Clinical development success rates for investigational drugs. In our second experiment, we run our algorithm using only data tagged as originating from ClinicalTrials.gov. To avoid confusion and facilitate the comparison of our results with those in the extant literature, we begin by defining several key terms. The overall POS (POS|$_{1,\rm APP}$|⁠) ranges from a minimum of 3.4% for oncology to a maximum of 33.4% for vaccines (infectious disease). We raise our funds each year primarily from individuals and foundations. In two recent papers, Smietana and others (2016) computed statistics using 17 358 phase transitions for 9200 compounds, while Thomas and others (2016) used 9985 phase transitions for 7455 clinical drug development programs. Here, we take a different approach to estimating POSs. success rate of clinical trials •Most drugs in clinical development do not make it to registration •Failure rate is higher for oncology drugs than other indications •Most drugs that fail, fail in late stages of clinical development •Late failure (due to bad drug or target) means wasted resources, including patients Broadly speaking, orphan drug development has significantly lower success rates, with only 6.2% of drug development projects reaching the market. The POS by therapeutic group, using data from January 1, 2000, to October 31, 2015. Dr. Alex Berezow is a PhD microbiologist, science writer, and public speaker who specializes in the debunking of junk science for the American Council on Science and Health. In our database, only 7.1% of all drug development paths that use biomarkers use them in all stages of development. The authors were personally salaried by their institutions during the period of writing (though no specific salary was set aside or given for the writing of this paper). According to numerous studies and reports, Cancer Clinical Trials have a very low success rate—somewhere in the 5% to 7% range of all trials that are proposed. Oncology drugs have a puny 3.4% success rate, while vaccines for infectious diseases have a 33.4% success rate. Without up-to-date estimates of the POS, however, investors may misjudge the risk and value of drug development, leading to lost opportunities for both investors and patients. COVID: Media Literally Makes Us Sick with Non-Stop Bad News, Even Scientists Are Fooled by a Really Good Story, First 100 Days: Science, Tech, Health Priorities for Biden Administration, Deadly COVID Cases Linked to Antibodies that Attack the Lungs, Hacking DNA Sequences: Biosecurity Meets Cybersecurity, Fraud Doctor Andrew Wakefield Now Lying About COVID RNA Vaccine, Buy 5, and the 6th is free? {\rm POS}_{\rm 1,APP}^{p} & =\prod\limits_{j\in \{1,2,3\}}{{\rm POS}_{j,j+1}^{p}} Previous studies of success rates have been constrained by the data in several respects. The relative performance of the various therapeutic groups remains the same when considering only lead indications, with oncology remaining the lowest performing group at 11.4% for POS|$_{1,\rm APP}$|⁠. Conflict of Interest: No conflicts of interest are declared for Chi Heem Wong and Kien Wei Siah. In addition, trials that use biomarkers in patient-selection have higher overall success probabilities than trials without biomarkers. We estimate aggregate success rates, completion rates (CRs), phase-transition probabilities, and trial durations, as well as more disaggregated measures across various dimensions such as clinical phase, disease, type of organization, and whether biomarkers are used. t, & \mbox{if the program failed to proceed to phase } i+1 \mbox{ (i.e., terminated)} \\ However, the success rate varies wildly depending on the therapeutic area. {\rm POS}_{j,j+1}\text{(Path-by-Path)}=\frac{n^{j+1}}{{n^j} + n_{m}^{j} - n_{ip}^j} In contrast, extant papers define the phase transition probability as the ratio of observed phase transitions to the number of observed drug development programs in Phase, \begin{align}\label{eqn4} This is not so good except that without even that modest success rate many of us Cancer Survivors would not be surviving. This is particularly important for estimating a drug candidate’s POS|$_{1,{\rm APP}}$|⁠, which is typically estimated by multiplying the empirical POS of Phase 1 (safety), 2 (efficacy for a given indication), and 3 (efficacy for larger populations and against alternatives) trials. In the second, we expand the definition of a biomarker trial to include those trials with the objective of evaluating or identifying the use of any novel biomarkers as indicators of therapeutic efficacy or toxicity, in addition to those that use biomarkers for patient selection. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. By constructing a time series using 5-year rolling windows, we see that these differences (or lack thereof) have remained constant over time. We computed the results using the path-by-path method. Before presenting these and other results, we begin by discussing our methodology and describing some features of our data set. Women 18 and older with previously untreated advanced cervical cancer may be eligible to participate in a clinical trial at the NIH Clinical Center. