scholarly journals Investigation-Based Drug Value Framework in Hodgkin Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2262-2262
Author(s):  
Ohad Oren
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Scoring System ◽  
Conflicts Of Interest ◽  
High Quality ◽  
Nccn Guidelines ◽  
Significant Toxicity ◽  
Anti Cancer ◽  
Quality Trial ◽  
High Quality Trial

Abstract Background Currently available drug value frameworks integrate data about a medication's benefits and risks. However, the strength of the research data supporting the use of one medication versus another is highly variable. The greater the number and quality of well-conducted trials underlying a certain intervention, the stronger its potential favorable contribution to public health. Drug value should therefore also be a function of the magnitude of clinical evidence gleaned from high-quality clinical trials. Methods We propose an investigation-driven value framework that determines the merit of a drug based on the overall available evidence, including the rigour of relevant trials. The NCCN Hodgkin Lymphoma guidelines were reviewed and data collected about commonly used regimens for Classic HL. Value scores were determined for each drug combination. Results A model was designed incorporating information about the number of RCTs conducted, the total number of participants enrolled, and the generalizability to real-world populations, in addition to the drug's efficacy, significant toxicity and cost (Figure 1). Practice-changing trials supporting each of the currently-endorsed regimens were collected from the HL NCCN guidelines (ABVD, 4; Stanford V 4; Esc BEACOPP 2). The average number of participants per trial was higher for ABVD (1,126) and Esc BEACOPP (1,890) than for Stanford V (267). The generalizability score for the three compounds was 0.5 (ABVD), 0.25 (Stanford V) and -1 (Esc BEACOPP). The mean 5-year overall survival rate was higher in the case of ABVD (96.2%) and Esc BEACOPP (96.1%) compared with Stanford V (92.0%). The toxicity score was 1.24 (ABVD), 3 (Stanford V) and 2.5 (Esc BEACOPP). Using a multi-factorial value scoring system, ABVD, Esc BEACOPP and Stanford V obtained 11.5, 9.5 and 8.5 points, respectively. A scoring system that focused on traditional factors alone (efficacy, toxicity, cost) yielded different scores (ABVD, 7.7; Stanford V 6.7; Esc BEACOPP, 6.5). Conclusion The robustness of clinical trials investigating anti-cancer regimens deserves special consideration when defining drug value. Three high-quality trial characteristics help stratify common regimens in HL into higher/lower value strata using a simple, easy to use algorithm. Disclosures No relevant conflicts of interest to declare.

scholarly journals Evidence-Based Guidelines Should Be Used to Inform COVID-19 Management

2020 ◽  
Author(s):  
Thomas L. Holland
Keyword(s):  
Treatment Algorithm ◽  
Trial Data ◽  
Evidence Based ◽  
High Quality ◽  
Recent Commentary ◽  
Quality Trial ◽  
High Quality Trial ◽  
Evidence Based Guidelines

A recent commentary by McCullough (1) includes a recommended COVID treatment algorithm that is outdated and parts of which are contradicted by high quality trial data.…

scholarly journals A Review of Ginseng Clinical Trials Registered in the WHO International Clinical Trials Registry Platform

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yingchun He ◽  
Juan Yang ◽  
Yinghua Lv ◽  
Junchao Chen ◽  
Fang Yin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Comprehensive Evaluation ◽  
Clinical Settings ◽  
Double Blind ◽  
Funding Sources ◽  
Quality Trial ◽  
High Quality Trial ◽  
Design Type ◽  
Duration Condition ◽  
Clinical Trials Registry

Although ginseng has long been broadly used in clinical settings around the world, few clinical trials on ginseng have been conducted. The objective of this study was to provide a comprehensive evaluation of the characteristics of ginseng clinical trials registered in the WHO International Clinical Trials Registry Platform (ICTRP) as of December 2017 regarding their frequency, design, type of ginseng, dosage, duration, condition, funding sources, and publication status. A total of 134 ginseng clinical studies were registered from 2002 to 2017, of which 60.4% were completed and 23.1% are actively recruiting participants. A large number of trials were associated with aspects of high-quality trial design. Overall, 94% of the trials employed randomized allocation to study arms, 78.4% were double-blind studies using placebo as one of the control groups, and 71% were published as completed trials. Trials whose sample size was restricted to fewer than 100 participants accounted for 74.7% of the total. Of the primary funding sources for ginseng studies, 67.2% were nonindustry organizations. The ginseng clinical trials were heterogeneous with respect to ginseng species and variety, indications, dose, duration, and participant characteristics. Clearly, stricter and methodologically suitable studies are needed to demonstrate the efficacy and safety of ginseng.

