Where is clinical research for radiotherapy going? Cross-sectional comparison of past and contemporary phase III clinical trials

Abstract Background: Covid-19 vaccine research and development is progressing and expected to be put into use in a predictable time, we aimed to learn the awareness and acceptance of the new vaccine by healthcare workers (HCWs) in Beijing, China. Methods: A cross-sectional survey was conducted to investigate HCWs including doctors, nurses and technicians from sixty hospitals in Beijing to obtain the perception of COVID-19 epidemic and the attitudes towards vaccination before before the completion of vaccine phase III clinical trials. Multivariate analysis was applied to evaluate the associated factors with intention to get vaccination.Results: A total of 8040 HCWs was recruited. 67.1% reported they would get vaccination, others said unsure or would not. Half of the HCWs were unsure whether the outbreak in China would come back and the global epidemic would last for a long time. 67.6% agreed the epidemic can be prevented by vaccination. Positive associated factors with willingness to get vaccination were mainly included epidemic situation prognosis, perception of disease severity, self infection risk and disease can be prevented by vaccine, etc. Two positive factors of “wanted the vaccine free of charge” (OR:5.807, 95%CI:5.083-6.635, P<0.001) and “believed vaccine approved for license have been fully evaluated in clinical trials” (OR:4.485, 95%CI:3.849-5.227, P<0.001) were strongly associated with willingness to get vaccination, while two factors of “highest academic degree” (OR:0.840, 95%CI:0.772-0.914, P<0.001) and “professional ranks and titles” (OR:0.930, 95%CI:0.865-1.000, P=0.049) were negative associated .Conclusions: A little above moderate willingness to get COVID-19 vaccination was found among HCWs in Beijing before the vaccine being licensed. Free vaccination strategy should be considered to implement, effective measures should be taken to remove barriers and convey correct information through appropriate ways to enhance the acceptance of COVID-19 vaccination among HCWs in China.

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Children’s Oncology Group (COG) clinical trials as exemplars of pragmatism in clinical research.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18188 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18188-e18188

Author(s):

Nupur Mittal ◽

Anil George ◽

Lizette Leanos ◽

Paul Kent

Keyword(s):

Clinical Trials ◽

Clinical Research ◽

Pragmatic Trial ◽

Standard Of Care ◽

The United States ◽

Phase Iii ◽

President Obama ◽

Explanatory Trial ◽

Phase Iii Clinical Trials ◽

Pragmatic Clinical Trials

e18188 Background: In 2016, President Obama announced the “Moonshot Cancer Initiative” to advance cancer research. One of the key components of this initiative is promoting enrollment in pragmatic clinical trials and data sharing. As described in 2009 by Thorpe et al, using the 9-domian PRECIS-2 tool, a ‘pragmatic’ trial, as opposed to an ‘explanatory’ trial used to confirm a physiologic hypothesis, is one in which the intervention can be immediately applied into real-world clinical practice (J of Clin Epi:2009). In the US, 60%-90% children are enrolled on COG research trials. State-of-the-art treatment for a child is derived from superior therapy identified in prior trials which then serves as the standard arm of subsequent phase-III trials and becomes the de facto practice guideline and ‘standard of care’ .To accomplish this goal, COG shares its data among the 242 member institutions.Our objective is to assess “pragmatism” in COG trials. Methods: We analyzed the 158 COG phase III clinical trials between 2006-2016 for all 9 domains of the PRECIS-2 (Table 1) and graded them from 1-5 (most explanatory to most pragmatic). Results: Out of 152 phase III clinical trials on the COG website, 138 (91%) scored 5/5 for all 9 PRECIS pragmatic domains and 148 (98%) scored >4. The scoring for all 9 domains is in table 1. Conclusions: COG provides nearly all children in the United States access to pragmatic phase III research as outlined in the Moonshot Goals. Goal of merging evidence-based standard care accessible to all and conducting well- designed clinical research to identify the best therapies has been accomplished by COG and should serve as an example to other cancer organizations. 9 domains of PRECIS-2 to assess pragmatism in clinical trials. [Table: see text]

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Discovery reliability

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19837015 ◽

2019 ◽

Vol 39 (6) ◽

pp. 1185-1187

Author(s):

Anders Hånell

Keyword(s):

Clinical Trials ◽

Clinical Research ◽

Statistical Power ◽

Neurological Diseases ◽

Phase Iii ◽

Treatment Benefit ◽

Phase Iii Clinical Trials ◽

Drug Studies ◽

Clinical Drug

Whenever an experiment yields a statistically significant outcome you should ask yourself: To what extent can I trust this result? This is especially important for pre-clinical drug studies because of the frequent failures of phase III clinical trials of neurological diseases, which has put the reliability of pre-clinical research into question. Two important factors, the pre-study likelihood of treatment benefit, and statistical power, affects the reliability of the result in a quantifiable way. This can be used to assess to what extent the result of a study can be trusted (discovery reliability), and to guide the design of pre-clinical research.

