Background: Indirect comparisons of competing treatments by network meta-analysis (NMA) are incre... more Background: Indirect comparisons of competing treatments by network meta-analysis (NMA) are increasingly in use. Reporting bias has received little attention in this context. We aimed to assess the impact of such bias in NMAs. Methods: We used data from 74 FDA-registered placebo-controlled trials of 12 antidepressants and their 51 matching publications. For each dataset, NMA was used to estimate the effect sizes for 66 possible pair-wise comparisons of these drugs, the probabilities of being the best drug and ranking the drugs. To assess the impact of reporting bias, we compared the NMA results for the 51 published trials and those for the 74 FDA-registered trials. To assess how reporting bias affecting only one drug may affect the ranking of all drugs, we performed 12 different NMAs for hypothetical analysis. For each of these NMAs, we used published data for one drug and FDA data for the 11 other drugs. Findings: Pair-wise effect sizes for drugs derived from the NMA of published data and those from the NMA of FDA data differed in absolute value by at least 100% in 30 of 66 pair-wise comparisons (45%). Depending on the dataset used, the top 3 agents differed, in composition and order. When reporting bias hypothetically affected only one drug, the affected drug ranked first in 5 of the 12 NMAs but second (n = 2), fourth (n = 1) or eighth (n = 2) in the NMA of the complete FDA network. Conclusions: In this particular network, reporting bias biased NMA-based estimates of treatments efficacy and modified ranking. The reporting bias effect in NMAs may differ from that in classical meta-analyses in that reporting bias affecting only one drug may affect the ranking of all drugs.
L’analyse de donnee textuelle est facilitee par l’utilisation du text mining (TM) permettant l’au... more L’analyse de donnee textuelle est facilitee par l’utilisation du text mining (TM) permettant l’automatisation de l’analyse de contenu et possede de nombreuses applications en sante. L’une d’entre elles est l’utilisation du TM pour explorer le contenu des messages echanges sur Internet.Nous avons effectue une revue de la litterature systematique afin d’identifier les applications du TM en sante mentale. De plus, le TM a permis d’explorer les preoccupations des utilisateurs du forum Doctissimo.com au sujet des antidepresseurs et anxiolytiques entre 2013 et 2015 via l’analyse des frequences des mots, des cooccurrences, de la modelisation thematique (LDA) et de la popularite des themes.Les quatre applications du TM en sante mentale sont l’analyse des recits des patients (psychopathologie), le ressenti exprime sur Internet, le contenu des dossiers medicaux, et les themes de la litterature medicale. Quatre grands themes ont ete identifies sur le forum: le sevrage (le plus frequent), l’esc...
Introduction: Dupilumab (DPL), a fully human anti-interleukin (IL)-4 Rα monoclonal antibody, inhi... more Introduction: Dupilumab (DPL), a fully human anti-interleukin (IL)-4 Rα monoclonal antibody, inhibits IL-4/IL-13 signalling, and improves endoscopic, radiographic, and clinical endpoints in patients (pts) with CRSwNP and asthma. Aims: Evaluate DPL effect on each of the 5 items of the Asthma Control Questionnaire (ACQ-5) in pts with CRSwNP and asthma. Methods: CRSwNP pts refractory to intranasal corticosteroids were assigned to weekly doses of DPL 300 mg s.c. or placebo (PBO), with mometasone furoate nasal spray. Asthma control was assessed using ACQ-5 at baseline and at Week 16. Results: Of 60 pts enrolled, 58.3% had asthma and used asthma medications. DPL showed clinically relevant improvements in total ACQ-5 (Table). Differences vs PBO were significant for each of the 5 items assessing asthma symptoms (shortness of breath; wheezing time; awake in the morning with symptoms), activity limitation and night-time awakenings (Table). Asthma-control improvement correlated with improvement in pt-reported outcomes (visual analogue scale; 22-item Sino-Nasal Outcome Test) and nasal polyp score. Injection-site reactions, headache, and nasopharyngitis were the most frequently reported adverse events with DPL. Conclusion: In CRSwNP pts with asthma, DPL significantly improved all asthma-related items. Improvement correlated with reduced nasal polyp burden.
Article type : Original Article: Experimental Allergy and Immunology Dupilumab improves health-re... more Article type : Original Article: Experimental Allergy and Immunology Dupilumab improves health-related quality of life in patients with chronic rhinosinusitis with nasal polyposis
Abstract 5074 Background NHL is the 10th most common cancer worldwide, and a major cause of cance... more Abstract 5074 Background NHL is the 10th most common cancer worldwide, and a major cause of cancer-related deaths despite major advances in therapy (GLOBOCAN 2008). It encompasses a heterogeneous group of hematological malignancies originating in lymphoid tissue, mainly B lymphocytes (B-cell NHL) with an overall 5-year survival of 50–60%. There is lack of published data on the distribution of patients across lines of therapy and by subtype. Method Epidemiological data was obtained for US and EU using the 'epic oncology' 2012 database (Epiphany Partners Inc.). The database includes line of therapy estimations using an advanced patient flow model combining survival by subset and course of treatment, response rates and outcomes, and treatment data from U. S. and EU cancer registries coupled with primary research with a representative sample of physicians and secondary therapeutic reviews. We analyzed projection estimates up to 2020 across US and EU5 countries by subtype and line of therapy with specific attention to relapsed/refractory patients. Refractory patients are those who do not respond (do not go into remission) following therapy. Relapsed patients are defined as those who have responded to therapy (enter remission) who then re-enter the treatment population due to progression of their cancer, recurrence of diagnostic markers, or symptomatology. Result Projection estimates from 2010 to 2020 by line of therapy varied by country. Among EU countries the highest number of treated patients was in Italy followed by Germany and UK. By 2020, the percentage of patients that will have relapsed and/or be refractory to all lines of therapy will increase by about 35% in US and 11% in EU with regional variation observed among France (18%), Italy (15. 2%), Spain (3%), and UK (18%). In both the US and EU, about 30% of patients relapse and 20% are refractory after 1st line treatment. In 2nd as well as 3rd line, about 35% relapse or are refractory after treatment in the respective lines. In the US, the percent increase from 2010 to 2020 by line of therapy (1st, 2nd, 3rd) is greatest for MCL patients (55, 58, 59%) followed by FL (40, 49, 41%) and DLBCL (28, 33, and 36%). Epidemiology projection trends for US and EU by line of therapy and sub type Conclusion Due to the indolent or aggressive nature of NHL, the proportion of patients who will progress from 1st line to 2nd line therapy varies between 35% in US and 29% in EU based on current treatment options. This, along with the high percentage of relapsed and refractory patients in 2nd or higher lines argues for continued efforts to be made for the development of more efficacious treatments for NHL. The observed three fold difference between US and EU increase could be due to an increased incidence in recent historical years or an association between one or more of the risk factors, such as hepatitis C, which is more common in US or autoimmune disorders such as HIV. Real world data and disease based registries can help in validating emerging trends in therapy through providing up to date global projection estimates across line of therapy. Disclosures: Trask: Sanofi: Employment. Mehta:Sanofi: Employment. Abbe:Sanofi: Employment, Equity Ownership. RuizSoto:Sanofi: Employment.
