The COPD Biomarker Qualification Consortium (CBQC)

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    ORIGINAL RESEARCH

    The COPD Biomarker Qualifi cation Consortium (CBQC)Richard Casaburi,1 Bartolome Celli,2 James Crapo,3 Gerard Criner,4 Thomas Croxton,5 Alasdair Gaw,6 Paul Jones,7 Nancy Kline-Leidy,8 David A. Lomas,9 Debora Merrill,10 Michael Polkey,11 Stephen Rennard,12 Frank Sciurba,13 Ruth Tal-Singer,14 Robert Stockley,15 Gerry Turino,16 Jorgen Vestbo,17 and John Walsh10

    1Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, California, USA; 2Harvard University, Department of Internal Medicine, Boston, MA, USA; 3Harvard University, Department of Internal Medicine, Boston, MA, USA; 4Temple University, Philadelphia, Pennsylvania, USA; 5National Heart, Lung and Blood Institute, Rockville, MD, USA; 6Technology Strategy Board, Leicester, UK; 7Department of Internal Medicine, University of London, London, UK; 8United BioSource Corporation, Washington, DC, USA; 9Department of Internal Medicine, University of Cambridge, Cambridge, UK; 10COPD Foundation, Washington, DC, USA; 11Department of Internal Medicine, Royal Brompton & Harefi eld NHS, London, UK; 12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA, 13Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 14GlaxoSmithKline, Research Triangle Park, NC, USA; 15Department of Internal Medicine, University Hospital Birmingham, NHS Foundation, Birmingham, UK; 16Department of Internal Medicine, Columbia University, New York, NY, USA; 17Department of Internal Medicine, University of Manchester, Manchester, UK

    The COPD Biomarker Qualifi cation Consortium (CBQC) is a collaborative project to develop new tools for the development and testing of treatments for Chronic Obstructive Pulmonary Disease. This report summarizes the origin, goals and current activities of the Consortium.

    Keywords: biomarker, biomarker qualifi cation, CBQC, COPD Exacerbations, COPD foundation, desmosine, exercise, exhaled breath biomarkers, fi brinogen, imaging, patient-reported outcomes, St. Georges respiratory questionnaire, six-minute walk test, sputum measures

    Correspondence to: Stephen I. Rennard, M.D., Pulmonary and Critical Care Medicine, 985910 Nebraska Medical Center, Omaha, Nebraska 68198-5910, phone: 402/559-7313, fax: 402/559-4878, email: srennard@unmc.edu

    Abstract

    Knowledge about the pathogenesis and pathophysiology of chronic obstructive pulmonary disease (COPD) has advanced dramatically over the last 30 years. Unfortunately, this has had little impact in terms of new treatments. Over the same time frame, only one new class of medication for COPD has been introduced. Even worse, the rate at which new treatments are being developed is slowing. The development of new tools for the assessment of new treatments has not kept pace with understanding of the disease. In part, this is because drug development tools require a regulatory review, and no interested party has been in a position to undertake such a process. In order to facilitate the development of novel tools to assess new treatments, the Food and Drug Administration, in collaboration with the COPD Foundation, the National Heart Lung and Blood Institute and scientists from the pharmaceutical industry and academia conducted a workshop to survey the available information that could contribute to new tools. Based on this, a collaborative project, the COPD Biomarkers Qualifi cation Consortium, was initiated. The Consortium in now actively preparing integrated data sets from existing resources that can address the problem of drug development tools for COPD.

    COPD, 10:367377, 2013ISSN: 1541-2555 print / 1541-2563 onlineCopyright Informa Healthcare USA, Inc.DOI: 10.3109/15412555.2012.752807

    Introduction

    Chronic obstructive pulmonary disease (COPD) is a major public health problem. It is currently the third-leading cause of death in the United States, is a major cause of morbidity and is a major driver of health care costs. Recent advances in understanding the pathogenetic mechanisms that under-lie COPD have lead to the identifi cation of many novel therapeutic targets. As a result, a large number of agents have been explored as potential treat-ments, both at the preclinical and clinical levels. However, the tools used to assess treatments for COPD have been limited and better tools are needed, as the number of new drugs (new molecular entities) being approved to treat COPD is declining and attrition rate is high.

    As discussed in the FDA draft guidance for industry, drug development for COPD can be aimed at diff erent aspects of the disease: improving air-fl ow, providing symptom relief, modifying or preventing exacerbations, altering the disease process, or modifying lung structure or treating extra-pulmonary manifestations. While there has been some success with drug therapies for the fi rst three of these disease aspects, it is in the most crucial areas of COPD treatment (i.e., altering the disease process, or modifying lung structure or treating extra-pulmonary manifestations) that eff ective therapies are lacking.

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    368 Casaburi et al.

    To date, the medications for the treatment of COPD have been FDA-approved primarily on the basis of improvements in lung function, i.e., FEV1. Although FEV1 may be adequate to evaluate treatments aimed at improving lung function and the airways obstruction that is associated with COPD, FEV1 (alone) may be inad-equate to evaluate the effi cacy of novel therapies target-ing disease progression, lung structure or extrapulmo-nary manifestations of the disease. In the last four years, three U.S.-approved products: Advair 250/50 (fl utica-sone propionate 250 mcg and salmeterol 50 mcg inhala-tion powder), Spiriva (tiotropium bromide inhalation powder) and Daliresp (rofl umilast) have obtained the claim of reduction in COPD exacerbations. However, the initial approved indication for two of these three products (improvement in lung function for Advair, and maintenance treatment of bronchospasm for Spiriva) was based on FEV1.

    Th e natural history of COPD is generally that of pro-gressive deterioration of lung function and functional status, worsening quality of life, and, in many cases, demise. However, this progression is slow, occurring over years or decades, complicating interventional studies using these endpoints. In addition, COPD is extremely heterogeneous and while a number of attempts have been made to defi ne subsets of COPD, effi cient strate-gies to develop treatments targeting specifi c groups of COPD patients have yet to emerge. Th e extrapulmonary manifestations of COPD are becoming increasingly rec-ognized as substantial causes of morbidity and mortality that need timely characterization and treatment. Bio-markers have the potential to refl ect reliably the disease process and activity, and provide a better understanding of the COPD subtypes, especially the systemic or non-pulmonary manifestations.

    Th us, biomarkers may allow for the development of therapies aimed at treating COPD using endpoints other than FEV1. A large number of biomarkers have been explored in this context. However, the use of biomark-ers in drug development requires rigorous evaluation of their utility. Recognizing the importance of biomarkers to advance the development of new treatments, the Food and Drug Administration (FDA) in the United States initiated a Biomarker Qualifi cation Process.

    Biomarker qualifi cationTh e Biomarker Qualifi cation Process is part of the Drug Development Tools Qualifi cation program recently ini-tiated at the FDA. Th e Biomarker Qualifi cation process was established to support FDAs work with external sci-entists and clinicians in developing biomarkers to serve as tools in clinical trials. Th e importance of this eff ort is evidenced by the FDA Critical Path initiative, which identifi es Biomarker qualifi cation as one of the Critical Path Opportunities (2). Furthermore, the importance of the Drug development Tools qualifi cation programs (including biomarker qualifi cation) is underscored by the recent (2010) publication of the draft guidance for

    industry onthe Qualifi cation Process forDrug develop-ment Tools (3), andby the identifi cation of Advancing Regulatory Science and Innovation as