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Testing Hope

Exploiting Hope ◽

10.1093/med/9780197501252.003.0006 ◽

2020 ◽

pp. 123-153

Author(s):

Jeremy Snyder

Keyword(s):

Clinical Trials ◽

Clinical Research ◽

Phase Iii ◽

Trial Participation ◽

Phase I Clinical Trials ◽

Middle Income ◽

Middle Income Countries ◽

Experimental Intervention ◽

Phase Iii Clinical Trials ◽

Experimental Cancer

Chapter 5 examines human participation in phase I clinical trials for experimental cancer interventions and phase III clinical trials in low- and middle-income countries. In both cases, these participants may take part in these trials in the hope of accessing an experimental intervention that will improve their own health or that of their communities. Exploitation of hope is most likely to take place in these contexts when there is a confusion about the roles of researchers and the aims of clinical research such that participants misunderstand the likely outcomes of the trial for themselves or their communities. Researchers and their sponsors can contribute to this misunderstanding by not communicating the aims of clinical research clearly or by using the language of hope to encourage trial participation.

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Rome I versus Rome II; Overlap in patients enrolled in tegaserod phase III clinical trials for irritable bowel syndrome (IBS)

Gastroenterology ◽

10.1016/s0016-5085(01)81411-6 ◽

2001 ◽

Vol 120 (5) ◽

pp. A284-A284

Author(s):

B NAULT ◽

S SUE ◽

J HEGGLAND ◽

S GOHARI ◽

G LIGOZIO ◽

...

Keyword(s):

Clinical Trials ◽

Irritable Bowel Syndrome ◽

Phase Iii ◽

Phase Iii Clinical Trials ◽

Irritable Bowel ◽

Rome I

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Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials

Seminars in Oncology ◽

10.1053/sonc.2001.28598 ◽

2001 ◽

Vol 28 (6) ◽

pp. 620-625 ◽

Cited By ~ 4

Author(s):

Pierre Falardeau ◽

Pierre Champagne ◽

Patrick Poyet ◽

Claude Hariton ◽

[Eacute]ric Dupont

Keyword(s):

Clinical Trials ◽

Phase Iii ◽

Phase Iii Clinical Trials ◽

Naturally Occurring ◽

Antiangiogenic Drug

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Animal and Human Vaccines against West Nile Virus

Pathogens ◽

10.3390/pathogens9121073 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1073

Author(s):

Juan-Carlos Saiz

Keyword(s):

Clinical Trials ◽

West Nile Virus ◽

Vaccine Development ◽

Phase Iii ◽

West Nile ◽

Specific Therapy ◽

Phase Iii Clinical Trials ◽

Neuroinvasive Disease ◽

The Us ◽

The Status

West Nile virus (WNV) is a widely distributed enveloped flavivirus transmitted by mosquitoes, which main hosts are birds. The virus sporadically infects equids and humans with serious economic and health consequences, as infected individuals can develop a severe neuroinvasive disease that can even lead to death. Nowadays, no WNV-specific therapy is available and vaccines are only licensed for use in horses but not for humans. While several methodologies for WNV vaccine development have been successfully applied and have contributed to significantly reducing its incidence in horses in the US, none have progressed to phase III clinical trials in humans. This review addresses the status of WNV vaccines for horses, birds, and humans, summarizing and discussing the challenges they face for their clinical advance and their introduction to the market.

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Exploring new uses for existing drugs: innovative mechanisms to fund independent clinical research

Trials ◽

10.1186/s13063-021-05273-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ciska Verbaanderd ◽

Ilse Rooman ◽

Isabelle Huys

Keyword(s):

