1) The study compared real-world outcomes of pomalidomide plus low-dose dexamethasone (POM+LoDEX) to other active treatments for relapsed and refractory multiple myeloma using individual patient data from clinical trials and retrospective analyses.
2) After adjusting for baseline characteristics, POM+LoDEX showed significantly better survival outcomes compared to other active treatments, with a median overall survival of 14.4 months versus 4.6 months for other treatments.
3) There was no significant difference in survival between bendamustine-containing regimens and other standard treatments used in this patient population.
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Mina Max
This meta-analysis examined 12 randomized controlled trials involving 6,844 patients with advanced non-small cell lung cancer (NSCLC). The analysis compared chemotherapy with or without gefitinib. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The meta-analysis found that gefitinib therapy significantly improved PFS compared to chemotherapy alone, but only modestly improved OS and this difference was not statistically significant. Gefitinib therapy was associated with higher objective response rates. The most common adverse events with gefitinib were rash, diarrhea, and dry skin.
This systematic review examined 67 studies on strategies to reduce or discontinue long-term opioid therapy (LTOT) for chronic pain and the effect of dose reduction on patient outcomes. The key findings were:
1) Interdisciplinary pain programs had the highest completion and opioid discontinuation rates, ranging from 76-100% and 29-100% respectively across 31 studies of varying quality.
2) Buprenorphine-assisted dose reduction resulted in opioid discontinuation rates ranging from 33-100% in 10 poor quality studies.
3) Among 40 studies of varying quality examining patient outcomes after dose reduction, improvement was reported in pain severity, function, and quality of life, though the overall evidence quality was very
A brief presentation about the abovementioned title, it covers historical aspects, about the process of therapeutic drug monitoring, its indications, criteria, team involved and so on and so forth.
2015 10-06 Building Bridges Biomarker symposium FIMM Helsinki, Alain van GoolAlain van Gool
A unique honour and opportunity to give a 1.5 hour lecture to young biomarker scientists to introduce biomarkers and their importance in translational medicine and personalized healthcare.
This document discusses antidepressant use in the Netherlands. It finds that while 900,000 patients are treated for depression each year, only 14% of patients meet eligibility criteria for clinical trials of antidepressants. Many patients do not continue antidepressant treatment as recommended by guidelines. Approximately 30% of patients stop treatment abruptly, experiencing discontinuation side effects, while others create homemade tapering schedules or use schedules from their doctor. The document examines patterns of initiation, adherence, and discontinuation of antidepressant treatment using pharmacy records data.
This document discusses pharmacovigilance challenges related to biotherapeutic medicines. It notes that biotherapeutics differ from chemically synthesized molecules in their complexity and sensitivity, posing challenges like immunogenicity and exaggerated pharmacology. Different regulatory pathways for biotherapeutics also require comprehensive pharmacovigilance planning. Effective pharmacovigilance requires identifying biotherapeutics, thorough record keeping and reporting, and ongoing safety monitoring due to factors like interchangeability of products and the potential for different safety profiles. The International Nonproprietary Name system also presents challenges for distinguishing biotherapeutics.
The document discusses the importance of selecting sensitive patient populations for clinical trials of biosimilar monoclonal antibodies to properly assess clinical similarity to the reference product. It provides examples of indications and populations that are more sensitive for detecting differences based on effect size, such as rheumatoid arthritis patients for assessing ACR20 response to anti-TNF antibodies. The document cautions that clinical trials must be designed appropriately to demonstrate equivalence or non-inferiority and should obtain data on relevant endpoints in sensitive populations as well as long-term safety and immunogenicity follow-up to justify extrapolation to other indications. It critiques examples of biosimilar clinical trials that failed to use a sensitive population or design.
This document discusses surrogate endpoints in clinical trials. It defines a surrogate endpoint as a substitute measurement used in trials instead of a direct clinical outcome. Surrogate endpoints are advantageous because they are measured earlier, more frequently, and less invasively than clinical endpoints. However, surrogate endpoints sometimes fail to accurately predict clinical benefit. For a surrogate to be valid, it must statistically correlate with the clinical endpoint and fully capture the treatment's effect on the clinical endpoint. Validation is difficult and surrogate endpoints may not generalize to different treatments, populations, or diseases. The FDA is working to develop frameworks to refine the use and validation of surrogate endpoints.
