how much does a clinical trial cost per patient

Guidance for Industry: Using a Centralized IRB Review Process in Multicenter Clinical Trials. Similar requirements are being considered for obesity drugs in the United States (Pollack, 2012). The average cost to recruit a new patient if one is lost due to non-compliance is $19,533. By contrast, a 100 percent in this field indicates that 100 percent SDV was used in every contract in the dataset for that phase and therapeutic area. Therefore, one important effect of this approach is shortened enrollment timelines. Seeking to avoid negative outcomes of rigorous site inspection audits (which could threaten drug approval), sponsors have voluntarily borne the extremely high costs of 100 percent SDV by on-site monitors in multicenter trials (Kramer, Smith, & Califf, 2012). For example, if there were two Phase 2 trials, and one took 1.5 years, while the other took 2 years, the total length of Phase 2 would be 2 years, assuming the trials were completed at the same time. In Phase 4, largest savings could be realized for respiratory system ($0.5 million) and oncology ($0.4 million) studies. Furthermore, simplified trial protocols might make trial participation less burdensome and exhausting to patients, thereby making it easier and perhaps cheaper to recruit and retain patients. The model also allows for a blend of default and custom values as may be desired by the user. In order to select a set of barriers/alternatives to analyze, the working group considered whether each proposed strategy could be alleviated by policies, whether the appropriate policies could be implemented or encouraged by FDA, and whether there was evidence in the literature that could be used to quantify the potential impacts of those policies on clinical trial costs. This estimate includes patient out-of-pocket costs of $16.22 billion and patient time costs of $4.87 billion. Medicare will cover 80% of the cost of the drug after patients meet their deductible . Retrieved November 7, 2012, from Tufts Center for the Study of Drug Development: http://csdd.tufts.edu/files/uploads/nov-dec_2012_ir_summary.pdf, U.S. Bureau of Labor Statistics. If there is any uncertainty about FDAs acceptance of your clinical trial data, are there reasons why you do not seek FDA review before a specific trial? Patient care costs are those costs related to treating your cancer, whether you are in a trial or receiving standard treatment. Nearly all of the company representatives and experts interviewed commented on what they perceived as a particularly risk-averse regulatory climate of recent years. Hay, M., Rosenthal, J., Thomas, D., & Craighead, J. Most U.S. health systems and clinical practice sites do not include research as part of their mission (Kramer, Smith, & Califf, 2012); thus, there are fewer physician referrals of patients to clinical research studies and fewer investigators available to conduct the research than there might be otherwise. For example, if the user indicates that there would be two Phase 1 trials, the user would see two pages of data to enter for Phase 1. For example, while HHS lowered the monetary threshold at which significant financial interests require disclosure from $10,000 to $5,000 in 2011(National Institutes of Health, 2011), FDAs reporting threshold is $25,000 (U.S. Food and Drug Administration, 2011b). Estimated Costs of Pivotal Trials for Therapeutic Agents Approved by FDA provides guidance to developers about what constitutes acceptable clinical trials and appropriate outcomes. Sponsors are required to educate clinical trial participants as to the purpose of the study, its duration, necessary procedures, potential risks and benefits, and their rights before they can enter the trial. Although experts debate the accuracy of various cost estimates, there is widespread agreement that clinical trial costs are substantial and rising. (2003), the Number of Site Management Months from Medidata, and the Number of Project Management Months from Medidata. Practically speaking, conducting trials at multiple sites across different countries magnifies the barriers associated with multicenter trials, including lack of harmonization among regulations across multiple jurisdictions and difficulties in enforcing consistency in protocol across multiple trial sites. Adding the lengths of time associated with each trial within a phase was somewhat more complex, as there are a range of possibilities. Given the size of the patient population and average wholesale price for similar drugs, the net revenue stream for the NME, if it is approved, is estimated at $973 million over 15 years. Apart from issues of mission and training, there exist some disincentives for clinicians to participate in research. Table 2 presents clinical trial costs by cost component across all therapeutic areas by trial phase. Appendix B provides the Medidata data elements and their descriptions. They are also looking for ways to move more rapidly to electronic data capture (EDC). Patient Privacy: U.S. Health Insurance Portability and Accountability Act (HIPAA) (45 CFR Part 160 and Subparts A and E of Part 