Triple therapy trials in COPD: a precision medicine opportunity

Suissa, Samy; Ariel, Amnon

doi:10.1183/13993003.01848-2018

Cited by 50 publications

(39 citation statements)

References 21 publications

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“…Furthermore, the subgroup that gained most benefit from triple therapy over the duration of the study was the group in which patients were not receiving ICS prior to study entry. The authors therefore stressed, correctly in our opinion, that according to the suggestions of Suissa and Ariel [27], ICS withdrawal might be considered in the first month of treatment with triple therapy, but we do not know whether withdrawing ICS could trigger subsequent exacerbations at a later time.…”

Section: What Do These Meta-analyses Suggest?mentioning

confidence: 95%

“…Suissa and Ariel [27] have pointed out that the lower rate of a first AECOPD with triple therapy observed in the IMPACT study [24] and also in the Extrafine Inhaled Triple Therapy versus Dual Bronchodilator Therapy in Chronic Obstructive Pulmonary Disease (TRIBUTE) study [28], which compared a single-inhaler triple combination of beclomethasone dipropionate, formoterol and glycopyrronium versus indacaterol plus glycopyrronium FDC in terms of the rate of moderate-to-severe AECOPDs over 52 weeks of treatment and enrolled 1532 patients who were symptomatic with severe or very severe airflow limitation and had at least one moderate or severe AECOPD in the previous year, was entirely due to a lower rate in the 1st month of follow-up, while the rate was comparable to LABA/LAMA in the subsequent 11 months. They defined this trend as a 'depletion of susceptibles'.…”

Section: What Do These Meta-analyses Suggest?mentioning

confidence: 99%

See 1 more Smart Citation

Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses

et al. 2019

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Guidelines are mainly based on evidence of well-designed randomized controlled trials (RCTs), but there are limitations to the transferability of conclusions of RCTs to usual care mainly because the patients enrolled in RCTs are selected and not representative of the population encountered in daily practice; moreover, the research environment is substantially different from that of the real world. Because of the scarcity of data generated in large unselected populations in everyday clinical practice, the possibility of using meta-analyses can be considered. Recently, several meta-analyses have attempted to clarify the role of triple therapy containing a long-acting b-agonist (LABA), a long-acting muscarinic antagonist

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Section: What Do These Meta-analyses Suggest?mentioning

confidence: 95%

Section: What Do These Meta-analyses Suggest?mentioning

confidence: 99%

Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses

et al. 2019

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confidence: 85%

“…The analysis by SUISSA and ARIEL [6] revealed another interesting observation in these trials. In the first month following ICS withdrawal, there was a transient surge in the exacerbation rate in the ICS-free arms (compared with the rate observed in the ICS-containing arms) with the rate returning back to "normal" levels thereafter, resulting in no difference in exacerbation rates between the ICS-containing and ICS-free arms by the end of the study period (figure 1a and b in [6]). This first month exacerbation surge was particularly notable in the IMPACT trial, which did not supplement patients with either LAMA or LABA/ LAMA during the first few weeks of ICS withdrawal, which may have resulted in exacerbation or exacerbation-like events related to sudden discontinuation of ICS.…”

mentioning

confidence: 85%

“…asthma-COPD overlap) [5]. As pointed out by SUISSA and ARIEL [6] in their very provocative and interesting commentary, the decision to include (or exclude) asthma-COPD overlap patients may explain why some studies of ICS-containing "double" or "triple" therapies were "positive" while others were "negative". The IMPACT [7] and TRIBUTE [8] trials, for instance, enrolled patients with a prior but not current history of asthma, and both found a reduced rate of moderate to severe exacerbations among those treated with ICS-containing combinations.…”

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confidence: 99%

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Inhaled corticosteroids in COPD: the final verdict is…

Leung

Sin

2018

Eur Respir J

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Emulation of Randomized Clinical Trials With Nonrandomized Database Analyses

Wang

Schneeweiß

Franklin

et al. 2023

JAMA

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126

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ImportanceNonrandomized studies using insurance claims databases can be analyzed to produce real-world evidence on the effectiveness of medical products. Given the lack of baseline randomization and measurement issues, concerns exist about whether such studies produce unbiased treatment effect estimates.ObjectiveTo emulate the design of 30 completed and 2 ongoing randomized clinical trials (RCTs) of medications with database studies using observational analogues of the RCT design parameters (population, intervention, comparator, outcome, time [PICOT]) and to quantify agreement in RCT-database study pairs.Design, Setting, and ParticipantsNew-user cohort studies with propensity score matching using 3 US claims databases (Optum Clinformatics, MarketScan, and Medicare). Inclusion-exclusion criteria for each database study were prespecified to emulate the corresponding RCT. RCTs were explicitly selected based on feasibility, including power, key confounders, and end points more likely to be emulated with real-world data. All 32 protocols were registered on ClinicalTrials.gov before conducting analyses. Emulations were conducted from 2017 through 2022.ExposuresTherapies for multiple clinical conditions were included.Main Outcomes and MeasuresDatabase study emulations focused on the primary outcome of the corresponding RCT. Findings of database studies were compared with RCTs using predefined metrics, including Pearson correlation coefficients and binary metrics based on statistical significance agreement, estimate agreement, and standardized difference.ResultsIn these highly selected RCTs, the overall observed agreement between the RCT and the database emulation results was a Pearson correlation of 0.82 (95% CI, 0.64-0.91), with 75% meeting statistical significance, 66% estimate agreement, and 75% standardized difference agreement. In a post hoc analysis limited to 16 RCTs with closer emulation of trial design and measurements, concordance was higher (Pearson r, 0.93; 95% CI, 0.79-0.97; 94% meeting statistical significance, 88% estimate agreement, 88% standardized difference agreement). Weaker concordance occurred among 16 RCTs for which close emulation of certain design elements that define the research question (PICOT) with data from insurance claims was not possible (Pearson r, 0.53; 95% CI, 0.00-0.83; 56% meeting statistical significance, 50% estimate agreement, 69% standardized difference agreement).Conclusions and RelevanceReal-world evidence studies can reach similar conclusions as RCTs when design and measurements can be closely emulated, but this may be difficult to achieve. Concordance in results varied depending on the agreement metric. Emulation differences, chance, and residual confounding can contribute to divergence in results and are difficult to disentangle.

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Triple therapy trials in COPD: a precision medicine opportunity

Cited by 50 publications

References 21 publications

Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses

Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses

Inhaled corticosteroids in COPD: the final verdict is…

Emulation of Randomized Clinical Trials With Nonrandomized Database Analyses

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