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Mina Max
This meta-analysis examined 12 randomized controlled trials involving 6,844 patients with advanced non-small cell lung cancer (NSCLC). The analysis compared chemotherapy with or without gefitinib. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The meta-analysis found that gefitinib therapy significantly improved PFS compared to chemotherapy alone, but only modestly improved OS and this difference was not statistically significant. Gefitinib therapy was associated with higher objective response rates. The most common adverse events with gefitinib were rash, diarrhea, and dry skin.
This systematic review examined 67 studies on strategies to reduce or discontinue long-term opioid therapy (LTOT) for chronic pain and the effect of dose reduction on patient outcomes. The key findings were:
1) Interdisciplinary pain programs had the highest completion and opioid discontinuation rates, ranging from 76-100% and 29-100% respectively across 31 studies of varying quality.
2) Buprenorphine-assisted dose reduction resulted in opioid discontinuation rates ranging from 33-100% in 10 poor quality studies.
3) Among 40 studies of varying quality examining patient outcomes after dose reduction, improvement was reported in pain severity, function, and quality of life, though the overall evidence quality was very
A brief presentation about the abovementioned title, it covers historical aspects, about the process of therapeutic drug monitoring, its indications, criteria, team involved and so on and so forth.
2015 10-06 Building Bridges Biomarker symposium FIMM Helsinki, Alain van GoolAlain van Gool
A unique honour and opportunity to give a 1.5 hour lecture to young biomarker scientists to introduce biomarkers and their importance in translational medicine and personalized healthcare.
This document discusses antidepressant use in the Netherlands. It finds that while 900,000 patients are treated for depression each year, only 14% of patients meet eligibility criteria for clinical trials of antidepressants. Many patients do not continue antidepressant treatment as recommended by guidelines. Approximately 30% of patients stop treatment abruptly, experiencing discontinuation side effects, while others create homemade tapering schedules or use schedules from their doctor. The document examines patterns of initiation, adherence, and discontinuation of antidepressant treatment using pharmacy records data.
This document discusses pharmacovigilance challenges related to biotherapeutic medicines. It notes that biotherapeutics differ from chemically synthesized molecules in their complexity and sensitivity, posing challenges like immunogenicity and exaggerated pharmacology. Different regulatory pathways for biotherapeutics also require comprehensive pharmacovigilance planning. Effective pharmacovigilance requires identifying biotherapeutics, thorough record keeping and reporting, and ongoing safety monitoring due to factors like interchangeability of products and the potential for different safety profiles. The International Nonproprietary Name system also presents challenges for distinguishing biotherapeutics.
The document discusses the importance of selecting sensitive patient populations for clinical trials of biosimilar monoclonal antibodies to properly assess clinical similarity to the reference product. It provides examples of indications and populations that are more sensitive for detecting differences based on effect size, such as rheumatoid arthritis patients for assessing ACR20 response to anti-TNF antibodies. The document cautions that clinical trials must be designed appropriately to demonstrate equivalence or non-inferiority and should obtain data on relevant endpoints in sensitive populations as well as long-term safety and immunogenicity follow-up to justify extrapolation to other indications. It critiques examples of biosimilar clinical trials that failed to use a sensitive population or design.
This document discusses surrogate endpoints in clinical trials. It defines a surrogate endpoint as a substitute measurement used in trials instead of a direct clinical outcome. Surrogate endpoints are advantageous because they are measured earlier, more frequently, and less invasively than clinical endpoints. However, surrogate endpoints sometimes fail to accurately predict clinical benefit. For a surrogate to be valid, it must statistically correlate with the clinical endpoint and fully capture the treatment's effect on the clinical endpoint. Validation is difficult and surrogate endpoints may not generalize to different treatments, populations, or diseases. The FDA is working to develop frameworks to refine the use and validation of surrogate endpoints.
The Cancer Drugs Fund in practice, under the new frameworkAlex Diamantopoulos
A review of the process and criteria used for consideration of treatments under the CDF framework. This work describes the extent of evidence collection while in the Fund.
The document discusses opportunities and challenges of using observational data from electronic health records and registries to answer clinical questions. It provides two case studies: 1) using the Scottish Early Rheumatoid Arthritis registry to study treatments for rheumatoid arthritis, and 2) using the UK Clinical Practice Research Datalink to compare sulfonylurea and DPP-4 inhibitors as add-ons to metformin for type 2 diabetes patients. While observational data can provide large sample sizes and be more generalizable, challenges include incomplete or inaccurate data, inability to control for all confounders, and not capturing the reasons for treatment changes.