164) HIPAA requires patient authorization to use their health information for research. (2011, October). Toward the end of the NDA review stage, FDA and the drug sponsor meet with an advisory committee made of experts to present data and solicit advice on drug safety, effectiveness, and labeling. In Phase 4, Administrative Staff Costs ($3.3 million) rank the highest, followed by Site Retention Costs ($1.8 million), and Clinical Procedure Costs ($1.7 million). Upon launching the operational model in Microsoft Excel, the user is automatically taken to the first page of the user form, which prompts the user to indicate whether he intends to examine the impacts of mitigating barriers to clinical trials, or go directly to the examination of clinical trial costs (see Figure C - 1). Tardiff, B. Bailey, W., Cruickshank, C., & Sharma, N. (n.d.). Agency for Healthcare Research and Quality. As you think about taking part in a clinical trial, you will face the issue of how to cover the costs of care. . The purpose of a clinical trial is to find a new and improved way to treat, prevent, or diagnose different types of illness. In Phases 2 and 3, the savings for pain and anesthesia studies, however, could be as high as $0.2 million and $0.4 million per study representing around 1 percent of study costs, respectively. If so, how many countries are typically involved? How To Manage And Reduce The Clinical Trial Cost Per Patient 11 The number of contracts by therapeutic area and trial phase cannot be publicly reported because they are confidential and proprietary. Sensible approaches for reducing clinical trial costs. Clinical trial cost per patient by therapeutic class 2015-2017 - Statista A 2010 study published in the Drug Information Journal found that sponsors could save up to 23.5 percent on Phase 3 oncology study costs by cutting SDV to 50 percent and reducing monitoring frequency accordingly from 6- to 10-week periods (Tantsyura, et al., 2010). Moreover, important issues flagged by one IRB may not ever be communicated to the other IRBs (Kramer, Smith, & Califf, 2012). If the attrition rate is reduced by 50 percent (to 12.5 percent), sponsors only need to enroll 1,714 patients to end up with the same number of patients (1,500) for the trial. According to a Tufts Center for the Study of Drug Development (CSDD) study, nearly 60 percent of all trial protocols require amendments, a third of which are avoidable. In particular, oncology research may be subject to the requirements and guidance of not only FDA, but also the Office for Human Research Protections (OHRP), the National Institutes of Health (NIH), and the Office for Civil Rights (OCR), depending on the study (U.S. Food and Drug Administration, 2012). A CRO representative interviewed provided examples: for instance, a protocol could require that magnetic resonance imaging (MRI) and a series of neurocognitive tests be performed within three days of each other at a site that does not have sufficient access to an MRI machine; or, a protocol might require a series of labs that are highly specialized and cannot be done by the site in house. For example, many sponsors are interested in pursuing anti-inflammatory drugs because the road to regulatory approval is clear and well-established for these drugs. Payment and Reimbursement to Research Subjects | FDA The development and engineering costs comprise approximately $2-5 million of this total. Legal advisors have traditionally encouraged sponsors to be nonselective in their reporting of unexpected SAEs to avoid any suspicion among regulators that they were withholding information (at least prior to March 2011, when a new drug safety reporting regulation was implemented) (Kramer, Smith, & Califf, 2012). On the other hand, for smaller markets, recruitment might be hindered by the simple fact that patients are few and far between. In addition to patient recruitment, difficulty finding investigators and sites was one of the issues most frequently raised by industry representatives in discussions with ERG. In Phase 3, the testing will be expanded to 4,000 patients. Average biopharmaceutical clinical trial per patient costs U - Statista Table 6 presents the expected cost savings from implementation of simplified clinical trial protocols and reduced amendments. Thus, we were able to use a similar method to that described above for extrapolating missing values to derive amendment counts by phase and therapeutic area; therapeutic areaspecific factors were calculated and then multiplied by the phase-specific amendment counts, allowing us to fully populate a new field called umber of IRB Amendments (per study). For therapeutic areas for which there was no counterpart in Getz, et al. Another significant barrier to conducting clinical trials in the United States is competition from sites in other countries; indeed, the clinical research footprint is shifting overseas. Finally, companies may solicit input from key opinion leaders (KOLs) on protocol design, and, while KOLs are practitioners and experts in their disease areas, they may be less well versed in study design and the specific data points that are needed for FDA approval. [Note: Probe about a recent clinical trial experience for more specifics.]