A novel model-based meta-analysis to indirectly estimate the comparative efficacy of two medications: an example using DPP-4 inhibitors, sitagliptin and linagliptin, in treatment of type 2 diabetes mellitus
Objectives To develop a longitudinal statistical model to indirectly estimate the comparative efficacies of two drugs, using model-based meta-analysis (MBMA). Comparison of two oral dipeptidyl peptidase (DPP)-4 inhibitors, sitagliptin and linagliptin, for type 2 diabetes mellitus (T2DM) treatment wa...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2013-03-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/3/3/e001844.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823857440816365568 |
|---|---|
| author | Yan Gong James Rogers Christian Friedrich Sanjay Patel Alexander Staab Jorge Luiz Gross Daniel Polhamus William Gillespie Brigitta Ursula Monz Silke Retlich |
| author_facet | Yan Gong James Rogers Christian Friedrich Sanjay Patel Alexander Staab Jorge Luiz Gross Daniel Polhamus William Gillespie Brigitta Ursula Monz Silke Retlich |
| author_sort | Yan Gong |
| collection | DOAJ |
| description | Objectives To develop a longitudinal statistical model to indirectly estimate the comparative efficacies of two drugs, using model-based meta-analysis (MBMA). Comparison of two oral dipeptidyl peptidase (DPP)-4 inhibitors, sitagliptin and linagliptin, for type 2 diabetes mellitus (T2DM) treatment was used as an example.Design Systematic review with MBMA.Data sources MEDLINE, EMBASE, http://www.ClinicalTrials.gov, Cochrane review of DPP-4 inhibitors for T2DM, sitagliptin trials on Food and Drug Administration website to December 2011 and linagliptin data from the manufacturer.Eligibility criteria for selecting studies Double-blind, randomised controlled clinical trials, ≥12 weeks’ duration, that analysed sitagliptin or linagliptin efficacies as changes in glycated haemoglobin (HbA1c) levels, in adults with T2DM and HbA1c >7%, irrespective of background medication.Model development and application A Bayesian model was fitted (Markov Chain Monte Carlo method). The final model described HbA1c levels as function of time, dose, baseline HbA1c, washout status/duration and ethnicity. Other covariates showed no major impact on model parameters and were not included. For the indirect comparison, a population of 1000 patients was simulated from the model with a racial composition reflecting the average racial distribution of the linagliptin trials, and baseline HbA1c of 8%.Results The model was developed using longitudinal data from 11 234 patients (10 linagliptin, 15 sitagliptin trials), and assessed by internal evaluation techniques, demonstrating that the model adequately described the observations. Simulations showed both linagliptin 5 mg and sitagliptin 100 mg reduced HbA1c by 0.81% (placebo-adjusted) at week 24. Credible intervals for participants without washout were −0.88 to −0.75 (linagliptin) and −0.89 to −0.73 (sitagliptin), and for those with washout, −0.91 to −0.76 (linagliptin) and −0.91 to −0.75 (sitagliptin).Conclusions This study demonstrates the use of longitudinal MBMA in the field of diabetes treatment. Based on an example evaluating HbA1c reduction with linagliptin versus sitagliptin, the model used seems a valid approach for indirect drug comparisons. |
| format | Article |
| id | doaj-art-9c08124f5c724bdb809f8b594e523f58 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2013-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-9c08124f5c724bdb809f8b594e523f582025-02-11T21:00:13ZengBMJ Publishing GroupBMJ Open2044-60552013-03-013310.1136/bmjopen-2012-001844A novel model-based meta-analysis to indirectly estimate the comparative efficacy of two medications: an example using DPP-4 inhibitors, sitagliptin and linagliptin, in treatment of type 2 diabetes mellitusYan Gong0James Rogers1Christian Friedrich2Sanjay Patel3Alexander Staab4Jorge Luiz Gross5Daniel Polhamus6William Gillespie7Brigitta Ursula Monz8Silke Retlich9Boehringer Ingelheim, Ingelheim, Germanyconsultant anaesthetist and flying instructor34 Medizinische Klinik II, Sana Klinikum Offenbach, Offenbach, Germany11 Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, New South Wales, AustraliaBoehringer Ingelheim, Biberach, GermanyEndocrine Division, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sol, BrazilMetrum Research Group, Tariffville, Connecticut, USAMetrum Research Group, Tariffville, Connecticut, USABoehringer Ingelheim, Ingelheim, GermanyBoehringer Ingelheim, Biberach, GermanyObjectives To develop a longitudinal statistical model to indirectly estimate the comparative efficacies of two drugs, using model-based meta-analysis (MBMA). Comparison of two oral dipeptidyl peptidase (DPP)-4 inhibitors, sitagliptin and linagliptin, for type 2 diabetes mellitus (T2DM) treatment was used as an example.Design Systematic review with MBMA.Data sources MEDLINE, EMBASE, http://www.ClinicalTrials.gov, Cochrane review of DPP-4 inhibitors for T2DM, sitagliptin trials on Food and Drug Administration website to December 2011 and linagliptin data from the