This timely presentation addresses the changes that are proposed under NICE's new value-based assessment (VBA) approach to assessing health technologies. It reviews NICE's current approach and decisions to date for all technologies and separately for orphan and cancer drugs. VBA's proposed calculations for burden of illness and societal impact use estimates of 'shortfall' are illustrated in the presentation. Also discussed are changes in QALY thresholds.
This document summarizes a consensus document from a European Society of Cardiology Heart Failure Association meeting regarding clinical outcome endpoints in heart failure trials. The group discussed challenges in endpoint selection for heart failure trials, including lack of consensus on optimal endpoints. They aimed to develop a framework to achieve common views on endpoints. Key endpoints discussed include mortality, morbidity, composites of morbidity and mortality, symptoms, function, and patient-reported outcomes. Each has strengths and weaknesses, and no single endpoint is ideal.
This document provides an overview of clinical trial design. It discusses the typical phases of clinical trials including:
- Phase I which focuses on safety and dose escalation
- Phase II which screens for therapeutic activity and further evaluates toxicity
- Phase III which uses a proper control group to further evaluate efficacy and monitors long-term safety
It also describes various study designs including randomized controlled trials, parallel designs, cross-over designs, and cohort studies. Key aspects of each design like advantages, disadvantages, and implementation are covered. The document provides a comprehensive yet concise primer on clinical trial methodology.
Personalised Medicine in the EU— Evolving Landscape and New HTA ConsiderationsOffice of Health Economics
The document discusses precision medicine and health technology assessment (HTA) of complementary diagnostics in Europe. It notes that precision medicine is moving from single biomarker tests to complex multi-parameter disease management, but markets have struggled to adopt even simple biomarkers. A new paper published by Epemed identifies additional elements of value for complementary diagnostics beyond traditional HTA considerations like life years gained and cost savings. These include reducing uncertainty, value of hope, and option value of future treatments. The paper recommends changing evidentiary requirements for HTA to consider broader clinical utility and value-based pricing approaches that account for all elements of value.
The document provides an introduction to clinical trials for cancer drug development. It discusses moving potential new therapies from preclinical testing in animal models through the different phases of clinical trials in humans. Phase I trials determine safety and dosing, phase II screens for anti-tumor activity, and phase III tests for efficacy in larger patient populations through randomized controlled trials. Ethical review and informed consent are required throughout the clinical trial process to protect patient safety and rights.
FACTORS ASSOCIATED WITH UNNECESSARY DRUG THERAPY AND INAPPROPRIATE DOSAGE IN ...Jing Zang
To assess factors associated with unnecessary drug therapy and inappropriate dosage in hospitalized patients. A hospital based cross-sectional study design was employed. The study was conducted in Jimma University Specialized Hospital, Jimma, which is 345 Km from South west of Addis Ababa. All patients who were admitted to medical ward from February 5 – March 21, 2011 were included in the study. Data on socio-demographic variables, past medical history, past medication history, current diagnosis, current medications, vital signs and relevant laboratory data were collected by using bed side patient interview guided semi-structured questionnaire and data abstraction formats for card review. The data were analysed by using SPSS version 16 for windows. Descriptive statistics, cross-tabs, chi-square and logistic regression were done. Out of 257 study participants 140(54.5%) had unnecessary drug therapy or inappropriate dosage. The only independent factors which predicted the unnecessary drug therapy in study population was polypharmacy while not considering organ function test, polypharmacy and clinically significant potential drug-drug interaction were independent factors associated with inappropriate dosage . The prevalence of unnecessary drug therapy or inappropriate dosage is significantly high.
This document compares the regulatory pathways for approval of advanced therapies in the European Union and United States. It finds that:
- 15 advanced therapies were approved in the EU and 9 in the US, with 7 approved in both regions.
- Over half of approved therapies in each region received orphan drug designation, though the US required less time on average for marketing application assessment.
- While EU and US procedures sometimes differed, most regulatory milestones like orphan designation, expedited review programs, and advisory committee involvement were similar between the two regions.
- Scientific advice from the EMA occurred on average 1.7 times per product, and protocol assistance 3.7 times on average. Most products had their first scientific
The document discusses recommendations from experts on treating rheumatoid arthritis (RA) to target specific treatment goals. It presents the results of a systematic literature review and consensus process to develop overarching principles and 10 recommendations for treating RA to target remission or low disease activity. The recommendations are based on evidence that abrogation of inflammation and regular measurement of disease activity to adjust treatment can optimize long-term outcomes for patients with RA.
This document provides information on the Dictionary of Pharmacoepidemiology including its author, publisher, copyright information, and references and addresses section. Specifically, it is authored by Bernard Begaud, published by John Wiley & Sons Ltd in 2000, and contains definitions of key terms in pharmacoepidemiology along with references.