. (2011), we used the counts for the Other category. According to a recent study conducted by Tufts CSDD, 22.3 percent of all procedures are considered to be non-core and can be considered extraneous (Tufts CSDD, 2012). Conservatively assuming that there would be no impacts on Phase 1 and Phase 4 trials, in which SDV is less critical, we calculated the percentage reductions in SDV Cost (per data field) by phase and therapeutic area for Phases 2 and 3. The first step in estimating the impact of this alternative is quantifying the effect on costs of a movement away from 100 percent SDV in an average clinical trial. The $777 million can then be used to do the same calculation for the chance node at Phase 3, and so forth until the value at the first chance node can be calculated. (2012c). Learn about the different types of costs related to taking part in a clinical trial, and who is expected to pay for which costs. Once approved, the drug may be marketed in the U.S. with FDAregulated labeling (Lipsky & Sharp, 2001). However, simply moving excessively long and complicated forms from paper to a tablet screen will not address the need to fundamentally streamline the informed consent process and improve both efficiency and understanding (U.S. Food and Drug Administration, 2012). CRN reports that theseservices can reduce projected enrollment times from approximately 12 months to 3 months, a reduction of 67 percent (Shapiro, 2008). Table 8 presents the costs savings estimates for this barrier mitigation strategy. Figure 1: New Molecular Entity (NME) and New Biologic Entity (NBE) Filings and Approvals. Research costs are those related to taking part in the trial. One issue that was frequently mentioned was the perceived concentration of too much responsibility and power in the hands of individual reviewers. In addition, clinical trial recruitment costs per patient can also be high, making it difficult for companies to find willing participants. Some Phase 2 studies are similar to subsequent Phase 3 studies. Next, we scheduled interviews with those who responded and were willing to participate. Medidata Solutions. Figure 5 presents an overview of the different types of costs constituting each phase and their magnitudes. We are grateful to all of them for sharing their expertise and experiences with us. However, there are also a number of barriers that drug sponsors voluntarily impose upon themselves, adding further cost and delay to the process unnecessarily. When asked about protocol amendments, many representatives from smaller drug companies indicated that they regarded them as just a cost of doing business or a necessary evil that comes with the territory. Large companies, by contrast, seemed to have done more internal analysis of their own protocol amendment costs and set goals to lessen their frequency. The authors propose that developers of treatments for neglected diseases receive a priority review voucher to incentivize production of these therapies. The estimated cost per patient was US$41 413 (IQR US$29 894-US$75 047), and each patient visit to the study clinic cost an estimated median of US$3685 (IQR US$2640-US$5498). PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2013 Through 2017. B. Figure 3: Clinical Trial Costs (in $ Millions) by Phase and Therapeutic Area. Both physicians and their patients are often unaware of clinical trial options, and often times it is only patients of higher socioeconomic status who have the resources, knowledge, and motivation to seek information about a disease, including clinical trials (English, Lebovitz, & Giffin, 2010). There is only a 41 percent likelihood that the drug will prove successful in treating Indication X. For instance, long trials mean large human labor costs, as investigators and staff must be compensated for many hours. The ranges for the number of trials for each phase were decided upon based on discussions with the U.S. Department of Health and Human Services (HHS) and the U.S. Food and Drug Administration (FDA) (we asked FDA for an estimate of the number of trials used to support efficacy for NME NDAs and were provided with a range of roughly one to nine trials for Phases 2 and 3). The Phase 2 savings are estimated at 16.7 percent. Possible areas of ambiguity or excess burden related to the safety reporting regulations themselves are discussed in Section 4.5. To illustrate our approach to modeling clinical trial decision-making, we consider a highly simplified example adapted from Damodaran (2007)the analysis of a New Molecular Entity (NME) for treating a hypothetical Indication X that has gone through preclinical testing and is about to enter Phase 1 clinical trials. Certain filed submissions are within their 60-day filing review period and may not be filed upon completion of the review. In response to these measures, drug sponsors might choose to devote more of their clinical research budgets to trials that compare their drug to a competitor drug, as opposed to trials that compare their drug to a placebo. By contrast, only half