Abstract 4782 Background: Hodgkin lymphoma represents 11.7% of all types of lymphoma diagnosed in... more Abstract 4782 Background: Hodgkin lymphoma represents 11.7% of all types of lymphoma diagnosed in 2011. (Leukemia and Lymphoma Society) In 2012, an estimated 9,060 of new HL cases and 1,190 deaths will occur in North America and mostly in either young adults between 15 and 30 years of age, or after the age of 45. (American Cancer Society) The five-year relative survival rate for all patients with HL is 86.3% from 2001 to 2007 and 92.8% for patients less than 45 years at diagnosis. (SEER Review) Initial treatment of HL depends on the stage of the disease at diagnosis. Chemotherapy with or without radiation therapy is the most common treatment approach for HL patients. Stem cell transplantation and chemotherapy are the treatment options for patients with relapse disease. There is lack of published data on the distribution of patients across lines of therapy as well as percentage of relapsed and refractory patients. Understanding the distribution of patients across lines of therapy is critical to identify the unmet need and to help tailor future therapies. Methods: Epidemiological data was obtained for US and EU using the 'epic oncology' 2012 database (Epiphany Partners Inc.). The database includes line of therapy estimations using an advanced patient flow model combining survival by subset and course of treatment, response rates and outcomes, and treatment data from US and EU cancer registries coupled with primary research with a representative sample of physicians and secondary therapeutic reviews. We analyzed projection estimates up to 2020 across US and EU5 countries by line of therapy with specific attention to relapsed/refractory patients. These projection estimates are based on the current treatment options and does not account for introduction of future therapies. Refractory patients are defined as those who do not respond (do not go into remission) following therapy. Relapsed Patients are defined as those who have responded to therapy (enter remission) but re-enter the treatment population at a later stage due to progression of their cancer, recurrence of diagnostic markers, or symptomatology. Results: Projection estimates from 2010 to 2020 by line of therapy varied by country. Among EU countries, the highest number of treated HL patients was in France, followed by Italy and Spain. By 2020, the percentage of patients that are either relapsed or refractory to first, second and third line of therapy will increase by about 25% in US and by about 15% in EU. Regional variation observed across Europe are as follows: an increase by 38% in Spain, 25% in France, 12% in UK and 6% in Italy, while Germany will show a decline of 2%, this is due to a continuous decline in incidence rates since the early 1990s. Drug treated Hodgkin lymphoma population by line of therapy*: Conclusions: Due to the highly chemosensitive nature of the malignancy, only about 25% of Hodgkin lymphoma patients progress to a second line therapy and 30% of those move into third line. Smaller sample sizes, variation in growth rate among US and EU countries, and a bimodal incidence curve could cause differences in projection trends. The creation of a Hodgkin's disease based registry can help in validating emerging trends in therapy through providing up to date global projection estimates across line of therapy. Our results provide a global understanding of the HL patient population distribution across lines of therapy and are critical to identify the unmet need and guide future therapies in HL patients. Disclosures: Mehta: Sanofi: Employment. Abbe:Sanofi: Employment, Equity Ownership. Trask:Sanofi: Employment. Neumann:Sanofi-aventis: Employment. Hamed:Sanofi: Employment.
A systematic literature review was performed to collect and review information on the clinical ef... more A systematic literature review was performed to collect and review information on the clinical efficacy and safety of treatments for relapsed/refractory (R/R) mantle cell lymphoma (MCL), with a meta-analysis, if possible. PubMed, Embase, and the Cochrane Library were searched for studies published in English from January 1, 1997, to August 2, 2012. Conference proceedings, bibliographic reference lists of included articles, recent reviews, and ClinicalTrials.gov were searched for phase II to IV studies displaying results. Studies were included if they reported on patients with R/R MCL who were ineligible to receive high-dose chemotherapy with stem cell transplant. Studies of patients with several non-Hodgkin lymphoma subtypes were only included if they reported MCL outcomes separately. We identified 59 studies in R/R MCL. Forty distinct treatment regimens were evaluated. Thirty studies included more than 15 patients with R/R MCL. Six studies were comparative (including 5 randomized controlled trials [RCTs]); 53 were single-arm. There were no common treatments among the RCTs; therefore, a meta-analysis was not feasible. Thirty-one of 59 studies reported baseline data for patients with R/R MCL. Of the 30 studies with > 15 patients with R/R MCL, 30 reported overall response rate data, 14 reported progression-free survival (PFS), and 12 reported overall survival (OS). The small number of RCTs in R/R MCL precludes identifying an optimal treatment. Small sample sizes, infrequent reporting of OS and PFS, and limited information on patient characteristics made a comparison of results difficult. High-quality comparative studies of novel therapies that have the potential to demonstrate OS advantages in R/R MCL are needed.
Clinical Lymphoma, Myeloma & Leukemia, Oct 1, 2014
This systematic literature review was designed to assess information on the clinical efficacy and... more This systematic literature review was designed to assess information on the clinical efficacy and safety of interventions used in the treatment of refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL) and to perform a metaanalysis if possible. We searched databases (PubMed, EMBASE, and Cochrane Library for articles from 1997 to August 2, 2012 reported in English), conference abstracts, bibliographic reference lists, and the ClinicalTrials.gov database for phase II to IV studies with results. Studies had to report on patients with R/R DLBCL who were not eligible to receive high-dose therapy (HDT) with stem cell transplantation (SCT) (autologous or allogeneic). Mixed-type non-Hodgkin lymphoma (NHL) studies were required to report R/R DLBCL outcomes separately. We identified 55 studies that presented outcomes data separately for patients with R/R DLBCL. Of 7 comparative studies, only 4 were randomized controlled trials (RCTs). In the 2 RCTs with a common regimen, the patient populations differed too greatly to perform a valid meta-analysis. The 48 single-arm studies identified were typically small (n < 50 in most), with 31% reporting median progression-free survival (PFS) or overall survival (OS) specifically for the R/R DLBCL population. In these studies, median OS ranged from 4 to 13 months. The small number of RCTs in R/R DLBCL precludes identifying optimal treatments. Small sample size, infrequent reporting of OS and PFS separated by histologic type, and limited information on patient characteristics also hinder comparison of results. Randomized studies are needed to demonstrate which current therapies have advantages for improving survival and other important clinical outcomes in patients with R/R DLBCL.
Journal of Oncology Pharmacy Practice, Jul 9, 2016
This systematic literature review with meta-analysis was conducted on the clinical efficacy and s... more This systematic literature review with meta-analysis was conducted on the clinical efficacy and safety of interventions used in the treatment of chronic lymphocytic leukemia (CLL). We systematically searched databases (PubMed, Cochrane Library, and Embase; 1997 to August 2, 2012), conference abstracts, bibliographic reference lists, recent reviews, and Clinicaltrials.gov. Primary efficacy outcomes were objective response rate, progression-free survival, and overall survival. Safety end points were Grade 3/4 toxicities, serious adverse events, withdrawals because of toxicity, and deaths due to toxicity. Studies were selected if they were randomized controlled trials (RCTs) reporting on the efficacy or safety of relapsed or refractory CLL and if outcomes for CLL were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 6 RCTs of pharmacologic treatment for relapsed/refractory CLL. The most common drugs investigated (alone or in combination) were fludarabine and cyclophosphamide. When reported, median overall survival ranged from 27.3 to 52.9 months, and overall response rate from 58% to 82%. Although meta-analysis of efficacy results was considered, details are not presented because only 3 studies qualified and the common comparator treatment was not clinically relevant. The relatively small number of RCTs, few overlapping treatment arms, and variability in end points studied make it difficult to formally compare therapies for relapsed/refractory CLL. Significant variability in RCT features presents a further challenge to meaningful comparisons. Additional welldesigned RCTs are needed to fully understand the relative efficacy and safety of older and more recently developed therapies.
Background Moderate-to-severe atopic dermatitis (AD) is a chronic disease characterized by intens... more Background Moderate-to-severe atopic dermatitis (AD) is a chronic disease characterized by intense, persistent and debilitating itch, resulting in sleep deprivation, signs of anxiety and depression, impaired quality of life and reduced productivity. The Peak Pruritus Numerical Rating Scale (NRS) was developed and validated as a single-item, patient-reported outcome (PRO) of itch severity. Objectives To describe the content validity and psychometric assessment (test-retest reliability, construct validity, known-groups validity, sensitivity to change) of the Peak Pruritus NRS, and to derive empirically a responder definition to identify adults with a meaningful change in itch. Methods Content validity was assessed through in-depth patient interviews. Psychometric assessments used data from phase IIb and phase III dupilumab clinical trials and included test-retest reliability, construct validity, known-groups validity and sensitivity to change in patients with moderate-to-severe AD. Results Interview participants indicated that the Peak Pruritus NRS was a relevant, clear and comprehensive assessment of itch severity. Peak Pruritus NRS scores showed large, positive correlations with existing PRO measures of itch, and weak or moderate correlations with clinician-reported measures assessing objective signs of AD. Peak Pruritus NRS score improvements were highly correlated with improvements in other itch PROs, and moderately correlated with improvements in clinician-reported measures assessing objective signs of AD. The most appropriate threshold for defining a clinically relevant, within-person response was ≥ 2-4-point change in the Peak Pruritus NRS. Conclusions The Peak Pruritus NRS is a well-defined, reliable, sensitive and valid scale for evaluating worst itch intensity in adults with moderate-to-severe AD. What's already known about this topic? • Moderate-to-severe atopic dermatitis is characterized by persistent and debilitating itch, which can greatly impair quality of life. • A validated, brief patient-reported outcome measure is needed to quantify the intensity of itch accurately and reliably in patients with atopic dermatitis in clinical trials.