Pharmacoepidemiology is the study of the use and effects of medications in large populations. It provides estimates of drug benefits and risks in real-world populations, helping to detect adverse effects that may have been missed in pre-market clinical trials due to limited sample sizes and patient populations that do not represent those seen in practice. Pharmacoepidemiology uses epidemiological methods like cohort studies and case-control studies to understand drug effects, interactions, and outcomes in patient populations. It also includes pharmacovigilance to monitor drug safety after market approval.
Knowledge and Perceptions Related to Hypertension, Lifestyle Behavior Modific...iosrjce
IOSR Journal of Nursing and health Science is ambitious to disseminate information and experience in education, practice and investigation between medicine, nursing and all the sciences involved in health care. Nursing & Health Sciences focuses on the international exchange of knowledge in nursing and health sciences. The journal publishes peer-reviewed papers on original research, education and clinical practice.
By encouraging scholars from around the world to share their knowledge and expertise, the journal aims to provide the reader with a deeper understanding of the lived experience of nursing and health sciences and the opportunity to enrich their own area of practice. The journal publishes original papers, reviews, special and general articles, case management etc.
This document describes a study aimed at creating a gold standard dataset of drug indications extracted from FDA drug labels. The researchers developed a semi-automatic method using natural language processing and expert annotation to identify drug-disease treatment relationships from 100 randomly selected drug labels. Two expert annotators worked independently to accept or reject automatically identified candidate indications, with their common judgments considered the gold standard. Results showed the experts achieved near-perfect joint precision and an average F1-measure of 0.95. Through iterative error analysis and guideline updates, agreement between the annotators improved from 76.2% initially to 93.9%, demonstrating the viability of the semi-automatic method for creating a structured, specific gold standard of drug indications from DailyMed drug labels
This presentation provides a knowledge about Safety Pharmacology, It's aim & objectives, issues, consideration in selection and design of study and test study, duration of study, various studies involved in safety pharmacology, its guidelines, preclinical safety pharmacology. An assignment for the subject, Clinical Research and Pharmacovigilance, 1st year M.Pharm, 2nd semester.
What I Learnt About Search Playing Championship Manager #thinkvisKelvin Newman
I’ve long suspected that’s there’s a strong correlation between people who mis-spent their youth playing Championship Manager (now known as Football Manager) and smart search marketers, but it’s only recently I’ve realised why. Playing Championship Manager is the reason why they are good SEOs. And I have proof! I’ll take you through why the game trains such excellent search marketers and why I’m considering making an addiction to the game part of any job advert I create in the future.
The Cancer Drugs Fund in practice, under the new frameworkAlex Diamantopoulos
A review of the process and criteria used for consideration of treatments under the CDF framework. This work describes the extent of evidence collection while in the Fund.
The document discusses opportunities and challenges of using observational data from electronic health records and registries to answer clinical questions. It provides two case studies: 1) using the Scottish Early Rheumatoid Arthritis registry to study treatments for rheumatoid arthritis, and 2) using the UK Clinical Practice Research Datalink to compare sulfonylurea and DPP-4 inhibitors as add-ons to metformin for type 2 diabetes patients. While observational data can provide large sample sizes and be more generalizable, challenges include incomplete or inaccurate data, inability to control for all confounders, and not capturing the reasons for treatment changes.
This timely presentation addresses the changes that are proposed under NICE's new value-based assessment (VBA) approach to assessing health technologies. It reviews NICE's current approach and decisions to date for all technologies and separately for orphan and cancer drugs. VBA's proposed calculations for burden of illness and societal impact use estimates of 'shortfall' are illustrated in the presentation. Also discussed are changes in QALY thresholds.
This document summarizes a consensus document from a European Society of Cardiology Heart Failure Association meeting regarding clinical outcome endpoints in heart failure trials. The group discussed challenges in endpoint selection for heart failure trials, including lack of consensus on optimal endpoints. They aimed to develop a framework to achieve common views on endpoints. Key endpoints discussed include mortality, morbidity, composites of morbidity and mortality, symptoms, function, and patient-reported outcomes. Each has strengths and weaknesses, and no single endpoint is ideal.
This document provides an overview of clinical trial design. It discusses the typical phases of clinical trials including:
- Phase I which focuses on safety and dose escalation
- Phase II which screens for therapeutic activity and further evaluates toxicity
- Phase III which uses a proper control group to further evaluate efficacy and monitors long-term safety
It also describes various study designs including randomized controlled trials, parallel designs, cross-over designs, and cohort studies. Key aspects of each design like advantages, disadvantages, and implementation are covered. The document provides a comprehensive yet concise primer on clinical trial methodology.
