Chronic Lung Disease Biomarker & Clinical Outcome Assessment Qualification Consortium (CBQC)
As a result of a workshop convened in 2011, the COPD Biomarker Qualification Consortium (CBQC) was created to help fast track regulatory acceptance of new COPD Drug Development Tools (DDTs) to enable the development of better treatments for COPD. The goals of using these tools are to improve the lives of people with COPD. For example, improved therapies could help stop or slow the worsening of symptoms, reduce the frequency or severity of exacerbation episodes, or ultimately prevent disease in individuals at risk for COPD. Description of the Consortium was published in 2013: Casaburi et al. in the Journal of COPD.
Based on the recognition that clinical outcome assessments such as the SGRQ, the CAT, Constant Work Exercise, Dyspnea, Physical Activity and Lung Imaging biomarkers are relevant in most chronic lung diseases such as Bronchiectasis, Pulmonary Fibrosis, A1AT deficiency and Asthma, the CBQC was renamed to Chronic Lung Disease Biomarker & Clinical Outcome Assessment Qualification Consortium (CBQC) in 2020.
What are Drug Development Tools
The US Food and Drug Administration (FDA) defines Drug Development Tools (DDTs) as "methods, materials, or measures that have the potential to facilitate drug development. Examples of DDTs may include, but are not limited to: a biomarker used for clinical trial enrichment, a clinical outcome assessment (COA) used to evaluate clinical benefit."
There are different types of DDTs, including Biomarkers and Clinical Outcomes Assessments as defined by the US National Institutes of Health (NIH) and the FDA joint taskforce. More information: the BEST (Biomarkers, EndpointS, and other Tools) Resource
The US FDA provides more detailed definitions to support the qualification (Regulatory Acceptance) of new Drug Development Tools (DDTs):
- A Biomarker as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Types of biomarkers: Molecular, histologic, radiographic, or physiologic characteristics
- Clinical Outcomes Assessments (COA) measure how an individual feels, functions, or survives
Similar guidelines are defined by the and European Medicines Agency (EMA).
In COPD and related diseases, DDTs can help researchers see if there are any treatment-related changes in the body. Biomarkers could include the results of lung imaging tests, or the levels of specific biomarkers (e.g. plasma fibrinogen) in the blood, sputum or urine. Examples of COAs in COPD include the results of exercise testing (the six-minute walk, cyclo-ergometry or shuttle walk tests, or physical activity monitors), and scores from questionnaires such as the St. Georges Respiratory Questionnaire for COPD (SGRQ-C) or the COPD Assessment Test (CAT)
What is qualification and why is the Consortium pursuing it?
Qualification is a process by which regulatory agencies can evaluate a biomarker and determine if it can be used in clinical trials that support regulatory submissions for the approval of new treatments. Qualified biomarkers may greatly accelerate the process of bringing new therapies to patients, as they may detect improvements in COPD sooner than traditional methods, and hence allow an evaluation of a new therapy in less time that would be possible using traditional methods, or they may allow a trial to be much smaller and therefore be completed sooner, potentially accelerating the development of new treatments.
Who are the members of the Consortium?
The COPD Foundation-led CBQC includes many volunteer academic disease experts, biomarkers, health outcomes and imaging experts, and members of Industry who provide scientific expertise, clinical trial data and funding. As described in Merrill D, Rennard S, Tal-Singer R. Lung Health Professional Magazine 2013;4(3): 30-36
Current Industry members include Astra Zeneca, GSK, Boehringer Ingelheim, (Founding companies) and Chiesi. While not current members, Novartis and Pfizer have contributed in the past.
Each commissioned Working Group is co-chaired by a leader from industry and a leader from academia, and supported by project management, administration and regulatory coordination from the COPD Foundation. Data to support qualification summaries are provided by industry partners, academic researchers and government agencies (specifically studies funded by the National Heart, Lung and Blood Institute and the National Institute of Health in the US).
COPD Biomarkers Qualification Consortium (CBQC) Collaborators
What did the CBQC Achieve thus far?
In 2016 the FDA (and in 2017 the EMA) qualified Plasma fibrinogen as the first biomarker qualified for COPD in the US.
