Characterization and implications of daily pain variability and response to treatment in osteoarthritis clinical trials

2021 ◽  
Vol 29 ◽  
pp. S277
Author(s):  
C. Bonin Pinto ◽  
J. Barroso ◽  
T.J. Schinitzer
Keyword(s):  
Clinical Trials ◽  
Response To Treatment ◽  
Daily Pain

scholarly journals Bone markers and osteoporosis therapy

2014 ◽  
Vol 58 (5) ◽  
pp. 504-513 ◽  
Author(s):  
Francisco Bandeira ◽  
Aline G. Costa ◽  
Manoel Aderson Soares Filho ◽  
Larissa Pimentel ◽  
Lourena Lima ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Bone Density ◽  
Bone Markers ◽  
Continuous Process ◽  
Osteoporosis Treatment ◽  
Response To Treatment ◽  
Cortical Porosity ◽  
Osteoporosis Therapy ◽  
Turn Over ◽  
Valid Information

Several factors are involved in determining bone quality including bone density, bone turnover, the extent of trabecular bone connectivity, cortical porosity and geometry. Metabolically active and in a continuous process of remodeling, approximately 20% of bone tissue is renewed annually. Bone turn over markers (BTM) are frequently used in clinical trials and to provide valid information about the effectiveness of osteoporosis treatment, reflecting the state of bone metabolism and its response to treatment, although they are not useful alone to estimate bone loss. In this review the behavior of BTM from different clinical trials or different osteoporotic drugs will be addressed.

scholarly journals Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials

Blood ◽  
2019 ◽  
Vol 133 (10) ◽  
pp. 1020-1030 ◽  
Author(s):  
U. Platzbecker ◽  
P. Fenaux ◽  
L. Adès ◽  
A. Giagounidis ◽  
V. Santini ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Myelodysplastic Syndromes ◽  
Working Group ◽  
Lower Risk ◽  
Response Assessment ◽  
Response To Treatment ◽  
Response Criteria ◽  
Patient Response ◽  
Erythroid Response ◽  
Clinical Responses

Abstract The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for “hematological improvement” criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between “procedures” and “criteria” for hematologic improvement–erythroid assessment and a new categorization of transfusion-burden subgroups.

scholarly journals Contemporary Tailored Oncology Treatment of Biliary Tract Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Fiona Turkes ◽  
Juliet Carmichael ◽  
David Cunningham ◽  
Naureen Starling
Keyword(s):  
Clinical Trials ◽  
Biliary Tract ◽  
Treatment Options ◽  
Prognostic Significance ◽  
Response To Treatment ◽  
Genomic Profiling ◽  
Biliary Tract Cancers ◽  
Comprehensive Genomic Profiling ◽  
Genomic Aberrations ◽  
Oncology Treatment

Biliary tract cancers (BTCs) are poor prognosis malignancies with limited treatment options. Capecitabine has recently emerged as an effective agent in the adjuvant setting; however, treatment of advanced disease is still limited to first-line cisplatin and gemcitabine chemotherapy. Recent global efforts in genomic profiling and molecular subtyping of BTCs have uncovered a wealth of genomic aberrations which may carry prognostic significance and/or predict response to treatment, and several targeted agents have shown promising results in clinical trials. As such, the uptake of comprehensive genomic profiling for patients with BTCs and the expansion of basket trials to include these patients are growing. This review describes the currently approved systemic therapies for BTCs and provides insight into the emerging targeted and immunotherapeutic agents, as well as conventional chemotherapeutic regimes, currently being investigated in clinical trials.

scholarly journals Current Concepts in Pharmacometabolomics, Biomarker Discovery, and Precision Medicine

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 129 ◽  
Author(s):  
Richard D. Beger ◽  
Michael A Schmidt ◽  
Rima Kaddurah-Daouk
Keyword(s):  
Clinical Trials ◽  
Drug Treatment ◽  
Precision Medicine ◽  
Metabolic Profile ◽  
Biomarker Discovery ◽  
Response To Treatment ◽  
Individual Response ◽  
Patient Response ◽  
Drug Mechanism ◽  
The Individual

