Decatastrophizing research irreproducibility.

The reported inability to replicate research findings from the published literature precipitated extensive efforts to identify and correct perceived deficiencies in the execution and reporting of biomedical research. Despite these efforts, quantification of the magnitude of irreproducible research or the effectiveness of associated remediation initiatives, across diverse biomedical disciplines, has made little progress over the last decade. The idea that science is self-correcting has been further challenged in recent years by the proliferation of unverified or fraudulent scientific content generated by predatory journals, paper mills, pre-print server postings, and the inappropriate use of artificial intelligence technologies. The degree to which the field of pharmacology has been negatively impacted by these evolving pressures is unknown. Regardless of these ambiguities, pharmacology societies and their associated journals have championed best practices to enhance the experimental rigor and reporting of pharmacological research. The value of transparent and independent validation of raw data generation and its analysis in basic and clinical research is exemplified by the discovery, development, and approval of Highly Effective Modulator Therapy (HEMT) for Cystic Fibrosis (CF) patients. This provides a didactic counterpoint to concerns regarding the current state of biomedical research. Key features of this important therapeutic advance include objective construction of basic and translational research hypotheses, associated experimental designs, and validation of experimental effect sizes with quantitative alignment to meaningful clinical endpoints with input from the FDA, which enhanced scientific rigor and transparency with real world deliverables for patients in need.