Prospective observational study in patients with obstructive lung disease: NOVELTY design

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) have overlapping clinical features and share pathobiological mechanisms but are often considered distinct disorders. Prospective, observational studies across asthma, COPD and asthma-COPD overlap are limited. NOVELTY is a global, prospective observational 3-year study enrolling ∼12 000 patients ≥12 years of age from primary and specialist clinical practices in 19 countries (ClinicalTrials.gov identifier: NCT02760329). NOVELTY's primary objectives are to describe patient characteristics, treatment patterns and disease burden over time, and to identify phenotypes and molecular endotypes associated with differential outcomes over time in patients with a diagnosis/suspected diagnosis of asthma and/or COPD. NOVELTY aims to recruit real-world patients, unlike clinical studies with restrictive inclusion/exclusion criteria. Data collected at yearly intervals include clinical assessments, spirometry, biospecimens, patient-reported outcomes (PROs) and healthcare utilisation (HCU). PROs and HCU will also be collected 3-monthly via internet/telephone. Data will be used to identify phenotypes and endotypes associated with different trajectories for symptom burden, clinical progression or remission and HCU. Results may allow patient classification across obstructive lung disease by clinical outcomes and biomarker profile, rather than by conventional diagnostic labels and severity categories. NOVELTY will provide a rich data source on obstructive lung disease, to help improve patient outcomes and aid novel drug development.