of academic/government/cooperative organizations reported always doing so (Morrison, et al., 2011). Guidance for Industry Oversight of Clinical Investigations A Risk-Based Approach to Monitoring. Brooks, C. (2012). Institute of Medicine of the National Academies, Forum on Drug Discovery, Development, and Translation. Which of these government actions you enumerated above would have the greatest impact/potential to promote more clinical research in the short term? http://www.actmagazine.com/appliedclinicaltrials/article/articleDetail.j http://www.appliedclinicaltrialsonline.com/appliedclinicaltrials/article http://license.icopyright.net/user/viewFreeUse.act?fuid=MTY0NDY1NDE%3D. Methods Representatives of ten CTUs and two grant-awarding bodies pooled their experiences in discussions over 1.5 years. (2012b, July 24). Additionally, more guidance is provided to help sponsors evaluate causality for adverse events and what types of reactions need to be reported. (2012a, March 25). The number of trials conducted in a given phase for the drug. The average cost of phase 1, 2, and 3 clinical trials across therapeutic areas is around $4, 13, and 20 million respectively. Office of the Assistant Secretary for Planning and Evaluation, Submitted to:Hui-Hsing WongAmber JessupU.S. Patient recruitment difficulties are caused by a number of factors, some of which are fairly universal across clinical trials, while others arise due to characteristics of a particular disease or trial. DiMasi, J., Hansen, R., & Grabowski, H. (2003). Want to use this content on your website or other digital platform? This means that your hourly/clinic rate is around $ 66.00 - in other words, this should be the minimum charged per hour in . Longer studies are needed to see if any safety issues arise when drugs are taken long-term to manage chronic diseases. The problem is a multi-faceted one that also serves to reinforce many of the barriers discussed in other sections, such as shortages of investigators and patients, high costs, and lengthy timelines. Correspondence: Experience and further development with the Voluntary Harmonization Procedure for multinational clinical trials in the European Union. The resulting discount rate is an average company cost-of-capital (DiMasi, Hansen, & Grabowski, 2003). Retrieved March 21, 2012, from http://www.fda.gov/downloads/Drugs//Guidances/UCM269919.pdf, U.S. Food and Drug Administration. Pharmaceutical companies conduct clinical trials for many reasons. Multiple trials within a phase might be required to test different dosages, for example. From the table, immunomodulation per-study costs ($6.6 million) are the highest in Phase 1 with costs of studies in ophthalmology ($5.3 million) and respiratory system ($5.2 million) ranking second and third, respectively. In some cases, the site may negotiate overhead only on certain portions of the contract such as clinical procedures. In general, adaptive designs suffer from this criticism. The most obvious goal of clinical trials is to demonstrate safety and efficacy to gain Food and Drug Administration (FDA) approval. Wider use of mobile technologies can result in very similar maximum savings; $0.4 million (8 percent) in Phase 1, $2.4 million (12 percent) in Phase 2, $6.1 million (12 percent) in Phase 3, and $6.7 million (13 percent) in Phase 4. (2012). As a result, sponsors compete with each other for these top investigators, creating the impression that there is a shortage even though less well-qualified investigators might be available. Clinical research centers are also more closely scrutinizing the types of clinical trials they will take on, with the fear that certain projects could put the center in a deficit (Collier, 2009). [a] The numbers in parentheses represent the rank in descending order. This total is comprised of the following direct costs associated with implementation of an amendment: increased study grants/site fees ($265,281); contract change orders to existing contracts ($109,523); new contracts with providers ($69,444); additional drug supply ($5,300); and IRB fees ($4,384). This document establishes fee rates for fiscal year (FY) 2013 for application fees for an application requiring clinical data ($1,958,800), for establishment fees ($526,500), and for product fees ($98,380). Figure C - 6 shows the results screen of the clinical trials model developed. If yes, to what extent have the FDA-initiated protocol amendments troublesome or expensive to accommodate compared to self-initiated ones? A final oft-repeated refrain among industry representatives is the lack of consistency among reviewers and divisions within FDAs Center for Drug Evaluation and Research (CDER). DiMasi, J. (2009). One respondent said the ideal scenario would be for sponsors to conduct large, simple trials that make use of information that already exists in patients electronic health records (EHR) rather than collecting lots of redundant data themselves. 