scholarly journals Children Are Not Just Small Adults: The Urgent Need for High-Quality Trial Evidence in Children

PLoS Medicine ◽  
2008 ◽  
Vol 5 (8) ◽  
pp. e172 ◽  
Author(s):  
Terry P Klassen ◽  
Lisa Hartling ◽  
Jonathan C Craig ◽  
Martin Offringa
Keyword(s):  
High Quality ◽  
Quality Trial ◽  
High Quality Trial ◽  
Trial Evidence

scholarly journals Aspirin for Primary Prevention in Adults Older than 70 Years is Not Supported by High-Quality Trial Data and May Cause Harm

2020 ◽  
Vol 133 (7) ◽  
pp. e389-e390
Author(s):  
Suzanne E. Mahady ◽  
Robyn L. Woods ◽  
Rory Wolfe ◽  
Mark R. Nelson ◽  
Anne M. Murray ◽  
...  
Keyword(s):  
Primary Prevention ◽  
Trial Data ◽  
High Quality ◽  
Quality Trial ◽  
High Quality Trial

scholarly journals A Simple Scoring System for Identifying Relapsed/Refractory Lymphoma Patients Prematurely Withdrawn from Phase I Trials: The Gustave Roussy Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1759-1759
Author(s):  
Lina Benajiba ◽  
Capucine Baldini ◽  
Laura Faivre ◽  
Jean-Marie Michot ◽  
Andrea Varga ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Hodgkin Lymphoma ◽  
Scoring System ◽  
Cell Lymphoma ◽  
Therapeutic Option ◽  
Performance Status ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Refractory Lymphoma

Abstract Background: Treating relapsed/refractory non-Hodgkin and Hodgkin lymphoma in fit young and elderly patients represents a considerable challenge for clinicians. Combined cytotoxic agents are rapidly ineffective, especially when relapse occurs after autologous stem cell transplantation (ASCT). Alternative regimens are often sparse. In the era of personalized medicine, phase I clinical trials offer an alternative therapeutic option through a multitude of immunotherapy and targeted drugs in development. Phase I trials aim to determine the recommended phase II dose (RP2D) through toxicity and pharmacokinetic assessments. Documenting signal of activity is also a major objective, underlying the importance of including patients susceptible to remain on study until first lymphoma response evaluation (usually 6 weeks, 2 cycles). We aimed to assess a simple scoring system that could identify patients who will discontinue phase I studies before 6 weeks. Patients and Methods: Data from all lymphoma patients treated within a phase I trial in Gustave Roussy (GR) Cancer Center were retrospectively collected. 83 consecutive patients were enrolled in 17 phase I trials at GR between January 2008 and May 2014. All patients had progressive lymphoma at time of enrollment, after a median of 3 prior therapeutic lines (range 1;13). 37 patients (45%) received an ASCT prior to phase I inclusion. Median age was 67 years (range: 23-92) and WHO performance status (PS) was 0 in 36 patients (43%), 1 in 43 patients (52%) and 2 in 4 patients (5%). Median time from lymphoma diagnosis to phase I inclusion was 47 months. Lymphoma histological subtypes were represented as follows: 21% Hodgkin lymphoma, 36% aggressive non-Hodgkin lymphoma (83% diffuse large B cell lymphoma, 17% T cell lymphoma), 24% indolent non-Hodgkin lymphoma (70% follicular lymphoma, 25% marginal zone lymphoma, 5% Waldenström macroglobulinemia) and 19% mantle cell lymphoma. Univariate analysis on this cohort allowed identifying simple factors significantly associated with overall survival (OS). A simple scoring system, predictive for OS was pre-established and validated through a multivariate analysis in 2 large cohorts of various hematological malignancies by our group. Statistical tests were conducted on this relapsed/refractory lymphoma cohort, to evaluate this score's OS and early study discontinuation predictive ability. Results: Within a median follow up of 19 months, median OS and progression free survival (PFS) were respectively 18 (CI95%: 12; 37) and 3 (CI95%: 1.7; 3.6) months. Best overall response rate (ORR) and disease control rate (DCR: objective response and stable disease rates) were respectively 18% and 61%. Thirty-four patients (41%) experienced grade 3 or 4 adverse events and 7 patients (8%) a dose limiting toxicity (DLT). WHO performance status (PS) > 0 at inclusion, baseline albumin ≤ 35 g/l and baseline LDH ≥ 250 UI/L were significantly associated with poorer OS. The predefined GR prognostic score combined 2 simple variables, PS and baseline serum albumin (+1 if PS 0, +1 if albumin≤ 35 g/l). In our lymphoma cohort, patients with a GR score = 0 experienced significantly better OS compared to patients with a score = 1 and a score = 2 (37 months vs 17 months vs 9 months; p = 0.007). This simple score, distinguishes patients most likely to remain on study for more than 6 weeks, considered as the minimum required period for response and toxicity evaluation (classical DLT and targeted therapies associated long term toxicities). Among patients prematurely withdrawn from clinical trials, 91% had a GR score ≥ 1 (p=0,007). Main study discontinuation reason was progressive disease (77%), drug related toxicity was only responsible for study discontinuation in 13 % of cases. Conclusion: Our data demonstrate efficacy and safety of phase I clinical trials in lymphoma, thus offering an interesting alternative therapeutic option for fit young and elderly relapsed/refractory lymphoma patients. The GR simple score, can both help in selecting patients most likely to benefit from a phase I trial (better OS) and to determine the phase II recommended dose (reduced early trial discontinuation). Disclosures No relevant conflicts of interest to declare.

