Comparison of the Basis for Approval and Pivotal Studies on Hematological Malignancies between the US and Japan.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5495-5495
Author(s):  
Fumitaka Nagamura ◽  
Tokiko Nagamura-Inoue ◽  
Arinobu Tojo
Keyword(s):  
Clinical Trials ◽  
Hematological Malignancies ◽  
Response Rate ◽  
Phase 1 ◽  
Regulatory Agencies ◽  
Remission Induction ◽  
Package Inserts ◽  
Number Of Patients ◽  
The Us ◽  
Efficacy Parameters

Abstract Introduction: Clinical trials are designed based on certain hypotheses and to meet the requirements for approval from regulatory agencies. We previously reported on differences in the trends of drug approvals for hematological malignancies between the US and Japan (Proc ASH #3120, 2005). This time, we report on differences in the basis for approval and designs of pivotal studies between the two countries. Methods: Drugs approved for hematological malignancies from January 1985 to December 2005 in both the US and Japan were selected. Of these candidates, only indications common to both countries were considered. Supportive care drugs, immunomodulators, biochemical modulators, and off-label use were excluded. Package inserts, reviews and analyses by regulatory agencies, and publications on clinical trials were examined. Results: Ten drugs (mitoxantrone, idarubicin, pentostatin, fludarabine, cladribine, tretinoin, rituximab, arsenic trioxide, imatinib mesylate, and gemtuzumab ozogamicin) were met the criteria. “Line or type of therapy (e.g. 1st line, or for remission induction)” was specified for all drugs in the US and three in Japan. Limitations on age, e.g., adults, were indicated in the package inserts of 5 drugs in the US and 1 in Japan. The phase of pivotal studies are summarized in Table 1. In Japan, no description on phase was seen in 2 drugs, and the result of 1 comparative study was applied. The number of patients enrolled into pivotal studies are summarized in Table 2. The number of efficacy parameters examined in each pivotal study (range, mean, and median) were 1–11, 4.7, and 3 in the US and 1–5, 2.3, and 2 in Japan, respectively. Survival was used as an efficacy parameter in 7 drugs in the US, but none in Japan (PFS: 1 drug). Differences in efficacy parameters between the two countries have decreased, and inappropriate uses of efficacy parameters, e.g., overall response rate for mitoxantrone and idarubicin, have disappeared recently in Japan. Conclusion: The high ratio of RCT and the large number of patients enrolled into clinical trials are characteristics of the US. The approved indications in Japan are broad-based, however, the description of package inserts, number of patients, and the use of efficacy parameters were inferior. The basic principle for approval of regulatory agencies in Japan had been response rate, however, the policy has become changing. So, the criticisms of Japanese clinical trials, such as poor design, insufficient information, and less utilization for approval by other countries, could be resolved. Table 1: Number of pivotal studies classified by phase # of drugs Randomized comparative trial (RCT) Single arm stdy (SA) Phase 1 study Combined data Others US 10 9 15 0 5 1 (data after cross-over) Japan 8 1 14 2 4 (foreign data) 0 Table 2: Number of patients enrolled into pivotal studies SA study (range, mean, range) RCT* (range, mean, median) *Number of patients on study arm US 31–532, 130.1, 89 40–553, 149.1, 111 Japan with foreign data 10–532, 88.9, 47.0 31: 1 study Japan without foreign data 10–74, 37.4, 38.5 31: 1 study

Trend of Drug Approval on Hematological Malignancies in the U.S. and Japan.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3120-3120
Author(s):  
Fumitaka Nagamura ◽  
Arinobu Tojo ◽  
Tokiko Nagamura-Inoue ◽  
Aikichi Iwamoto
Keyword(s):  
Clinical Trials ◽  
Hematological Malignancies ◽  
Drug Evaluation ◽  
Geographical Location ◽  
Drug Approval ◽  
New Concepts ◽  
The Us ◽  
Accelerated Approval ◽  
Outstanding Result ◽  
The U.S

