Analysis on the success rate of clinical trials of orphan drugs

Dr Andrew W lo, Chair Professor of Charles E and Susan T Harris at MIT Sloan School of business, is known as the founder of "bio finance" The paper published by Professor Luo Wenquan's research team analyzed in detail the success rate of drugs entering phase 1 clinical trials to obtain regulatory approval, including the related success rate of orphan drugs The industry often prudently allocates resources based on accurate and timely risk assessment results However, without the latest POS estimation, investors may misjudge the risk and value of drug development, resulting in the loss of opportunities for both investors and patients How to understand the accurate information of clinical trial characteristics and outcome is one of the biggest challenges to estimate the success rate of clinical trials Collecting such data is costly, time-consuming and error prone Previous studies on the success rate of clinical trials were limited by data and data processing ability in several aspects In recent years, the most cited research is Thomas et al Published by bio, the world's largest industry organization, in May 2016 In general, the probability of successfully obtaining drug regulatory agencies is 9.6%, which can be described as "nine dead" What is the probability of success in clinical trials of orphan drugs that are more difficult to develop than those for public diseases? Using a different approach than the previous studies, Chi Heem Wong, Kien Wei Siah, and Dr Andrew W lo, Chair Professor of Charles E and Susan T Harris, Ph.D., of Sloan School of business at MIT, published their paper in biostatistics in April this year In contrast, the previously published literature used the "phase by phase" method to estimate the success rate (POS) from the random samples observed entering the next phase of clinical trials In addition to improving efficiency, the MIT team uses algorithms that allow previously infeasible calculations to be performed For example, generate time series estimates of POS and related parameters The MIT team assessed the overall success rate, completion rate (CRS), probability of entering the next phase of clinical trials, trial duration, and more detailed measurement indicators across different dimensions, such as clinical phase, disease, tissue type, and whether biomarkers were used or not The author uses citeline data provided by informa Pharma intelligence, which is a superset of the most commonly used data sources, which combines clinical trial information from trialtrove and drug approval data from pharmaprojects In addition to merging multiple data streams, including supplements from official sources such as clinicaltrials.gov, citeline also includes data from sources such as agency press releases, financial reports, research reports, and approved drug labeling statements, as well as second-hand data from analyst reports from consulting companies Secondary source data is particularly important to reduce the potential bias that may result from tissue reporting only successful clinical trials In particular, for reports before the food and Drug Administration Amendments Act of 2007 came into force, the amendment requires that all clinical trials be registered and tracked through clinicaltrials.gov The database used in the study includes information from the United States and countries and regions outside the United States Previous estimation of drug development success rate depends on relatively small samples in the database established and maintained by the pharmaceutical industry, which may lead to potential selection bias MIT team used 406038 entries from the database of trialtrove and pharmaprojects of informa Pharma intelligence during the period from January 1, 2000 to October 31, 2015, corresponding to 185994 clinical trial data samples of 21143 compounds in the above period, to estimate the overall clinical trial success rate and duration The authors also calculated the classification and estimation of several experimental characteristics, including disease type, clinical stage, industry or academic sponsor, presence or absence of biomarkers, lead indication status, time, etc In some aspects, the results of this study, compared with the statistics widely quoted in recent years, have significant differences in details For example, the structure of the study shows that the relative success rate of cancer medication is 3.4%, compared with 5.1% in the previous study However, after falling to 1.7% in 2012, the ratio increased to 2.5% in 2014 and 8.3% in 2015 In addition, compared with the trials without biomarkers, the trials using biomarkers in patient selection have a higher overall success rate In May 2016, bio issued a report based on the research results of Thomas et al The report analyzed a total of 9985 clinical trials and clinical trial phase transitions recorded in the biometracker database between 2006 and 2015; the data covered 7455 development plans from 1103 companies The results showed that 9.6% of the drugs in phase 1 clinical trials were approved by drug regulatory authorities, and 25.3% of the orphan drugs in phase 1 clinical trials were approved by drug regulatory authorities However, the research results of MIT team are significantly different from the above results The MIT team's research, using a rare disease classification, came from the European Union, orphanet, and the United States, NIH gard Rare diseases may belong to any treatment group, and the statistical calculation of orphan drugs is the same as other drugs The results show that compared with other drugs, the success rate of orphan drug development is significantly lower, only 6.2% of orphan drug research projects can be finally listed Compared with other drugs, although the success rate of phase 1 clinical trial of orphan drugs is 75.9%, higher than 66.4% of other drugs, the success rate of phase 2 is 48.8%, lower than 58.3% of other drugs; the success rate of phase 3 clinical trial of orphan drugs is 46.7%, also lower than 59.0% of other drugs (see the figure below) According to the data of MIT research team, more than half of clinical trials of orphan drugs focus on tumor drugs, but the related success rate of orphan drugs is only 1.2% (see the table above) The overall success rate related to orphan drugs was 6.2%, far lower than that reported by Thomas et al in 2016, which was 25.3% According to the researchers, the reason for such a significant difference lies in the fact that the "rare diseases" covered in the previous relevant studies only cover the non-tumor rare diseases and adopt the "stage exhaustion method" After removing all tumor indications in the calculation, the success rate of orphan drug clinical trials estimated by the researchers increased to 13.6% Original title: viewpoint orphan drug: what is the success rate of clinical trials? 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