Personalised Medicine in the EU— Evolving Landscape and New HTA ConsiderationsOffice of Health Economics
The document discusses precision medicine and health technology assessment (HTA) of complementary diagnostics in Europe. It notes that precision medicine is moving from single biomarker tests to complex multi-parameter disease management, but markets have struggled to adopt even simple biomarkers. A new paper published by Epemed identifies additional elements of value for complementary diagnostics beyond traditional HTA considerations like life years gained and cost savings. These include reducing uncertainty, value of hope, and option value of future treatments. The paper recommends changing evidentiary requirements for HTA to consider broader clinical utility and value-based pricing approaches that account for all elements of value.
The document provides an introduction to clinical trials for cancer drug development. It discusses moving potential new therapies from preclinical testing in animal models through the different phases of clinical trials in humans. Phase I trials determine safety and dosing, phase II screens for anti-tumor activity, and phase III tests for efficacy in larger patient populations through randomized controlled trials. Ethical review and informed consent are required throughout the clinical trial process to protect patient safety and rights.
FACTORS ASSOCIATED WITH UNNECESSARY DRUG THERAPY AND INAPPROPRIATE DOSAGE IN ...Jing Zang
To assess factors associated with unnecessary drug therapy and inappropriate dosage in hospitalized patients. A hospital based cross-sectional study design was employed. The study was conducted in Jimma University Specialized Hospital, Jimma, which is 345 Km from South west of Addis Ababa. All patients who were admitted to medical ward from February 5 – March 21, 2011 were included in the study. Data on socio-demographic variables, past medical history, past medication history, current diagnosis, current medications, vital signs and relevant laboratory data were collected by using bed side patient interview guided semi-structured questionnaire and data abstraction formats for card review. The data were analysed by using SPSS version 16 for windows. Descriptive statistics, cross-tabs, chi-square and logistic regression were done. Out of 257 study participants 140(54.5%) had unnecessary drug therapy or inappropriate dosage. The only independent factors which predicted the unnecessary drug therapy in study population was polypharmacy while not considering organ function test, polypharmacy and clinically significant potential drug-drug interaction were independent factors associated with inappropriate dosage . The prevalence of unnecessary drug therapy or inappropriate dosage is significantly high.
This document compares the regulatory pathways for approval of advanced therapies in the European Union and United States. It finds that:
- 15 advanced therapies were approved in the EU and 9 in the US, with 7 approved in both regions.
- Over half of approved therapies in each region received orphan drug designation, though the US required less time on average for marketing application assessment.
- While EU and US procedures sometimes differed, most regulatory milestones like orphan designation, expedited review programs, and advisory committee involvement were similar between the two regions.
- Scientific advice from the EMA occurred on average 1.7 times per product, and protocol assistance 3.7 times on average. Most products had their first scientific
The document discusses recommendations from experts on treating rheumatoid arthritis (RA) to target specific treatment goals. It presents the results of a systematic literature review and consensus process to develop overarching principles and 10 recommendations for treating RA to target remission or low disease activity. The recommendations are based on evidence that abrogation of inflammation and regular measurement of disease activity to adjust treatment can optimize long-term outcomes for patients with RA.
This document provides information on the Dictionary of Pharmacoepidemiology including its author, publisher, copyright information, and references and addresses section. Specifically, it is authored by Bernard Begaud, published by John Wiley & Sons Ltd in 2000, and contains definitions of key terms in pharmacoepidemiology along with references.
Pharmacoepidemiology is the study of the use and effects of medications in large populations. It provides estimates of drug benefits and risks in real-world populations, helping to detect adverse effects that may have been missed in pre-market clinical trials due to limited sample sizes and patient populations that do not represent those seen in practice. Pharmacoepidemiology uses epidemiological methods like cohort studies and case-control studies to understand drug effects, interactions, and outcomes in patient populations. It also includes pharmacovigilance to monitor drug safety after market approval.
Knowledge and Perceptions Related to Hypertension, Lifestyle Behavior Modific...iosrjce
IOSR Journal of Nursing and health Science is ambitious to disseminate information and experience in education, practice and investigation between medicine, nursing and all the sciences involved in health care. Nursing & Health Sciences focuses on the international exchange of knowledge in nursing and health sciences. The journal publishes peer-reviewed papers on original research, education and clinical practice.
