Global drug development in cancer: A cross-sectional study of clinical trial registries

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2520-2520
Author(s):  
P. Hertz ◽  
B. Seruga ◽  
L. W. Le ◽  
I. F. Tannock
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Drug Development ◽  
Phase Ii ◽  
New Drugs ◽  
Phase Iii ◽  
Cancer Site ◽  
Cancer Type ◽  
Clinical Trial Registries ◽  
Global Drug Development

2520 Background: Clinical trials are increasingly funded by industry. High costs of drug development may lead to attempts to develop new drugs in more ‘profitable’ (i.e., more prevalent) as compared to ‘less profitable’ (i.e., more deadly) cancers. Here we determine the focus of current global drug development. Methods: We determined characteristics of phase II and III clinical trials evaluating new drugs in oncology, which were registered with WHO International Clinical Trial Registries between 01/2008 and 06/2008. Estimates of incidence, mortality, and prevalence in the more- and less-developed world (MDW, LDW) were obtained from GLOBOCAN 2002. Simple correlation analysis was performed between the number of clinical trials and incidence, mortality and prevalence per cancer site after log transformation of variables. Results: We identified 399 newly registered trials. Of 374 trials with information about recruitment, 322 (86.1%) and 39 (10.4%) recruited patients only from the MDW and LDW, respectively, while 13 (3.5%) had worldwide recruitment. 229 (58%) of trials were sponsored by industry and 324 trials were phase II (81%). Most trials (and most phase III trials) evaluated treatments for globally prevalent cancers: breast, lung, prostate, and colorectal cancer (Table). Prevalence of a particular cancer type in both the MDW and LDW correlated significantly with the number of clinical trials (Pearson r = 0.63 and 0.55; p = 0.01 and 0.03, respectively). In contrast, mortality in the MDW (Pearson r = 0.73; p= 0.002), but not in the LDW (Pearson r = 0.38; p= 0.17), correlated significantly with the number of clinical trials. Conclusions: Global drug development in cancer predominates in globally prevalent cancers, which are a more important cause of mortality in the MDW than in the LDW. Cancer sites that are major killers globally, and especially in the LDW (e.g., stomach, liver, and esophageal cancer) should receive priority for clinical research. [Table: see text] No significant financial relationships to disclose.

A pooled analysis of phase II trials of gemcitabine (GEM)-containing doublets plus bevacizumab (BEV):  Should combination chemotherapy serve as the backbone in clinical trials of advanced pancreatic cancer (APC)?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4038-4038
Author(s):  
Katherine Van Loon ◽  
George P. Kim ◽  
Anne Marie Espinoza ◽  
David R. Fogelman ◽  
Renuka V. Iyer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase Ii ◽  
Trial Design ◽  
Bowel Perforation ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Cardiac Events ◽  
Phase Ii Trials ◽  
Grade 3

4038 Background: GEM has served as the chemotherapy platform for most phase III clinical trials in APC, inc. CALGB 80303 (GEM +/- BEV). However, GEM-based combination regimens may confer superior outcomes in select pts and represent a preferred backbone in clinical trial design testing targeted agents. Methods: Data was pooled from 5 phase II trials evaluating GEM-based cytotoxic doublets plus BEV in APC. 1o endpoint was OS. 2o endpoints included ORR, CA19-9 response, and adverse events (AEs). Kaplan-Meier methods estimated time-to-event endpoints. The Cox proportional hazard model estimated univariate hazard ratios (HR) of death. Results: Of 261 pts, 90.7% were Caucasian, 95.4% had an ECOG PS 0-1, and 91.6% had metastatic disease. Median age = 60y. Pooled OS data (in mos), stratified for PS and stage, is shown in the table. ORR across all trials: CR 1.6%, PR 22.9%, SD 50.8%, PD 20.2%, NA 4.7%. HR for pts who achieved disease control (CR/PR/SD) was 0.35 vs. those with PD (95% CI 0.23-0.54, p<0.001). 76.5% of pts had elevated baseline CA19-9; of these, 62% achieved ≥50% reduction (HR 0.50; 95% CI 0.34-0.73, p<0.001). BEV-related AEs ≥grade 3: HTN (10.6%), hemorrhage (9.5%), VTE (10.1%), cardiac events (3.4%), and bowel perforation (2.2%). Median OS in pts with grade 3-4 HTN was 13.4 mos vs. 9.8 mos in those without (HR 0.77; 95% CI 0.48-1.24, p=0.29). Conclusions: Recognizing the limitations of single-arm phase II trial design and cross-study comparisons, these results compare favorably to those from CALGB 80303. The standard paradigm of GEM +/- drug X in clinical trial development for APC needs to be reconsidered. Based on our data as well as the recent phase III FOLFIRINOX study, building on more intensive combination chemo regimens in future trials may represent a better strategy, especially for pts with good PS. [Table: see text]

