Randomised controlled trials (RCTs) conducted before market authorisation can generate evidence on effectiveness in addition to evidence on efficacy and safety. Evidence of effectiveness may be generated by including elements of pragmatism in the design of the study (for more about the pragmatic and explanatory continuum, see Study Design: Pragmatic Trial).
As part of the GetReal project, a systematic literature review was performed to identify pre-authorisation RCTs that aimed to generate evidence on effectiveness.
What was examined?
The systematic review aimed to identify pre-authorisation RCTs published between 2004 and 2016. The studies were examined for their attempts to be more pragmatic, based on the PRECIS domains (Loudon et al., 2015) of study design.
What were the findings and conclusions?
- The review identified 29 pre-authorisation RCTs which aimed to generate evidence on effectiveness.
- The most frequent PRECIS domains that were found to be relaxed (i.e. more pragmatic) included:
- Eligibility: the extent to which a trial’s participants are similar to those who would receive the intervention in usual care
- Flexibility: the extent to which the way the intervention is delivered in the trial compares to how it would be delivered in usual care
- Primary outcome: the extent to which the trial’s primary outcome is directly relevant to participants
- The PRECIS dimensions that were found to be less pragmatic included: recruitment, setting, organisation and primary analyses.
- Only 1 RCT which included more than 6 PRECIS dimensions was classified as pragmatic: the ‘Salford Lung Study’.
- Over the last decade, the use of ‘pragmatism’ in pre-authorisation trials has typically been implemented for only some elements of trial design.
Helene Karcher, Clementine Norden, Monika Neumann, Mateusz Nikodem, Agnieszka Zyla and Lucien Abenhaim, LASER
Helene Chevrou-Severac, Takeda
Javier Jiménez, AstraZeneca
Mohan Bala, Sanofi