Evaluation of Clinical Utility and Validation of Gene Signatures in Clinical Trials

2015 ◽  
pp. 205-222
Keyword(s):  
Clinical Trials ◽  
Clinical Utility ◽  
Gene Signatures

scholarly journals Genetic testing for choroideremia

2017 ◽  
Vol 1 (s1) ◽  
pp. 26-28
Author(s):  
Andi Abeshi ◽  
Alessandra Zulian ◽  
Tommaso Beccari ◽  
Munis Dundar ◽  
Francesco Viola ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Clinical Trials ◽  
Optical Coherence Tomography ◽  
Differential Diagnosis ◽  
Clinical Utility ◽  
Scientific Literature ◽  
Genetic Test ◽  
Fundus Autofluorescence ◽  
Clinical Findings ◽  
Ophthalmological Examination

Abstract We studied the scientific literature and disease guidelines in order to summarize the clinical utility of the genetic test for choroideremia (CHM). CHM is an inherited X-linked recessive disorder associated with variations in the CHM gene. The overall prevalence of CHM varies from 1 in 50 000 to 1 in 100 000. Clinical diagnosis is based on clinical findings, ophthalmological examination, visual field, fundus autofluorescence, optical coherence tomography and electroretinography. The genetic test is useful for confirming diagnosis and for differential diagnosis, couple risk assessment and access to clinical trials.

scholarly journals Targeting Multiple Aminoacyl-tRNA Synthetases Overcomes the Resistance Liabilities Associated with Antibacterial Inhibitors Acting on a Single Such Enzyme

2016 ◽  
Vol 60 (10) ◽  
pp. 6359-6361 ◽  
Author(s):  
Christopher P. Randall ◽  
Dace Rasina ◽  
Aigars Jirgensons ◽  
Alex J. O'Neill
Keyword(s):  
Clinical Trials ◽  
High Frequency ◽  
Drug Targets ◽  
Clinical Utility ◽  
Bacterial Resistance ◽  
Antibacterial Drug ◽  
Resistance Development ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Potential Clinical Utility

ABSTRACTBacterial aminoacyl-tRNA synthetases (aaRSs) represent promising antibacterial drug targets. Unfortunately, the aaRS inhibitors that have to date reached clinical trials are subject to rapid resistance development through mutation, a phenomenon that limits their potential clinical utility. Here, we confirm the intuitively correct idea that simultaneous targeting of two different aaRS enzymes prevents the emergence of spontaneous bacterial resistance at high frequency, a finding that supports the development of multitargeted anti-aaRS therapies.

Ultrasound-mediated targeted drug delivery: recent success and remaining challenges

2013 ◽  
Vol 304 (3) ◽  
pp. H350-H357 ◽  
Author(s):  
Jason Castle ◽  
Matthew Butts ◽  
Andrew Healey ◽  
Kevin Kent ◽  
Michael Marino ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Drug Delivery System ◽  
Targeted Drug Delivery ◽  
Clinical Utility ◽  
Clinical Value ◽  
Recent Success ◽  
Targeted Drug ◽  
Successes And Challenges ◽  
Scientific Validation

The potential clinical value of developing a novel, nonviral, ultrasound-directed gene and drug delivery system is immense. Investigators soon will initiate clinical trials with the goal of treating a wide variety of maladies using noninvasive, ultrasound-based technology. The ongoing, scientific validation associated with promising preclinical success portents a novel range of therapeutics. The clinical utility and eventual clinical successes await vigorous testing. This review highlights the recent successes and challenges within the field of ultrasound-mediated drug delivery.

Measures of Response: RECIST, WHO, and New Alternatives

2006 ◽  
Vol 24 (20) ◽  
pp. 3245-3251 ◽  
Author(s):  
C. Carl Jaffe
Keyword(s):  
Clinical Trials ◽  
Clinical Utility ◽  
Evaluation Criteria ◽  
Response To Therapy ◽  
Added Value ◽  
Molecular Response ◽  
Clinical Events ◽  
Wide Acceptance ◽  
Positron Emission ◽  
Ready Availability

