scholarly journals The case for introducing pre-registered confirmatory pharmacological pre-clinical studies

2018 ◽  
Vol 38 (5) ◽  
pp. 749-754 ◽  
Author(s):  
Olivia Kiwanuka ◽  
Bo-Michael Bellander ◽  
Anders Hånell
Keyword(s):  
Clinical Trial ◽  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
Network Analysis ◽  
Clinical Studies ◽  
Phase Iii ◽  
Phase Iii Clinical Trial ◽  
Phase Iii Clinical Trials ◽  
Experimental Drugs

When evaluating the design of pre-clinical studies in the field of traumatic brain injury, we found substantial differences compared to phase III clinical trials, which in part may explain the difficulties in translating promising experimental drugs into approved treatments. By using network analysis, we also found cases where a large proportion of the studies evaluating a pre-clinical treatment was performed by inter-related researchers, which is potentially problematic. Subjecting all pre-clinical trials to the rigor of a phase III clinical trial is, however, likely not practically achievable. Instead, we repeat the call for a distinction to be made between exploratory and confirmatory pre-clinical studies.

scholarly journals Effect of applying inclusion and exclusion criteria of phase III clinical trials to multiple sclerosis patients in routine clinical care

2021 ◽  
pp. 135245852098511
Author(s):  
Kris Oliver Jalusic ◽  
David Ellenberger ◽  
Paulus Rommer ◽  
Alexander Stahmann ◽  
Uwe Zettl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Care ◽  
Routine Care ◽  
Phase Iii ◽  
Exclusion Criteria ◽  
Phase Iii Clinical Trial ◽  
Phase Iii Clinical Trials ◽  
Multiple Sclerosis Patients

Background: Newly approved, drug-modifying therapies are associated with still unknown adverse events, although clinical trials leading to approval have strict inclusion and exclusion criteria and analyse safety and efficacy. Objectives: The aim of this study was to analyse the eligibility of multiple sclerosis (MS) patients treated in routine care into the phase III clinical trial of the respective drug. Methods: In total, 3577 MS patients with 4312 therapies were analysed. Patients with primary-progressive MS were excluded. Inclusion and exclusion criteria of phase III clinical trials in relapsing–remitting MS were adopted and subsequently applied. A comparison in clinical and sociodemographic characteristics was made between patient who met the criteria and those who did not. Results: 83% of registered patients would not have been eligible to the respective phase III clinical trial. Relapse was the single most frequent criterion not fulfilled (74.7%), followed by medication history (21.2%). Conclusion: The majority of MS patients treated in routine care would not have met clinical trials criteria. Thus, the efficacy and safety of therapies in clinical trials can differ from those in the real world. Broader phase III inclusion criteria would increase their eligibility and contribute to a better generalizability of the results in clinical trials.

scholarly journals Feasibility of progesterone treatment for ischaemic stroke

2015 ◽  
Vol 36 (3) ◽  
pp. 487-491 ◽  
Author(s):  
Claire L Gibson ◽  
Philip M Bath
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Brain Injury ◽  
Ischaemic Stroke ◽  
Clinical Development ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Progesterone Treatment

Two multi-centre phase III clinical trials examining the protective potential of progesterone following traumatic brain injury have recently failed to demonstrate any improvement in outcome. Thus, it is timely to consider how this impacts on the translational potential of progesterone treatment for ischaemic stroke. A wealth of experimental evidence supports the neuroprotective properties of progesterone, and associated metabolites, following various types of central nervous system injury. In particular, for ischaemic stroke, studies have also begun to reveal possible mechanisms of such neuroprotection. However, the results in traumatic brain injury now question whether further clinical development of progesterone for ischaemic stroke is relevant.

scholarly journals A Review of Phase III Clinical Trials of Prostate Cancer Chemoprevention

2007 ◽  
Vol 89 (3) ◽  
pp. 207-211 ◽  
Author(s):  
JF Thorpe ◽  
S Jain ◽  
TH Marczylo ◽  
AJ Gescher ◽  
WP Steward ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Cancer Prevention ◽  
Age Of Onset ◽  
Cancer Chemoprevention ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Prostate Cancer Prevention ◽  
Phase Iii Trials