Clinical trial risk reduction in non-small cell lung cancer though the use of biomarkers and receptor-targeted therapies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8040-8040
Author(s):  
Adam Falconi ◽  
Gilberto Lopes ◽  
Jayson L. Parker
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Drug Development ◽  
Phase I ◽  
Success Rate ◽  
Targeted Therapies ◽  
Phase Iii ◽  
Clinical Testing ◽  
Phase Ii Trials ◽  
Phase Iii Trials

8040 Background: We analyzed the risk of clinical trial failure duringnon-small cell lung cancer (NSCLC) drug development between 1998 and 2012. Methods: NSCLC drug development was investigated using trial disclosures from publically available resources. Compounds were excluded from the analysis if they began phase I clinical testing before 1998 and if they did not use treatment relevant endpoints. Analysis was conducted in regards to treatment indication, compound classification and mechanism of action. Costs of clinical drug development for advanced NSCLC were calculated using industry data and assumptions, a 9% yearly discount rate and assuming a clinical trial length of 2.5 years for phase I trials, 4 years for phase II trials, 5 years for phase III trials and an average of 5 phase I trials, 7 phase II trials, and 4 phase III trials per approved drug. All funding costs are in US dollars (USD). Results: 2,407 clinical trials met search criteria. 676 trials and 199 unique compounds met our inclusion criteria. The likelihood, or cumulative clinical trial success rate, that a new drug would pass all phases of clinical testing and be approved was found to be 11%, which is less than the expected industry aggregate rates (16.5%). The success of phase III trials was found to be the biggest obstacle for drug approval with a success rate of only 28%. Biomarker-guided targeted therapies (with a success rate of 62%) and receptor targeted therapies (with a success rate of 31%) were found to have the highest likelihood of success in clinical trials. The risk-adjusted cost for NSCLC clinical drug development was calculated to be 1.89 billion US dollars. Use of biomarkers decreased drug development cost by 26% to 1.4 billion US dollars. Potential savings may be even higher if fewer clinical trials are required for successful development. Conclusions: Physicians that enroll patients in NSCLC trials should prioritize their participation in clinical trial programs that involve either a biomarker or receptor targeted therapy, which appear to carry the best chances for a successful treatment response. Given the high adjusted cost of clinical testing alone in NSCLC, efforts to mitigate the risk of trial failure need to explore these factors more fully.

scholarly journals Strategic inclusion of regions in multiregional clinical trials

2018 ◽  
Vol 16 (1) ◽  
pp. 98-105
Author(s):  
Seung Yeon Song ◽  
Deborah Chee ◽  
EunYoung Kim
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Phase Ii ◽  
Phase Iii ◽  
Local Study ◽  
International Conference ◽  
Trial Conduct ◽  
Increasing Trend ◽  
Phase Iii Trials