RECIST (Response Evaluation Criteria in Solid Tumors) is a widely employed method introduced in 2000 to assess change in tumor size in response to therapy. The simplicity of the technique, however, contrasts sharply with the increasing sophistication of imaging instrumentation. Anatomically based imaging measurement, although supportive of drug development and key to some accelerated drug approvals, is being pressed to improve its methodologic robustness, particularly in the light of more functionally-based imaging that is sensitive to tissue molecular response such as fluorodeoxyglucose positron emission tomography. Nevertheless ready availability of computed tomography and magnetic resonance imaging machines largely assures anatomically based imaging a continuing role in clinical trials for the foreseeable future. Recent advances in image processing enabled by the computational power of modern clinical scanners open a considerable opportunity to characterize tumor response to therapy as a complement to image acquisition. Various alternative quantitative volumetric approaches have been proposed but have yet to gain wide acceptance by clinical and regulatory communities, nor have these more complex techniques shown incontrovertible evidence of greater reproducibility or predictive value of clinical events and outcome. Unless plans are created for clinical trials that incorporate the design needed to prove the added value and unique clinical utility of these novel approaches, any theoretical benefit of these more elaborate methods could remain unfulfilled.

scholarly journals Genetic testing for lymphedema-distichiasis syndrome

2018 ◽  
Vol 2 (s1) ◽  
pp. 13-15
Author(s):  
Yeltay Rakhmanov ◽  
Paolo Enrico Maltese ◽  
Stefano Paolacci ◽  
Carla Marinelli ◽  
Matteo Bertelli
Keyword(s):  
Risk Assessment ◽  
Clinical Trials ◽  
Differential Diagnosis ◽  
Genetic Testing ◽  
Clinical Utility ◽  
Autosomal Dominant ◽  
Scientific Literature ◽  
Genetic Test ◽  
Double Row ◽  
Primary Lymphedema

AbstractWe studied the scientific literature and disease guidelines to summarize the clinical utility of genetic testing for lymphedema distichiasis (LD) syndrome. LD is inherited in an autosomal dominant manner, and has unknown prevalence. It is caused by variations in the FOXC2 gene. Clinical diagnosis involves clinical examination, targeted at identifying primary lymphedema (chronic swelling of the extremities) and distichiasis (double row of eyelashes). The genetic test is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

scholarly journals Impact of Variable RNA-Sequencing Depth on Gene Expression Signatures and Target Compound Robustness: Case Study Examining Brain Tumor (Glioma) Disease Progression

2018 ◽  
pp. 1-17 ◽  
Author(s):  
Alexey Stupnikov ◽  
Paul G. O’Reilly ◽  
Caitriona E. McInerney ◽  
Aideen C. Roddy ◽  
Philip D. Dunne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Tumor ◽  
Clinical Utility ◽  
Gene Signature ◽  
Sequencing Depth ◽  
Rna Seq ◽  
Data Loss ◽  
Target Compound ◽  
Gene Signatures ◽  
Connectivity Mapping

Purpose Gene expression profiling can uncover biologic mechanisms underlying disease and is important in drug development. RNA sequencing (RNA-seq) is routinely used to assess gene expression, but costs remain high. Sample multiplexing reduces RNA-seq costs; however, multiplexed samples have lower cDNA sequencing depth, which can hinder accurate differential gene expression detection. The impact of sequencing depth alteration on RNA-seq–based downstream analyses such as gene expression connectivity mapping is not known, where this method is used to identify potential therapeutic compounds for repurposing. Methods In this study, published RNA-seq profiles from patients with brain tumor (glioma) were assembled into two disease progression gene signature contrasts for astrocytoma. Available treatments for glioma have limited effectiveness, rendering this a disease of poor clinical outcome. Gene signatures were subsampled to simulate sequencing alterations and analyzed in connectivity mapping to investigate target compound robustness. Results Data loss to gene signatures led to the loss, gain, and consistent identification of significant connections. The most accurate gene signature contrast with consistent patient gene expression profiles was more resilient to data loss and identified robust target compounds. Target compounds lost included candidate compounds of potential clinical utility in glioma (eg, suramin, dasatinib). Lost connections may have been linked to low-abundance genes in the gene signature that closely characterized the disease phenotype. Consistently identified connections may have been related to highly expressed abundant genes that were ever-present in gene signatures, despite data reductions. Potential noise surrounding findings included false-positive connections that were gained as a result of gene signature modification with data loss. Conclusion Findings highlight the necessity for gene signature accuracy for connectivity mapping, which should improve the clinical utility of future target compound discoveries.

