new models, exemplified by the I-SPY 2 TRIAL for breast cancer, could address the need to more efficiently review and advance new drug and biomarker combinations. A three-tier model for trial development best describes this process. As practiced in I SPY 2, integrating imaging and biomarker information obtained through adaptive trials in the neoadjuvant breast cancer care setting is the first step. The second tier is replicable structural processes, including real-time data collection. The third is partner alignment achieved through pre-competitive collaboration and the potential to position successful drugs for accelerated regulatory approval in the neoadjuvant setting, where patients are likely to have the greatest benefit. Many elements of this model were incorporated into a new FDA draft guidance document which was released for public comment on May 31, 2012.



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Review article
peer-reviewed

A Model for Accelerating Identification and Regulatory Approval of Effective Investigational Agents


Author Information

Laura J. Esserman Corresponding Author

University of California, San Francisco

Anna D. Barker

Arizona State University

Janet Woodcock

Center for Drug Evaluation and Research (CDER), Food and Drug Administration

Meredith A. Buxton

Carol Franc Buck Breast Care, University of California, San Francisco

Donald A. Berry

Department of Biostatistics, The University of Texas MD Anderson Cancer Center

Robert Patterson

Quantum Leap Healthcare Collaborative

Michael King. Jolly

Quintiles Innovation

Angela DeMichele

University of Pennsylvania School of Medicine

Nola Hylton

Radiology and Biomedical Imaging, University of California, San Francisco

Eric H. Rubin

Merck Research Laboratories

David Parkinson

New Enterprise Associates

David Wholley

Foundation for the National Institutes of Health

Laura van't Veer

University of California, San Francisco

Douglas Yee

Medicine – Hematology, Oncology and Transplantation Office, University of Minnesota

John Park

University of California, San Francisco

Debu Tripathy

University of Southern California

Jane Perlmutter

Gemini Group

Kenneth Buetow

Arizona State University

Mike Hogarth

University of California, Davis

Joe Gray

Oregon Health and Science University

David M. Dilts

Oregon Health Science University School of Medicine


Ethics Statement and Conflict of Interest Disclosures

Conflicts of interest: The authors have declared the following conflicts of interest: Financial relationships: David Parkinson declare(s) an alternate financial activity from New Enterprise Associates. Employment or leadership position. David M. King Jolly declare(s) an alternate financial activity from Quintiles. Employment or leadership position. Robert Patterson declare(s) an alternate financial activity from Mondobiotech Holdings AG. Employment or leadership position; ownership. Donald A. Berry declare(s) an alternate financial activity from Berry Consultants. Employment or leadership position; ownership. Laura van 't Veer declare(s) an alternate financial activity from Agendia. Employment or leadership position; ownership. John Park declare(s) an alternate financial activity from Merrimack Pharmaceuticals. Consultant or advisory role; ownership. Eric Rubin declare(s) an alternate financial activity from Merck & Co. Employment or leadership position; ownership. David Parkinson declare(s) an alternate financial activity from Abbott Pharmaceuticals. Consultant or advisory role.


Review article
peer-reviewed

A Model for Accelerating Identification and Regulatory Approval of Effective Investigational Agents


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Review article
peer-reviewed

A Model for Accelerating Identification and Regulatory Approval of Effective Investigational Agents

  • Author Information
    Laura J. Esserman Corresponding Author

    University of California, San Francisco

    Anna D. Barker

    Arizona State University

    Janet Woodcock

    Center for Drug Evaluation and Research (CDER), Food and Drug Administration

    Meredith A. Buxton

    Carol Franc Buck Breast Care, University of California, San Francisco

    Donald A. Berry

    Department of Biostatistics, The University of Texas MD Anderson Cancer Center

    Robert Patterson

    Quantum Leap Healthcare Collaborative

    Michael King. Jolly

    Quintiles Innovation

    Angela DeMichele

    University of Pennsylvania School of Medicine

    Nola Hylton

    Radiology and Biomedical Imaging, University of California, San Francisco

    Eric H. Rubin

    Merck Research Laboratories

    David Parkinson

    New Enterprise Associates

    David Wholley

    Foundation for the National Institutes of Health

    Laura van't Veer

    University of California, San Francisco

    Douglas Yee

    Medicine – Hematology, Oncology and Transplantation Office, University of Minnesota

    John Park

    University of California, San Francisco

    Debu Tripathy

    University of Southern California

    Jane Perlmutter

    Gemini Group

    Kenneth Buetow

    Arizona State University

    Mike Hogarth

    University of California, Davis

    Joe Gray

    Oregon Health and Science University

    David M. Dilts

    Oregon Health Science University School of Medicine


    Ethics Statement and Conflict of Interest Disclosures

    Conflicts of interest: The authors have declared the following conflicts of interest: Financial relationships: David Parkinson declare(s) an alternate financial activity from New Enterprise Associates. Employment or leadership position. David M. King Jolly declare(s) an alternate financial activity from Quintiles. Employment or leadership position. Robert Patterson declare(s) an alternate financial activity from Mondobiotech Holdings AG. Employment or leadership position; ownership. Donald A. Berry declare(s) an alternate financial activity from Berry Consultants. Employment or leadership position; ownership. Laura van 't Veer declare(s) an alternate financial activity from Agendia. Employment or leadership position; ownership. John Park declare(s) an alternate financial activity from Merrimack Pharmaceuticals. Consultant or advisory role; ownership. Eric Rubin declare(s) an alternate financial activity from Merck & Co. Employment or leadership position; ownership. David Parkinson declare(s) an alternate financial activity from Abbott Pharmaceuticals. Consultant or advisory role.

