Dr. Kenneth Mahaffey
Prof. Stefan James,
Presenter abstractDiscussant reportAll the Scientific resources on ESC Congress 365
By Stefan JamesOther Authors: Ole Fröbert, Örebro University Sweden; Göran Olivecrona, Lund University Sweden; David Erlinge, Lund University Sweden; Tomas Jernberg, Karolinska Institute, Stockholm Sweden; Bertil Lindahl, Uppsala University Sweden; Lars Wallenting, Uppsala University Sweden; Bo Lagerqvist, Uppsala University SwedenBackground:While providing the highest level of evidence, prospective randomized trials are often limited by including highly selected populations through multiple inclusion and exclusion criteria. For practical and financial reasons many potentially important therapeutic interventions are not being evaluated. Observational studies are inexpensive and often reflect clinically relevant populations but have limited value for evaluation of therapeutic options due to known or concealed confounding factors that cannot be adjusted for.
Methods:We incorporated a randomization module in a clinical nationwide SCAAR/SWEDEHEART registry to combine the most important features of a prospective randomized trial with those of a large scale clinical registry, enabling an inexpensive, unselective enrollment of large numbers of patients in a prospective Registry based Randomized Clinical Trial (RRCT) with complete follow-up on mortality through registries.
Results:In a prospective RRCT we investigated manual thrombus aspiration as an adjunct to primary PCI in a trial powered for 30-day mortality as the primary endpoint. The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE) trial recently completed enrollment of 7244 patients, comprising 60% of all patients undergoing primary PCI, by all interventional Cardiologists at all PCI hospitals in Sweden in addition to one Danish and one Icelandic center during 2.5 years. Two RRCTs in myocardial infarction are in progress using the SCAAR/SWEDEHEART platform: one trial of oxygen therapy versus room air evaluating mortality (DETOX) and one pharmaceutical trial of heparin versus bivalirudin during PCI evaluating death, myocardial infarction, and major bleeding (VALIDATE).
Conclusions:The RRCT concept is an effective, inexpensive way to appropriately assess hard clinical endpoints in large patient cohorts. RRCTs are ideal to evaluate old therapeutic dogmas and novel treatments with limited economic revenue potential and thus offer hope to break the current deadlock in clinical trial progress.
Giuseppe AmbrosioIn the era of evidence-based medicine, randomized clinical trials (RCTs) have become the mainstay to evaluate new therapeutic strategies, and as such they play a major role in defining optimal medical management as outlined in international guidelines. However, there is also disenchantment with respect to the actual applicability of results from RCTs to the majority of patients with a given conditions. This stems from inherent limitations of RCTs, which unavoidably require strict inclusion criteria.On the other hand, “real-life” registries, while potentially open to all-comers, suffer from the presence of a number of possible confounders which tend to cloud the picture. Thus, data derived from observational studies are considered non-definitive and hypothesis generating.Registry-based Randomized Clinical Trials (RRCT) is an innovative approach to circumvent such limitations. To avoid selection bias, randomisation of patients may be performed within a clinical registry, combining some of the most important features of a prospective randomised trial with the strengths of a large-scale clinical registry. Prospective use of registries could potentially revolutionise clinical trials through fast inclusion of large patient numbers, focus on hard endpoints and complete follow-up, at a fraction of the costs of RCTs.However, duration of RRCT enrollment and follow-up should be clearly determined, as is required sample size. Correct development of RRCTs may require careful attention regarding internal validity; precise criteria in this respect need to be established. Patients receiving different treatments should to be similar in all measured or unmeasured characteristics, and that may be difficult to achieve in “real life” settings.Also, it has to be established how to deal with the situation in which a registry enrolls only a fraction (however large) of a given patients population, as this can give rise to an unwanted selection bias, and/or to the possibility that inclusion is not uniformly distributed across sites with different facilities or case load. Finally, by definition real-life registries can only assess the effects of treatments already largely available: new drugs or devices can only be tested through phase III RCTs.
TASTE: Prospective Registry based Randomized Clinical Trials (RRCT) - a new concept for clinical research
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