Human Clinical Trials and Drug Approvals

2015 ◽  
pp. 37-49
Author(s):  
Ben Haas ◽  
Shira N. Epstien
Keyword(s):  
Clinical Trials ◽  
Drug Approvals

scholarly journals Disparity of Race Reporting and Representation in Clinical Trials Leading to Cancer Drug Approvals From 2008 to 2018

JAMA Oncology ◽  
2019 ◽  
Vol 5 (10) ◽  
pp. e191870 ◽  
Author(s):  
Jonathan M. Loree ◽  
Seerat Anand ◽  
Arvind Dasari ◽  
Joseph M. Unger ◽  
Anirudh Gothwal ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Drug ◽  
Drug Approvals

New Drug Approvals by FDA: An Update

2018 ◽  
pp. 1-6
Keyword(s):  
Clinical Trials ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
New Products ◽  
New Therapies ◽  
New Drug ◽  
Arduous Task ◽  
Drug Approvals ◽  
Preclinical Safety

Bringing a drug into the market is an arduous task, and involved testing from preclinical safety to clinical trials. With its understanding of the science used to create new products, testing and manufacturing procedures, and the diseases and conditions that new products are designed to treat, FDA (U.S. Food and Drug Administration) provides scientific and regulatory advice needed to bring new therapies to market. This article provides an overview of the steps involved during development of a drug and its launch into the market.

scholarly journals Level of Evidence for FDA Drug Approvals in Pivotal Clinical Trials of Hematological Malignancies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Samer Al Hadidi ◽  
Carlos A. Ramos
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
Hematological Malignancies ◽  
Phase Iii ◽  
Clinical Activity ◽  
Level Of Evidence ◽  
Phase Iii Clinical Trials ◽  
Early Phase Trials ◽  
Phase Iii Trials ◽  
Drug Approvals

BACKGROUND Clinical trials are integral to improve treatment outcomes for patients with hematological malignancies. Although early phase (I/II) clinical trials may provide evidence of clinical efficacy, the main goal for early phase trials is to assess safety signal. Results of phase III clinical trials provide the strongest evidence to support the use of new cancer medications. The Food and Drug Administration (FDA) is responsible to ensure appropriate control and supervision of pharmaceutical drugs. METHODS On the basis of publicly available study protocols and FDA reviews, the authors reviewed the level of evidence in 52 clinical trials supporting 49 drug approvals from 2016 to 2020. Data cut point was May 2020. These trials resulted in approval of medications to treat leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, myelodysplastic syndrome, myeloproliferative neoplasms and multiple myeloma. RESULTS A total of 52 clinical trials were assessed in the 5 years period. Phase III trials supported 61.5% while earlier phase trials supported 36.5% of subsequent FDA hematological malignancies approvals. The level of evidence to support FDA approvals improved with time with 50% of approvals in 2016 and 2017 supported by phase III clinical trials compared to 69% in 2019. Approvals were based on early phase trials in mantle cell lymphoma (100%), chronic myeloid leukemia (100%), diffuse large B cell lymphoma (100%), classic Hodgkin's lymphoma (67%) and acute myeloid leukemia (56%). Phase III trials enrolled 87% of the patients (14238 from16429 patients). Eighteen drug approvals (37% of all approvals) were based on 13% of the total number of patients in the studied period. CONCLUSIONS Level of evidence to support drug approvals in hematological malignancies was based on early phase trials in more than a third of the times. Although early phase studies are appropriate for safety signals, further clinical activity assessment should be done to support the use of new drugs to treat hematological malignancies. Previous successful early phase studies failed to show clinical activity in phase III studies. Despite the fact that use of new approved drugs based on early phase studies evidence may be needed, patients and healthcare providers should be aware of such possibility when using newly approved medications. Figure Disclosures Ramos: Novartis: Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Kuur Therapeutics: Research Funding.

The impact of NCI-sponsored network group clinical trials on guideline care and new drug indications.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6604-6604
Author(s):  
Joseph M. Unger ◽  
Van T. Nghiem ◽  
Dawn L. Hershman ◽  
Riha Vaidya ◽  
Michael Leo LeBlanc ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Guidelines ◽  
Research Network ◽  
Phase Iii ◽  
Cancer Clinical Trials ◽  
New Drug ◽  
Public Data ◽  
Drug Approvals ◽  
The Impact

6604 Background: National Cancer Institute Clinical Trial Network (NCTN) groups serve a vital role in identifying new antineoplastic regimens. However, the clinical impact of their trials has not been systematically examined. We analyzed the influence of network group cancer clinical trials on clinical guidelines and new drug approvals. Methods: We evaluated Phase III cancer clinical trials which the SWOG Cancer Research Network coordinated or participated in (1980-2017). Included trials were completed and its results published. A documented practice influential (DPI) trial was one with verified influence on National Comprehensive Cancer Network (NCCN) clinical guidelines (available starting in 1996) or on U.S. Food and Drug Administration (FDA)-approved package inserts. We estimated the rate of DPI trials overall and over time. The total federal investment supporting the set of trials was also determined based on public data. Results: In total, 182 trials comprising 148,028 patients were studied. We identified 79 DPI studies (43.4%); 73 influenced NCCN guidelines, 12 influenced new drug approvals, and 6 influenced both. The rate of DPI trials was 72.3% (47/65) among formally positive trials (i.e., achieved their protocol specified endpoint) and 27.4% (32/117) among negative trials. Thus 40.5% (32/79) of DPI trials were based on negative studies, half of which (16/32 = 50.0%) reaffirmed standard of care over experimental therapy. There were no differences between DPI and non-DPI trials in key study design characteristics. Total federal investment for the programs conducting the trials was $1.36 billion (USD2017), a rate of $7.5 million per trial, or $17.2 million per DPI trial. Conclusions: Nearly half of all phase III trials by one of the NCTN’s largest groups had documented practice influence on clinical care guidelines or new drug approvals. Even many negative trials impacted guideline recommendations. Compared to the costs of a new drug approval in pharmaceutical companies – typically estimated at > $1 billion – the amount invested by federal funders to provide this valuable evidence was modest. These findings highlight the major role of the NCTN’s clinical trial program in advancing oncology practice.