By encouraging scholars from around the world to share their knowledge and expertise, the journal aims to provide the reader with a deeper understanding of the lived experience of nursing and health sciences and the opportunity to enrich their own area of practice. The journal publishes original papers, reviews, special and general articles, case management etc.
This document describes a study aimed at creating a gold standard dataset of drug indications extracted from FDA drug labels. The researchers developed a semi-automatic method using natural language processing and expert annotation to identify drug-disease treatment relationships from 100 randomly selected drug labels. Two expert annotators worked independently to accept or reject automatically identified candidate indications, with their common judgments considered the gold standard. Results showed the experts achieved near-perfect joint precision and an average F1-measure of 0.95. Through iterative error analysis and guideline updates, agreement between the annotators improved from 76.2% initially to 93.9%, demonstrating the viability of the semi-automatic method for creating a structured, specific gold standard of drug indications from DailyMed drug labels
This presentation provides a knowledge about Safety Pharmacology, It's aim & objectives, issues, consideration in selection and design of study and test study, duration of study, various studies involved in safety pharmacology, its guidelines, preclinical safety pharmacology. An assignment for the subject, Clinical Research and Pharmacovigilance, 1st year M.Pharm, 2nd semester.
What I Learnt About Search Playing Championship Manager #thinkvisKelvin Newman
I’ve long suspected that’s there’s a strong correlation between people who mis-spent their youth playing Championship Manager (now known as Football Manager) and smart search marketers, but it’s only recently I’ve realised why. Playing Championship Manager is the reason why they are good SEOs. And I have proof! I’ll take you through why the game trains such excellent search marketers and why I’m considering making an addiction to the game part of any job advert I create in the future.
Everyone says you need to build a brand for SEO success, but actually how do you do that? In this presentation I share the top advice from my four branding heros.
Every classified website needs to do well on Google in this hands on workshop Kelvin Newman, from SiteVisibility will share the most common SEO mistakes made by classified sites and how to quickly and easily solve them plus dedicating some time to helping the audience solves their own unique challenges with Google & co.
Digital marketing is dominated by four main themes: social media, mobile marketing, local search optimization, and analytics. Social media allows companies to connect directly with customers, mobile marketing focuses on smartphones and tablets, local search optimization improves local listings and visibility, and analytics provides data to measure success and inform strategies.
SEO Tactics Off Limits After the ASA Changes #SMXKelvin Newman
You no doubt will have heard about the changes in the ASA remit which affects how you do internet marketing and SEO.
In this presentation originally delivered at SMX London 2011 and goes into detail of how link building may be affected.
Forty five talks we’ve got lined up for the the next brightonSEO.Kelvin Newman
The document outlines 45 talks that will be presented at the brightonSEO conference on April 7th, 2017 at the Brighton Centre in Brighton, UK. It provides links to photos related to each talk's topic, which include talks on Google AMP case studies, boosting SEO audit recommendations with machine learning, supercharging websites with real-time APIs, A/B testing app store listings, and inventive uses of the canonical tag. The document also notes that free tickets were released on November 7th and VIP tickets are available now by registering on the conference website.
Tofacitinib, an oral janus kinase inhibitor, analysis of malignancies across ...Paul Pérez
1) An analysis was conducted of malignancy data from clinical trials of tofacitinib, an oral Janus kinase inhibitor for rheumatoid arthritis (RA). Over 5,600 patients were treated with tofacitinib across phase 2, 3, and long-term extension studies.
2) 107 patients treated with tofacitinib developed malignancies excluding non-melanoma skin cancer (NMSC), with rates similar to those expected in RA patients and the general population. The most common malignancies were lung cancer, breast cancer, and lymphoma.
3) The incidence of malignancies was stable over time with tofacitinib exposure and was not higher than placebo or the active control ad
Slides from the presentation on extrapolation from progression free survival to overall survival in oncology given at the 2017 HTAi Annual Meeting in Rome
This document summarizes the current management of mesothelioma. It is a rare cancer associated with asbestos exposure. Treatment involves a multidisciplinary approach, with systemic chemotherapy as the mainstay. Around 20% of patients may be candidates for surgical resection combined with radiation and chemotherapy, though the evidence for an overall survival benefit is limited. Immunotherapy with nivolumab and ipilimumab shows benefit compared to chemotherapy for non-epithelioid histologies. Ongoing trials are further evaluating the roles of surgery, radiation therapy, and novel systemic therapies in treatment.
