There is no doubt that whenever a randomised clinical trial (RCT) is feasible and ethical, it is preferred over other late-stage trial designs. RCTs are considered the gold standard of experimental investigation as they provide powerful, robust and statistically significant evidence of between-treatment differences, based on data from relatively large numbers of recruited patients. Moreover, using information gained from genomic studies, RCTs have recently evolved to include enrichment and adaptive designs, which provide an insight into targeted interventions in subgroups of patients harbouring specific genomic aberrations. This development means that in some cases, RCTs offer sufficiently robust evidence in smaller patient populations than would be necessary if patients were not specially selected.The evolution of RCTs responds to increasing requests from international regulatory authorities for the inclusion of more diverse patient subgroups in clinical trials. A commonly debated drawback is that RCTs, despite having robust internal validity, sometimes lack generalisability to populations beyond the study patients. More recently, we have seen that the newer trial designs, such as umbrella, basket and platform trials are useful in relatively small subgroups of patients with distinct characteristics, such as those with tumours harbouring specific biomarkers. However, during the development of a new treatment, confirmation of its efficacy and safety is usually required in a randomised setting, often necessitating RCTs.Yet, despite seemingly rapid scientific progress in the research setting, swift access of new treatments to patients in clinical practice can be hindered by the slow pace at which rigorous evidence is obtained from RCTs. Will other types of trials ever replace RCTs? I do not think so, although I believe that the development of new medicines may include greater reliance on real-world data to supplement evidence from traditional clinical trials.
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