Background With the recent publication of the International Conference on Harmonisation E17 guideline and major reforms in China underway, the platform for clinical trial conduct is expected to change. This study aims to assess the strategic inclusion of regions in clinical trials and its change in trends over the past decade. Methods The ClinicalTrials.gov registry was searched for clinical trials registered by the top 10 pharmaceutical companies between 1 January 2008 and 31 December 2017. Extracted data included phase, disease type, intervention, study start year, and region. Trial type was classified as either a local study or a multiregional clinical trial as per the International Conference on Harmonisation E17 guideline. Results Of 2488 phase I, 1855 phase II, and 1999 phase III trials included, the majority of phase I trials were local studies (76.8%), while the majority of phase II (66.0%) and phase III (72.2%) trials were multiregional clinical trials. The proportion of multiregional clinical trials showed an increasing trend for all phases ( p < 0.01). Although North America and Europe remained the main locations, increasing trends of inclusion of other regions, such as East Asia, were noted. Conclusion Globalization of drug development is evident with the increasing trend of multiregional clinical trial. Regulatory authorities as well as the pharmaceutical industry should prepare for the evolving setting of clinical research and problems that can arise from these changes.

Progression-Free Survival Rate As Primary End Point for Phase II Cancer Clinical Trials: Application to Mesothelioma—The EORTC Lung Cancer Group

2006 ◽  
Vol 24 (19) ◽  
pp. 3007-3012 ◽  
Author(s):  
Julie Francart ◽  
Catherine Legrand ◽  
Richard Sylvester ◽  
Martine Van Glabbeke ◽  
Jan P. van Meerbeeck ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Survival Rate ◽  
Phase Ii ◽  
Progression Free Survival ◽  
New Drugs ◽  
Phase Iii ◽  
Cancer Clinical Trials ◽  
Phase Ii Trials ◽  
Free Survival ◽  
End Point

Purpose Phase II cancer clinical trials play a key role in the development of new drugs. These trials should be designed to accurately determine if the drug should be abandoned or if it is sufficiently promising for further investigation in phase III trials. With new cytostatic agents or when the response assessment is difficult, using the progression-free survival rate (PFSR) at a fixed time point, such as 3, 4, 5, or 6 months, instead of the response rate (RR) as the primary end point is an alternative approach. To design future phase II trials, reference values for PFSRs that correspond to drugs with insufficient (P0) and sufficient (P1) clinical activity (CA) are necessary. This article provides these values in mesothelioma. Materials and Methods The European Organisation for Research and Treatment of Cancer database registered ten closed mesothelioma trials (nine phase II trials and one phase III trial) with 523 total patients. Trials were grouped into three categories according to the published RR: significant (n = 259), moderate (n = 142), and insufficient (n = 122) CA. Results The PFSRs at 3, 4, 5, and 6 months, respectively, were as follows: 72%, 67%, 51%, and 43% in the group with significant CA; 59%, 51%, 42%, and 35% with moderate CA; and 52%, 40%, 34%, and 28% with insufficient CA. Conclusion These values may be used to define relevant P0 and P1 values in future phase II mesothelioma trials that use PFSR as the primary end point.

scholarly journals New drug and clinical trial rules, 2019: an overview

2020 ◽  
Vol 7 (4) ◽  
pp. 278
Author(s):  
Swathi A. Annapurna ◽  
Srinivasa Y. Rao
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Pharmaceutical Industry ◽  
Drug Development ◽  
New Drugs ◽  
Development Method ◽  
New Drug ◽  
The Government

<p>Clinical trials are indispensable to the drug development method to confirm the effectiveness and safety of any new drug. India has undergone a big restrictive transformation about clinical trials. Numerous establishments taking part in a distinguished role in guiding the trial in India embody DCGI, DBT, ICMR, CBN, RCGM and GEAC. The government notified the new drugs and trial rules on 19 March 2019, to supersede part XA and schedule Y of the drugs and cosmetics rules 1945. Updating our knowledge about these is of utmost importance in today’s turbulent scenario that prevails in the pharmaceutical industry. Thus, this review gives an idea about the recent changes regarding the regulations of clinical trials.</p>

scholarly journals EVALUASI KHASIAT DAN KEAMANAN OBAT (UJI KLINIK)

