Eligibility for COPD Clinical Trials of Inhaled Triple Therapy: Analysis of the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS)

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Eligibility for COPD Clinical Trials of Inhaled Triple Therapy: Analysis of the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS)


washington; spokane; pmrc


Rationale: Clinical trial eligibility criteria are employed to efficiently determine intervention effects but may have limited generalizability to target populations. Observational designs, including cohort studies, offer the opportunity to evaluate the potential external validity of clinical trials. In this analysis, we determined the prevalence of COPD participants from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort who would be eligible for inclusion in three trials of triple therapy in COPD (ETHOS, IMPACT, KRONOS) based on key enrollment criteria. Methods: SPIROMICS is a multicenter cohort study including current and former smokers and non-smoking controls with and without spirometry-defined COPD. This analysis included all SPIROMICS participants with spirometry-confirmed COPD at baseline or follow-up visit for those with incident COPD. Key enrollment criteria from ETHOS, IMPACT and KRONOS applied to SPIROMICS participants included age, smoking pack-years, asthma history, FEV1, COPD Assessment Test (CAT) score, self-reported maintenance inhaler use and exacerbation history. The proportion (and 95% confidence interval) of SPIROMICS participants who would be eligible based on key enrollment criteria for the three clinical trials was determined. Results: A total of 1,868 SPIROMICS participants were examined, with the following characteristics: mean age 65 years, median 45 pack-years smoked, 25% current asthma, mean FEV1 63% predicted, 72% with CAT score ≥10, 40% not prescribed inhaled maintenance therapy, and 71% without moderate and 84% without severe COPD exacerbation in prior year. Prevalence of eligibility for clinical trials of triple therapy was low: ETHOS 6.6% (95% CI 5.5-7.8%), IMPACT 11.0% (9.6-12.4%), and KRONOS 23% (21-25%). When examining individual eligibility criteria, the presence or absence of exacerbations and enrollment criteria inhaled maintenance therapy contributed most to ineligibility (Table), with 18% and 22% of SPIROMICS participants meeting exacerbation criteria for ETHOS and IMPACT, respectively (KRONOS did not have exacerbation criteria). When examining enrollment criteria inhaled maintenance therapy, the following proportions of SPIROMICS participants were eligible: ETHOS 44%, IMPACT 60%, and KRONOS 44%. Discussion: Applying clinical trials eligibility criteria to an observational COPD cohort, we found that 6-23% of participants would be eligible for clinical trials of inhaled triple therapies in COPD. Trial ineligibility among SPIROMICS participants was largely driven by insufficiently frequent exacerbations and insufficient prior inhaled maintenance therapy, suggesting that SPIROMICS may represent a healthier COPD cohort than the target population of these trials. These results highlight the importance of examining clinical trial eligibility criteria when considering application of trial findings to diseased populations.

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Kidney & Diabetes






A. A. Lambert 1 , L. Gravens-Mueller 2 , L. Bateman 2 , I. Barjaktarevic 3 , R. Paine 4 , N. Putcha 5 , N. N. Hansel 6 , J. A. Krishnan 7 , M. T. Dransfield 8 , S. L. Rogers 9 , A. Shaikh 10 , P. Woodruff 11 , D. Couper 12 , M. B. Drummond 13 ; 1Pulmonary and Critical Care, University of Washington, Spokane, WA, United States, 2University of North Carolina, Chapel Hill, NC, United States, 3Pulmonary and Critical Care, UCLA, Los Angeles, CA, United States, 4Univ of Utah, Salt Lake City, UT, United States, 5Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, United States, 6Johns Hopkins Univ, Baltimore, MD, United States, 7Univ of Illinois, Chicago, IL, United States, 8Univ of Alabama Birmingham & Birmingham VA Med Ctr, Birmingham, AL, United States, 9Medical Affairs, Boehringer Ingelheim, Ridgefield, CT, United States, 10Medical Affairs, Boehringer-Ingelheim, Ridgefield, CT, United States, 11Medicine, University of California, San Francisco, San Francisco, CA, United States, 12Biostatistics, Chapel Hill, NC, United States, 13Medicine-Pulmonary, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States