scholarly journals Implementation and Clinical Utility of an Integrated Academic-Community Regional Molecular Tumor Board

2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mark E. Burkard ◽  
Dustin A. Deming ◽  
Benjamin M. Parsons ◽  
Paraic A. Kenny ◽  
Marissa R. Schuh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Precision Medicine ◽  
Clinical Utility ◽  
Journal Club ◽  
Academic Community ◽  
Tumor Board ◽  
Observational Research ◽  
Evidence Based ◽  
Precision Oncology ◽  
Molecular Tumor Board

Purpose Precision oncology develops and implements evidence-based personalized therapies that are based on specific genetic targets within each tumor. However, a major challenge that remains is the provision of a standardized, up-to-date, and evidenced-based precision medicine initiative across a geographic region. Materials and Methods We developed a statewide molecular tumor board that integrates academic and community oncology practices. The Precision Medicine Molecular Tumor Board (PMMTB) has three components: a biweekly Web-based teleconference tumor board meeting provided as a free clinical service, an observational research registry, and a monthly journal club to establish and revise evidence-based guidelines for off-label therapies. The PMMTB allows for flexible and rapid implementation of treatment, uniformity in practice, and the ability to track outcomes. Results We describe the implementation of the PMMTB and its first year of activity. Seventy-seven patient cases were presented, 48 were enrolled in a registry, and 38 had recommendations and clinical follow-up. The 38 subjects had diverse solid tumors (lung, 45%; GI, 21%; breast, 13%; other, 21%). Of these subjects, targeted therapy was recommended for 32 (84%). Clinical trials were identified for 24 subjects (63%), and nontrial targeted medicines for 16 (42%). Nine subjects (28%) received recommended therapy with a response rate of 17% (one of six) and a clinical benefit rate (partial response + stable disease) of 38% (three of eight). Although clinical trials often were identified, patients rarely enrolled. Conclusion The PMMTB provides a model for a regional molecular tumor board with clinical utility. This work highlights the need for outcome registries and improved access to clinical trials to pragmatically implement precision oncology.

Clinical utility of targeted next generation sequencing assay in IDH-wildtype glioblastoma for therapy decision-making

2021 ◽  
Author(s):  
Mary Jane Lim-Fat ◽  
Gilbert C Youssef ◽  
Mehdi Touat ◽  
J Bryan Iorgulescu ◽  
Sydney Whorral ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Clinical Utility ◽  
Clinical Care ◽  
Clinical Trial Design ◽  
Off Label ◽  
Survival Difference ◽  
Clinical Trial Enrollment ◽  
Clinical Records

Abstract BACKGROUND Targeted gene NGS testing is available through many academic institutions and commercial entities and is increasingly incorporated in practice guidelines for glioblastoma (GBM). This single-center retrospective study aimed to evaluate the clinical utility of incorporating NGS results in the management of GBM patients at a clinical trials-focused academic center. METHODS We identified 1,011 consecutive adult patients with pathologically confirmed GBM (IDHwt or IDHmut) who had somatic tumor sequencing (Oncopanel, ~500 cancer gene panel) at DFCI from 2013-2019. Clinical records of all IDHwt GBM patients were reviewed to capture clinical trial enrollment and off-label targeted therapy use based on NGS results. RESULTS Of the 557 IDHwt GBM patients with sequencing, 182 entered clinical trials at diagnosis (32.7%) and 213 (38.2%) entered after recurrence. Sequencing results for 130 patients (23.3%) were utilized for clinical trial enrollment for either targeted therapy indications (6.9 % upfront and 27.7% at recurrent clinical trials and 3.1% for off-label targeted therapy) or exploratory studies (55.4% upfront and 6.9% recurrent clinical trials). Median overall survival was 20.1 months with no survival difference seen between patients enrolled in clinical trials compared to those who were not, in a post hoc analysis. CONCLUSIONS While NGS testing has become essential for improved molecular diagnostics, our study illustrates that targeted gene panels remain underutilized for selecting therapy in GBM-IDHwt. Targeted therapy and clinical trial design remain to be improved to help leverage the potential of NGS in clinical care.

Sign in / Sign up

Export Citation Format

Share Document