Secondary MDS/AML In Hodgkin Lymphoma Patients Treated within German Hodgkin Study Group (GHSG) Clinical Trials After Introduction of the BEACOPP Protocol

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2682-2682 ◽  
Author(s):  
Dennis A. Eichenauer ◽  
Heinz Haverkamp ◽  
Karolin Behringer ◽  
Teresa Halbsguth ◽  
Michael Fuchs ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
Secondary Malignancy ◽  
Study Group ◽  
Gnrh Analogues ◽  
German Hodgkin Study Group ◽  
Increased Risk ◽  
Secondary Mds ◽  
The Impact

Abstract Abstract 2682 Background: With modern multi-agent chemotherapy regimens optionally combined with radiotherapy, even patients with advanced Hodgkin lymphoma (HL) are cured in over 80% of cases. Since there is only little room for further therapeutic improvements, one major focus of current clinical research in HL consists in reducing treatment-related late effects such as secondary malignancies. Secondary MDS/AML represents a relevant problem since it was reported to be associated with a very poor prognosis. To shed some more light on incidence, course and outcome of patients with secondary MDS/AML after HL treatment, we performed an analysis addressing this issue. Patients treated within German Hodgkin Study Group (GHSG) clinical trials after introduction of the BEACOPP protocol were included. Methods and patients: 11891 HL patients of all stages aged 16 to 75 and treated within the third (HD7-HD9, 1993–1998), fourth (HD10-HD12, 1998–2003) and fifth (HD13-HD15, 2003–2009) GHSG trial generation, the BEACOPP14 pilot study (1997-2000) and a phase II trial evaluating the role of GnRH analogues and oral contraceptives in female patients receiving BEACOPPescalated were retrospectively analyzed. Treatment consisted of radiotherapy alone, chemotherapy alone or combined-modality approaches. Results: With a median follow-up of 70 months, overall secondary MDS/AML rate was 0.8% (99 patients). However, 13 patients had a concurrent event (i.e. progress/relapse of HL or another secondary malignancy requiring salvage treatment) prior to MDS/AML diagnosis so that 86 patients were included in the present analyses. Median time from HL treatment to MDS/AML diagnosis was 28.3 months. The median age of patients developing secondary MDS/AML was significantly higher than the median age in the whole patient group (41 vs 34 years, p=.0002). To determine the impact of treatment intensity on the risk to develop secondary MDS/AML, patients were assigned into three groups. Groups consisted of patients who had received no BEACOPP-containing treatment, less than four cycles of BEACOPPescalated and four or more cycles of BEACOPPesclated, respectively. As a result, patients receiving four or more cycles of BEACOPPescalated had a significantly increased risk to develop secondary MDS/AML when compared to the other groups (5-year cumulative incidence 1.5% vs 0.5% and 0.3%, respectively, log-rank p<.0001). In 36 patients included in this analysis, allogeneic stem cell transplantation (aSCT) was applied to treat secondary MDS/AML. Patients who received aSCT had a significantly lower median age than those treated with conventional chemotherapy or supportive care only (35 vs 50 years, p=.0016) and showed an improved outcome. However, median overall survival (OS) after MDS/AML diagnosis was only 7.2 months. Conclusions: Secondary MDS/AML is a relevant problem after HL therapy particularly in patients diagnosed with advanced stages treated with intensive first-line protocols. However, the clinical benefit achieved by the use of these more intensive protocols clearly outweighs the risk of developing secondary MDS/AML. To reduce the risk of developing secondary MDS/AML, novel treatment strategies should include risk-adapted early treatment stratification based on modern tools such as positron emission tomography (PET) to prevent overtreatment whenever possible. Disclosures: No relevant conflicts of interest to declare.