1 The number represents applications for New Molecular Entities (NMEs) filed under New Drug Applications (NDAs) and therapeutic biologics filed under original Biologic License Applications (BLAs). There are a number of factors, including cost savings and shorter timelines, driving this shift and making it cheaper and easier to conduct trials outside the U.S. Table 1 presents the total costs for each of the therapeutic areas included in our model by clinical trial phase (assuming one trial per phase and not inclusive of failures). Site overhead charged on contracts by the site estimated at 25 percent of total per-study costs, Advertising costs associated with recruitment of patients at the per-patient level, Amount paid to the patient for study participation, which might include financial compensation, reimbursement for travel, meals, etc. Modernizing the Regulation of Clinical Trials and Approaches to Good Clinical Practice. A case report form (CRF) is a tool used by investigators to collect data for each participant throughout the trial. Further, the model assumes that all costs associated with each phase are incurred at the start of the phase; therefore, Phase 1 costs are not discounted, Phase 2 costs are discounted over the length of Phase 1, Phase 3 costs are discounted over the combined lengths of Phases 1 and 2, and so forth. Washington, D.C.: The National Academies Press. In incorporating the 2001 EU Clinical Trials Directive into national laws and regulations, divergent practices emerged across member states with regard to application dates, timelines for review of clinical trial applications, content/format/language requirements, distribution of responsibilities between authorities and ethics committees, and workload among authorities (Clinical Trials Facilitation Groups (CTFG), 2010). Cutting Edge Information. Regulations Governing Serious Adverse Events (SAEs) Reporting for Investigational New Drugs and Biologics (INDs) (21 CFR 312) In the past, FDA and investigators in multicenter trials have been flooded with expedited reports of serious adverse events which lack sufficient context from the aggregate data to be interpretable. Awareness of deceptive, exploitative, and racist past practices in experiments, such as the Tuskegee syphilis study, continues to fuel this distrust, particularly among some minorities and cultures within the United States (Weisfeld, English, & Claiborne, 2011; Shavers, Lynch, & Burmeister, 2000). Depending on how EHR is used, it may also contribute to lower data collection costs, but these effects are also yet unquantifiable. The NDA submission decision will take one year. There is more widespread agreement that there is a shortage of investigators who can enroll high-quality patients. Onethird of all amendments are related to protocol description and patient eligibility criteria; other change categories include dosage/administration, statistical methods, and trial objectives. Clinical Research Regulation For India | ClinRegs Aside from the uncertainties involved, participating in clinical research may simply be inconvenient or overly burdensome to patients. In the course of clinical investigations conducted under investigational new drug (IND) applications, information regarding adverse events must be communicated among investigators, sponsors, IRBs, and FDA in safety reports. The aging of a larger segment of the population has resulted in a shift to chronic and degenerative disease research and an ensuing increase in development costs. GlaxoSmithKline. (1996, April). Systematic review on costs and resource use of randomized - PubMed There is competition for limited patient pools for certain conditions, such as rare cancers and multiple sclerosis. Therefore, holding everything constant, these options may be less appealing as strategies to stimulate drug development than alternatives which substantially lower costs, especially early on in the clinical research process (i.e., in earlier phases). Global Clinical Trials Activity in the Details. In addition, there has been a shift in the biopharmaceutical industry toward chronic and degenerative disease research, which, given the aging of a large segment of the population, has the potential to secure steady and sizeable revenue streams for companies who can capture a share of these markets (Collier, 2009; DiMasi, Hansen, & Grabowski, 2003). Participants who were unemployed earned the most income from clinical trials compared to . Do you feel that, as a (small/large) firm, you face a different set of barriers compared to (larger/smaller) firms? Eighty-two percent of pharmaceutical industry sponsors reported always verifying CRF data against source data. As enrollment rate is not a parameter in our cost model, we translate this increase in enrollment rates number to a 27.1 percent decrease in recruitment costs per patient. Analysis of that companys own protocol amendments found that roughly half could be categorized as avoidable and the other half as unavoidable. Another large company representative estimated the cost per amendment to be $500,000 to $1 million (including implementation costs), depending on what is involved, as some changes require costly new training or equipment, or add a whole new arm to the study and are therefore more expensive.
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