The translational challenge in the development of new and effective therapies for endometriosis: a review of confidence from published preclinical efficacy studies

BACKGROUND: Endometriosis is a benign gynaecological condition that presents symptoms of chronic pelvic pain and the ectopic growth of endometrial lesions at sites on the peritoneum. Few new approaches to the management of the disease symptoms and progression have emerged in decades. The cornerstone of developing new therapies is the confidence and translational value placed in the preclinical models used to assess efficacy of emerging approaches. METHODS: We systematically reviewed preclinical efficacy data from rodent and non-human primates, evaluating the effects of an investigational agent or target reported in PubMed between 2000 and 2010. We evaluated the reports for which model and end-points had been used to determine efficacy, whether there was evidence of independent replication, whether techniques had been incorporated into the experimental design to eliminate potential bias and whether there was a confirmation of drug exposure or target engagement in the study. RESULTS: We identified 94 publications that met our criteria for review. Efficacy studies were conducted in a wider range of different models with no clear consensus on which model or end-point has the most translational value. The large majority of studies either did not report what measures were incorporated into the design to address potential bias or account for it or did not confirm whether the specified target was engaged. CONCLUSIONS: Greater scrutiny of the preclinical efficacy models, end-points and experimental designs is needed if the desire of translating novel treatment approaches is to be realized for women with endometriosis.