scholarly journals The Risk-Escalation Model: A Principled Design Strategy for Early-Phase Trials

2014 ◽  
Vol 24 (2) ◽  
pp. 121-139 ◽  
Author(s):  
Spencer Phillips Hey ◽  
Jonathan Kimmelman
Keyword(s):  
Early Phase ◽  
Design Strategy ◽  
Early Phase Trials ◽  
Principled Design

scholarly journals Biomarkers in early-phase trials: fundamental issues

Bioanalysis ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 933-944 ◽  
Author(s):  
Laura M Yee ◽  
Tracy G Lively ◽  
Lisa M McShane
Keyword(s):  
Early Phase ◽  
Early Phase Trials

scholarly journals A novel method to interpret early phase trials shows how the narrowing of the coronary sinus concordantly improves symptoms, functional status and quality of life in refractory angina

Heart ◽  
2020 ◽  
Vol 107 (1) ◽  
pp. 41-46
Author(s):  
E Marc Jolicoeur ◽  
Stefan Verheye ◽  
Timothy D Henry ◽  
Lawrence Joseph ◽  
Serge Doucet ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Coronary Sinus ◽  
Early Phase ◽  
Exercise Duration ◽  
Control Group ◽  
Refractory Angina ◽  
Group Level ◽  
Early Phase Trials ◽  
Level Analysis

BackgroundReduction of the coronary sinus was shown to improve angina in patients unsuitable for revascularisation. We assessed whether a percutaneous device that reduces the diameter of the coronary sinus improved outcomes across multiple endpoints in a phase II trial.MethodsWe conducted a novel analysis performed as a post hoc efficacy analysis of the COSIRA (Coronary Sinus Reducer for Treatment of Refractory Angina) trial, which enrolled patients with Canadian Cardiovascular Society (CCS) class 3–4 refractory angina. We used four domains: symptoms (CCS Angina Scale), functionality (total exercise duration), ischaemia (imaging) and health-related quality of life. For all domains, we specified a meaningful threshold for change. The primary endpoint was defined as a probability of ≥80% that the reducer exceeded the meaningful threshold on two or more domains (group-level analysis) or that the average efficacy score in the reducer group exceeded the sham control group by at least two points (patient-level analysis).ResultsWe randomised 104 participants to either a device that narrows to coronary sinus (n=52) or a sham implantation (n=52). The reducer group met the prespecified criteria for concordance at the group level and demonstrated improvement in symptoms (0.59 CCS grade, 95% credible interval (CrI)=0.22 to 0.95), total exercise duration (+27.9%, 95% CrI=2.8% to 59.8%) and quality of life (stability +11.2 points, 95% CrI=3.3 to 19.1; perception +11.0, 95% CrI=3.3 to 18.7).ConclusionsThe reducer concordantly improved symptoms, functionality and quality of life compared with a sham intervention in patients with angina unsuitable for coronary revascularisation. Concordant analysis such as this one can help interpret early phase trials and guide the decision to pursue a clinical programme into a larger confirmatory trial.Trail registration numberClinicalTrials.gov identifier: NCT01205893.

Immunology and Early Phase Trials

2009 ◽  
pp. 47-62
Author(s):  
M. Elizabeth Halloran ◽  
Ira M. Longini ◽  
Claudio J. Struchiner
Keyword(s):  
Early Phase ◽  
Early Phase Trials

scholarly journals Methods for comparing durability of immune responses between vaccine regimens in early-phase trials

2019 ◽  
Vol 29 (1) ◽  
pp. 78-93
Author(s):  
Ted Westling ◽  
Michal Juraska ◽  
Kelly E. Seaton ◽  
Georgia D. Tomaras ◽  
Peter B. Gilbert ◽  
...  
Keyword(s):  
Immune Response ◽  
Early Phase ◽  
Nonlinear Models ◽  
Hiv Vaccine ◽  
Two Phase ◽  
Hiv Vaccine Trials ◽  
Statistical Inferences ◽  
Vaccine Trials ◽  
Early Phase Trials ◽  
The Mean