INTRODUCTION Prostate cancer is an excellent target for chemoprevention strategies; given its late age of onset, any delay in carcinogenesis would lead to a reduction in its incidence. This article reviews all the completed and on-going phase III trials in prostate cancer chemoprevention. PATIENTS AND METHODS All phase III trials of prostate cancer chemoprevention were identified within a Medline search using the keywords ‘clinical trial, prostate cancer, chemoprevention’. RESULTS In 2003, the Prostate Cancer Prevention Trial (PCPT) became the first phase III clinical trial of prostate cancer prevention. This landmark study was terminated early due to the 24.8% reduction of prostate cancer prevalence over a 7-year period in those men taking the 5α-reductase inhibitor, finasteride. This article reviews the PCPT and the interpretation of the excess high-grade prostate cancer (HGPC) cases in the finasteride group. The lack of relationship between cumulative dose and the HGPC cases, and the possible sampling error of biopsies due to gland volume reduction in the finasteride group refutes the suggestion that this is a genuine increase in HGPC cases. The other on-going phase III clinical trials of prostate cancer chemoprevention – the REDUCE study using dutasteride, and the SELECT study using vitamin E and selenium – are also reviewed. CONCLUSIONS At present, finasteride remains the only intervention shown in long-term prospective phase III clinical trials to reduce the incidence of prostate cancer. Until we have the results of trials using alternative agents including the on-going REDUCE and SELECT trials, the advice given to men interested in prostate cancer prevention must include discussion of the results of the PCPT. The increased rate of HGPC in the finasteride group continues to generate debate; however, finasteride may still be suitable for prostate cancer prevention, particularly in men with lower urinary tract symptoms.

scholarly journals Obtaining Valid Laboratory Data in Clinical Trials Conducted in Resource Diverse Settings: Lessons Learned from a Microbicide Phase III Clinical Trial

PLoS ONE ◽  
2010 ◽  
Vol 5 (10) ◽  
pp. e13592 ◽  
Author(s):  
Tania Crucitti ◽  
Katrien Fransen ◽  
Rashika Maharaj ◽  
Tom Tenywa ◽  
Marguerite Massinga Loembé ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Laboratory Data ◽  
Lessons Learned ◽  
Phase Iii ◽  
Phase Iii Clinical Trial

Paucity of economic analyses of phase III clinical trials conducted by the cooperative oncology groups: A review of the evidence

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17052-17052
Author(s):  
K. Fitzner ◽  
J. McKoy ◽  
C. L. Bennett
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Cost Effectiveness ◽  
Cancer Care ◽  
Phase Iii ◽  
Economic Data ◽  
Direct Medical Costs ◽  
Phase Iii Clinical Trials ◽  
Need To Evaluate ◽  
Economic Analyses

17052 Background: Cancer care is expensive, accounting for $72 billion in direct medical costs. New oncology drugs are frequently costly, and can be > $100,000 per patient. Hence, assessments of the costs and cost-effectiveness of cancer pharmaceuticals alongside phase III clinical trials conducted by the NCI-sponsored cooperative oncology groups represents an important opportunity to generate relevant economic data. Methods: Review of published cost and cost-effectiveness analyses for cancer drugs conducted alongside phase III clinical trials conducted by the NCI-sponsored cooperative clinical trial groups. Results: See Table . Conclusions: Despite increasing concerns over the high costs of cancer pharmaceuticals and the need to evaluate the costs and cost-effectiveness of these agents, NCI sponsored phase III clinical trials rarely include economic assessments. Future phase III clinical trials with expensive new cancer agents conducted by cooperative clinical trials groups should include prospective economic assessments. [Table: see text] No significant financial relationships to disclose.