Publications for this work include:
- Mannino et al. Plasma Fibrinogen as a Biomarker for Mortality and Hospitalized Exacerbations in People with COPD. J COPDF 201
- Miller et al. Plasma Fibrinogen Qualification as a Drug Development Tool in Chronic Obstructive Pulmonary Disease, Perspective of the Chronic Obstructive Pulmonary Disease Biomarker Qualification Consortium. AJRCCM 2016.
The 6MWT data integration and analysis resulted in a decision not to pursue qualification as a COPD DDT at that time as described in the following publication:
- Celli et al. The 6-Minute-Walk Distance Test as a Chronic Obstructive Pulmonary Disease Stratification Tool. Insights from the COPD Biomarker Qualification Consortium. AJRCCM 201
In 2017 The SGRQ was added to the FDA COA Compendium and a draft guidance for its application as a DDT was issued by the FDA. The work resulted in 6 publications:
- Tabberer and Jones The COPD Biomarkers Qualification Consortium St George’s Respiratory Questionnaire Manuscripts: Output of a Consortium to Advance Drug Development. JCOPDF 2017
- Jones et al. Responder Analyses for Treatment Effects in COPD Using the St. George’s Respiratory Questionnaire. JCOPDF 2017
- Tabberer et al. The COPD Biomarkers Qualification Consortium Database: Baseline Characteristics of the St. George’s Respiratory Questionnaire Dataset. JCOPDF 2017
- Jones et al. Baseline Severity as Predictor of Change in St. George’s Respiratory Questionnaire Scores in Trials of Long-Acting Bronchodilators with COPD Patients. JCOPDF 2017
- Mullerova et al. St. George’s Respiratory Questionnaire Score Predicts Outcomes in Patients with COPD: Analysis of Individual Patient Data in the COPD Biomarkers Qualification Consortium Database. JCOPDF 2017
- Hardin et al. What's New with the St. George's Respiratory Questionnaire and Why Do We Care? JCOPDF 2017
- Jones et al. Socioeconomic Status as a Determinant of Health Status Treatment Response in COPD Trials. JCOPDF 2017
- Rennard et al. The St. George's Respiratory Questionnaire Appendix to the Food and Drug Administration Draft Guidance on COPD: Why a Small Step Forward Is so Important. Chest 2017
In 2019, the CBQC Letter of Intent for blood eosinophils was rejected by the FDA following submission of a responses to questions from the FDA. Discussions are ongoing with regard to the next steps.
Discussions with Dr Janet Woodcock Director of the Center for Drug Evaluation and Research (CDER) and Dr Peter Stein Director of the Office of New Drugs in the FDA led to a decision to convene a group of experts and patient advocates (including those with eosinophilic COPD) in late 2020/Early 2021.
Our revised aim is to propose a chronic lung disease patient-centered "concept of interest framework" and agree to next steps toward DDTs qualification.
In 2020, the High Impact journal AJRCCM accepted two CBQC position papers on the CAT tool and Blood eosinophils:
- Mullerova et al. COPD Assessment Test (CAT): A Relevant Clinical Outcome Assessment Instrument for Health-Related Quality of Life and Disease Burden in Chronic Obstructive Pulmonary Disease. AJRCCM (in press published online)
- Singh et al. Blood Eosinophil Counts in Clinical Trials for Chronic Obstructive Pulmonary Disease (in press, published online)
- A Drug Master File containing compiled data on CAT has been submitted to the FDA and can be referenced for regulatory submissions by interested companies by contacting Debbie Merrill at email@example.com/li>
What is the CBQC working on now?
- A Qualification Plan for Constant Work Rate Exercise is currently under review by the FDA, and the Working Group plans to submit the Full Qualification Package soon.
- Letters of Intent for the biomarkers sRAGE and lungs CT Imaging were submitted in early 2020 and are currently under review by the FDA.
- A new Working group focused on Dyspnea (Shortness of Breath) as a COA has been formed in July 2020 following a favorable Critical Path Innovation Meeting discussion with the FDA.
- Three Manuscripts resulting from a review of Physical Activity Monitoring and Lung Imaging potential as a DDT are under peer review.
How can a company join the CBQC
To join as a Steering Committee member, a company must sign the Consortium Agreement, pay membership fees, share data and substantially support at least one working group by providing analytic, scientific or Regulatory expertise.
Interested in joining the CBQC?
Debbie Merrill firstname.lastname@example.org
Vice President of COPD Biomarker Qualification Consortium (CBQC)