    Acknowledgements


    Article Information

    Published: December 08, 2012

    DOI

    10.7759/cureus.76

    Cite this article as:

    Esserman L J., Barker A D., Woodcock J, et al. (December 08, 2012) A Model for Accelerating Identification and Regulatory Approval of Effective Investigational Agents. Cureus 4(12): e76. doi:10.7759/cureus.76

    Publication history

    Peer review began: November 17, 2012
    Published: December 08, 2012

    Copyright

    © Copyright 2012
    Esserman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    License

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

A path for accelerated regulatory review of new drug and biomarker combinations is badly needed to transform the current clinical drug development process into an efficient, effective system that meets current and future healthcare needs. However, this type of radical transformation will not occur by layering regulatory change on existing clinical practice patterns. Here, we summarize a May 2011 I-SPY 2 TRIAL (Investigating Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular AnaLysis) workshop that included key leaders from the Food and Drug Administration (FDA), academia, industry, advocacy, and clinical trial-focused foundations that addressed this critical need. The workshop identified key aspects of the organization, trial design, and regulatory and industry alignment required to rapidly move successful agents from trial to clinical care. The workshop specifically focused on providing input for the development of a new evidence-based regulatory path for review of drugs and biomarkers that derive from neoadjuvant, modular, adaptive phase 2 screening trials achieved through precompetitive collaborations. The workshop participants agreed that new models, exemplified by the I-SPY 2 TRIAL for breast cancer, could address the need to more efficiently review and advance new drug and biomarker combinations. A three-tier model for trial development best describes this process. As practiced in I SPY 2, integrating imaging and biomarker information obtained through adaptive trials in the neoadjuvant breast cancer care setting is the first step. The second tier is replicable structural processes, including real-time data collection. The third is partner alignment achieved through pre-competitive collaboration and the potential to position successful drugs for accelerated regulatory approval in the neoadjuvant setting, where patients are likely to have the greatest benefit. Many elements of this model were incorporated into a new FDA draft guidance document which was released for public comment on May 31, 2012.



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Laura J. Esserman, M.D.

University of California, San Francisco

For correspondence:
laura.esserman@ucsfmedctr.org

Anna D. Barker, Ph.D.

Arizona State University

Janet Woodcock, None

Center for Drug Evaluation and Research (CDER), Food and Drug Administration

Meredith A. Buxton, None

Carol Franc Buck Breast Care, University of California, San Francisco

Donald A. Berry, Ph.D.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center

Robert Patterson, None

Quantum Leap Healthcare Collaborative

Michael King. Jolly, None

Quintiles Innovation

Angela DeMichele, M.D.

University of Pennsylvania School of Medicine

Nola Hylton, Ph.D.

Radiology and Biomedical Imaging, University of California, San Francisco

Eric H. Rubin, Other

Merck Research Laboratories

David Parkinson, M.D., M.D.

New Enterprise Associates

David Wholley, None

Foundation for the National Institutes of Health

Laura van't Veer, Ph.D.

University of California, San Francisco

Douglas Yee, M.D.

Medicine – Hematology, Oncology and Transplantation Office, University of Minnesota

John Park, None

University of California, San Francisco

Debu Tripathy, M.D.

University of Southern California

Jane Perlmutter, None

Gemini Group

Kenneth Buetow, None

Arizona State University

Mike Hogarth, None

University of California, Davis

Joe Gray, None

Oregon Health and Science University

David M. Dilts, Ph.D.

Oregon Health Science University School of Medicine

Laura J. Esserman, M.D.

University of California, San Francisco

For correspondence:
laura.esserman@ucsfmedctr.org

Anna D. Barker, Ph.D.

Arizona State University

Janet Woodcock, None

Center for Drug Evaluation and Research (CDER), Food and Drug Administration

Meredith A. Buxton, None

Carol Franc Buck Breast Care, University of California, San Francisco

Donald A. Berry, Ph.D.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center

Robert Patterson, None

Quantum Leap Healthcare Collaborative

Michael King. Jolly, None

Quintiles Innovation

Angela DeMichele, M.D.

University of Pennsylvania School of Medicine

Nola Hylton, Ph.D.

Radiology and Biomedical Imaging, University of California, San Francisco

Eric H. Rubin, Other

Merck Research Laboratories

David Parkinson, M.D., M.D.

New Enterprise Associates

David Wholley, None

Foundation for the National Institutes of Health

Laura van't Veer, Ph.D.

University of California, San Francisco

Douglas Yee, M.D.

Medicine – Hematology, Oncology and Transplantation Office, University of Minnesota

John Park, None

University of California, San Francisco

Debu Tripathy, M.D.

University of Southern California

Jane Perlmutter, None

Gemini Group

Kenneth Buetow, None

Arizona State University

Mike Hogarth, None

University of California, Davis

Joe Gray, None

Oregon Health and Science University

David M. Dilts, Ph.D.

Oregon Health Science University School of Medicine