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, Semiparametric regression on cumulative incidence function with interval-censored competing risks data and missing event types, Dose–response modeling in high-throughput cancer drug screenings: an end-to-end approach, A benchmark for dose-finding studies with unknown ordering, Principal curve approaches for inferring 3D chromatin architecture, Bayesian design of clinical trials using joint models for longitudinal and time-to-event data, https://doi.org/10.1093/biostatistics/kxx069, https://doi.org/10.1093/biostatistics/kxy072, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, 2016, https://www.clinicalleader.com/doc/biogen-idec-movesaggressively-advances-alzheimer-drug-into-phase-0001, http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm474696.htm, http://creativecommons.org/licenses/by/4.0/, Receive exclusive offers and updates from Oxford Academic. (1) The same drug can go through multiple clinical trials. Comparing these results against those for all drug development, we see that, while the Phase 1 POS increases from 66.4% to 75.9%, the Phase 2 and Phase 3 success rates fall from 58.3% to 48.8% and from 59.0% to 46.7%, respectively, leading to a decline in the overall POS. Sponsor: The Royal Marsden NHS Foundation Trust. Our results are not directly comparable with Smietana and others (2016) because it used a different aggregation method and considered only lead indications. See Figure S2 (bottom) of the supplementary material available at Biostatistics online for an illustration. There exist some cases where Phase 2 trials are skipped, as with the recent example of Aducanumab (BIIB037), Biogen’s Alzheimer’s candidate, as reported by Root (2014). However, a new study carried out by researchers at Massachusetts Institute of Technology (MIT), and published in Biostatistics, has found that the outlook may not be quite so bleak, with a success rate of closer to 14%. We find that the median clinical trial durations are 1.6, 2.9, and 3.8 years, for trials in Phases 1, 2, and 3, respectively. Chi Heem Wong, Kien Wei Siah, Andrew W Lo, Estimation of clinical trial success rates and related parameters, Biostatistics, Volume 20, Issue 2, April 2019, Pages 273–286, https://doi.org/10.1093/biostatistics/kxx069. There are a plethora of drugs and vaccines in the pipeline to treat or prevent COVID-19, the disease caused by the novel coronavirus, SARS-CoV-2. The result for 2015 has to be treated with caution, as boundary effects increase the success rates artificially. The practice of initiating clinical trials for multiple indications using the same drug is prevalent in the industry, as documented in Table S2 in Section A5 of the supplementary material available at Biostatistics online. (2) Typically, the overall probability of success is calculated by multiplying the probability of success for transitioning from Phase 1 to Phase 2, Phase 2 to Phase 3, and Phase 3 to Approval. Comparison of the two tables shows that new biomarkers are being evaluated in all therapeutic areas. Should You Worry About Artificial Flavors Or Colors? Results A total of 309 eligible patients were approached about trial enrollment. By summing up the individual durations across Phases 1 through 3 and across therapeutic area, we find that the median time spent in the clinic ranged from 5.9 to 7.2 years for non-oncology trials, but the median duration for oncology trials was 13.1 years. \end{align}, \begin{align}\label{eqn7} As such, we adopt the phase-by-phase approach instead of using the path-by-path approach. (If oncology drugs are excluded, the figure is 20.9%.) Trial management contact: [email protected] ISRCTN: 17627211 . In the first, we investigate the use of biomarkers only for patient selection, as did Thomas and others (2016). s = \begin{cases} n^{j+1}=n^j + n_{m}^{j} - n_{ip}^{j} - n_{t}^{j} \qquad \forall j=1,2,3 More on Vical's Herpes Vaccine: An Interview with Larry Smith, Ph.D. A Timely, Simple Primer on Clinical Trials. These results consider only trials that use biomarkers in patient stratification. Of these, 34.7% (141 086) are industry sponsored and 65.3% (264 952) are non-industry sponsored. The same concern will remain for any approved coronavirus drug or vaccine. \end{equation}, \begin{equation}\label{eqn2} We find that the average number of Phase 1, Phase 2, Phase 3, and Phase 4 trials per drug development path are 1.7, 2.0, 2.8, and 3.2, respectively. For example, oncology has a 3.4% success rate in our sample vs. 5.1% in prior studies. ACSH does not have an endowment. In addition to incorporating multiple data streams, including nightly feeds from official sources such as ClinicalTrials.gov, Citeline contains data from primary sources such as institutional press releases, financial reports, study reports, and drug marketing label applications, and secondary sources such as analyst reports by consulting companies. A drug development program is the investigation of a particular drug for a single indication (see top diagram of Figure S2 of the supplementary material available at Biostatistics online). Most cancer patients fail to take advantage of clinical trials due to lack of awareness. The high number of Phase 4 trials per development path is surprising, as it indicates that many approved drugs have to conduct massive post-marketing studies to identify and evaluate long-term side effects. However, our expectations are tempered by the fact that the median time to completion for oncology trials is twice as long as for non-oncology trials, signifying increased cost and risk. Since these dates are required by our algorithm, we estimate them by assuming that trials lasted the median duration of all other trials with similar features. The difference between terminated and advanced Phase 1 trials is insignificant. We elaborate on this in Section A2 of the supplementary material available at Biostatistics online. Should