Purpose: Patient perspective is an important and increasingly sought-after complement to clinical... more Purpose: Patient perspective is an important and increasingly sought-after complement to clinical assessment. The aim of this study was to transcribe individual patients' experience of treatment in a dupilumab clinical trial through free-text responses with analysis using natural language processing (NLP) to obtain the unique perspective of patients on disease impact and unmet needs with existing treatment to inform future trial design. Patients and Methods: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) who were enrolled in a Phase IIa randomized controlled trial comparing dupilumab with placebo (NCT01920893) were invited to complete a self-assessment of treatment (SAT) tool at the end of treatment, asking, "What is your opinion on the treatment you had during the trial? What did you like or dislike about the treatment?" Free-text responses were analyzed for the overall cohort and according to treatment assignment using natural language processing including sentiment scoring. In a mixed-methods approach, quantitative patient-reported outcome (PRO) results were utilized to complement the qualitative analysis of free-text responses. Results: Of 60 patients enrolled in the study, 43 (71.6%) completed the SAT and responses from 37 patients were analyzed (placebo, n = 16; dupilumab, n = 21). Word analyses showed that the most common words were "smell," "improve," "staff," "great," "time," and "good." Across the whole cohort, "smell" was the most common symptom-related word. The words "smell" and "experience" were more likely to occur in patients treated with dupilumab. Patients treated with dupilumab also had more positive sentiment in their SAT responses than those who received placebo. The results from this qualitative analysis were reflected in quantitative PRO results. Conclusion: "Smell" was important to patients with CRSwNP, highlighting its importance as a patient-centric efficacy outcome measure in the context of clinical trials in CRSwNP. Trial Registration: ClinicalTrials.gov, NCT01920893. Registered 12 August 2013, https:// www.clinicaltrials.gov/ct2/show/NCT01920893.
Introduction: Atopic dermatitis (AD) is an incurable, inflammatory skin disease characterized by ... more Introduction: Atopic dermatitis (AD) is an incurable, inflammatory skin disease characterized by skin barrier disruption and immune dysregulation. Although AD is considered a childhood disease, adult onset is possible, presenting with daily sleep disturbance and functional impairment associated with itch, neuropsychiatric issues (anxiety and depression), and reduced health-related quality of life. Although such aspects of adult AD disease burden have been measured through standardized assessments and based on population-level data, the understanding of the disease experienced at the patient level remains poor. This text-mining study assessed the impact of AD on the lives of adult patients as described from an experiential perspective. Methods: Natural language processing (NLP) was applied to qualitative patient response data from two large-scale international cross-sectional surveys conducted in the USA and countries outside of the USA (non-USA; Canada, France, Germany, Italy, Spain, and the UK). Descriptive analysis was conducted on patient responses to an open-ended question on how they felt about their AD and how the disease affected their life. Character length, word count, and stop word (common words) count were evaluated; centrality analysis identified concepts that were most strongly interlinked. Results: Patients with AD in all countries were most frequently impacted by itch, pain, and embarrassment across all levels of disease severity. Patients with moderate-to-severe AD were more likely than patients with mild AD to describe sleep disturbances, fatigue, and feelings of depression, anxiety, and a lack of hope that were directly associated with AD. Centrality analysis revealed sleep disturbance was strongly Enhanced Digital Features To view enhanced digital features for this article go to .
International Journal of Methods in Psychiatric Research, Jul 17, 2015
The expansion of biomedical literature is creating the need for efficient tools to keep pace with... more The expansion of biomedical literature is creating the need for efficient tools to keep pace with increasing volumes of information. Text mining (TM) approaches are becoming essential to facilitate the automated extraction of useful biomedical information from unstructured text. We reviewed the applications of TM in psychiatry, and explored its advantages and limitations. A systematic review of the literature was carried out using the CINAHL, Medline, EMBASE, PsycINFO and Cochrane databases. In this review, 1103 papers were screened, and 38 were included as applications of TM in psychiatric research. Using TM and content analysis, we identified four major areas of application: (1) Psychopathology (i.e. observational studies focusing on mental illnesses) (2) the Patient perspective (i.e. patients' thoughts and opinions), (3) Medical records (i.e. safety issues, quality of care and description of treatments), and (4) Medical literature (i.e. identification of new scientific information in the literature). The information sources were qualitative studies, Internet postings, medical records and biomedical literature. Our work demonstrates that TM can contribute to complex research tasks in psychiatry. We discuss the benefits, limits, and further applications of this tool in the future.
e12554 Background: Hodgkin Lymphoma (HL) is an uncommon lymphoid malignancy with an estimated 9,0... more e12554 Background: Hodgkin Lymphoma (HL) is an uncommon lymphoid malignancy with an estimated 9,060 new cases and 1,170 patients dying of disease each year in the US. High dose chemotherapy followed by autologous stem cell transplant (ASCT) is standard treatment for relapsed or refractory HL. Patients who do not respond to or relapse after ASCT have a short survival and are candidates for investigational agents. In the absence of published studies, the primary objective of this study was to estimate the percent and number of patients with HL who relapsed after ASCT. Methods: Number of ASCT performed for HL patients and relapse rate reported in the literature was used to estimate number of HL patients who relapsed after ASCT. Number of ASCT in US with HL was extracted from 2008-2010 CIBMTR (Center for International Blood and Marrow Transplant Research) data assuming a stable number for 2010-2012. A literature review (1993-2012) using EMBASE identified relapse rate after ASCT in HL. A model was built using relapse rates at 12, 24, 36, 48 and 60 months. If there was no relapse rate at a time point, it was estimated by dividing nearest data point following relapse rate by period length. Rate differences at 12 and 24 months were used to estimate relapse rate for 2ndyear. Same methods were used to calculate other year rates. Results: An estimated 791 patients underwent ASCT for HL in 2012 based on prior years data. Three clinical trials and 9 epidemiological studies providing post-ASCT relapse rate were identified from the literature review. Relapse rates over 5 years and number of patients with relapsed HL after ASCT were estimated to be 44.7% and 352 patients, respectively, in 2012. Conclusions: : In the absence of published literature, a model was built to estimate the number of HL patients who relapsed after ASCT suggesting a high rate at 44.7% over 5 years. Because not all US centers participate in the CIBMTR registry, these numbers are likely to be conservative and actual rate may be higher. Clinical trials targeting this relatively small patient population with clear unmet medical need require collaborative efforts to enroll patients and more research to understand factors for patients relapsing post-ASCT.
Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphom... more Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphoma (NHL) cases in Western countries. Although two-thirds of patients may be cured with combination chemotherapy, in the event of treatment failure and for those who are refractory to treatment, survival is usually measured in months. Several therapeutic modalities have been utilized for patients with relapsed or refractory disease, but among patients who are not eligible for high-dose chemotherapy with stem cell transplant, a comprehensive assessment of efficacy and safety is lacking. This systematic literature review (SLR) was designed to exhaustively collect and review information on the clinical efficacy and safety of the different interventions used in the treatment of refractory or relapsed DLBCL, and if possible to perform a meta-analysis. Methods Electronic databases (PubMed, Cochrane Library, Embase) were searched for relevant studies published from 1997 to August 2, 2012. In addition, conference abstracts, bibliographic reference lists of included articles and recent reviews, and the Clinicaltrials.gov database were searched for phase 2, 3, or 4 studies displaying results, potentially unpublished in peer-reviewed journals. Main efficacy outcomes included objective response rate (ORR), complete response, partial response, duration of response, progression-free survival (PFS), and overall survival (OS). Safety endpoints focused on grade 3/4 toxicities and treatment discontinuation due to toxicity. Studies had to report on relapsed or refractory DLBCL after at least one standard treatment and patients who were not eligible to receive high-dose chemotherapy or stem cell transplant (autologous or allogeneic). Mixed type NHL studies were required to report DLBCL outcomes separately for inclusion. Results A total of 3,308 publications were identified in the first pass of a broad SLR on NHL; of these, 57 provided relevant data for DLBCL representing 54 unique studies. Of the 54 studies, there was 1 phase 3 study, 33 phase 2 studies, and 4 phase 1/2 studies (15 studies did not report the study phase and 1 was an observational study). Six studies were comparative (3 randomized trials; 3 nonrandomized trials) with two treatment arms; 48 studies were single arm. Of the 48 regimens evaluated, few regimens were represented more than once. Overall survival and PFS were often not reported or not reported separately for the patients with DLBCL in studies that enrolled patients with any of the multiple lymphoma histologies. Refractory and relapsed criteria were often not defined, and definitions were heterogeneous when available. The ORR from the few comparative studies ranged from 27% to 100%, with most estimates between 40% and 70%. PFS with low and high doses of obintuzumab was 2 months and 3 months, respectively in one study, and OS was 4 months with MEP and 7 months with C-MEP in another study. There was a common regimen in two of the randomized controlled trials, but the patient populations in these studies differed too greatly to allow a valid meta-analysis to be performed. In the single-arm studies, ORR ranged from 11% to 100%, with the estimates evenly distributed across that range. Progression-free survival was approximately 1 to 10 months. Reported median OS ranged from 1 to 13 months. Main safety concerns included thrombocytopenia, leukopenia, and neutropenia. Conclusions There is a high unmet need for effective therapies for patients with relapsed or refractory DLBCL who are ineligible for stem cell transplant. Although numerous regimens have been evaluated in single-arm trials and a handful in comparative studies, there is no clearly superior regimen for patients with relapsed or refractory DLBCL, especially in third- and later lines of therapy. FA is supported by a Clinical Career Development Award from the Lymphoma Research Foundation Disclosures: Colosia: RTI Health Solutions: Employment. Trask: Sanofi: Employment. Olivares: Sanofi: Employment. Khan: RTI Health Solutions: Employment. Abbe: Sanofi: Employment. Police: RTI Health Solutions: Employment. Njue: RTI Health Solutions: Employment. Wang: RTI Health Solutions: Employment. Sherrill: RTI Health Solutions: Employment. Ruiz-Soto: Sanofi: Employment. Kaye: RTI Health Solutions: Employment. Awan: Lymphoma Research Foundation (Career Development Award): Research Funding.