2015 ◽  
Vol 34 (1) ◽  
pp. 31
Author(s):  
Rahmatini Rahmatini
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Phase Ii ◽  
Phase Ii Clinical Trial ◽  
Phase I Clinical Trial ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Trial Phase

AbstrakUji klinik adalah suatu pengujian khasiat obat baru pada manusia, dimana sebelumnya diawali oleh pengujian pada binatang atau uji pra klinik. Pada dasarnya uji klinik memastikan efektivitas, keamanan dan gambaran efek samping yang sering timbul pada manusia akibat pemberian suatu obat. Bila uji klinik tidak dilakukan maka dapat terjadi malapetaka pada banyak orang bila langsung dipakai secara umum seperti pernah terjadi dengan talidomid (1959-1962) dan obat kontrasepsi pria (gosipol) di Cina. Setiap obat yang ditemukan melalui eksperimen in vitro atau hewan coba tidak terjamin bahwa khasiatnya benar-benar akan terlihat pada penderita. Pengujian pada manusia sendirilah yang dapat “menjamin” apakah hasil in vitro atau hewan sama dengan manusia.Uji klinik terdiri dari 4 fase, yaitu uji klinik fase I.Uji klinik fase II, uji klinik fase III dan uji klinik fase IV. Uji klinik fase I dilakukan pada manusia sehat, bertujuan untuk menentukan dosis tunggal yang dapat diterima, Uji klinik fase II, dilakukan pada 100-200 orang penderita untuk melihat apakah efek farmakologik yang tampak pada fase I berguna atau tidak untuk pengobatan. Uji klinik fase III dilakukan pada sekitar 500 penderita yang bertujuan untuk memastikan bahwa suatu obat baru benar-benar berkhasiat. Uji klinik fase IV merupakan pengamatan terhadap obat yang telah dipasarkan. Fase ini bertujuan menentukan pola penggunaan obat di masyarakat serta pola efektifitas dan keamanannya pada penggunaan yang sebenarnya.Uji klinik yang baik dilakukan dengan prosedur yang sudah digariskan dan komponen- komponennya disiapkan dengan matang sehingga hasilnya betul- betul dapat dimanfaatkan sebagai acuan pengobatan.Kata kunci : Khasiat- keamanan- uji klinikAbstractClinical trials is a new drug efficacy testing in humans, which previously preceded by testing on animals or pre-clinical testing. Basically, clinical trials confirm description of effectiveness, safety and side effects that often arise in humans because given of a drug. If clinical trials are not done then it can be evil in many people when directly used in general as once happened with thalidomide (1959-1962) and male contraceptive drugs (gossypol) in China. Any drug that is found through experiments in vitro or animal is not guaranteed that the propertiesTINJAUAN PUSTAKA32will actually be seen in patients. Tests on humans themselves who can "guarantee" if the results of in vitro or animal similar to humans.Clinical trial consisted of 4 phases, namely phase I clinical trial, phase II clinical trial, phase III clinical trials, and phase IV clinical trial. Phase I clinical trial, performed on healthy humans, aims to determine an acceptable single-dose, phase II clinical trial, performed on 100-200 patiens to see whether the pharmacologic effects seen in Phase I is useful or not for treatment. Phase III clinical trials conducted on about 500 patients which aims to ensure that a new drug is really efficacy. Phase IV clinical trial is an observation of the drug has been marketed. This phase aims to determine patterns of drug use in society and patterns of effectiveness and safety in actual use.Good clinical trials conducted with procedures that have been outlined and its components prepared and thus the results can actually be used as a reference treatment. Key words : Efficacy – Safety - Clinical trial

Sign in / Sign up

Export Citation Format

Share Document