Concordance between abstracts, virtual meeting (VM) presentations, and final publication of phase III clinical trials presented at the Annual Meeting of the American Society of Clinical Oncology.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6622-6622 ◽  
Author(s):  
Suneil Kumar Khanna ◽  
Matthew John Boyko ◽  
Daniel Yick Chin Heng ◽  
Michael M. Vickers ◽  
Vincent Channing Tam
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Annual Meeting ◽  
Primary Endpoint ◽  
Statistical Significance ◽  
Phase Iii ◽  
Key Comparisons ◽  
Inclusion Criteria ◽  
Phase Iii Clinical Trials ◽  
Clinical Trial Results

6622 Background: Phase III clinical trial results described in abstracts in the ASCO Annual Meeting Proceedings often differ from final results seen in publication. We hypothesize that the abstracts may act only as place holders, while the results presented at the ASCO Annual Meeting are more highly concordant with the final publication. Methods: A retrospective review of all abstracts submitted to the ASCO Annual Meeting in 2005 to 2007 was conducted. Inclusion Criteria: randomized, prospective phase III clinical trials of greater than 200 patients with at least one quantitative primary endpoint such as OS or PFS. For each abstract, we viewed the VM presentation and searched Pubmed and Medline for the corresponding publications. Data regarding the clinical trials was extracted from all three sources and statistical comparisons were made. Results: A total of 7,900 abstracts were screened from the ASCO 2005 and 2007 Annual Meetings, of which 124 met the inclusion criteria. An additional 43 studies were excluded due to absence of either a VM presentation or publication. The majority (96%) of these trials were presented as either an oral presentation or poster discussion. Key comparisons of the concordance between the abstract or VM presentation and the final publication are shown in the Table below. Conclusions: While the statistical significance of the primary endpoint and conclusions from all three sources are very similar, the results reported in VM presentations at ASCO Annual Meetings are a better representation of the final publication compared to the abstract. When relying on clinical trial results from these meetings to change clinical practice, physicians should refer to the VM presentation rather than the abstract. [Table: see text]

scholarly journals Enhanced antipneumococcal antibody electrochemiluminescence assay: validation and bridging to the WHO reference ELISA

Bioanalysis ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 1363-1375
Author(s):  
Katrina M Nolan ◽  
Yuhua Zhang ◽  
Joseph M Antonello ◽  
Adrienne H Howlett ◽  
Cyrille J Bonhomme ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Conjugate Vaccine ◽  
Threshold Value ◽  
Phase Iii ◽  
Capsular Polysaccharides ◽  
Acceptance Criteria ◽  
Phase Iii Clinical Trial ◽  
Assay Validation ◽  
Clinical Trial Program

Aim: To re-optimize the pneumococcal (Pn) electrochemiluminescence (ECL) assay and to validate and bridge the enhanced assay to the WHO ELISA, to support the Phase III clinical trial program for V114, a 15-valent Pn conjugate vaccine. Materials & methods: The Pn ECL assay was re-optimized, validated and formally bridged to the WHO ELISA. Results: The enhanced Pn ECL assay met all prespecified validation acceptance criteria and demonstrated concordance with the WHO ELISA. The corresponding threshold value remains at 0.35 μg/ml for all 15 serotypes. Conclusion: The enhanced Pn ECL assay has been validated for the measurement of antibodies to 15 Pn capsular polysaccharides and is concordant with the WHO ELISA, supporting its use in clinical trials.

scholarly journals Progress in Clinical Neurosciences: Therapeutic Hypothermia in Severe Traumatic Brain Injury

2003 ◽  
Vol 30 (4) ◽  
pp. 307-313 ◽  
Author(s):  
David A. Zygun ◽  
Christopher J. Doig ◽  
Roland N. Auer ◽  
Kevin B. Laupland ◽  
Garnette R. Sutherland
Keyword(s):  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Severe Traumatic Brain Injury ◽  
Clinical Studies ◽  
Current Evidence ◽  
Optimal Temperature ◽  
Widespread Acceptance ◽  
The Future

Severe traumatic brain injury (sTBI) is a relatively common problem with few therapies proven effective. Despite its use for over 50 years, therapeutic hypothermia has not gained widespread acceptance in the treatment of sTBI due to conflicting results from clinical trials. This review will summarize the current evidence from animal, mechanistic and clinical studies supporting the use of therapeutic hypothermia. In addition, issues of rewarming and optimal temperature will be discussed. Finally, the future of hypothermia in sTBI will be addressed.

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