The ability to produce a long-lasting, or durable, immune response is a crucial characteristic of many highly effective vaccines. A goal of early-phase vaccine trials is often to compare the immune response durability of multiple tested vaccine regimens. One parameter for measuring immune response durability is the area under the mean post-peak log immune response profile. In this paper, we compare immune response durability across vaccine regimens within and between two phase I trials of DNA-primed HIV vaccine regimens, HVTN 094 and HVTN 096. We compare four estimators of this durability parameter and the resulting statistical inferences for comparing vaccine regimens. Two of these estimators use the trapezoid rule as an empirical approximation of the area under the marginal log response curve, and the other two estimators are based on linear and nonlinear models for the marginal mean log response. We conduct a simulation study to compare the four estimators, provide guidance on estimator selection, and use the nonlinear marginal mean model to analyze immunogenicity data from the two HIV vaccine trials.

scholarly journals Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: the MAST study

2021 ◽  
Author(s):  
Valentina Gambardella ◽  
Pasquale Lombardi ◽  
Juan Antonio Carbonell-Asins ◽  
Noelia Tarazona ◽  
Juan Miguel Cejalvo ◽  
...  
Keyword(s):  
Early Phase ◽  
Progression Free Survival ◽  
Tumor Board ◽  
Prior Therapy ◽  
Early Phase Trials ◽  
Molecular Tumor Board ◽  
Early Phase Clinical Trials ◽  
The Impact ◽  
To Receive

Abstract Introduction Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution. Methods Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. The primary endpoint was progression-free survival (PFS) assessed by the ratio of patients presenting 1.3-fold longer PFS on matched therapy (PFS2) than with prior therapy (PFS1). Results Of a total of 231 molecularly screened patients, 87 were eligible for analysis. Patients who received matched therapy had a higher median PFS2 (6.47 months; 95% CI, 2.24–14.43) compared to those who received standard therapy (2.76 months; 95% CI, 2.14–3.91, Log-rank p = 0.022). The proportion of patients with a PFS2/PFS1 ratio over 1.3 was significantly higher in the experimental arm (0.33 vs 0.08; p = 0.008). Discussion We demonstrate the pivotal role of the institutional molecular tumor board in evaluating the results of a customized NGS panel. This process optimizes the selection of available therapies, improving disease control. Prospective randomized trials are needed to confirm this approach and open the door to expanded drug access.

Understanding patient expectations in early-phase clinical trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6543-6543
Author(s):  
K. P. Weinfurt ◽  
D. M. Seils ◽  
J. P. Tzeng ◽  
K. L. Compton ◽  
D. P. Sulmasy ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
Positive Attitude ◽  
Phase 1 ◽  
Experimental Therapy ◽  
High Expectations ◽  
Early Phase Trials ◽  
Semistructured Interviews ◽  
Two Factors ◽  
Early Phase Clinical Trials

6543 Background: Participants in early-phase clinical trials have reported high expectations of benefit from their participation. There is concern that participants misunderstand the trials to which they have consented. Such concerns are based on assumptions about what patients mean when they respond to questions about likelihood of benefit. In this study, we explored some of these assumptions. Methods: Participants were 27 women and 18 men in phase 1 or 2 oncology trials and randomized to 1 of 3 interview protocols corresponding to 3 target questions about likelihood of benefit: frequency-type (‘Out of 100 patients who participate in this study, how many do you expect will have their cancer controlled as a result of the experimental therapy?‘); belief-type (‘How confident are you that the experimental therapy will control your cancer?‘); and vague (‘What is the chance that the experimental therapy will control cancer?‘). In semistructured interviews, we queried participants about how they understood and answered the target question. Each participant then answered and discussed one of the other target questions. Results: Participants tended to provide higher expectations in response to the belief-type question (median, 80) than in response to the frequency-type or vague questions (medians, 50) (P=.02). Only 7 (16%) participants said their answers were based on what they were told during the consent process. The most common justifications for responses involved positive attitude (n=27 [60%]) and references to physical health (n=23 [51%]). References to positive attitude were most common among participants with high (>70%) expectations of benefit (n=11 [85%]) and least common among those with low (<50%) expectations of benefit (n=3 [27%]) (P=.04). Conclusions: We identified two factors that should be considered when determining whether high expectations of benefit are signs of misunderstanding. First, participants report different expectations of benefit depending on how the question is asked. Second, the justifications participants give for their answers suggest that many participants use their responses to express hope rather than to describe their understanding of the clinical trial. These findings should inform methods for evaluating the quality of informed consent in early-phase trials. No significant financial relationships to disclose.

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