Registry-based randomized clinical trials (R-RCT) are prospective randomised trials that use a clinical registry for one or several major functions for trial conduct and outcomes reporting.
Swedish national quality registries enable follow-up of all patients in a given disease group and are therefore a gold mine for research. As the costs of performing gold standard randomised clinical trials (RCT) are constantly increasing, clinical researchers now turn to alternative study designs, such as the significantly cheaper registry-based randomised clinical trials (R-RCT), where applicable.
R-RCTs study real-life patients in real-life clinical settings
Registry-based studies make it possible to recruit a large number of unselected patients and thereby reflect the clinical reality. Randomisation modules can be integrated with quality registries so that patient recruitment and randomisation are conducted during regular health care visits. The follow-up process can also rely on registries and thereby reduce the impact on regular health care to a minimum.
R-RCT studies require more technical development and validation, leading to longer start-up times compared to regular RCT trials, but quickly catch up through rapid inclusion and follow-up of large numbers of patients. The reduced work load for participating clinics also lowers costs.
R-RCTs should be viewed as a complement to standard RCTs, not a replacement, as the different study designs are better suited to answer different research questions, see table below. R-RCTs are particularly valuable for comparing drugs or treatments already used in clinical practice.
Table. Suitability of study design according to research question.
|Medical devices: CE-marked, used in clinical practice||+|
|Approved drugs: evaluation in clinical practice||+|
|Approved drugs: new indication||+||+|
|Medical devices: first in man||+|
|New drugs - high safety concern||+|
UCR world-leading in R-RCT development
UCR held a pivotal role in TASTE, one of the first R-RCTs. TASTE used the SWEDEHEART registry to show that blood clot aspiration in patients with myocardial infarction undergoing percutaneous coronary intervention (PCI) had no effect on survival. The SWEDEHEART registry covers health care of patients with acute cardiac infarction, planned catheter-borne coronary vessel surgery, and valve replacement in cardiac surgery. As the registry centre for SWEDEHEART, UCR developed the complete technical solution required for the success of the TASTE study. The technical solution now undergoes continuous development to meet new requirements and to enable larger and more complex trials in a growing number of registries.
The R-RCT concept has gathered substantial international interest and UCR is recognised as world-leading in the field. Following the success with TASTE, UCR has continued to develop the R-RCT solution in studies such as iFR-SWEDEHEART, DETO2X-AMI, and VALIDATE-SWEDEHEART. All studies maintained high quality yet were significantly cheper than conventional randomised clinical trials. Moreover, they have permitted evaluation of established treatment options that have no commercial interest for the pharmaceutical industry.
R-RCTs conducted at UCR are changing clinical practice
Several R-RCTs conducted at UCR have led to immediate and important changes in international guidelines:
- Prior to TASTE, thrombectomy was highly recommended for routine use in all patients with ST-elevation myocardial infarction treated with PCI. The TASTE trial changed the recommendation to something that should not be performed.
- Oxygen has been the top recommended medical treatment for decades. The DETO2X trial changed international guidelines to only give oxygen in patients with clear hypoxia.
- Bivalirudin has been strongly recommended during PCI for ST-elevation myocardial infarction. The VALIDATE trial showed that simple heparin is just as effective and safe in modern care which gives an opportunity to make enormous savings for the society.