Conflict of interest statement

Conflict of interest: H.K. Reddel reports that this study is funded by AstraZeneca. She received reimbursement from AstraZeneca for time spent working on the study design but not for manuscript preparation. Medical writing support was provided by AstraZeneca, as stated in the support statement. She has served on a data and safety monitoring board (DSMB) and advisory boards, and has received unconditional research grants and honoraria from AstraZeneca and GlaxoSmithKline for providing independent medical education, consulting and studying inhalers. She has served on a DSMB for Merck. She has served on a DSMB and an advisory board for, and received an honorarium from Novartis for providing independent medical education. She has received honoraria from Teva and Mundipharma for providing independent medical education. She has received an honorarium from Boehringer Ingelheim for providing independent medical education from and serving on an advisory board. Conflict of interest: M. Gerhardsson de Verdier is an employee of AstraZeneca. Conflict of interest: A. Agustí reports receiving personal fees from AstraZeneca during the conduct of the study; and grants and personal fees from AstraZeneca and Menarini, and personal fees from Chiesi, Teva and Novartis, outside the submitted work. Conflict of interest: G. Anderson has received honoraria from and serves on an advisory board for Novartis; has received honoraria from, serves on an advisory board for and was employed on a sabbatical basis from 2016 to 2017 by AstraZeneca; and has received honoraria and serves on advisory boards for GlaxoSmithKline, Pieris Pharmaceuticals and Boehringer Ingelheim. Conflict of interest: R. Beasley reports receiving personal fees from Astra Zeneca during the conduct of the study; and grants and personal fees from AstraZeneca, GlaxoSmithKline and the Health Research Council of New Zealand, and grants from Genentech, outside the submitted work. Conflict of interest: E.H. Bel reports receiving grants and personal fees from Novartis, GSK and AstraZeneca, grants from Roche, personal fees from Sanofi Regeneron, Teva, Vectura and Boehringer, outside the submitted work. Conflict of interest: C. Janson reports receiving personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Teva, outside the submitted work. Conflict of interest: Related to the topic of COPD, B. Make reports funding from the NHLBI for the COPDGene study; grants and personal fees from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, and Sunovian; personal fees for DSMB from Spiration and Baxalta; CME personal fees from Consensus Medical Education, Integrity Medical Education, WebMD, National Jewish Health, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, SPIRE Learning, Peer Review Institute, and Medscape; personal fees and other from Mt. Sinai Medical Center; royalties from Up-To-Date; personal fees from Novartis; personal fees from CSL Bering; other from Cleveland Clinic; grants from Pearl (a member of the AstraZeneca Group); and personal fees from Verona, outside the submitted work. Conflict of interest: R.J. Martin reports receiving personal fees from AstraZeneca for service on a steering committee during the conduct of the study; and travel fees from Respiratory Effectiveness Group, consultancy fees from PMD Healthcare, and grants from MedImmune, Chiesi Farmaceutici SpA and NHLBI, outside the submitted work. Conflict of interest: I. Pavord reports receiving speaker fees, advisory board honoraria and sponsorship to attend scientific meetings from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline, a speaker fee from Aerocrine, speaker fees and advisory board honoraria from Almirall and Novartis, advisory board honoraria from Genentech, Regeneron, Merck & Co., Schering-Plough and Mylan Speciality (Dey Pharma) and Respivert, advisory board honoraria and sponsorship to attend scientific meetings from Napp Pharmaceuticals, outside the submitted work. Conflict of interest: D. Price reports receiving funding from AstraZeneca for the conduct of this study; and board membership (fees paid to Observational and Pragmatic Research Institute) from Aerocrine, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Mundipharma, Napp, Novartis, and Teva Pharmaceuticals, consultancy agreements (fees paid to Observational and Pragmatic Research Institute) with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Napp, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance, grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute) from Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Mylan, Mundipharma, Napp, Novartis, Pfizer, Respiratory Effectiveness Group, Teva Pharmaceuticals, Theravance, UK National Health Service and Zentiva, lectures/speaking engagements (fees paid to Observational and Pragmatic Research Institute) for Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, CIPLA, GlaxoSmithKline, Kyorin, Mylan, Merck, Mundipharma, Novartis, Pfizer, Skyepharma, and Teva Pharmaceuticals, manuscript preparation (fees paid to Observational and Pragmatic Research Institute) from Mundipharma and Teva Pharmaceuticals, payment for travel/accommodation/meeting expenses (fees paid to Observational and Pragmatic Research Institute) from Aerocrine, AstraZeneca, Boehringer Ingelheim, Mundipharma, Napp, Novartis and Teva Pharmaceuticals, funding for patient enrolment or completion of research (fees paid to Observational and Pragmatic Research Institute) from Chiesi, Novartis, Teva Pharmaceuticals and Zentiva, payment for the development of educational materials (fees paid to Observational and Pragmatic Research Institute) from Mundipharma and Novartis, peer review for grant committees for the Efficacy and Mechanism Evaluation programme and Health Technology Assessment, outside the submitted work; and stock/stock options in AKL Research and Development Ltd, which produces phytopharmaceuticals. He owns 74% of the social enterprise Optimum Patient Care Ltd (Australia, Singapore and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore). Conflict of interest: C. Keen is an employee of AstraZeneca. Conflict of interest: A. Gardev is an employee of AstraZeneca. Conflict of interest: S. Rennard is an employee of AstraZeneca and retains professorship and a part-time appointment at the University of Nebraska Medical Center, Omaha, NE, USA. He reports personal fees from ABIM, Able Associates, Advantage Healthcare, Align2Action, Almirall, APT, ATS, AstraZeneca, Baxter, Boehringer Ingelheim, Cheisi, CIPLA, ClearView Healthcare, the Cleveland Clinic, CME Incite, Complete Medical Group, the COPD Foundation, Cory Paeth, CSA, CSL, CTS Carmel, Dailchi Sankyo, Decision Resources, the Dunn Group, Easton Associates, Elevation Pharma, FirstWord, Forest, the Frankel Group, Gerson, GlaxoSmithKline, Gilead, Grifols, GroupH, Guidepoint Global, Haymarket, HealthStar, Huron Cosulting, Incite, Inthought, IntraMed (Forest), Johnson & Johnson, LEK, McKinsey, Medical Knowledge, MedImmune, the Methodist Health System (Dallas, TX, USA), Navigant, NCI Consulting, Novartis, Nuvis, Pearl (a member of the AstraZeneca Group), Penn Technology, Pfizer, PlanningShop, Prescott, Pro Ed Comm, ProiMed, PSL FirstWord, Pulmatrix, Quadrant, Qwessential, Regeneron, Saatchi and Saatchi, Schlesinger Associates, Strategic North, Synapse, Takeda, Theron, WebMD, NHLBI, the Nebraska DHHS, Otsuka, Pfizer, GlaxoSmithKline, Boehringer Ingelheim, Nycomed, AstraZeneca, Centocor, and Almirall, outside the submitted work. Please note that he has had tobacco industry funding. Specifically, he has received funding from the tobacco industry for studies relating to harm reduction and to the impact of tobacco smoke on stem cells. He has also consulted with R.J. Reynolds, without personal fees, on the topic of harm reduction. He received funding from R.J. Reynolds to evaluate the effect of a harm reduction product in normal smokers (1996) and in subjects with chronic bronchitis (1999) and to assess the effect of smoking cessation on lower respiratory tract inflammation (2000); he participated in a Philip Morris multicentre study to assess biomarkers of smoke exposure (2002); he received funding for a clinical trial from the Institute for Science and Health (2005), which receives support from the tobacco industry, to evaluate biomarkers in exhaled breath associated with smoking cessation and reduction. This study was supplemented with funding from Lorillard and R.J. Reynolds. He has received a grant from the Philip Morris External Research Program (2005) to assess the impact of cigarette smoking on circulating stem cells in the mouse. He has consulted with R.J. Reynolds on the topic of harm reduction until 2007 but did not receive personal remuneration for this. He has no active tobacco industry-funded projects. All ties with tobacco industry companies and entities supported by tobacco companies were terminated in 2007. Conflict of interest: A. Sveréus is an employee of AstraZeneca. Conflict of interest: A.T. Bansal has nothing to disclose. Conflict of interest: L. Brannman is an employee of AstraZeneca. Conflict of interest: N. Karlsson is an employee of AstraZeneca. Conflict of interest: J. Nuevo is an employee of AstraZeneca. Conflict of interest: F. Nyberg is an employee of AstraZeneca. Conflict of interest: S.S. Young is an employee of AstraZeneca. Conflict of interest: J. Vestbo reports receiving an honorarium from AstraZeneca for being a co-principal investigator of the NOVELTY study; and personal fees from GlaxoSmithKline for consultancy for COPD Phase 2 and 3 programme, personal fees from Chiesi Pharmaceuticals, Boeehringer Ingelheim, Novartis and AstraZeneca for consultancy for COPD Phase 2 and 3 programme and payment for lectures including service in speaker bureaus, outside the submitted work.

Figures

FIGURE 1

NOVELTY study design. COPD: chronic obstructive pulmonary disease; eCRF: electronic case report form; EMR: electronic medical record; HCU: healthcare utilisation; HRQoL: health-related quality of life; PRO: patient-reported outcome.