Previous analyses provide an industry benchmark of ∼10% for the success rate in clinical development. However, prior analyses were limited by a narrow timeframe, a diverse research focus, biases in phase-to-phase transition methodology or a focus on specific use cases. We calculated unbiased input:output ratios (Phase I to FDA new drug approval) to analyze the likelihood of first approval using data from clinicaltrials.gov, encompassing a total of 2092 active ingredients, 19 927 clinical trials conducted by 18 leading pharmaceutical companies (2006-2022) and 274 new drug approvals. Our study reveals an average likelihood of first approval rate of 14.3% across leading research-based pharmaceutical companies, broadly ranging from 8% to 23%.