What are the key clinical costs of new drugs? Much less than you think!

TextWu Yanzu wufor many therapeutic areas, innovative drugs have irreplaceable clinical value, or to meet the unmet clinical needs, or can better than existing therapies to better address the needs of patientsPrice needs match value, and innovative drugs with high clinical value are often accompanied by high pricesIn addition, innovative drugs in the patent protection period, for an indication of the disease often does not have or only a small number of competing products, complete monopoly or oligopoly market pattern further pushed up pricesthe high price of innovative drugs has led to conflicts between pharmaceutical companies and patients (or payers), just as nova and patients in the film I am not a drug god, the contradiction between the high price of the innovative drug "Glenin." The often used explanation for the high price of innovative drugs is the high cost of research and development, the need for appropriate profits to reward research and development personnel, and the investment in new research and development projects to promote sustainable development of enterprisesAn article published in the Journal of Health Economics in 2016 by Tufts Research Center for Drug Development and Research notes that the average cost of bringing an innovative drug to market (considering failed projects) is $2.6 billion, including $1.4 billion in cash expenses and $1.2 billion in time costsThis is by far the most popular and widely accepted of the data cited by pharmaceutical companies in defending research and development costsChart 1Tufts CSDD estimates the cost of listing an innovative drug (in 2013 Dollars)clinical trial costs are an important part of the cost of research and development of innovative drugs, of which Phase III clinical trial costs are a top priorityHowever, neither the law nor the editorial board of the International Medical Journal requires public disclosure of the cost of conducting clinical trialsThe Tufts Center for Drug Development research may not be well known for its average cost of Phase III clinical trials, which is $255 million (in 2013 dollars)Recently, a new study successfully challenged this valuationThomas JMoore of the Institute for Safe Drug Practices, ISMP, and others systematically studied and estimated the cost of critical clinical trials of therapeutic and innovative drugs approved by the FDA from 2015 to 2017Key Trials is a human study that, under U.S law, provides "substantial evidence" of drug safety and efficacy, and is key to obtaining market approval for innovative drugs Key trials are usually Phase III clinical trials, and for some drugs that are included in the special approval process (e.g orphan drugs, breakthrough therapies) can be clinical Phase II trials for each critical trial, the researchers collected 52 items of information from three open sources: clinicaltrials.gov, drugs@FDA, and published peer-reviewed studies A set of variables is used to describe the basic characteristics of a clinical trial, including the indications of treatment, the number of patients screened, the number of people enrolled, and the duration of treatment Another set of variables indicates the different types of treatment benefits being measured and how they are measured, including the type of endpoint (alternative endpoint, biomarkers, clinical scale, clinical benefits) and the form of the control group/comparison group (non-control, placebo, active drugs) The third set of variables was related to the characteristics that affected the execution of the trial, including the number of outpatient follow-up visits by patients, the geographical location and number of research sites, the number of languages required for the research materials, and the time required for the research site to complete the trial agreement Chart 2 The researchers (partially) the information items (partially) for key experiments The researchers then used IQVIA's CostPro intermediate tool to get a cost estimate for each trial CostPro's valuation is derived from actual data from 2,000 final-review pilot schemes and incorporates cost information for 200,000 pilot sites in 60 countries Based on industry benchmark data, CostPro produces one low, medium and high valuation for each trial Preliminary research by the researchers suggests that some of the cost of trials is driven by undisclosed test execution characteristics These implementation features include the number of revisions to the pilot programme, the number of institutional review committees (IBS) and the frequency of monitoring of test sites After consulting experienced experimenters, the researchers calculated two sets of valuations, one assuming that the experiment was performed more efficiently and the other that was less efficient The trial costs were averaged by all six valuations, and the two efficiency assumption groups each had three low valuations The data collected by the researchers included 101 new drugs and 225 key clinical trials that included 156,140 patients and 224,1401 outpatient follow-up studies on the