Abstract Introduction: Characteristics on hematological malignancies, e.g., many of them arise from one chromosomal abnormality and there are many molecules discriminating malignancies from normal cells, have recently played very important role on the development of novel therapeutic options. Molecular-targeted therapies, such as antibodies and signal inhibitors, are good examples. On the other hand, drug evaluation and approval methods have been suffered from the difficulties in fastening approval periods and evaluating efficacies and safeties more precisely, especially in the case of these entirely new concepts of drugs. In this study, we clarified the trends of drug approval on hematological malignancies in the U.S. and Japan. By the comparison, the trends were made more clearly. Methods: Drugs for hematological malignancies, including CMPDs, which approved by December 2004 in the US or Japan were eligible. Supportive drugs, immunomodulators, biochemical modulators, and “off-label use” were excluded. Package inserts, reviews by agencies, publications on clinical trials were examined. The geographical analysis on clinical trials of oncologic drugs was based on the previous report (Proc ASCO2003; 22:534a). Results: Forty-six drugs were approved in the U.S., and 43 were in Japan. Twenty-seven drugs were approved in both countries. Twenty-two of 27 drugs were approved earlier in the U.S., and the dates of approval were considerably earlier in the U.S. (median: 46.0 Mo, mean: 54.7 Mo). These differences have not been shorten when compared in every 10-year period. Eight drugs were approved as “Accelerated Approval”, which stated in CFRs as “Subpart H”. Seven of eight “accelerated approval” drugs were approved only in the U.S. Furthermore, around one-thirds of drugs (7/19: 36.8%) approved only in the U.S. were based on “accelerated approval”. However, one drug approved as “accelerated approval” could have shown its clinical benefit in the designated clinical trial. Among the drugs approve only in the U.S., the number of drugs for “first line”, “second line or thereafter”, and “not specified” were 2, 13, 4, respectively. The geographical comparison of clinical trials was summarized in the Table below. The ratio of non-U.S. studies was considerably low in hematological malignancies. In Japan, the data on clinical trials exclusively performed in Japan was generally stated. Five drugs approved only in Japan were approved in the US for diseases other than hematological malignancies, while no drug was approved in the reverse case. Conclusion: “Accelerated approval” is useful for fastening the period until the approval, although the problem whether “surrogate markers” leads to “survival and/or QOL benefit” has not been clarified, yet. The outstanding result that most of pivotal/supportive studies were not “non-U.S.” studies may be caused by the superiority of drug development, especially in new concepts of drugs for hematological malignancies and the ability to conduct appropriate clinical trials in the U.S. On the contrary, the expansion of the indication would be the problem in the U.S. to be considered. Geographical Location of Studies U.S. only U.S. & Canada U.S. & Europe Non-U.S. Total All oncology drugs (1986.1–2002.9) 77 (43.5%) 23 (13.0%) 35 (19.8%) 42 (23.7%) 177 studies Hematological malignancies (1986.1–2004.12) 27 (62.8%) 4 (9.3%) 9 (20.9%) 3 (7.0%) 42 studies

Immune related adverse events (irAE) of mono-, combination, and sequential therapy regimens of ipilimumab (IPI), nivolumab (NIV), and pembrolizumab (PEM) for advanced melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21011-e21011
Author(s):  
Abdulaali Almutairi ◽  
Ali McBride ◽  
Srinath Sundararajan ◽  
Ivo Abraham
Keyword(s):  
Clinical Trials ◽  
Meta Analysis ◽  
Phase 1 ◽  
Random Effect ◽  
Sequential Therapy ◽  
Incidence Rates ◽  
Advanced Melanoma ◽  
Regulatory Agencies ◽  
Regulatory Documents ◽  
Grade 3

e21011 Background: The immunotherapy agents IPI, NIV, and PEM have transformed the management of advanced melanoma but are associated with irAEs. We estimated the incidence of irAEs as observed in clinical trials of mono, combination , and sequential regimens of these agents in the advanced melanoma setting. Methods: We searched the Medline, Embase, and Cochrane databases; clinicaltrials.gov; and websites of regulatory agencies in USA, Europe, Australia, and Japan for phase 1-3 trials of IPI, NIV, and PEM in advanced melanoma. Random effect meta-analysis was utilized to estimate the incidence of irAEs (expressed as % with 95%CI) for all agents in mono-, combination, and sequential regimens. Results: 56 reports (32 published articles, 7 updates, 15 results published on clinicaltrials.gov and 2 regulatory documents) of 37 trials and relating unique and independent irAE data were included in the analysis. See Table. Conclusions: IPI mono had higher incidence rates of all grade and ≥ grade 3 hypophysitis and colitis but lower rates of all grade hypothyroidism, pneumonitis, and vitiligo than NIV or PEM mono. Combination and sequential regimens had higher irAE incidence rates compared to monotherapies except for grade ≥3 hypophysitis in PEM+IPI and NIV→IPI, and grade ≥3 vitiligo as well as all grade colitis and hypophysitis in IPI →NIV. Table. Incidence rates of select irAEs expressed as % with 95%CI (‡ all grade; * ≥ grade 3). [Table: see text]