Female representation in clinical trials leading to FDA cancer drug approvals for gastrointestinal (GI) cancers between 2008 to 2018.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 809-809 ◽  
Author(s):  
Shehara Ramyalini Mendis ◽  
Seerat Anand ◽  
Arvind Dasari ◽  
Joseph M. Unger ◽  
Anirudh Gothwal ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Incidence ◽  
Drug Approval ◽  
Cancer Drug ◽  
Representation Of Women ◽  
Gi Cancer ◽  
Enrollment Rates ◽  
Gi Cancers ◽  
Drug Approvals ◽  
The U.S

809 Background: Proportionate representation of women in health research is an area for improvement. This study aims to assess the representation of women in gastrointestinal (GI) cancer clinical trials leading to FDA cancer drug approvals over the past 10 years. Methods: FDA cancer drug approvals between 07/2008-06/2018 were identified and trial reports supporting approvals sourced. The ratio of female to male (F:M) enrollment was compared with F:M cancer incidence in the U.S., and U.S. cancer prevalence and mortality. Results: Although F:M enrollment for all 229 trials leading to FDA cancer drug approvals in this period was similar to overall F:M cancer incidence in the U.S. (0.89 vs 0.86; Odds Ratio for female enrollment (OR) 1.05, 95% Confidence Interval (CI) 1.03-1.06, P<0.0001), in 17 trials that led to drug approvals in GI cancers there was lower F:M trial enrollment compared to cumulative U.S. incidence at those tumor sites (0.55 vs 0.79, OR 0.71, 95% CI 0.68-0.74, P<0.0001). F:M enrollment and U.S. incidence by the main GI tumor sites where approvals occurred is shown in Table. Female enrollment rates were also lower than U.S. female cancer mortality and prevalence rates in these tumor sites (P<0.0001 for all). Female enrollment in GI trials fell between 2008-2013 and 2014-2018 (38 vs 33%, OR 0.80, 95% CI 0.74-0.87, P<0.0001). Conclusions: Although disparity in female enrollment may be improving across combined FDA cancer drug approval trials, underrepresentation of females has persisted in GI cancer trials when compared to F:M cancer incidence, prevalence and mortality in the U.S. More work is required to determine the drivers of this disparity, in order to mitigate it. [Table: see text]

scholarly journals Sex Representation in Clinical Trials Associated with FDA Cancer Drug Approvals Differs Between Solid and Hematologic Malignancies

2020 ◽  
Author(s):  
Shehara Mendis ◽  
Seerat Anand ◽  
Joanna M. Karasinska ◽  
Arvind Dasari ◽  
Joseph M. Unger ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hematologic Malignancies ◽  
Cancer Drug ◽  
Drug Approvals

Surrogate Endpoints and Drug Regulation: What Is Needed to Clarify the Evidence

2019 ◽  
Vol 47 (3) ◽  
pp. 381-387 ◽  
Author(s):  
Spencer Phillips Hey ◽  
William B. Feldman ◽  
Emily H. Jung ◽  
Elvira D'Andrea ◽  
Aaron S. Kesselheim
Keyword(s):  
Clinical Trials ◽  
Drug Regulation ◽  
Surrogate Endpoints ◽  
Drug Approvals

The FDA's new table of surrogate endpoints used for drug approvals is an important step forward for overseeing the use of biomarkers in clinical trials. Nevertheless, we present several ways in which the table can be improved.

scholarly journals Landmark Cancer Clinical Trials and Real-World Patient Populations: Examining Race and Age Reporting

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5770
Author(s):  
Thejus Jayakrishnan ◽  
Sonikpreet Aulakh ◽  
Mizba Baksh ◽  
Kianna Nguyen ◽  
Meghna Ailawadhi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Real World ◽  
Age Distribution ◽  
Mean Difference ◽  
Cancer Drug ◽  
P Value ◽  
World Population ◽  
Drug Approvals ◽  
Age Disparity

Background: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially in underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity. Methods: Food and Drug Administration (FDA) drug approvals from July 2007 to June 2019 were reviewed to identify oncology approvals, and trials with age details were selected. The outcomes studied were the weighted mean difference in age between the clinical trial population and real-world population for various cancers, the prevalence of race reporting and association of age and race reporting with each other. Results: Of the 261 trials, race was reported in 223 (85.4%) of the trials, while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time: 29 (85.3%) in 2007–2010 vs. 49 (80.3%) in 2011–2014 vs. 145 (85.4%) during the period 2015–2019 (p-value = 0.41). Age discrepancy between the clinical trial population and the real-world population was higher for studies that did not report race (mean difference −8.8 years (95% CI −12.6 to −5.0 years)) vs. studies that did report it (mean difference −5.1 years, (95% CI −6.4 to −3.7 years), p-value = 0.04). Conclusion: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations, and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations.

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