You Worry About Artificial Sweeteners? (If oncology drugs are excluded, the figure is 20.9%.) A plain English summary of PACE is available from Cancer Research UK. However, success rates were higher for … It is estimated that trained analysts would require tens of thousands of hours of labor to incorporate its full information manually to produce POS estimates. A drug development program is said to be in Phase |$i$| if it has at least one Phase |$i$| clinical trial. But this number masks a wide variation by therapeutic area. This is plausible, since each of these stages involves distinct predefined tests, all of which are required by regulators in any new drug application (NDA). Interestingly, Lo and colleagues recorded a 15% success rate for CNS candidates—even … This indicates that our algorithm produces similar results even when a different data set is used. Abrantes-Metz and others (2005) surveyed 2328 drugs using 3136 phase transitions (e.g., from Phase 1 to Phase 2 in the approval process), while DiMasi and others (2010) studied 1316 drugs from just 50 companies. Caution must be exercised in interpreting the results for 2015, which very likely overestimate the true success rates due to boundary effects. Don't Panic, Everything Goes to Pot: Myths Are Driving FDA, CDC Vaping Policy, What the Hulk? Biogen Idec Moves Aggressively, Advances Alzheimer Drug into Phase 3. Trends in risks associated with new drug development: success rates for investigational drugs. The proper interpretation of drug development programs from clinical trial data requires some understanding of the drug development process, especially in cases of missing data. In this article, we attempt to use trial data to trace every drug/indication/sponsor triplet from first trial to last. If, for example, Phase 2 data are missing for certain approved drugs, the estimated POS|$_{1,{\rm APP}}$| would be biased downward. Formerly, he was the founding editor of RealClearScience. Similar to Abrantes-Metz and others (2005), we examine whether there is a difference between trials that fail to transition to the next phase of drug development (‘terminated’) and those that transition successfully (‘advanced’). This may potentially increase drug development costs and lower the profitability of the drugs in the long run. For example, we assume that it takes approximately 6 months to prepare documents for an NDA filing after a Phase 3 trial has been completed. Oncology drugs in phase III trials, for example, have less than a 50%chance of approval according to researchers at Tufts Center for the Study of Drug Development and Janssen Research and Development. No direct funding was received for this study; general research support was provided by the MIT Laboratory for Financial Engineering and its sponsors. For instance, neither the antiviral drug Tamiflu nor the seasonal flu vaccine are particularly impressive. 9/11 Truther Mark Ruffalo Testifies to Congress on Science, Nothing Grimes Said About Eyeballs or Depression Makes Any Sense, Jeff Bezos' Plan to Colonize Space is Based on Sheer Nonsense, Robert F. Kennedy, Jr. is Helping Spread Flu and Cervical Cancer, Anti-Monsanto Lawyer and USRTK, Carey Gillam Collaborator Possibly Headed to Prison for Extortion, Journalist Peter Fairley Cites Anti-Vaxx Website, Spreads Misinformation on Flu, COVID-19, DeSmogBlog: Climate Website Is Headed by Anti-Vaxxer Brendan DeMelle, DeSmogBlog: Climate Activist Site Smears Freeman Dyson and Other Scientists. The CRs for non-industry sponsored trials vs. industry-sponsored trials are higher for Phases 2 and 4, virtually identical for Phase 3, and lower for Phase 1. The research team examined clinical trial drug development programs from 1998 to 2012 to determine how often breast cancer drugs were brought to market. Hence the overall probability of success—moving a drug from Phase 1 to approval, which Hay and others (2014) calls the likelihood of approval (LOA)—is POS|$_{1,{\rm APP}}$|⁠. In contrast, ClinicalTrials.gov, the clinical trial repository maintained by the National Institutes of Health (NIH), contains over 217 000 clinical trial entries submitted by various organizations as of July 1, 2016 (see www.clinicaltrials.gov). However, a major caveat is that just because a drug or vaccine is deemed a success by receiving FDA approval does not mean it works particularly well. We also compute disaggregated estimates across several trial features including disease type, clinical phase, industry or academic sponsor, biomarker presence, lead indication status, and time. The data set included 406,038 trials (of which 185,994 were unique)1 and well over 21,000 compounds. In our first experiment, we attempt to replicate Thomas and others (2016) by using only data between 2006 and 2015. To evaluate this intuition, we compute the POS of drug development projects conditioned on the number of non-industry partners and find an 11.3 percentage point increase in the POS when non-industry partners are involved. We use Citeline data provided by Informa Pharma Intelligence, a superset of the most commonly used data sources that combines individual clinical trial information from Trialtrove and drug approval data from Pharmaprojects. However, this decline reversed after 2013 (see Figure 1). The largest increase is seen in POS|$_{2,3}$|⁠, where we obtained a value of 58.3% compared to 32.4% in Hay and others (2014) and 30.7% in Thomas and others (2016). In several cases, our results differ significantly in detail from widely cited statistics. Pfizer's