scholarly journals Disparity in Clinical Trial Opportunities for Patients with B-Cell Malignancies in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4861-4861
Author(s):  
Sikander Ailawadhi ◽  
Sri Lekha Bodepudi ◽  
Zan Tahir Shareef ◽  
Fabiola Coromoto Cardozo ◽  
Salman Ahmed ◽  
...  
Keyword(s):  
United States ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Geographical Distribution ◽  
Research Funding ◽  
Phase 1 ◽  
The United States ◽  
Phase 2 ◽  
B Cell Malignancies ◽  
The Us

Abstract Background: Clinical trials are fundamental to advance therapeutics systematically and improve patient outcomes. Despite this, enrollment on clinical trials remains dismal in the United States (US) and is a constant focus of healthcare policy. We studied distribution of clinical trials for B-cell malignancies over time across the US and unique clinical trial opportunities i.e. individual clinical trials for the given diagnosis at a site that patients may have access to participate. Methods: We abstracted data from clinicaltrials.gov for all trials that had non-Hodgkin lymphoma (NHL) or multiple myeloma (MM) as an inclusion indication between 1999-2018. Clinical trial characteristics and distribution over US geographical divisions (West, Midwest, Northeast, and South) were studied, and differences were assessed by Chi-square test. Results: A total of 1930 trials were identified (NHL: 982, MM: 948), of which 483 were recruiting at the time of data abstraction (NHL: 250, MM: 233). Over the past 2 decades, 182691 patients were enrolled on the various trials (NHL: 81592, MM: 101099). Trials by phase of study included phase 1: 629, phase 1/2: 316, phase 2: 813, phase 2/3: 11 and phase 3: 161. Number of trials by phase separated by NHL and MM are shown in Figure 1. Of these, 197 trials were randomized (NHL: 67, MM: 130). Geographical distribution of trials by diagnosis type is shown in Figure 2. A total of 31806 unique trial opportunities were noted for MM and NHL, of which 9,513 were international and 22,293 were in the US, with a geographical distribution of 5080 in West, 8198 in Midwest, 3944 in Northeast, and 5071 in South. 4,883 of the unique trial opportunities were available at NCI/NCCN accredited sites and 17,410 were at non-NCI/NCCN sites in the US. Treatment characteristics of the trials included monoclonal antibodies in 1218, other targeted agents in 2641, stem cell transplant in 526, and other agents in 517 trials with several trials utilizing more than one of these therapeutic options. There was no statistically significant difference in the distribution of clinical trials by phase of study across various US geographical regions for MM (p=0.71), NHL (p=0.98) or combined MM+NHL (p=0.16). On the other hand, unique trial opportunities were significantly different by study phase and geographical distribution for MM, NHL or MM+NHL (all p<0.001) (Figure 3). Conclusions: Widespread access to clinical trials within a cancer diagnosis is imperative for generalizability of trial results. In a comprehensive, national analysis we noted that while it may appear that clinical trials are available across the US, sites where they are open are distributed unevenly, giving rise to a disparity in access to evidence-based therapeutic advancements for patients. Disclosures Ailawadhi: Janssen: Consultancy; Amgen: Consultancy; Pharmacyclics: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Sher:Affimed: Research Funding.