Background Follicular lymphoma (FL), the most frequent form of indolent NHL (iNHL), accounts for ... more Background Follicular lymphoma (FL), the most frequent form of indolent NHL (iNHL), accounts for 20% to 30% of non-Hodgkin lymphomas (NHL). Median survival is 8–15 years (yrs) for patients (pts) with advanced disease. Approximately 2/3 of pts relapse or become refractory to 1st line treatment. Progression-free survival (PFS) for pts with RRFL is usually less than 2 yrs. This SLR examined current literature on RRFL, comparing the efficacy of treatments by meta-analysis where possible. Methods PubMed, Cochrane Library, and Embase were systematically searched for studies on the efficacy and safety of treatments for RRFL published from 1997 to August 2, 2012. In addition, conference abstracts, reference lists of included articles, recent reviews, and the Clinicaltrials.gov database were searched for otherwise unpublished comparative studies. Main efficacy outcomes were objective response rate (ORR), complete response, partial response, duration of response, PFS, and overall survival (OS). Safety endpoints were grade 3/4 toxicities and treatment withdrawals for toxicity. Studies were selected if they reported on RRFL after ≥ 1 standard treatment in pts ineligible for stem cell transplant and if they were specific to or reported FL outcomes separately. We used the Bucher method for conducting adjusted indirect comparisons. Results 3,308 publications of potential interest were identified; 280 provided relevant data for iNHL; 29 reported on 23 randomized clinical trials (RCTs) in iNHL; 10 were specific to FL and 5 included FL findings in a mixed histology population. OS and PFS were infrequently reported. Criteria for relapsed or refractory disease were often not defined, with only 8 studies providing varying definitions. The most commonly evaluated therapy in patients with FL was rituximab (R) either alone or with bortezomib (B) or lenalidomide (L). ORR, reported in 5 studies, ranged from 49% to 93%. Median PFS in 5 studies ranged from 10 to 25 months but was…
Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphom... more Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphoma (NHL) cases in Western countries. Although two-thirds of patients may be cured with combination chemotherapy, in the event of treatment failure and for those who are refractory to treatment, survival is usually measured in months. Several therapeutic modalities have been utilized for patients with relapsed or refractory disease, but among patients who are not eligible for high-dose chemotherapy with stem cell transplant, a comprehensive assessment of efficacy and safety is lacking. This systematic literature review (SLR) was designed to exhaustively collect and review information on the clinical efficacy and safety of the different interventions used in the treatment of refractory or relapsed DLBCL, and if possible to perform a meta-analysis. Methods Electronic databases (PubMed, Cochrane Library, Embase) were searched for relevant studies published from 1997 to August 2, 2012. In addition, conference abstracts, bibliographic reference lists of included articles and recent reviews, and the Clinicaltrials.gov database were searched for phase 2, 3, or 4 studies displaying results, potentially unpublished in peer-reviewed journals. Main efficacy outcomes included objective response rate (ORR), complete response, partial response, duration of response, progression-free survival (PFS), and overall survival (OS). Safety endpoints focused on grade 3/4 toxicities and treatment discontinuation due to toxicity. Studies had to report on relapsed or refractory DLBCL after at least one standard treatment and patients who were not eligible to receive high-dose chemotherapy or stem cell transplant (autologous or allogeneic). Mixed type NHL studies were required to report DLBCL outcomes separately for inclusion. Results A total of 3,308 publications were identified in the first pass of a broad SLR on NHL; of these, 57 provided relevant data for DLBCL representing 54 unique studies. Of the 54 studies, there was 1 phase 3 study, 33 phase 2 studies, and 4 phase 1/2 studies (15 studies did not report the study phase and 1 was an observational study). Six studies were comparative (3 randomized trials; 3 nonrandomized trials) with two treatment arms; 48 studies were single arm. Of the 48 regimens evaluated, few regimens were represented more than once. Overall survival and PFS were often not reported or not reported separately for the patients with DLBCL in studies that enrolled patients with any of the multiple lymphoma histologies. Refractory and relapsed criteria were often not defined, and definitions were heterogeneous when available. The ORR from the few comparative studies ranged from 27% to 100%, with most estimates between 40% and 70%. PFS with low and high doses of obintuzumab was 2 months and 3 months, respectively in one study, and OS was 4 months with MEP and 7 months with C-MEP in another study. There was a common regimen in two of the randomized controlled trials, but the patient populations in these studies differed too greatly to allow a valid meta-analysis to be performed. In the single-arm studies, ORR ranged from 11% to 100%, with the estimates evenly distributed across that range. Progression-free survival was approximately 1 to 10 months. Reported median OS ranged from 1 to 13 months. Main safety concerns included thrombocytopenia, leukopenia, and neutropenia. Conclusions There is a high unmet need for effective therapies for patients with relapsed or refractory DLBCL who are ineligible for stem cell transplant. Although numerous regimens have been evaluated in single-arm trials and a handful in comparative studies, there is no clearly superior regimen for patients with relapsed or refractory DLBCL, especially in third- and later lines of therapy. FA is supported by a Clinical Career Development Award from the Lymphoma Research Foundation Disclosures: Colosia: RTI Health Solutions: Employment. Trask: Sanofi: Employment. Olivares: Sanofi: Employment. Khan: RTI Health Solutions: Employment. Abbe: Sanofi: Employment. Police: RTI Health Solutions: Employment. Njue: RTI Health Solutions: Employment. Wang: RTI Health Solutions: Employment. Sherrill: RTI Health Solutions: Employment. Ruiz-Soto: Sanofi: Employment. Kaye: RTI Health Solutions: Employment. Awan: Lymphoma Research Foundation (Career Development Award): Research Funding.
Purpose: Patient perspective is an important and increasingly sought-after complement to clinical... more Purpose: Patient perspective is an important and increasingly sought-after complement to clinical assessment. The aim of this study was to transcribe individual patients' experience of treatment in a dupilumab clinical trial through free-text responses with analysis using natural language processing (NLP) to obtain the unique perspective of patients on disease impact and unmet needs with existing treatment to inform future trial design. Patients and Methods: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) who were enrolled in a Phase IIa randomized controlled trial comparing dupilumab with placebo (NCT01920893) were invited to complete a self-assessment of treatment (SAT) tool at the end of treatment, asking, "What is your opinion on the treatment you had during the trial? What did you like or dislike about the treatment?" Free-text responses were analyzed for the overall cohort and according to treatment assignment using natural language processing including sentiment scoring. In a mixed-methods approach, quantitative patient-reported outcome (PRO) results were utilized to complement the qualitative analysis of free-text responses. Results: Of 60 patients enrolled in the study, 43 (71.6%) completed the SAT and responses from 37 patients were analyzed (placebo, n = 16; dupilumab, n = 21). Word analyses showed that the most common words were "smell," "improve," "staff," "great," "time," and "good." Across the whole cohort, "smell" was the most common symptom-related word. The words "smell" and "experience" were more likely to occur in patients treated with dupilumab. Patients treated with dupilumab also had more positive sentiment in their SAT responses than those who received placebo. The results from this qualitative analysis were reflected in quantitative PRO results. Conclusion: "Smell" was important to patients with CRSwNP, highlighting its importance as a patient-centric efficacy outcome measure in the context of clinical trials in CRSwNP. Trial Registration: ClinicalTrials.gov, NCT01920893. Registered 12 August 2013, https:// www.clinicaltrials.gov/ct2/show/NCT01920893.
