Open AccessGeometry of the Randomized Evidence for Treatments of Pulmonary Hypertension
Author(s) -
Tonelli Adriano R.,
Zein Joe,
Ioannidis John P.A.
Publication year - 2013
Publication title -
cardiovascular therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 46
eISSN - 1755-5922
pISSN - 1755-5914
DOI - 10.1111/1755-5922.12050
Subject(s) - medicine , randomized controlled trial , treprostinil , placebo , cochrane library , medline , clinical trial , sildenafil , meta analysis , endothelin receptor antagonist , alternative medicine , physical therapy , pulmonary hypertension , endothelin receptor , pathology , receptor , political science , law
Summary Objective We studied the entire agenda of randomized clinical trials in pulmonary hypertension ( PH ) using sociological methods. We explored the geometry of the PH network to interpret the evidence on multiple competing treatments for the same indication. Design We searched MEDLINE , Embase and Cochrane Library Databases for published studies. We queried clinicaltrials.gov and WHO International Clinical Trials Registry platform for non‐published studies. Results We found 75 randomized trials (41 published [n = 4136 participants] and 34 registered unpublished [planned n = 3470 participants]). Of the published randomized studies, all used placebo as the comparator arm except for two nonindustry‐sponsored comparisons between phosphodiestearase‐5 ( PDE ‐5) inhibitors and endothelin receptor antagonists ( ERA ), and one study comparing two different regimens of treprostinil. Similarly, only five unpublished/ongoing trials used an active PH treatment as comparator ( PDE ‐5 inhibitors versus ERA (n = 3), different doses of sildenafil (n = 1) and two formulations of epoprostenol (n = 1). Of the 75 trials, 47 were sponsored by the manufacturer of the tested active product(s), and only two trials were sponsored by two companies comparing their products. Conclusions The relative merits of different treatment options are not directly known, as there are very few head‐to‐head comparisons. A limited number of ongoing studies are using active FDA ‐approved PH ‐treatments for comparison. This lack of information can be overcome by carefully designing comparative effectiveness trials.