Asian representation in clinical trials of new drugs for the treatment of cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6564-6564 ◽  
Author(s):  
Lola A. Fashoyin-Aje ◽  
Laura L. Fernandes ◽  
Steven Lemery ◽  
Patricia Keegan ◽  
Rajeshwari Sridhara ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Far East ◽  
Mainland China ◽  
Asian Population ◽  
The Philippines ◽  
New Drugs ◽  
Asian Patients ◽  
Number Of Patients ◽  
The Us ◽  
Demographic Subgroup

6564 Background: In the US, statistics for Asians are often aggregated with other racial groups. This poses challenges in estimating the cancer burden and in defining cancer clinical trial enrollment targets in this demographic subgroup. ‘Asian‘ refers to persons with origins in the Far East, Southeast Asia, or the Indian sub-continent. Asians comprise 6% of the US population and the largest Asian subgroups in the US are of Chinese (22%), Filipino (19%), Asian Indian (19%), Vietnamese (10%), Korean (9%), and Japanese (7%) descent. The representation of Asian patients in global clinical trials may not be reflective of the Asian subgroups in the US. FDA conducted an analysis to describe patients categorized as ‘Asian’ in clinical trials supporting the approval of new drugs. Methods: We reviewed the marketing applications of 33 new molecular entities approved for the treatment of solid tumor malignancies between 2011- 2016 to identify trials that provided the primary evidence of safety and efficacy. Results: A total of 29,941 patients were enrolled; 17 % were Asian. Most Asian patients were enrolled in Korea (20%), Taiwan (20%), mainland China (20%), Japan (16%), and US (5%). Few patients were enrolled in India (3%); the Philippines (1%); Vietnam (0). In the US, Asian patients comprised 3% of the total number of patients enrolled. Conclusions: Asian patients represented a heterogeneous mix. A large proportion was enrolled in Taiwan (20%) and Korea (20%), whereas the largest proportion of US Asians have origins in mainland China (22%), the Philippines (19%), India (19%), and Vietnam (10%). Nevertheless, although Asians share a common ancestry, it is not clear whether data from global clinical trials are generalizable to Asian patients in the US. Therefore, strategies to improve the enrollment of US Asian patients in clinical trials are needed. Among patients enrolled in the US, 3% were Asians, a proportion that is below US Asian population estimates (6%). While most site-specific cancer incidence and death rates are lower in US Asians compared to Whites, the rates of some cancers (e. g., stomach and liver) are higher in this group. Therefore, studies are needed to determine adequate enrollment targets in this demographic subgroup.

Hematopoietic Stem Cell Transplantation Phase III Clinical Trials for Patients with Hematological Malignancies in the US: Lessons To Be Learned from the European Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 229-229
Author(s):  
Sejal S. Kuthiala ◽  
Gary H. Lyman ◽  
Oscar F. Ballester
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematological Malignancies ◽  
Care Delivery ◽  
Physician Attitudes ◽  
Phase Iii ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
The Us

Introduction: Evidence-based medicine defines standard therapies primarily from Phase III randomized controlled trials (RCT), when available. In this report we examined trends in ther number and characteristics of phase III RCT addressing the management of adult patients with hematological malignancies, comparing the patterns of activity in the US and Europe. Materials and Methods: We attempted to identify all phase III RCT published in the English medical literature from 1/1992 to 12/2003. A systematic search of Medline and published references was conducted using multiple keywords for each malignancy as well as for hematopoeitic stem cell transplant (HSCT). We cross-referenced the data by searching individual journals, as well as the ASH education books from 1998–2003. Studies published in abstract form only were not included. Results: We identified 306 published RCT that accrued a total of 4899 patients. Eighty-three of these studies included HSCT with a total accrual of 2081 patients. Country of origin included: US (n= 25), Europe (n=54), other (n=4). Four European countries (France, Italy, Germany and UK: FIGU) with a combined population similar to that of the US produced 32 studies. This figure for FIGU does not include their contributions to 12 separate European cooperative trials. There were no significant trends in the number of trials published per year during the study period. However, significant differences emerged when the focus of the studies and the accrual numbers were analyzed. RCTs comparing HSCT to standard dose therapy represented 34.9% of the 83 trials and 59.4% of FIGU trials, but only 4% (1 out of 25) of US studies (p <.001). US trials accrued a mean of 110.2 patients per study, as compared to 205.3 in other countries and 222.6 in FIGU studies (p= .006). In multivariate analysis, only focus of study was independently related to greater study size (p<.001). Among the remaining 223 trials not involving HSCT (US produced 68 and FIGU 77), a significant trend for increasing numbers of trials published per year during the study period was documented (p=.015). No significant differences in the mean number of patients accrued per trial (US= 279.5, other countries= 302.8 and FIGU= 347.8), or in the focus of the studies were observed in univariate or multivariate analysis. Conclusions: While there has been an increase in the number of Phase III RTCs in patients with hematological malignancies published during 1992–2003, the activity for HSCT trials has remained stationary. US HSCT trials have focused on issues other than the comparison of HSCT to standard therapies, such as graft manipulation, growth factors and graft versus host disease. US HSCT have accrued significantly fewer patients per study. The reasons for these differences are not apparent from our data, and may include patient and/or physician attitudes/biases toward phase III trials, issues of financial coverage for the HSCT procedure and/or health care delivery policies. There is a serious paucity of US trials defining the role of HSCT in the management of hematological malignancies.

