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Network meta-analysis combining individual patient and aggregate data from a mixture of study designs with an application to pulmonary arterial hypertension.

Thom HH, Capkun G, Cerulli A, Nixon RM, Howard LS - BMC Med Res Methodol (2015)

Bottom Line: However, the credible intervals of our posterior estimates were wide so the overall results were inconclusive.We also built on many recent innovations to enable researchers to use both aggregate data and IPD.This method could be used in similar situations where treatment comparisons have not been possible due to restrictions to RCT evidence and where a mixture of aggregate data and IPD are available.

View Article: PubMed Central - PubMed

Affiliation: School of Social and Community Medicine, Bristol, UK. howard.thom@bristol.ac.uk.

ABSTRACT

Background: Network meta-analysis (NMA) is a methodology for indirectly comparing, and strengthening direct comparisons of two or more treatments for the management of disease by combining evidence from multiple studies. It is sometimes not possible to perform treatment comparisons as evidence networks restricted to randomized controlled trials (RCTs) may be disconnected. We propose a Bayesian NMA model that allows to include single-arm, before-and-after, observational studies to complete these disconnected networks. We illustrate the method with an indirect comparison of treatments for pulmonary arterial hypertension (PAH).

Methods: Our method uses a random effects model for placebo improvements to include single-arm observational studies into a general NMA. Building on recent research for binary outcomes, we develop a covariate-adjusted continuous-outcome NMA model that combines individual patient data (IPD) and aggregate data from two-arm RCTs with the single-arm observational studies. We apply this model to a complex comparison of therapies for PAH combining IPD from a phase-III RCT of imatinib as add-on therapy for PAH and aggregate data from RCTs and single-arm observational studies, both identified by a systematic review.

Results: Through the inclusion of observational studies, our method allowed the comparison of imatinib as add-on therapy for PAH with other treatments. This comparison had not been previously possible due to the limited RCT evidence available. However, the credible intervals of our posterior estimates were wide so the overall results were inconclusive. The comparison should be treated as exploratory and should not be used to guide clinical practice.

Conclusions: Our method for the inclusion of single-arm observational studies allows the performance of indirect comparisons that had previously not been possible due to incomplete networks composed solely of available RCTs. We also built on many recent innovations to enable researchers to use both aggregate data and IPD. This method could be used in similar situations where treatment comparisons have not been possible due to restrictions to RCT evidence and where a mixture of aggregate data and IPD are available.

No MeSH data available.


Related in: MedlinePlus

PRISMA flowchart for selection of monotherapy and combination therapy observational studies.
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Fig3: PRISMA flowchart for selection of monotherapy and combination therapy observational studies.

Mentions: The results of a systematic literature review were available and was used to identify a network of studies to be included in the analysis. In this review, the MEDLINE® and EMBASE® databases were searched simultaneously. Patient Intervention Comparator Outcome Study type (PICOS) [33] criteria were followed and the quality assessment was performed according to the NICE checklist for RCTs [34]. Details of the PICOS terms are included in Additional file 1. Search terms included a combination of free-text and thesaurus terms relevant to PAH, ERA, prostacyclins, PDE5i, and RCTs, although case-control and cohort studies were also included. The Cochrane Central Register of Controlled Trials was also searched using a similar strategy. The relevance of each citation identified from the databases was based on title and abstract according to the PICOS criteria. As we wanted to explore the effects of covariates, studies that did not report two or more of the 6 covariates of interest were excluded, while we would use IMPRES data to perform single imputation when only one covariate is missing. From this review, we identified and included 5 monotherapy [35-39] and 4 combination therapy [28,40-42] RCTs, summary statistics for which are provided in Table 2 and Table 3, respectively. Additionally, 6 before-and-after studies investigating monotherapies and combination therapies were included [43-48] and their summary statistics are reported in Table 4. PRISMA flowcharts are provided for the systematic searches in Figure 2 and Figure 3 and a PRISMA checklist is provided in Additional file 2 [49]. Although there were substantial differences across trials in the doses of the administered treatments, as recorded in Tables 2, 3 and 4, clinical opinion was such that their effects would be comparable.Table 2


Network meta-analysis combining individual patient and aggregate data from a mixture of study designs with an application to pulmonary arterial hypertension.