effectiveness of treatment (Figure 3) Chart 3 The number of patients, trials and drugs in key trials Overall, the estimated median cost of critical trials to support the approval of a new drug is $48 million (in 2020 dollars, followed by the same) and the quart distance (IQR) is $20-102 million The estimated cost of each drug-critical trial, broken down in the field of treatment, is shown in figure 4 Chart 4 The cost of critical trials for each drug The median estimated cost of each critical trial is $19 million, with a quart distance of $12-33 million The estimated median cost of the trial per patient is $41,413 ($29,894-75047, and the median cost per patient per outpatient follow-up is estimated at $3,685 ($2640-5498) It is important to note that the average trial cost per patient is sometimes close to the cost of treatment for a single patient by a pharmaceutical company after the drug is approved for market critical clinical costs for each drug depend to a large extent on the number of critical trials to support market approval Of the 101 treatmentdrugs approved by the FDA in 2015-2017, 45 were approved based on a single critical trial at a median cost of $28 million (quart s13-62 million) The estimated cost of 29 drugs approved for two trials almost doubled to a median of $45 million ($28-69 million in quarts) In addition, the estimated median cost for each of the 27 drugs approved for 3-11 trials amounted to $91 million ($56-128 million in quarts) Three or more trials are conducted because they seek approval for multiple indications, usually combined or complementary treatments From the perspective of a single clinical trial, the single factor that has the greatest impact on estimated costs is the number of patients needed to determine the effectiveness of treatment The median number of patients included in these trials was 495, but the difference scants ranged from 4 to 8446 One factor that requires more patients to be enrolled is the trial of drugs that have been approved for indications At this point, measuring the effectiveness of the new drug requires a controlled active drug as a control, rather than an inactive placebo The median of 62 trial signed-up patients with an active drug control group was 653, compared with 547 in the placebo control group and 145 in non-control trials while the number of patients required by the trial is the most important cost driver, we can still observe changes in the cost of each patient trial Figure 5 shows how the cost per patient varies depending on the treatment area Chart 5 Estimated critical trial costs per patient The second largest factor affecting the estimated cost of key trials was the number of outpatient follow-ups required for screening, baseline randomization, treatment, and benefit assessment The median test follow-up number of critical tests was 11 (4-17), ranging from 2 to 166 Each additional test follow-up increased the median estimate of the overall test cost by $2 million (quart distance of $1-3 million) More experimental follow-up may reflect greater treatment intensity and longer treatment or observation time Based on the Tufts Center for Drug Development and Research (Tufts CSDD) of 1,442 self-research compounds from the global top50 pharmaceutical companies between 1997 and 2007, the probability of transition from Phase III clinical trials to new drug listing/bioproduct registration (NDA/BLA) is 61.95% (Figure 6) Chart 6 The probability of the estimated phase transition and the overall success rate of clinical approval are Moore et al study new drugs approved by the FDA in 2015-2017, when based on Phase II clinically approved rare disease drugs and breakthrough therapies are not very large, it can be considered that the critical trial cost of $48 million per approved new drug (in 2020 U.S dollars) is the phase III trial cost, and then consider 61.95 percent of the transition probability of each approved new drug iii phase of the trial cost of $778 million This is well below the average cost of Phase III clinical trials at Tufts CSDD at $255 million and the median cost of $200 million (in 2013 dollars) If sustained inflation in the US dollar in 2013-2020 is taken into account, the valuation of Tufts CSDD will be higher, further widening the gap with Moore's research valuation Since Tufts CSDD is overvalued for Phase III trials, the average research and development cost of innovative drugs is likely to be too high However, we need to acknowledge the limitations of Moore et al on critical pilot cost estimates As the researchers say, these numbers are their best estimates, not their actual costs They were unable to determine all the experimental characteristics and could only use the default values in CostPro that might not be accurate Since the study focused on THE cost of CRO, the cost of hosting the trial design, monitoring or supply of the drug itself was excluded At the very least, Moore et al.'s research somehow refutes the notion that the average research and development cost of $2.6 billion for innovative drugs, which are popular with pharmaceutical companies and supported.