Background: Indirect comparisons of competing treatments by network meta-analysis (NMA) are incre... more Background: Indirect comparisons of competing treatments by network meta-analysis (NMA) are increasingly in use. Reporting bias has received little attention in this context. We aimed to assess the impact of such bias in NMAs. Methods: We used data from 74 FDA-registered placebo-controlled trials of 12 antidepressants and their 51 matching publications. For each dataset, NMA was used to estimate the effect sizes for 66 possible pair-wise comparisons of these drugs, the probabilities of being the best drug and ranking the drugs. To assess the impact of reporting bias, we compared the NMA results for the 51 published trials and those for the 74 FDA-registered trials. To assess how reporting bias affecting only one drug may affect the ranking of all drugs, we performed 12 different NMAs for hypothetical analysis. For each of these NMAs, we used published data for one drug and FDA data for the 11 other drugs. Findings: Pair-wise effect sizes for drugs derived from the NMA of published data and those from the NMA of FDA data differed in absolute value by at least 100% in 30 of 66 pair-wise comparisons (45%). Depending on the dataset used, the top 3 agents differed, in composition and order. When reporting bias hypothetically affected only one drug, the affected drug ranked first in 5 of the 12 NMAs but second (n = 2), fourth (n = 1) or eighth (n = 2) in the NMA of the complete FDA network. Conclusions: In this particular network, reporting bias biased NMA-based estimates of treatments efficacy and modified ranking. The reporting bias effect in NMAs may differ from that in classical meta-analyses in that reporting bias affecting only one drug may affect the ranking of all drugs.
L’analyse de donnee textuelle est facilitee par l’utilisation du text mining (TM) permettant l’au... more L’analyse de donnee textuelle est facilitee par l’utilisation du text mining (TM) permettant l’automatisation de l’analyse de contenu et possede de nombreuses applications en sante. L’une d’entre elles est l’utilisation du TM pour explorer le contenu des messages echanges sur Internet.Nous avons effectue une revue de la litterature systematique afin d’identifier les applications du TM en sante mentale. De plus, le TM a permis d’explorer les preoccupations des utilisateurs du forum Doctissimo.com au sujet des antidepresseurs et anxiolytiques entre 2013 et 2015 via l’analyse des frequences des mots, des cooccurrences, de la modelisation thematique (LDA) et de la popularite des themes.Les quatre applications du TM en sante mentale sont l’analyse des recits des patients (psychopathologie), le ressenti exprime sur Internet, le contenu des dossiers medicaux, et les themes de la litterature medicale. Quatre grands themes ont ete identifies sur le forum: le sevrage (le plus frequent), l’esc...
Introduction: Dupilumab (DPL), a fully human anti-interleukin (IL)-4 Rα monoclonal antibody, inhi... more Introduction: Dupilumab (DPL), a fully human anti-interleukin (IL)-4 Rα monoclonal antibody, inhibits IL-4/IL-13 signalling, and improves endoscopic, radiographic, and clinical endpoints in patients (pts) with CRSwNP and asthma. Aims: Evaluate DPL effect on each of the 5 items of the Asthma Control Questionnaire (ACQ-5) in pts with CRSwNP and asthma. Methods: CRSwNP pts refractory to intranasal corticosteroids were assigned to weekly doses of DPL 300 mg s.c. or placebo (PBO), with mometasone furoate nasal spray. Asthma control was assessed using ACQ-5 at baseline and at Week 16. Results: Of 60 pts enrolled, 58.3% had asthma and used asthma medications. DPL showed clinically relevant improvements in total ACQ-5 (Table). Differences vs PBO were significant for each of the 5 items assessing asthma symptoms (shortness of breath; wheezing time; awake in the morning with symptoms), activity limitation and night-time awakenings (Table). Asthma-control improvement correlated with improvement in pt-reported outcomes (visual analogue scale; 22-item Sino-Nasal Outcome Test) and nasal polyp score. Injection-site reactions, headache, and nasopharyngitis were the most frequently reported adverse events with DPL. Conclusion: In CRSwNP pts with asthma, DPL significantly improved all asthma-related items. Improvement correlated with reduced nasal polyp burden.
Article type : Original Article: Experimental Allergy and Immunology Dupilumab improves health-re... more Article type : Original Article: Experimental Allergy and Immunology Dupilumab improves health-related quality of life in patients with chronic rhinosinusitis with nasal polyposis
Abstract 5074 Background NHL is the 10th most common cancer worldwide, and a major cause of cance... more Abstract 5074 Background NHL is the 10th most common cancer worldwide, and a major cause of cancer-related deaths despite major advances in therapy (GLOBOCAN 2008). It encompasses a heterogeneous group of hematological malignancies originating in lymphoid tissue, mainly B lymphocytes (B-cell NHL) with an overall 5-year survival of 50–60%. There is lack of published data on the distribution of patients across lines of therapy and by subtype. Method Epidemiological data was obtained for US and EU using the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;epic oncology&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; 2012 database (Epiphany Partners Inc.). The database includes line of therapy estimations using an advanced patient flow model combining survival by subset and course of treatment, response rates and outcomes, and treatment data from U. S. and EU cancer registries coupled with primary research with a representative sample of physicians and secondary therapeutic reviews. We analyzed projection estimates up to 2020 across US and EU5 countries by subtype and line of therapy with specific attention to relapsed/refractory patients. Refractory patients are those who do not respond (do not go into remission) following therapy. Relapsed patients are defined as those who have responded to therapy (enter remission) who then re-enter the treatment population due to progression of their cancer, recurrence of diagnostic markers, or symptomatology. Result Projection estimates from 2010 to 2020 by line of therapy varied by country. Among EU countries the highest number of treated patients was in Italy followed by Germany and UK. By 2020, the percentage of patients that will have relapsed and/or be refractory to all lines of therapy will increase by about 35% in US and 11% in EU with regional variation observed among France (18%), Italy (15. 2%), Spain (3%), and UK (18%). In both the US and EU, about 30% of patients relapse and 20% are refractory after 1st line treatment. In 2nd as well as 3rd line, about 35% relapse or are refractory after treatment in the respective lines. In the US, the percent increase from 2010 to 2020 by line of therapy (1st, 2nd, 3rd) is greatest for MCL patients (55, 58, 59%) followed by FL (40, 49, 41%) and DLBCL (28, 33, and 36%). Epidemiology projection trends for US and EU by line of therapy and sub type Conclusion Due to the indolent or aggressive nature of NHL, the proportion of patients who will progress from 1st line to 2nd line therapy varies between 35% in US and 29% in EU based on current treatment options. This, along with the high percentage of relapsed and refractory patients in 2nd or higher lines argues for continued efforts to be made for the development of more efficacious treatments for NHL. The observed three fold difference between US and EU increase could be due to an increased incidence in recent historical years or an association between one or more of the risk factors, such as hepatitis C, which is more common in US or autoimmune disorders such as HIV. Real world data and disease based registries can help in validating emerging trends in therapy through providing up to date global projection estimates across line of therapy. Disclosures: Trask: Sanofi: Employment. Mehta:Sanofi: Employment. Abbe:Sanofi: Employment, Equity Ownership. RuizSoto:Sanofi: Employment.