Semi-Quantitative Evaluation of Pre-Transplant FDG-PET in Relapsed and Refractory Hodgkin Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2015-2015
Author(s):  
Alison Moskowitz ◽  
Jocelyn C Maragulia ◽  
Anita Kumar ◽  
Craig H. Moskowitz
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Quantitative Evaluation ◽  
Fdg Pet ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Rank Test ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Visual Interpretation

Abstract Abstract 2015 Introduction: We previously reported the prognostic impact of pre-transplant functional imaging (FI) on outcome following autologous stem cell transplant (ASCT) for patients with relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) (Moskowitz AJ, et al. Blood 2010). This analysis was based upon patients treated on 3 consecutive Memorial Sloan-Kettering Cancer Center (MSKCC) clinical trials from 1994 to 2003. The cohort included patients evaluated by gallium or FDG-PET and the 5 year event free survival (EFS) for patients with normal vs abnormal pre-transplant FI was 75% and 31% respectively. Based upon these results, our treatment program has focused on the use of FDG-PET to determine eligibility for ASCT. While determination of FI results in our series was based upon visual interpretation, we now aim to investigate whether semi-quantitative evaluation of pre-transplant FDG-PET could better distinguish favorable and less favorable cohorts. Methods: Patients with rel/ref HL treated on MSKCC clinical trials who underwent pre-salvage and pre-transplant evaluation with FDG-PET were included in this analysis. Pre-salvage and pre-transplant FDG-PET reports were reviewed and maximum SUV values for each scan were recorded. The delta-SUV was a calculation of the percent change in maximum SUV between pre-salvage and pre-transplant FDG-PET. EFS was calculated using the Kaplan-Meier method. The prognostic impact of FDG-PET results by visual interpretation and semi-quantitative interpretation was evaluated using the log-rank test. Results: One hundred and thirty nine patients with rel/ref HL treated on consecutive MSKCC clinical trials from October 2000 through August 2010 were evaluated. Of the 139 patients, 104 (75%) achieved FDG-PET normalization prior to ASCT. The median follow-up for survivors was 6 years. The 6 year EFS for FDG-PET negative and FDG-PET positive patients was 79% and 53% respectively (p<0.001, figure 1). Among the patients with abnormal pre-transplant FDG-PET, the median maximum SUV value was 4.3 and the median delta-SUV was 60%. We tested absolute pre-transplant maximum SUV values of 2, 3, 4, and 5 and we were unable to find a value of prognostic significance among FDG-PET positive patients. We tested delta-SUV values of 50%, 60%, 63%, 66%, and 72.9%. Patients with positive pre-transplant FDG-PET and ≥63% delta-SUV were found to have similar outcomes as patients with negative pre-transplant FDG-PET (p=.47, figure 2). The 6 year EFS for delta-SUV ≥63% patients was 77% compared to 44% for delta-SUV < 63% (p=0.12). Conclusion: For rel/ref HL patients undergoing ASCT, semi-quantitative evaluation of pre-transplant FDG-PET using delta-SUV of 63% identifies a favorable cohort among patients with positive pre-transplant FDG-PET. The difference in outcome for patients with ≥63% delta-SUV and < 63% delta-SUV was not statistically significant, however, likely due to the small number of FDG-PET positive patients in our series. Nevertheless, patients who achieve delta-SUV of at least 63% prior to ASCT achieved similar outcomes as those with negative pre-transplant FDG-PET. The prognostic significance of the 63% delta-SUV cutoff needs to be evaluated further in prospective studies. Disclosures: No relevant conflicts of interest to declare.

Feynman-Kac path-integral calculations with high-quality trial wave functions

2000 ◽  
Vol 61 (3) ◽  
Author(s):  
Sumita Datta ◽  
J. L. Fry ◽  
N. G. Fazleev ◽  
S. A. Alexander ◽  
R. L. Coldwell
Keyword(s):  
Path Integral ◽  
Wave Functions ◽  
High Quality ◽  
Quality Trial ◽  
High Quality Trial

Multifunctional Anti-Cancer Nano-Platforms are Moving to Clinical Trials

2013 ◽  
Vol 14 (5) ◽  
pp. 583-604 ◽  
Author(s):  
Claudio Esposito ◽  
Annalisa Crema ◽  
Antonio Ponzetto ◽  
Giovanni Murtas ◽  
Guido Carloni
Keyword(s):  
Clinical Trials ◽  
Anti Cancer

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Review Article ◽  
Therapeutic Drug ◽  
Akt Signaling Pathway ◽  
Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

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