scholarly journals The NIMH-MATRICS project for developing cognition-enhancing agents for schizophrenia

2006 ◽  
Vol 8 (1) ◽  
pp. 109-113 ◽  
Keyword(s):  
Mental Health ◽  
Clinical Trials ◽  
Drug Development ◽  
Trial Design ◽  
Molecular Target ◽  
Regulatory Agencies ◽  
Consensus Building ◽  
Pharmacological Agents ◽  
Building Process ◽  
The Us

The US National Institute of Mental Health supported an initiative to facilitate the development of pharmacological agents for enhancing neurocognition in patients with schizophrenia. This has been accomplished through a consensus-building process that has included representatives from academia, the pharmaceutical industry, and government. The group has addressed obstacles to drug development that include (i) the lack of a well-accepted instrument for measuring neurocognition in clinical trials; (ii) the lack of a consensus on the best molecular target or targets for drug development; (iii) the lack of a consensus regarding the optimal trial design for either comedication that improves cognition when added to an antipsychotic or a broad spectrum agent that improves cognition and treats psychosis; and (iv) the approaches of regulatory agencies such as the US Food and Drug Administration to approving and labeling a new agent.

scholarly journals Variation in the estimated costs of pivotal clinical benefit trials supporting the US approval of new therapeutic agents, 2015–2017: a cross-sectional study

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e038863 ◽  
Author(s):  
Thomas J Moore ◽  
James Heyward ◽  
Gerard Anderson ◽  
G Caleb Alexander
Keyword(s):  
Clinical Trials ◽  
Software Tool ◽  
Cross Sectional Study ◽  
Therapeutic Agents ◽  
Secondary Outcome ◽  
Sectional Study ◽  
Cross Sectional ◽  
Number Of Patients ◽  
The Us ◽  
Clinic Visits

ObjectivesLittle is routinely disclosed about the costs of the pivotal clinical trials that provide the key scientific evidence of the treatment benefits of new therapeutic agents. We expand our earlier research to examine why the estimated costs may vary 100-fold.DesignA cross-sectional study of the estimated costs of the pivotal clinical trials supporting the approval of 101 new therapeutic agents approved by the US Food and Drug Administration from 2015 to 2017.MethodsWe licensed a software tool used by the pharmaceutical industry to estimate the likely costs of clinical trials to be conducted by contract research organisations. For each trial we collected 52 study characteristics. Linear regression was used to assess the most important factors affecting costs.Primary and secondary outcome measuresThe mean and 95% CI of 225 pivotal clinical trials using varying assumptions. We also assessed median estimated costs per patient, per clinic visit and per drug.ResultsMeasured as pivotal trials cost per approved drug, the 101 new molecular entities had an estimated median cost of US$48 million (IQR US$20 million–US$102 million). The 225 individual clinical trials had a median estimate of US$19 million (IQR US$12 million–US$33 million) per trial and US$41 413 (IQR, US$29 894–US$75 047) per patient. The largest single factor driving cost was the number of patients required to establish the treatment effects and varied from 4 patients to 8442. Next was the number of trial clinic visits, which ranged from 2 to 166. Our statistical model showed trial costs rose exponentially with these two variables (R2=0.696, F=257.9, p<0.01).ConclusionsThe estimated costs are modest for measuring the benefits of new therapeutic agents but rise exponentially as more patients and clinic visits are required to establish a drug effect.

scholarly journals Proportion of Patients with FLT3 Positive AML Required to Enroll on Clinical Trials to Satisfy the Recruitment Needs of FLT3 Inhibitor Trials: Are We Running out of Patients?