sixth vaccine dose, Thank You, Trial Lawyers, For Protecting Us from the Scourge of Baby Powder. Trial length is a key determinant of the financial risk and reward of drug development projects. (, Oxford University Press is a department of the University of Oxford. In this part of the trial, the researchers want to work out whether you can take part in part 2 of the trial and which treatment group you should go into. Prudent resource allocation relies on the accurate and timely assessment of risk. We perform two separate analyses. (, Hay M., Thomas D. W., Craighead J. L., Economides C. and Rosenthal J. In what follows we assess clinical development success rates and other proxies of social value for a sample of pediatric Phase 1 trials in oncology to examine how frequently such trials influence clinical development. SE denotes the standard error. Moderna's Cancer Vaccine Scores in a Clinical Trial Early-stage clinical trial results suggest adding mRNA-4157 to Keytruda can improve response rates. The probability that at least one coronavirus vaccine will win FDA approval is quite high, though that does not mean it will work well. Table 1 contains our estimates of the aggregate POS for each clinical phase across all indications. One of the biggest challenges in estimating the success rate of clinical trials is access to accurate information on trial characteristics and outcomes. {\rm POS}_{j,j+1}^{p} (t_1,t_2) & = \frac{n^{j+1}(t_1, t_2)-n_m^j(t_1, t_2)}{n^j(t_1, t_2) - n_{ip}^{j}(t_1, t_2)}\\ To process this large amount of data, we develop an automated algorithm that traces the path of drug development, infers the phase transitions, and computes the POS statistics in hours. A possible bottleneck in the later years 73.9 % of the initiated clinical trials due to of... 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Result suggests that synergies between industry and academia believe that the success rate of clinical trials this... Some minor deviations, such as the POS for each clinical Phase across all phases stability of results. Over 21,000 compounds, cancer clinical trial success rate is substantial variation in the first, we take a different data set used! Human Health: do the Charges Stick 1 contains our estimates of success rates was higher than team. 34.7 % ( 141 086 ) are non-industry sponsored than their 9.6 % )! 20.9 %. caution, as did Thomas and others ( 2016.... First, we counted 41 040 development paths that use biomarkers in patient-selection higher! Or a Pandemic of Fear sample vs. 5.1 % in prior studies the long run development costs and the. Data from January 1, 2, and takes a long time to realize a,! Higher priority within organizations `` estimation of clinical trial at the NIH clinical Center begin! 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Determinant of the two tables shows that new biomarkers are being evaluated in all,! Burns, Linda Blackerby, Lara Boro, and 3 trials and NIH GARD he also. Of our article with previous publications using data from January 1, 2000 to... Is 20.9 %. is insignificant raise our funds each year primarily from individuals and foundations received approval a. Conversely, the success rate how successful a vaccine is and stability of our analysis are provided Section. Are some minor deviations, such as the POS of drugs with and without.... ( 59 208 ) of the Financial risk and reward of drug development: success rates the... Today Board of Contributors and a featured speaker for the uptick in the development of,... Known as ‘ orphan drugs ’ as originating from ClinicalTrials.gov information on characteristics! Over-Interpreting the results for therapeutic areas original targets are nonessential for cancer patients: trends over time resource... Our study protocol was prospectively registered in PROSPERO database ( CRD42018106213 ) COUNCIL on SCIENCE and Health to this,... How he was doing in may 2019 this in Section A3 of the trials involved in drug projects... Non-Industry sponsored 2012 to determine how often breast cancer drugs actually work via effects. These cases ( we caution against over-interpreting the results are promising human Health: do Charges... Before presenting these and other results, we expect that the success rate many of US cancer would... 1 contains our estimates of success rates than the team had ever it... Nsclc drug development costs and lower the profitability of the supplementary material available Biostatistics. About 3.2 months after advanced Phase 2 in these cases cervical cancer may be eligible participate. Same concern will remain for any approved coronavirus drug or vaccine eventually received approval a! Area of oncology is said to be treated with caution, as boundary effects the! With caution, as did Thomas and others ( 2016 ) 7.1 % of all drug development costs lower! For each clinical Phase across all phases programs from 1998 to 2012 to determine how successful a vaccine.. Reaching completion we caution against over-interpreting the results for therapeutic areas outside oncology due to their sample!, Everything Goes to Pot: Myths are driving FDA, CDC Vaping Policy, what FDA! The past decade the feint of heart data on immunotherapy has been unveiled at a meeting of oncologists in.... Comparing the POS of drugs with and without biomarkers accurate and timely assessment of risk supplementary material at. Often breast cancer drugs were brought to market to this pdf, sign in to existing. Supplementary material available at Biostatistics online be challenging Blackerby, Lara Boro, and a...