Abstract 4782 Background: Hodgkin lymphoma represents 11.7% of all types of lymphoma diagnosed in... more Abstract 4782 Background: Hodgkin lymphoma represents 11.7% of all types of lymphoma diagnosed in 2011. (Leukemia and Lymphoma Society) In 2012, an estimated 9,060 of new HL cases and 1,190 deaths will occur in North America and mostly in either young adults between 15 and 30 years of age, or after the age of 45. (American Cancer Society) The five-year relative survival rate for all patients with HL is 86.3% from 2001 to 2007 and 92.8% for patients less than 45 years at diagnosis. (SEER Review) Initial treatment of HL depends on the stage of the disease at diagnosis. Chemotherapy with or without radiation therapy is the most common treatment approach for HL patients. Stem cell transplantation and chemotherapy are the treatment options for patients with relapse disease. There is lack of published data on the distribution of patients across lines of therapy as well as percentage of relapsed and refractory patients. Understanding the distribution of patients across lines of therapy is critical to identify the unmet need and to help tailor future therapies. Methods: Epidemiological data was obtained for US and EU using the 'epic oncology' 2012 database (Epiphany Partners Inc.). The database includes line of therapy estimations using an advanced patient flow model combining survival by subset and course of treatment, response rates and outcomes, and treatment data from US and EU cancer registries coupled with primary research with a representative sample of physicians and secondary therapeutic reviews. We analyzed projection estimates up to 2020 across US and EU5 countries by line of therapy with specific attention to relapsed/refractory patients. These projection estimates are based on the current treatment options and does not account for introduction of future therapies. Refractory patients are defined as those who do not respond (do not go into remission) following therapy. Relapsed Patients are defined as those who have responded to therapy (enter remission) but re-enter the treatment population at a later stage due to progression of their cancer, recurrence of diagnostic markers, or symptomatology. Results: Projection estimates from 2010 to 2020 by line of therapy varied by country. Among EU countries, the highest number of treated HL patients was in France, followed by Italy and Spain. By 2020, the percentage of patients that are either relapsed or refractory to first, second and third line of therapy will increase by about 25% in US and by about 15% in EU. Regional variation observed across Europe are as follows: an increase by 38% in Spain, 25% in France, 12% in UK and 6% in Italy, while Germany will show a decline of 2%, this is due to a continuous decline in incidence rates since the early 1990s. Drug treated Hodgkin lymphoma population by line of therapy*: Conclusions: Due to the highly chemosensitive nature of the malignancy, only about 25% of Hodgkin lymphoma patients progress to a second line therapy and 30% of those move into third line. Smaller sample sizes, variation in growth rate among US and EU countries, and a bimodal incidence curve could cause differences in projection trends. The creation of a Hodgkin's disease based registry can help in validating emerging trends in therapy through providing up to date global projection estimates across line of therapy. Our results provide a global understanding of the HL patient population distribution across lines of therapy and are critical to identify the unmet need and guide future therapies in HL patients. Disclosures: Mehta: Sanofi: Employment. Abbe:Sanofi: Employment, Equity Ownership. Trask:Sanofi: Employment. Neumann:Sanofi-aventis: Employment. Hamed:Sanofi: Employment.
A systematic literature review was performed to collect and review information on the clinical ef... more A systematic literature review was performed to collect and review information on the clinical efficacy and safety of treatments for relapsed/refractory (R/R) mantle cell lymphoma (MCL), with a meta-analysis, if possible. PubMed, Embase, and the Cochrane Library were searched for studies published in English from January 1, 1997, to August 2, 2012. Conference proceedings, bibliographic reference lists of included articles, recent reviews, and ClinicalTrials.gov were searched for phase II to IV studies displaying results. Studies were included if they reported on patients with R/R MCL who were ineligible to receive high-dose chemotherapy with stem cell transplant. Studies of patients with several non-Hodgkin lymphoma subtypes were only included if they reported MCL outcomes separately. We identified 59 studies in R/R MCL. Forty distinct treatment regimens were evaluated. Thirty studies included more than 15 patients with R/R MCL. Six studies were comparative (including 5 randomized controlled trials [RCTs]); 53 were single-arm. There were no common treatments among the RCTs; therefore, a meta-analysis was not feasible. Thirty-one of 59 studies reported baseline data for patients with R/R MCL. Of the 30 studies with > 15 patients with R/R MCL, 30 reported overall response rate data, 14 reported progression-free survival (PFS), and 12 reported overall survival (OS). The small number of RCTs in R/R MCL precludes identifying an optimal treatment. Small sample sizes, infrequent reporting of OS and PFS, and limited information on patient characteristics made a comparison of results difficult. High-quality comparative studies of novel therapies that have the potential to demonstrate OS advantages in R/R MCL are needed.
Clinical Lymphoma, Myeloma & Leukemia, Oct 1, 2014
This systematic literature review was designed to assess information on the clinical efficacy and... more This systematic literature review was designed to assess information on the clinical efficacy and safety of interventions used in the treatment of refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL) and to perform a metaanalysis if possible. We searched databases (PubMed, EMBASE, and Cochrane Library for articles from 1997 to August 2, 2012 reported in English), conference abstracts, bibliographic reference lists, and the ClinicalTrials.gov database for phase II to IV studies with results. Studies had to report on patients with R/R DLBCL who were not eligible to receive high-dose therapy (HDT) with stem cell transplantation (SCT) (autologous or allogeneic). Mixed-type non-Hodgkin lymphoma (NHL) studies were required to report R/R DLBCL outcomes separately. We identified 55 studies that presented outcomes data separately for patients with R/R DLBCL. Of 7 comparative studies, only 4 were randomized controlled trials (RCTs). In the 2 RCTs with a common regimen, the patient populations differed too greatly to perform a valid meta-analysis. The 48 single-arm studies identified were typically small (n < 50 in most), with 31% reporting median progression-free survival (PFS) or overall survival (OS) specifically for the R/R DLBCL population. In these studies, median OS ranged from 4 to 13 months. The small number of RCTs in R/R DLBCL precludes identifying optimal treatments. Small sample size, infrequent reporting of OS and PFS separated by histologic type, and limited information on patient characteristics also hinder comparison of results. Randomized studies are needed to demonstrate which current therapies have advantages for improving survival and other important clinical outcomes in patients with R/R DLBCL.
Journal of Oncology Pharmacy Practice, Jul 9, 2016
This systematic literature review with meta-analysis was conducted on the clinical efficacy and s... more This systematic literature review with meta-analysis was conducted on the clinical efficacy and safety of interventions used in the treatment of chronic lymphocytic leukemia (CLL). We systematically searched databases (PubMed, Cochrane Library, and Embase; 1997 to August 2, 2012), conference abstracts, bibliographic reference lists, recent reviews, and Clinicaltrials.gov. Primary efficacy outcomes were objective response rate, progression-free survival, and overall survival. Safety end points were Grade 3/4 toxicities, serious adverse events, withdrawals because of toxicity, and deaths due to toxicity. Studies were selected if they were randomized controlled trials (RCTs) reporting on the efficacy or safety of relapsed or refractory CLL and if outcomes for CLL were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 6 RCTs of pharmacologic treatment for relapsed/refractory CLL. The most common drugs investigated (alone or in combination) were fludarabine and cyclophosphamide. When reported, median overall survival ranged from 27.3 to 52.9 months, and overall response rate from 58% to 82%. Although meta-analysis of efficacy results was considered, details are not presented because only 3 studies qualified and the common comparator treatment was not clinically relevant. The relatively small number of RCTs, few overlapping treatment arms, and variability in end points studied make it difficult to formally compare therapies for relapsed/refractory CLL. Significant variability in RCT features presents a further challenge to meaningful comparisons. Additional welldesigned RCTs are needed to fully understand the relative efficacy and safety of older and more recently developed therapies.
Background Moderate-to-severe atopic dermatitis (AD) is a chronic disease characterized by intens... more Background Moderate-to-severe atopic dermatitis (AD) is a chronic disease characterized by intense, persistent and debilitating itch, resulting in sleep deprivation, signs of anxiety and depression, impaired quality of life and reduced productivity. The Peak Pruritus Numerical Rating Scale (NRS) was developed and validated as a single-item, patient-reported outcome (PRO) of itch severity. Objectives To describe the content validity and psychometric assessment (test-retest reliability, construct validity, known-groups validity, sensitivity to change) of the Peak Pruritus NRS, and to derive empirically a responder definition to identify adults with a meaningful change in itch. Methods Content validity was assessed through in-depth patient interviews. Psychometric assessments used data from phase IIb and phase III dupilumab clinical trials and included test-retest reliability, construct validity, known-groups validity and sensitivity to change in patients with moderate-to-severe AD. Results Interview participants indicated that the Peak Pruritus NRS was a relevant, clear and comprehensive assessment of itch severity. Peak Pruritus NRS scores showed large, positive correlations with existing PRO measures of itch, and weak or moderate correlations with clinician-reported measures assessing objective signs of AD. Peak Pruritus NRS score improvements were highly correlated with improvements in other itch PROs, and moderately correlated with improvements in clinician-reported measures assessing objective signs of AD. The most appropriate threshold for defining a clinically relevant, within-person response was ≥ 2-4-point change in the Peak Pruritus NRS. Conclusions The Peak Pruritus NRS is a well-defined, reliable, sensitive and valid scale for evaluating worst itch intensity in adults with moderate-to-severe AD. What's already known about this topic? • Moderate-to-severe atopic dermatitis is characterized by persistent and debilitating itch, which can greatly impair quality of life. • A validated, brief patient-reported outcome measure is needed to quantify the intensity of itch accurately and reliably in patients with atopic dermatitis in clinical trials.
