This study estimates aggregate clinical trial success rates and related parameters using data from 406,038 clinical trial entries for over 21,143 compounds from January 1, 2000, to October 31, 2015. The data come from Informa Pharma Intelligence's Trialtrove and Pharmaprojects databases. The study introduces a "path-by-path" approach to estimate success probabilities, which tracks the proportion of development paths that progress through clinical phases. This method differs from the "phase-by-phase" approach, which estimates success probabilities based on observed phase transitions. The study finds that the overall success rate for drug development is 13.8%, higher than previously reported estimates. For oncology, the success rate is 3.4%, compared to 5.1% in prior studies. The success rate for oncology has improved over time, reaching 2.5% in 2014 and 8.3% in 2015. Trials that use biomarkers for patient selection have higher success probabilities. The study also finds that the success rate for Phase 2 to Phase 3 trials is 58.3%, higher than previous estimates. The study further examines the success rates of orphan drugs, finding that only 6.2% of drug development projects reach the market. The success rate for orphan drugs increases to 13.6% when excluding oncology indications. The study also finds that the success rate of clinical drug development projects has decreased between 2005 and 2013, but has increased since then. The study concludes that the success rates of clinical trials are influenced by various factors, including the use of biomarkers, the type of drug, and the therapeutic area. The study provides a more accurate and comprehensive estimate of clinical trial success rates and related parameters, which can help inform decisions in drug development and investment.This study estimates aggregate clinical trial success rates and related parameters using data from 406,038 clinical trial entries for over 21,143 compounds from January 1, 2000, to October 31, 2015. The data come from Informa Pharma Intelligence's Trialtrove and Pharmaprojects databases. The study introduces a "path-by-path" approach to estimate success probabilities, which tracks the proportion of development paths that progress through clinical phases. This method differs from the "phase-by-phase" approach, which estimates success probabilities based on observed phase transitions. The study finds that the overall success rate for drug development is 13.8%, higher than previously reported estimates. For oncology, the success rate is 3.4%, compared to 5.1% in prior studies. The success rate for oncology has improved over time, reaching 2.5% in 2014 and 8.3% in 2015. Trials that use biomarkers for patient selection have higher success probabilities. The study also finds that the success rate for Phase 2 to Phase 3 trials is 58.3%, higher than previous estimates. The study further examines the success rates of orphan drugs, finding that only 6.2% of drug development projects reach the market. The success rate for orphan drugs increases to 13.6% when excluding oncology indications. The study also finds that the success rate of clinical drug development projects has decreased between 2005 and 2013, but has increased since then. The study concludes that the success rates of clinical trials are influenced by various factors, including the use of biomarkers, the type of drug, and the therapeutic area. The study provides a more accurate and comprehensive estimate of clinical trial success rates and related parameters, which can help inform decisions in drug development and investment.