Pharmacometabolomics (PMx) studies use information contained in metabolic profiles (or metabolome) to inform about how a subject will respond to drug treatment. Genome, gut microbiome, sex, nutrition, age, stress, health status, and other factors can impact the metabolic profile of an individual. Some of these factors are known to influence the individual response to pharmaceutical compounds. An individual’s metabolic profile has been referred to as his or her “metabotype.” As such, metabolomic profiles obtained prior to, during, or after drug treatment could provide insights about drug mechanism of action and variation of response to treatment. Furthermore, there are several types of PMx studies that are used to discover and inform patterns associated with varied drug responses (i.e., responders vs. non-responders; slow or fast metabolizers). The PMx efforts could simultaneously provide information related to an individual’s pharmacokinetic response during clinical trials and be used to predict patient response to drugs making pharmacometabolomic clinical research valuable for precision medicine. PMx biomarkers can also be discovered and validated during FDA clinical trials. Using biomarkers during medical development is described in US Law under the 21st Century Cures Act. Information on how to submit biomarkers to the FDA and their context of use is defined herein.

Trajectories of response to treatment with atypical antipsychotic medication in patients with schizophrenia pooled from 6 double-blind, randomized clinical trials

2011 ◽  
Vol 130 (1-3) ◽  
pp. 11-19 ◽  
Author(s):  
Virginia Stauffer ◽  
Michael Case ◽  
Sara Kollack-Walker ◽  
Haya Ascher-Svanum ◽  
Tamara Ball ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Atypical Antipsychotic ◽  
Antipsychotic Medication ◽  
Randomized Clinical Trials ◽  
Response To Treatment ◽  
Double Blind ◽  
Atypical Antipsychotic Medication

scholarly journals The Emerging Role of c-Met in Carcinogenesis and Clinical Implications as a Possible Therapeutic Target

2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Antonio Faiella ◽  
Ferdinando Riccardi ◽  
Giacomo Cartenì ◽  
Martina Chiurazzi ◽  
Livia Onofrio
Keyword(s):  
Clinical Trials ◽  
Epithelial Mesenchymal Transition ◽  
Target Therapy ◽  
Treatment Options ◽  
Survival Rates ◽  
Response To Treatment ◽  
Tyrosine Kinase Receptor ◽  
Mesenchymal Transition ◽  
Surface Receptors ◽  
Clinical Consequences

Background. c-MET is a receptor tyrosine kinase receptor (RTK) for the hepatocyte growth factor (HGF). The binding of HGF to c-MET regulates several cellular functions: differentiation, proliferation, epithelial cell motility, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, it is known to be involved in carcinogenesis. Comprehension of HGF-c-MET signaling pathway might have important clinical consequences allowing to predict prognosis, response to treatment, and survival rates based on its expression and dysregulation. Discussion. c-MET represents a useful molecular target for novel engineered drugs. Several clinical trials are underway for various solid tumors and the development of new specific monoclonal antibodies depends on the recent knowledge about the definite c-MET role in each different malignance. Recent clinical trials based on c-MET molecular targets result in good safety profile and represent a promising therapeutic strategy for solid cancers, in monotherapy or in combination with other target drugs. Conclusion. The list of cell surface receptors crosslinking with the c-MET signaling is constantly growing, highlighting the importance of this pathway for personalized target therapy. Research on the combination of c-MET inhibitors with other drugs will hopefully lead to discovery of new effective treatment options.

scholarly journals Clinical trials in multiple sclerosis: potential future trial designs

2019 ◽  
Vol 12 ◽  
pp. 175628641984709 ◽  
Author(s):  
Navid Manouchehri ◽  
Yinan Zhang ◽  
Amber Salter ◽  
Rehana Z. Hussain ◽  
Hans-Peter Hartung ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Study Groups ◽  
Response To Treatment ◽  
Disease Biomarkers ◽  
Disease Modifying Therapies ◽  
Early Validation ◽  
Response Profiles ◽  
New Treatments ◽  
Individual Disease