Purpose: Patient perspective is an important and increasingly sought-after complement to clinical... more Purpose: Patient perspective is an important and increasingly sought-after complement to clinical assessment. The aim of this study was to transcribe individual patients' experience of treatment in a dupilumab clinical trial through free-text responses with analysis using natural language processing (NLP) to obtain the unique perspective of patients on disease impact and unmet needs with existing treatment to inform future trial design. Patients and Methods: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) who were enrolled in a Phase IIa randomized controlled trial comparing dupilumab with placebo (NCT01920893) were invited to complete a self-assessment of treatment (SAT) tool at the end of treatment, asking, "What is your opinion on the treatment you had during the trial? What did you like or dislike about the treatment?" Free-text responses were analyzed for the overall cohort and according to treatment assignment using natural language processing including sentiment scoring. In a mixed-methods approach, quantitative patient-reported outcome (PRO) results were utilized to complement the qualitative analysis of free-text responses. Results: Of 60 patients enrolled in the study, 43 (71.6%) completed the SAT and responses from 37 patients were analyzed (placebo, n = 16; dupilumab, n = 21). Word analyses showed that the most common words were "smell," "improve," "staff," "great," "time," and "good." Across the whole cohort, "smell" was the most common symptom-related word. The words "smell" and "experience" were more likely to occur in patients treated with dupilumab. Patients treated with dupilumab also had more positive sentiment in their SAT responses than those who received placebo. The results from this qualitative analysis were reflected in quantitative PRO results. Conclusion: "Smell" was important to patients with CRSwNP, highlighting its importance as a patient-centric efficacy outcome measure in the context of clinical trials in CRSwNP. Trial Registration: ClinicalTrials.gov, NCT01920893. Registered 12 August 2013, https:// www.clinicaltrials.gov/ct2/show/NCT01920893.
Introduction: Atopic dermatitis (AD) is an incurable, inflammatory skin disease characterized by ... more Introduction: Atopic dermatitis (AD) is an incurable, inflammatory skin disease characterized by skin barrier disruption and immune dysregulation. Although AD is considered a childhood disease, adult onset is possible, presenting with daily sleep disturbance and functional impairment associated with itch, neuropsychiatric issues (anxiety and depression), and reduced health-related quality of life. Although such aspects of adult AD disease burden have been measured through standardized assessments and based on population-level data, the understanding of the disease experienced at the patient level remains poor. This text-mining study assessed the impact of AD on the lives of adult patients as described from an experiential perspective. Methods: Natural language processing (NLP) was applied to qualitative patient response data from two large-scale international cross-sectional surveys conducted in the USA and countries outside of the USA (non-USA; Canada, France, Germany, Italy, Spain, and the UK). Descriptive analysis was conducted on patient responses to an open-ended question on how they felt about their AD and how the disease affected their life. Character length, word count, and stop word (common words) count were evaluated; centrality analysis identified concepts that were most strongly interlinked. Results: Patients with AD in all countries were most frequently impacted by itch, pain, and embarrassment across all levels of disease severity. Patients with moderate-to-severe AD were more likely than patients with mild AD to describe sleep disturbances, fatigue, and feelings of depression, anxiety, and a lack of hope that were directly associated with AD. Centrality analysis revealed sleep disturbance was strongly Enhanced Digital Features To view enhanced digital features for this article go to .
International Journal of Methods in Psychiatric Research, Jul 17, 2015
The expansion of biomedical literature is creating the need for efficient tools to keep pace with... more The expansion of biomedical literature is creating the need for efficient tools to keep pace with increasing volumes of information. Text mining (TM) approaches are becoming essential to facilitate the automated extraction of useful biomedical information from unstructured text. We reviewed the applications of TM in psychiatry, and explored its advantages and limitations. A systematic review of the literature was carried out using the CINAHL, Medline, EMBASE, PsycINFO and Cochrane databases. In this review, 1103 papers were screened, and 38 were included as applications of TM in psychiatric research. Using TM and content analysis, we identified four major areas of application: (1) Psychopathology (i.e. observational studies focusing on mental illnesses) (2) the Patient perspective (i.e. patients' thoughts and opinions), (3) Medical records (i.e. safety issues, quality of care and description of treatments), and (4) Medical literature (i.e. identification of new scientific information in the literature). The information sources were qualitative studies, Internet postings, medical records and biomedical literature. Our work demonstrates that TM can contribute to complex research tasks in psychiatry. We discuss the benefits, limits, and further applications of this tool in the future.
e12554 Background: Hodgkin Lymphoma (HL) is an uncommon lymphoid malignancy with an estimated 9,0... more e12554 Background: Hodgkin Lymphoma (HL) is an uncommon lymphoid malignancy with an estimated 9,060 new cases and 1,170 patients dying of disease each year in the US. High dose chemotherapy followed by autologous stem cell transplant (ASCT) is standard treatment for relapsed or refractory HL. Patients who do not respond to or relapse after ASCT have a short survival and are candidates for investigational agents. In the absence of published studies, the primary objective of this study was to estimate the percent and number of patients with HL who relapsed after ASCT. Methods: Number of ASCT performed for HL patients and relapse rate reported in the literature was used to estimate number of HL patients who relapsed after ASCT. Number of ASCT in US with HL was extracted from 2008-2010 CIBMTR (Center for International Blood and Marrow Transplant Research) data assuming a stable number for 2010-2012. A literature review (1993-2012) using EMBASE identified relapse rate after ASCT in HL. A model was built using relapse rates at 12, 24, 36, 48 and 60 months. If there was no relapse rate at a time point, it was estimated by dividing nearest data point following relapse rate by period length. Rate differences at 12 and 24 months were used to estimate relapse rate for 2ndyear. Same methods were used to calculate other year rates. Results: An estimated 791 patients underwent ASCT for HL in 2012 based on prior years data. Three clinical trials and 9 epidemiological studies providing post-ASCT relapse rate were identified from the literature review. Relapse rates over 5 years and number of patients with relapsed HL after ASCT were estimated to be 44.7% and 352 patients, respectively, in 2012. Conclusions: : In the absence of published literature, a model was built to estimate the number of HL patients who relapsed after ASCT suggesting a high rate at 44.7% over 5 years. Because not all US centers participate in the CIBMTR registry, these numbers are likely to be conservative and actual rate may be higher. Clinical trials targeting this relatively small patient population with clear unmet medical need require collaborative efforts to enroll patients and more research to understand factors for patients relapsing post-ASCT.
Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphom... more Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphoma (NHL) cases in Western countries. Although two-thirds of patients may be cured with combination chemotherapy, in the event of treatment failure and for those who are refractory to treatment, survival is usually measured in months. Several therapeutic modalities have been utilized for patients with relapsed or refractory disease, but among patients who are not eligible for high-dose chemotherapy with stem cell transplant, a comprehensive assessment of efficacy and safety is lacking. This systematic literature review (SLR) was designed to exhaustively collect and review information on the clinical efficacy and safety of the different interventions used in the treatment of refractory or relapsed DLBCL, and if possible to perform a meta-analysis. Methods Electronic databases (PubMed, Cochrane Library, Embase) were searched for relevant studies published from 1997 to August 2, 2012. In addition, conference abstracts, bibliographic reference lists of included articles and recent reviews, and the Clinicaltrials.gov database were searched for phase 2, 3, or 4 studies displaying results, potentially unpublished in peer-reviewed journals. Main efficacy outcomes included objective response rate (ORR), complete response, partial response, duration of response, progression-free survival (PFS), and overall survival (OS). Safety endpoints focused on grade 3/4 toxicities and treatment discontinuation due to toxicity. Studies had to report on relapsed or refractory DLBCL after at least one standard treatment and patients who were not eligible to receive high-dose chemotherapy or stem cell transplant (autologous or allogeneic). Mixed type NHL studies were required to report DLBCL outcomes separately for inclusion. Results A total of 3,308 publications were identified in the first pass of a broad SLR on NHL; of these, 57 provided relevant data for DLBCL representing 54 unique studies. Of the 54 studies, there was 1 phase 3 study, 33 phase 2 studies, and 4 phase 1/2 studies (15 studies did not report the study phase and 1 was an observational study). Six studies were comparative (3 randomized trials; 3 nonrandomized trials) with two treatment arms; 48 studies were single arm. Of the 48 regimens evaluated, few regimens were represented more than once. Overall survival and PFS were often not reported or not reported separately for the patients with DLBCL in studies that enrolled patients with any of the multiple lymphoma histologies. Refractory and relapsed criteria were often not defined, and definitions were heterogeneous when available. The ORR from the few comparative studies ranged from 27% to 100%, with most estimates between 40% and 70%. PFS with low and high doses of obintuzumab was 2 months and 3 months, respectively in one study, and OS was 4 months with MEP and 7 months with C-MEP in another study. There was a common regimen in two of the randomized controlled trials, but the patient populations in these studies differed too greatly to allow a valid meta-analysis to be performed. In the single-arm studies, ORR ranged from 11% to 100%, with the estimates evenly distributed across that range. Progression-free survival was approximately 1 to 10 months. Reported median OS ranged from 1 to 13 months. Main safety concerns included thrombocytopenia, leukopenia, and neutropenia. Conclusions There is a high unmet need for effective therapies for patients with relapsed or refractory DLBCL who are ineligible for stem cell transplant. Although numerous regimens have been evaluated in single-arm trials and a handful in comparative studies, there is no clearly superior regimen for patients with relapsed or refractory DLBCL, especially in third- and later lines of therapy. FA is supported by a Clinical Career Development Award from the Lymphoma Research Foundation Disclosures: Colosia: RTI Health Solutions: Employment. Trask: Sanofi: Employment. Olivares: Sanofi: Employment. Khan: RTI Health Solutions: Employment. Abbe: Sanofi: Employment. Police: RTI Health Solutions: Employment. Njue: RTI Health Solutions: Employment. Wang: RTI Health Solutions: Employment. Sherrill: RTI Health Solutions: Employment. Ruiz-Soto: Sanofi: Employment. Kaye: RTI Health Solutions: Employment. Awan: Lymphoma Research Foundation (Career Development Award): Research Funding.