Edward B. Garon, MD, MS, Jamie E. Chaft, MD, and Matthew D. Hellmann, MD, prepared useful Practice Aids pertaining to lung cancer management for this CME/MOC/CE activity titled "Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Cancer Continuum: State of the Science and Implications for Practice." For the full presentation, monograph, complete CME/MOC/CE information, and to apply for credit, please visit us at http://bit.ly/2ATq0qp. CME/MOC/CE credit will be available until November 21, 2019.
Comparison of remission criteria in a tumour necrosis factor inhibitor treate...Younis I Munshi
This study compared remission rates in a cohort of 273 rheumatoid arthritis patients treated with tumor necrosis factor inhibitors, using the Disease Activity Score 28 (DAS28) remission criteria and the new American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission criteria. At 12 months, 102 patients met DAS28 remission but only 27 met ACR/EULAR Boolean remission, as the latter criteria requires lower disease activity levels. Patients meeting DAS28 but not Boolean remission most commonly missed the criteria due to high patient global health scores. The study suggests that more stringent remission criteria may help ensure further resolution of disease activity and better long-term outcomes.
Homeopathic treatment of elderly patients - a prospective observational study...home
The severity of disease showed marked and sustained improvements under homeopathic treatment,
but this did not lead to an improvement of quality of life. Our findings might indicate that homeopathic medical
therapy may play a beneficial role in the long-term care of older adults with chronic diseases and studies on
comparative effectiveness are needed to evaluate this hypothesis.
Corticosteroids for sore throat sr ma bmj 2018Mayra Serrano
This systematic review and meta-analysis found that a single low dose of corticosteroids, such as oral dexamethasone up to 10 mg, provides moderate to high quality evidence of pain relief for patients with sore throat. Patients who received corticosteroids were twice as likely to experience pain relief after 24 hours and 1.5 times more likely to have no pain at 48 hours, with no increase in serious adverse effects. The mean time to complete pain resolution was about 11 hours shorter with corticosteroids. Included trials enrolled over 1400 individuals and assessed outcomes up to 48 hours, but did not evaluate risks of repeated corticosteroid use for recurrent sore throats.
This clinical trial protocol summarizes a phase 2 double-blind randomized placebo-controlled trial to evaluate the safety and efficacy of TJ301 for the treatment of active ulcerative colitis. The trial will enroll 90 patients to receive either 600mg of TJ301 biweekly, 300mg of TJ301 biweekly, or placebo biweekly for 12 weeks. The primary endpoint is clinical and endoscopic remission at week 12. Secondary endpoints include safety assessments, pharmacokinetic measures, and changes in disease activity scores from baseline to week 12. The protocol outlines the study design, patient selection criteria, treatments, assessments, data management, and statistical analysis plan.
Presentació resultats Estudi multicèntric amb telemedicina Red Promete per pa...brnmomentum
1) The PROMETE II study was a randomized controlled trial evaluating the use of home telemonitoring (HTM) compared to routine clinical practice (RCP) in elderly patients with severe COPD requiring long-term oxygen therapy.
2) The primary outcome of reducing hospitalizations and emergency room visits was not significantly different between the HTM and RCP groups.
3) However, the duration of hospital stays appeared to be shorter in the HTM group, with the mean duration of hospitalization being approximately 4 days less, though this was not statistically significant.
Mark Frisse gave an outstanding presentation at the Redwood Mednet 2013 Conference "Connecting California to Improve Patient Care in 2013"
http://www.redwoodmednet.org/projects/events/20130725/index.html
This paper reports phase II clinical data on galunisertib, a novel small molecule TGF-beta receptor inhibitor in patients with advanced non-operable hepatocellular carcinoma. This poster was presented at ASCO 2016 in Chicago. Results show activity and mild toxicity.
Dr. Julie Li-Yu presented updated recommendations on how to screen and treat tuberculosis in patients with rheumatic diseases. Dr. Li-Yu and Dr Juan Javier Lichauco were representatives of the Philippine Rheumatology Association to the Task Force developing guidelines for TB management in the country. The slides posted were presented during the Joint Rheumatoid Arthritis - Osteoarthritis Special Interest Symposium held at the F1 Hotel in Taguig City last 28 November 2014.
Meaningful Use Workgroup Recommendations Brian Ahier
The document summarizes the recommendations of the Meaningful Use Workgroup to the HIT Policy Committee regarding the objectives for Stage 2 of Meaningful Use. The Workgroup aligned the objectives with national healthcare priorities and recommended raising thresholds or expanding criteria for many Stage 1 objectives. They also proposed maintaining the current timeline but allowing a 90-day reporting period for providers to address concerns about implementation feasibility.