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 713-713
Author(s):  
Taylor Bucy ◽  
John Zoscak ◽  
Motomi Mori ◽  
Vinayak Prasad ◽  
Uma Borate
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Cooperative Group ◽  
Participation Rates ◽  
Therapeutic Trials ◽  
Fda Approval ◽  
Number Of Patients ◽  
The Us ◽  
Flt3 Mutations ◽  
Flt3 Inhibitors

Abstract Introduction. The push for personalized medicine in oncology has generated an influx of therapies targeting similar pathways, despite only 5% of clinically tested agents receiving FDA approval (Mattina 2017). Acute myeloid leukemia (AML) is a malignancy where identification of prognostically significant mutations suggests growing potential for therapeutic inhibition. FMS-like tyrosine kinase 3 (FLT3) mutations are deemed one of few "actionable" mutations and include 30% of de novo AML cases (25% ITD, 5% TKD) (Garcia 2017; Fathi 2016). In 2017 there will be approximately 21000 new AML cases, roughly 6000 of these patients will be FLT3+ (ACS 2017). In line with prior research in melanoma elucidating the growing number of trials aimed at personalized medicine, we sought to identify the total number of therapeutic trials studying FLT3 inhibitors (Tang 2018). We analyzed the total number of FLT3+ patients required for recruitment to these trials to ensure successful completion compared to incidence of this molecular abnormality within the AML patient population. Methods.A systematic review of therapeutic clinical trials focusing on adult FLT3+ AML from 2000-2017 was conducted using the PRISMA 2009 guidelines (Figure 1). We identified 78 therapeutic trials of FLT3 targeted therapies by cross-referencing ClinicalTrials.gov (66) and PubMed publications (12). Assuming constant accrual rate over the duration of each trial and constant rate of FLT3 mutations at 30% since 2000, statistical analysis was performed using the study start dates and primary completion dates of all trials from ClinicalTrials.gov. Incidence data was collected from the CDC, SEER database, and literature review (De Kouchkovsky 2016; ASCO 2018). Projections of discrepancies between anticipated clinical trial enrollment were provided using consistently cited rates of adult participation of 1%, 3% and 5% versus participant enrollment needed to satisfy current projected trends (Rinde 2018; Unger 2016). Results. Twenty-four therapeutic FLT3 inhibitors being investigated were identified in 78 distinct clinical trials. Pharmaceutical versus cooperative group support was 2.23:1, with 29 different pharmaceutical sponsors and 13 cooperative group/non-profit/academic sponsors(Table 1). Thirty-eight (48.7%) trials/publications accrued in the US only, 21 (26.9%) at international sites only, 15 (19.2%) accrued in both the US and internationally, and 4 (5.1%) had no location listed at time of search. Only one study (NCT03258931) proposed a head-to-head comparison of midostaurin versus crenolanib. The number of patients needed to satisfy enrollment began to surpass the upper bound of estimated participation in 2010, dropping slightly from 2013-2014 and noticeably surpassing projected participation rates from 2015-2016 (Figures 2 & 3). In 2017, approximately 21380 patients were diagnosed with AML, roughly 6414 were FLT3 positive. Assuming 5% participation rate, 320.7 FLT3 positive patients would be expected to enroll in clinical trials. However, the total number of patients needed to satisfy enrollment in 2017 was 1235; after excluding international and completed trials, the total number needed is 844.49 patients. Based on statistical analyses, we estimate that 13.2% of all US patients with FLT3 pos AML would have to enroll to satisfy eligibility in 2017; roughly 3 times the upper level of historical clinical trial participation rates in the US. Conclusions. The current clinical trial process investigating targeted therapies in AML requires an unusually high and unsustainable enrollment, given the discrepancy between the incidence of AML patients with targetable mutations and the number of pharmaceutical agents being studied for these small patient populations. This discrepancy becomes even more startling when considering barriers to enrollment, including insurance market restrictions, geographical, socioeconomic, and demographic factors. Most of these trials do not compare available agents to identify the drug that may provide the most patient benefit. Whether this method of finding new therapies eventually leading to FDA approval continues to be sustainable or whether such duplicative trials dilute the valuable resource of AML patients with rare, targetable mutations, thus impeding development of the most effective therapeutic agents, must considered by the research and regulatory community. Disclosures Borate: Novartis: Consultancy; Agios: Consultancy.

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