@article{ecfcaa55727546589292dc8fb36ba288,
title = "Pulmonary and cardiovascular safety of inhaled insulin in routine practice: The Exubera Large Simple Trial (VOLUME)",
abstract = "Objective: VOLUME is a randomized, open-label, post-approval pragmatic trial aiming to evaluate long-term pulmonary and cardiovascular safety of Exubera{\textregistered} (EXU; insulin human [rDNA origin] Inhalation Powder) in routine clinical practice. The primary study objective is to compare risk of persistent decline in forced expiratory volume in 1 second (FEV1) among patients treated with and without EXU. Research design and methods: Patients eligible to take EXU per approved local label were randomized to EXU or routine care and followed per usual care, with scheduled FEV1 tests at baseline, 6 months, and yearly. Randomization halted in October 2007 after Pfizer announced it would stop marketing EXU due to low sales. EXU patients were subsequently transitioned to usual care and all patients were followed for 6 additional months. Results: Although there was insufficient power to evaluate the primary endpoint (37% of the planned 5,300 were randomized), the study provided important descriptive information. Per the primary endpoint definition, more EXU group patients (n = 8) experienced a persistent decline in FEV1 (n = 0 in usual care). Using a broader, clinically relevant pre-specified supplementary definition of persistent decline, similar numbers were observed in the EXU (n = 27) and usual care (n = 24) groups. Slightly more pulmonary and allergic serious adverse event composite endpoints were seen in the EXU group. There were no consistent treatment group differences in the cardiovascular composite endpoint, all-cause mortality, or glycemic control. Conclusions: Clinically important declines in lung function that persisted more than 60 days were uncommon and of similar frequency in Exubera and usual care. Clinicaltrials.gov: NCT00359801.",
keywords = "Effectiveness, Inhaled insulin, Large simple trial, Pragmatic trial, Real World evidence, Safety",
author = "Gatto, {Nicolle M.} and Bracken, {Michael B.} and Francesca Kolitsopoulos and Duggan, {William T.} and Koch, {Gary G.} and Wise, {Robert A.} and Jackson, {Neville C.}",
note = "Funding Information: Drs. Bracken, Koch, Wise, and Cohen were paid consultants to Pfizer for their roles on the VOLUME steering committee. Dr. Bracken has served as a paid consultant to Pfizer, Forest Labs, GlaxoSmithKline, Lilly, Procter and Gamble, and Sanofi-Aventis. Dr. Wise has served as a paid consultant to Pfizer, Mannkind, and Sanofi-Aventis. Dr. Cohen has served as a paid consultant to Pfizer for work related to clinical trials. Dr. Koch is the principal investigator of a biostatistical agreement between Pfizer and the University of North Carolina at Chapel Hill, and that agreement provided the structure for his activity on the Steering Committee of the study reported in this manuscript. He is also the principal investigator of many such biostatistical agreements with other biopharmaceutical sponsors, including ARENA, AstraZeneca, Eli Lilly and Company, Forest Research Institute (Allergan), GlaxoSmithKline, Merck, Novartis, and Sanofi, although his activities for those other sponsors are not related to the content of this manuscript. Information concerning all biostatistical agreements for which Dr. Koch is the principal investigator is publicly available through the University of North Carolina at Chapel Hill. Dr. Koch has no conflicts to report.This study was sponsored by Pfizer. We are indebted to the 1,976 participants in the VOLUME Study; to the VOLUME Data Monitoring Committee (Peter Lange, Martin Simoons, and Mark Buyse); to the VOLUME Scientific Steering Committee (Michael Bracken, Chair; James Goldstein, Gary Koch, Robert Wise, Robert Ratner); to the VOLUME Endpoint Committee (Michael Lewis, Chair; Atul Malhotra; Richard deShazo; Sherryn Roth; Cecilia Bahit; Paul Hauptman; Richard Leung; Raphael Heinzer; Phil Lieberman; Stephen Kemp); to Pfizer Medical, Research and Development, and Safety colleagues: Robert Reynolds, Sol Klioze, Richard Riese, Pamela Schwartz, Anne Cropp, Susan DeCorte, Susan Gannon, Valerie Vandevoorde, Kevin Sweetland, and Vivianne Dillon. Study management was provided by Claudia Schaefer/Vera Weilburg (in Germany), Glenn Hare/Dean Spurden (in the United Kingdom), and Tina Ljungh (in Sweden), and by United Biosource Corporation (UBC) (in the US) under Bruce Smith, and was funded by Pfizer. Statistical support was provided by Inventiv Clinical under Eugenia and Earl Webb Henry. We thank all of the investigators and coordinators who took part in this study (a complete list of whom can be found in the appendices). Dr. Gatto (guarantor) led the study design and implementation, and drafted/revised the manuscript. Dr. Bracken chaired the scientific steering committee, and was involved in implementation, data assessment and manuscript review/editing. Dr. Koch was a member of the Scientific Steering Committee, contributed to amending the SAP, and contributed to manuscript review/editing. Dr. Wise served on the Scientific Steering Committee and was involved in the protocol design, implementation, data assessment and manuscript review/editing. Mrs. Kolitsopoulos served as project manager and was involved in protocol design, implementation, data assessment and manuscript drafting/review/editing. Dr. Duggan contributed to amending the SAP, producing final tables, producing post-hoc analyses, and reviewing/editing manuscript. Dr. Jackson was involved in protocol design, implementation, study governance, data assessment and manuscript review. The design and results of VOLUME were previously presented in poster format at the International Society of Pharmacoepidemiology annual meetings in August 2008 and August 2010 (respectively) with the accompanying abstracts published in Pharmacoepidemiology and Drug Safety (Volume 17, Supplement S1, 13 Aug 2008 and Volume 19, Supplement S1, 24 Aug 2010). The basic study design and results are posted on clinicaltrials.gov (identifier: NCT00359801). Funding Information: This study was sponsored by Pfizer . We are indebted to the 1,976 participants in the VOLUME Study; to the VOLUME Data Monitoring Committee (Peter Lange, Martin Simoons, and Mark Buyse); to the VOLUME Scientific Steering Committee (Michael Bracken, Chair; James Goldstein, Gary Koch, Robert Wise, Robert Ratner); to the VOLUME Endpoint Committee (Michael Lewis, Chair; Atul Malhotra; Richard deShazo; Sherryn Roth; Cecilia Bahit; Paul Hauptman; Richard Leung; Raphael Heinzer; Phil Lieberman; Stephen Kemp); to Pfizer Medical, Research and Development, and Safety colleagues: Robert Reynolds, Sol Klioze, Richard Riese, Pamela Schwartz, Anne Cropp, Susan DeCorte, Susan Gannon, Valerie Vandevoorde, Kevin Sweetland, and Vivianne Dillon. Study management was provided by Claudia Schaefer/Vera Weilburg (in Germany), Glenn Hare/Dean Spurden (in the United Kingdom), and Tina Ljungh (in Sweden), and by United Biosource Corporation (UBC) (in the US) under Bruce Smith, and was funded by Pfizer . Statistical support was provided by Inventiv Clinical under Eugenia and Earl Webb Henry . We thank all of the investigators and coordinators who took part in this study (a complete list of whom can be found in the appendices). Publisher Copyright: {\textcopyright} 2019",
year = "2020",
month = jun,
doi = "10.1016/j.conctc.2019.100427",
language = "English (US)",
volume = "18",
journal = "Contemporary Clinical Trials Communications",
issn = "2451-8654",
publisher = "Elsevier Inc.",
}