A critical analysis of clinical research methods to study regenerative endodontics.

Regenerative endodontic treatment such as revitalization provides a treatment option for immature teeth with pulp necrosis. The main difference to the alternative procedure, the apical plug, is the induction of a blood clot inside the canal as a scaffold for healing and new tissue formation. Due to the biology-based and minimally-invasive nature of the treatment, revitalization has raised considerable interest in recent years. Whereas the procedure is fairly new and recommendations from endodontic societies have been in place only for a few years, the treatment protocol has evolved over the past two decades. Evidence has been created, not only from laboratory and animal work, but also from clinical studies including case reports, cohort studies and eventually prospective randomized controlled clinical trials, systematic reviews and meta-analyses. However, the research methods and clinical studies with subsequent reports oftentimes present with methodical limitations, which makes it difficult to objectively assess the value of this treatment modality. Several open questions remain, including the need for a more differentiated indication of revitalization after different traumatic injuries, the long-term prognosis of treated teeth and the true benefits for the patient. Therefore, this review aims to identify and reflect on such limitations, scrutinizing study design, diagnostic tools, procedural details and outcome parameters. A core outcome set is also proposed in this context, which can be considered in future clinical investigations. These considerations may lead to a more detailed and stringent planning and execution of future studies in order to create high-quality evidence for the treatment modality of revitalization and thus provide more robust data, create a larger body of knowledge for clinicians and further specify current recommendations.