manufacturer.Eligibility criteria for selecting studies Double-blind, randomised controlled clinical trials, ≥12 weeks’ duration, that analysed sitagliptin or linagliptin efficacies as changes in glycated haemoglobin (HbA1c) levels, in adults with T2DM and HbA1c >7%, irrespective of background medication.Model development and application A Bayesian model was fitted (Markov Chain Monte Carlo method). The final model described HbA1c levels as function of time, dose, baseline HbA1c, washout status/duration and ethnicity. Other covariates showed no major impact on model parameters and were not included. For the indirect comparison, a population of 1000 patients was simulated from the model with a racial composition reflecting the average racial distribution of the linagliptin trials, and baseline HbA1c of 8%.Results The model was developed using longitudinal data from 11 234 patients (10 linagliptin, 15 sitagliptin trials), and assessed by internal evaluation techniques, demonstrating that the model adequately described the observations. Simulations showed both linagliptin 5 mg and sitagliptin 100 mg reduced HbA1c by 0.81% (placebo-adjusted) at week 24. Credible intervals for participants without washout were −0.88 to −0.75 (linagliptin) and −0.89 to −0.73 (sitagliptin), and for those with washout, −0.91 to −0.76 (linagliptin) and −0.91 to −0.75 (sitagliptin).Conclusions This study demonstrates the use of longitudinal MBMA in the field of diabetes treatment. Based on an example evaluating HbA1c reduction with linagliptin versus sitagliptin, the model used seems a valid approach for indirect drug comparisons.https://bmjopen.bmj.com/content/3/3/e001844.full |
| spellingShingle | Yan Gong James Rogers Christian Friedrich Sanjay Patel Alexander Staab Jorge Luiz Gross Daniel Polhamus William Gillespie Brigitta Ursula Monz Silke Retlich A novel model-based meta-analysis to indirectly estimate the comparative efficacy of two medications: an example using DPP-4 inhibitors, sitagliptin and linagliptin, in treatment of type 2 diabetes mellitus BMJ Open |
| title | A novel model-based meta-analysis to indirectly estimate the comparative efficacy of two medications: an example using DPP-4 inhibitors, sitagliptin and linagliptin, in treatment of type 2 diabetes mellitus |
| title_full | A novel model-based meta-analysis to indirectly estimate the comparative efficacy of two medications: an example using DPP-4 inhibitors, sitagliptin and linagliptin, in treatment of type 2 diabetes mellitus |
| title_fullStr | A novel model-based meta-analysis to indirectly estimate the comparative efficacy of two medications: an example using DPP-4 inhibitors, sitagliptin and linagliptin, in treatment of type 2 diabetes mellitus |
| title_full_unstemmed | A novel model-based meta-analysis to indirectly estimate the comparative efficacy of two medications: an example using DPP-4 inhibitors, sitagliptin and linagliptin, in treatment of type 2 diabetes mellitus |
| title_short | A novel model-based meta-analysis to indirectly estimate the comparative efficacy of two medications: an example using DPP-4 inhibitors, sitagliptin and linagliptin, in treatment of type 2 diabetes mellitus |
| title_sort | novel model based meta analysis to indirectly estimate the comparative efficacy of two medications an example using dpp 4 inhibitors sitagliptin and linagliptin in treatment of type 2 diabetes mellitus |
| url | https://bmjopen.bmj.com/content/3/3/e001844.full |
| work_keys_str_mv | AT yangong anovelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT jamesrogers anovelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT christianfriedrich anovelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT sanjaypatel anovelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT alexanderstaab anovelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT jorgeluizgross anovelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT danielpolhamus anovelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT williamgillespie anovelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT brigittaursulamonz anovelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT silkeretlich anovelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT yangong novelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT jamesrogers novelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT christianfriedrich novelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT sanjaypatel novelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT alexanderstaab novelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT jorgeluizgross novelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT danielpolhamus novelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT williamgillespie novelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT brigittaursulamonz novelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus AT silkeretlich novelmodelbasedmetaanalysistoindirectlyestimatethecomparativeefficacyoftwomedicationsanexampleusingdpp4inhibitorssitagliptinandlinagliptinintreatmentoftype2diabetesmellitus |