Thom HH, Capkun G, Cerulli A, Nixon RM, Howard LS - BMC Med Res Methodol (2015)

PRISMA flowchart for selection of monotherapy and combination therapy observational studies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4403724&req=5

Fig3: PRISMA flowchart for selection of monotherapy and combination therapy observational studies.
Mentions: The results of a systematic literature review were available and was used to identify a network of studies to be included in the analysis. In this review, the MEDLINE® and EMBASE® databases were searched simultaneously. Patient Intervention Comparator Outcome Study type (PICOS) [33] criteria were followed and the quality assessment was performed according to the NICE checklist for RCTs [34]. Details of the PICOS terms are included in Additional file 1. Search terms included a combination of free-text and thesaurus terms relevant to PAH, ERA, prostacyclins, PDE5i, and RCTs, although case-control and cohort studies were also included. The Cochrane Central Register of Controlled Trials was also searched using a similar strategy. The relevance of each citation identified from the databases was based on title and abstract according to the PICOS criteria. As we wanted to explore the effects of covariates, studies that did not report two or more of the 6 covariates of interest were excluded, while we would use IMPRES data to perform single imputation when only one covariate is missing. From this review, we identified and included 5 monotherapy [35-39] and 4 combination therapy [28,40-42] RCTs, summary statistics for which are provided in Table 2 and Table 3, respectively. Additionally, 6 before-and-after studies investigating monotherapies and combination therapies were included [43-48] and their summary statistics are reported in Table 4. PRISMA flowcharts are provided for the systematic searches in Figure 2 and Figure 3 and a PRISMA checklist is provided in Additional file 2 [49]. Although there were substantial differences across trials in the doses of the administered treatments, as recorded in Tables 2, 3 and 4, clinical opinion was such that their effects would be comparable.Table 2

Bottom Line: However, the credible intervals of our posterior estimates were wide so the overall results were inconclusive.We also built on many recent innovations to enable researchers to use both aggregate data and IPD.This method could be used in similar situations where treatment comparisons have not been possible due to restrictions to RCT evidence and where a mixture of aggregate data and IPD are available.

View Article: PubMed Central - PubMed

Affiliation: School of Social and Community Medicine, Bristol, UK. howard.thom@bristol.ac.uk.

ABSTRACT

Background: Network meta-analysis (NMA) is a methodology for indirectly comparing, and strengthening direct comparisons of two or more treatments for the management of disease by combining evidence from multiple studies. It is sometimes not possible to perform treatment comparisons as evidence networks restricted to randomized controlled trials (RCTs) may be disconnected. We propose a Bayesian NMA model that allows to include single-arm, before-and-after, observational studies to complete these disconnected networks. We illustrate the method with an indirect comparison of treatments for pulmonary arterial hypertension (PAH).

Methods: Our method uses a random effects model for placebo improvements to include single-arm observational studies into a general NMA. Building on recent research for binary outcomes, we develop a covariate-adjusted continuous-outcome NMA model that combines individual patient data (IPD) and aggregate data from two-arm RCTs with the single-arm observational studies. We apply this model to a complex comparison of therapies for PAH combining IPD from a phase-III RCT of imatinib as add-on therapy for PAH and aggregate data from RCTs and single-arm observational studies, both identified by a systematic review.

Results: Through the inclusion of observational studies, our method allowed the comparison of imatinib as add-on therapy for PAH with other treatments. This comparison had not been previously possible due to the limited RCT evidence available. However, the credible intervals of our posterior estimates were wide so the overall results were inconclusive. The comparison should be treated as exploratory and should not be used to guide clinical practice.

Conclusions: Our method for the inclusion of single-arm observational studies allows the performance of indirect comparisons that had previously not been possible due to incomplete networks composed solely of available RCTs. We also built on many recent innovations to enable researchers to use both aggregate data and IPD. This method could be used in similar situations where treatment comparisons have not been possible due to restrictions to RCT evidence and where a mixture of aggregate data and IPD are available.

No MeSH data available.


Related in: MedlinePlus