Clinical Trials ◽

Clinical Research ◽

Financial Support ◽

Social Impact ◽

Grey Literature ◽

Economic Incentives ◽

Phase Iii ◽

Medical Needs ◽

The Future ◽

Funding Mechanisms

Abstract Background Finding new therapeutic uses for existing medicines could lead to safe, affordable and timely new treatment options for patients with high medical needs. However, due to a lack of economic incentives, pharmaceutical developers are rarely interested to invest in research with approved medicines, especially when they are out of basic patent or regulatory protection. Consequently, potential new uses for these medicines are mainly studied in independent clinical trials initiated and led by researchers from academia, research institutes, or collaborative groups. Yet, additional financial support is needed to conduct expensive phase III clinical trials to confirm the results from exploratory research. Methods In this study, scientific and grey literature was searched to identify and evaluate new mechanisms for funding clinical trials with repurposed medicines. Semi-structured interviews were conducted with 16 European stakeholders with expertise in clinical research, funding mechanisms and/or drug repurposing between November 2018 and February 2019 to consider the future perspectives of applying new funding mechanisms. Results Traditional grant funding awarded by government and philanthropic organisations or companies is well known and widely implemented in all research fields. In contrast, only little research has focused on the application potential of newer mechanisms to fund independent clinical research, such as social impact bonds, crowdfunding or public-private partnerships. Interviewees stated that there is a substantial need for additional financial support in health research, especially in areas where there is limited commercial interest. However, the implementation of new funding mechanisms is facing several practical and financial challenges, such as a lack of expertise and guidelines, high transaction costs and difficulties to measure health outcomes. Furthermore, interviewees highlighted the need for increased collaboration and centralisation at a European and international level to make clinical research more efficient and reduce the need for additional funding. Conclusions New funding mechanisms to support clinical research may become more important in the future but the unresolved issues identified in the current study warrant further exploration.

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The role of future treatments in the management of neovascular age-related macular degeneration in Europe

European Journal of Ophthalmology ◽

10.1177/11206721211018348 ◽

2021 ◽

pp. 112067212110183

Author(s):

Laurent Kodjikian ◽

Carl Joe Mehanna ◽

Salomon-Yves Cohen ◽

François Devin ◽

Sam Razavi ◽

...

Keyword(s):

Clinical Trials ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Phase Iii ◽

Vascular Endothelial ◽

Real World Data ◽

Phase Iii Clinical Trials ◽

Age Related ◽

Injection Frequency ◽

Endothelial Growth Factor

Anti-vascular endothelial growth factor (VEGF) agents have transformed the management of patients with neovascular age-related macular degeneration (nAMD) over the past two decades. However, as more long-term real-world data become available, it is clear that treatment outcomes are inferior to those reported in large, controlled clinical trials. This is largely driven by undertreatment, that is, not maintaining a consistent injection frequency to achieve sustained VEGF suppression, whether due to patient non-compliance, an important injection burden, or non/incomplete anatomical response. Newer therapeutic advances under evaluation hold promise in achieving more, for less. We review the latest drugs currently in or having successfully finished phase III clinical trials, and determine their potential place in the management of patients with nAMD in Europe.

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Matching comparisons of therapeutic efficacy suggest better clinical outcomes for patients treated with peginterferon beta-1a than with glatiramer acetate

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286420975916 ◽

2021 ◽

Vol 14 ◽

pp. 175628642097591

Author(s):

Thomas F. Scott ◽

Ray Su ◽

Kuangnan Xiong ◽

Arman Altincatal ◽

Carmen Castrillo-Viguera ◽

...

Keyword(s):

Clinical Trials ◽

Propensity Score ◽

Clinical Outcomes ◽

Glatiramer Acetate ◽

Therapeutic Efficacy ◽

Individual Patient Data ◽

Patient Data ◽

Phase Iii ◽

Lower Probability ◽

Phase Iii Clinical Trials

Background: Peginterferon beta-1a and glatiramer acetate (GA) are approved first-line therapies for the treatment of relapsing forms of multiple sclerosis, but their therapeutic efficacy has not been compared directly. Methods: Clinical outcomes at 2 years, including no evidence of disease activity (NEDA), for patients receiving peginterferon beta-1a 125 mcg every 2 weeks (Q2W) or GA 20 mg/ml once daily (QD) were compared by propensity score matching analysis using individual patient data from ADVANCE and CONFIRM phase III clinical trials. In addition, clinical outcomes at 1–3 years for patients receiving peginterferon beta-1a Q2W or GA 40 mg/ml three times a week (TIW) were evaluated using a matching-adjusted comparison analysis of individual patient data from ADVANCE and the ADVANCE extension study, ATTAIN, and aggregate patient data from the phase III GALA and the GALA extension studies. Results: Propensity-score-matched peginterferon beta-1a patients ( n = 336) had a significantly lower annualized relapse rate [ARR (0.204 versus 0.282); rate ratio = 0.724; p = 0.045], a significantly lower probability of 12-week confirmed disability worsening (10.0% versus 14.6%; hazard ratio = 0.625; p = 0.048), and a significantly higher rate of NEDA (20.3% versus 11.5%; p = 0.047) compared with GA 20 mg/ml QD patients after 2 years of treatment. Matching-adjusted peginterferon beta-1a patients (effective n = 276) demonstrated a similar ARR at 1 year (0.278 versus 0.318; p = 0.375) and significantly lower ARR at 2 years (0.0901 versus 0.203; p = 0.032) and 3 years (0.109 versus 0.209; p = 0.047) compared with GA 40 mg/ml TIW patients ( n = 834). Conclusion: Results from separate matching comparisons of phase III clinical trials and extension studies suggest that peginterferon beta-1a 125 mcg Q2W may provide better clinical outcomes than GA (20 mg/ml QD or 40 mg/ml TIW).

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