Background Follicular lymphoma (FL), the most frequent form of indolent NHL (iNHL), accounts for ... more Background Follicular lymphoma (FL), the most frequent form of indolent NHL (iNHL), accounts for 20% to 30% of non-Hodgkin lymphomas (NHL). Median survival is 8–15 years (yrs) for patients (pts) with advanced disease. Approximately 2/3 of pts relapse or become refractory to 1st line treatment. Progression-free survival (PFS) for pts with RRFL is usually less than 2 yrs. This SLR examined current literature on RRFL, comparing the efficacy of treatments by meta-analysis where possible. Methods PubMed, Cochrane Library, and Embase were systematically searched for studies on the efficacy and safety of treatments for RRFL published from 1997 to August 2, 2012. In addition, conference abstracts, reference lists of included articles, recent reviews, and the Clinicaltrials.gov database were searched for otherwise unpublished comparative studies. Main efficacy outcomes were objective response rate (ORR), complete response, partial response, duration of response, PFS, and overall survival (OS). Safety endpoints were grade 3/4 toxicities and treatment withdrawals for toxicity. Studies were selected if they reported on RRFL after ≥ 1 standard treatment in pts ineligible for stem cell transplant and if they were specific to or reported FL outcomes separately. We used the Bucher method for conducting adjusted indirect comparisons. Results 3,308 publications of potential interest were identified; 280 provided relevant data for iNHL; 29 reported on 23 randomized clinical trials (RCTs) in iNHL; 10 were specific to FL and 5 included FL findings in a mixed histology population. OS and PFS were infrequently reported. Criteria for relapsed or refractory disease were often not defined, with only 8 studies providing varying definitions. The most commonly evaluated therapy in patients with FL was rituximab (R) either alone or with bortezomib (B) or lenalidomide (L). ORR, reported in 5 studies, ranged from 49% to 93%. Median PFS in 5 studies ranged from 10 to 25 months but was…
Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphom... more Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphoma (NHL) cases in Western countries. Although two-thirds of patients may be cured with combination chemotherapy, in the event of treatment failure and for those who are refractory to treatment, survival is usually measured in months. Several therapeutic modalities have been utilized for patients with relapsed or refractory disease, but among patients who are not eligible for high-dose chemotherapy with stem cell transplant, a comprehensive assessment of efficacy and safety is lacking. This systematic literature review (SLR) was designed to exhaustively collect and review information on the clinical efficacy and safety of the different interventions used in the treatment of refractory or relapsed DLBCL, and if possible to perform a meta-analysis. Methods Electronic databases (PubMed, Cochrane Library, Embase) were searched for relevant studies published from 1997 to August 2, 2012. In addition, conference abstracts, bibliographic reference lists of included articles and recent reviews, and the Clinicaltrials.gov database were searched for phase 2, 3, or 4 studies displaying results, potentially unpublished in peer-reviewed journals. Main efficacy outcomes included objective response rate (ORR), complete response, partial response, duration of response, progression-free survival (PFS), and overall survival (OS). Safety endpoints focused on grade 3/4 toxicities and treatment discontinuation due to toxicity. Studies had to report on relapsed or refractory DLBCL after at least one standard treatment and patients who were not eligible to receive high-dose chemotherapy or stem cell transplant (autologous or allogeneic). Mixed type NHL studies were required to report DLBCL outcomes separately for inclusion. Results A total of 3,308 publications were identified in the first pass of a broad SLR on NHL; of these, 57 provided relevant data for DLBCL representing 54 unique studies. Of the 54 studies, there was 1 phase 3 study, 33 phase 2 studies, and 4 phase 1/2 studies (15 studies did not report the study phase and 1 was an observational study). Six studies were comparative (3 randomized trials; 3 nonrandomized trials) with two treatment arms; 48 studies were single arm. Of the 48 regimens evaluated, few regimens were represented more than once. Overall survival and PFS were often not reported or not reported separately for the patients with DLBCL in studies that enrolled patients with any of the multiple lymphoma histologies. Refractory and relapsed criteria were often not defined, and definitions were heterogeneous when available. The ORR from the few comparative studies ranged from 27% to 100%, with most estimates between 40% and 70%. PFS with low and high doses of obintuzumab was 2 months and 3 months, respectively in one study, and OS was 4 months with MEP and 7 months with C-MEP in another study. There was a common regimen in two of the randomized controlled trials, but the patient populations in these studies differed too greatly to allow a valid meta-analysis to be performed. In the single-arm studies, ORR ranged from 11% to 100%, with the estimates evenly distributed across that range. Progression-free survival was approximately 1 to 10 months. Reported median OS ranged from 1 to 13 months. Main safety concerns included thrombocytopenia, leukopenia, and neutropenia. Conclusions There is a high unmet need for effective therapies for patients with relapsed or refractory DLBCL who are ineligible for stem cell transplant. Although numerous regimens have been evaluated in single-arm trials and a handful in comparative studies, there is no clearly superior regimen for patients with relapsed or refractory DLBCL, especially in third- and later lines of therapy. FA is supported by a Clinical Career Development Award from the Lymphoma Research Foundation Disclosures: Colosia: RTI Health Solutions: Employment. Trask: Sanofi: Employment. Olivares: Sanofi: Employment. Khan: RTI Health Solutions: Employment. Abbe: Sanofi: Employment. Police: RTI Health Solutions: Employment. Njue: RTI Health Solutions: Employment. Wang: RTI Health Solutions: Employment. Sherrill: RTI Health Solutions: Employment. Ruiz-Soto: Sanofi: Employment. Kaye: RTI Health Solutions: Employment. Awan: Lymphoma Research Foundation (Career Development Award): Research Funding.
Purpose: Patient perspective is an important and increasingly sought-after complement to clinical... more Purpose: Patient perspective is an important and increasingly sought-after complement to clinical assessment. The aim of this study was to transcribe individual patients' experience of treatment in a dupilumab clinical trial through free-text responses with analysis using natural language processing (NLP) to obtain the unique perspective of patients on disease impact and unmet needs with existing treatment to inform future trial design. Patients and Methods: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) who were enrolled in a Phase IIa randomized controlled trial comparing dupilumab with placebo (NCT01920893) were invited to complete a self-assessment of treatment (SAT) tool at the end of treatment, asking, "What is your opinion on the treatment you had during the trial? What did you like or dislike about the treatment?" Free-text responses were analyzed for the overall cohort and according to treatment assignment using natural language processing including sentiment scoring. In a mixed-methods approach, quantitative patient-reported outcome (PRO) results were utilized to complement the qualitative analysis of free-text responses. Results: Of 60 patients enrolled in the study, 43 (71.6%) completed the SAT and responses from 37 patients were analyzed (placebo, n = 16; dupilumab, n = 21). Word analyses showed that the most common words were "smell," "improve," "staff," "great," "time," and "good." Across the whole cohort, "smell" was the most common symptom-related word. The words "smell" and "experience" were more likely to occur in patients treated with dupilumab. Patients treated with dupilumab also had more positive sentiment in their SAT responses than those who received placebo. The results from this qualitative analysis were reflected in quantitative PRO results. Conclusion: "Smell" was important to patients with CRSwNP, highlighting its importance as a patient-centric efficacy outcome measure in the context of clinical trials in CRSwNP. Trial Registration: ClinicalTrials.gov, NCT01920893. Registered 12 August 2013, https:// www.clinicaltrials.gov/ct2/show/NCT01920893.
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