Clinical trials of new treatments in multiple sclerosis (MS) currently require large sample sizes and long durations in order to yield reliable results. The differential responses of an already heterogeneous population of MS patients to individual disease-modifying therapies (DMTs) will further complicate future trials. MS trials with smaller samples and faster outcomes are conceivable through the substitution of current clinical and MRI outcomes with objectively measureable genomic and proteomic biomarkers. Currently, biomarkers that could be utilized for diagnosis and monitoring of MS disease activity are in the early validation phase. The power of single biomarkers or multiple correlated biomarkers to predict prognosis and response to treatment could initially be compared with currently accepted methods. These prospectively validated disease biomarkers could then be used to subcategorize the spectrum of MS patients into a finite number of endophenotypes with demonstrable different molecular pathogeneses and DMT response profiles. Newly developed DMT could potentially be assessed within specific endophenotypes and compared with pharmacogenomically relevant active comparator DMT. This approach may increase the efficiency of MS trials through homogenization of patient population and minimization of nonresponders in study groups, providing the potential for the development of targeted therapies.

Molecular Characterization and Clinical Utility of Circulating Tumor Cells in the Treatment of Prostate Cancer

2014 ◽  
pp. e197-e203 ◽  
Author(s):  
David Lorente ◽  
Joaquin Mateo ◽  
Johann S. de Bono
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Tumor Cells ◽  
Molecular Characterization ◽  
Circulating Tumor Cells ◽  
Predictive Biomarkers ◽  
Phase Iii ◽  
Response To Treatment ◽  
Molecular Characteristics ◽  
Wide Range

Circulating tumor cells (CTCs) are rare cancer cells that can be detected in the blood of patients with solid malignancies. The Veridex CellSearch Assay was analytically and clinically validated, and has received U.S. Food and Drug Administration (FDA) clearance for the enumeration of CTCs in breast, colorectal, and prostate cancer. A number of alternative assays, with potential advantages, are currently undergoing clinical and/or analytic validation before their routine use can be established. In prostate cancer, high pretreatment CTC counts have been associated with worse survival, and changes in CTC counts in response to treatment have been established as indicators of response to treatment. Additional analyses are ongoing to establish the value of CTC counts as a surrogate of survival in prospective, phase III trials, which could influence the process of drug development and regulatory approval. Additionally, CTCs have a potential role in the molecular characterization of prostate cancer, serving as “liquid biopsies” to determine the molecular characteristics of the disease. The study of androgen receptor (AR) mutations or amplification, chromosomal rearrangements, or the determination of DNA repair biomarkers has been evaluated in clinical trials. CTCs have a wide range of potential applications, from their prognostic use in stratification of patients in clinical trials or the assessment of response to treatment, to the pharmacodynamic evaluation of novel agents, or the discovery and use of predictive biomarkers that can aid in the development of personalized medicine.

Clinical Features of Depression and the Response to Imipramine (“Tofranil”)

1962 ◽  
Vol 108 (452) ◽  
pp. 101-104 ◽  
Author(s):  
J. J. Fleminger ◽  
Bernard M. Groden
Keyword(s):  
Clinical Trials ◽  
Clinical Features ◽  
Antidepressant Drugs ◽  
Depressive Illness ◽  
Response To Treatment ◽  
Depressive State ◽  
Important Place ◽  
Depressed Patients ◽  
Better Than

Since it was first reported by Kuhn in 1957, the value of imipramine in the treatment of depressive illness has become generally recognized and confirmed by clinical trials (Blair, 1960; Daneman, 1961; Rees et al., 1961). It continues to hold an important place in therapy despite the introduction of many other antidepressant drugs and the occasional adverse report (Ashby & Collins 1961). Nevertheless the indications for its use are by no means established. It has been claimed that certain types of depression respond better than others: “psychotic” better than “neurotic” (Azima, 1959), “endogenous” better than “reactive” (Ball and Kiloh, 1959). Yet the difficulty of making these categorical distinctions, and of making reliable comparisons between the findings based upon them by different workers remains notorious. It is clear, however, that only a proportion of depressed patients respond well to imipramine. It is also certain that within the group which does respond well are to be found representatives of every type and degree of depressive state. There is evident need, therefore, for information that will help to indicate which characteristics of an individual will render him more or less susceptible to imipramine, and there does not appear to have been any study particularly devoted to this. In this paper we give the results of correlating certain clinical features of depression with the response to treatment by this drug.

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