The document discusses issues related to measuring and modeling medication adherence using claims data. It covers calculating adherence measures like MPR and PDC, defining adherence thresholds, handling primary non-compliance, and addressing endogeneity and selection bias when modeling adherence as an independent variable to estimate its impact on outcomes. Regression adjustment, propensity score matching, and instrumental variables are some methods discussed to address biases in observational studies of adherence.
Outcome Measures in Cancer: Do disease specific instruments offer greater sen...Office of Health Economics
Paula's slides for her presentation on Outcomes Measures in Cancer given at the C2E2 Rounds Conference at the University of British Columbia on July 5th, 2017.
This document discusses treatment simplification strategies for HIV management. It defines treatment simplification as changing an established effective therapy to reduce pill burden, dosing frequency, or other requirements to enhance tolerability. Optimal candidates are those with controlled viremia and no tolerability issues. Simplification strategies discussed include within-class changes like protease inhibitor substitutions and out-of-class changes such as switching from a protease inhibitor regimen to an NNRTI or integrase inhibitor. Clinical trials support the efficacy and safety of certain simplification approaches.
This document summarizes the results of a study that evaluated the health care resource utilization and costs of patients with symptomatic multiple myeloma in the United Kingdom. The study found that the average total cost per treatment line was £34,296, with most costs attributed to anti-tumor drugs. The average cost per month of active treatment was £5,168. For patients receiving best supportive care after discontinuing active treatment, the average total cost was £1,444 if they progressed or £2,480 if they did not progress before death.
Projecting ‘time to event’ outcomes in technology assessment: an alternative ...cheweb1
This document discusses alternative methods for projecting survival outcomes in technology assessments beyond what is observed in clinical trials.
The standard method of fitting parametric survival functions to trial data and extrapolating is problematic as it assumes a single mechanism and does not account for trial design or changes in risk over time. LRiG proposes examining trial data to understand risk trajectories and formulating hypotheses based on clinical context rather than selecting a model solely on fit. A case study demonstrates modeling progression-free survival, post-progression survival, and overall survival as separate phases using exponential convolution functions. LRiG advocates understanding empirical data and developing more informative multi-phase models rather than relying on standard projections.
Survival Outcomes Associated With 177lu-Dotatate Therapy in Advanced Stage Ge...semualkaira
Peptide receptor radionuclide therapy in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has been used
in the past two decades with a considerable prevalence of literature. However, due to the inherently indolent nature of GEP-NETs
it is critical to evaluate the patients for a longer duration to assess the sustainability of treatment, survival patterns, and observe
for late-side effects from treatment. The purpose of this study is
to give an overview of an 11-year experience from a single centre on 177Lu-DOTATATE peptide receptor radionuclide therapy
(177Lu-PRRT) in advanced stage GEP-NETs
Similar to Goldschmidt (LM Poster D3) Comp Effect (Oct 20 2015) (20)
This healthcare survey of 836 patients with castration-resistant prostate cancer (CRPC) in Germany found:
1) 44% of patients presented with metastatic disease at initial diagnosis. Bone pain, performance status decline, and micturition disorders were common symptoms leading to CRPC diagnosis.
2) After failing primary LHRHa therapy, 41% of patients received abiraterone acetate + prednisone and 11% received enzalutamide as first-line CRPC treatment.
3) Urologists supervised most CRPC treatments, initiating 42% of endocrine therapies and 25% of chemotherapies as first-line treatment.
The survey analyzed treatment patterns for multiple myeloma in Germany between 2008-2011 based on data from 478 patients. Key findings include:
- Bortezomib-chemotherapy regimens are now preferred for first-line treatment regardless of planned autologous stem cell transplantation (ASCT), which was performed in around 30% of eligible patients.
- Thalidomide- and lenalidomide-based therapies are commonly used in the second-line setting in 31% of patients.
- Cytogenetic testing increased from 23% in 2008 to 53% in 2011 and influences treatment decisions, though age and comorbidities remain major factors.
- Supportive care needs decreased
The document summarizes the results of a nationwide survey in Germany that monitored treatment decisions for chronic lymphocytic leukemia (CLL) patients from 2006 to 2011. The survey found that over this period:
1) The percentage of patients diagnosed in early disease stages increased from 66% in 2006 to 77% in 2011.
2) Treatment options shifted from chlorambucil in 2006 to fludarabine-containing regimens in 2009 and the combination of rituximab and bendamustine in 2011.
3) Immune-chemotherapy treatments were administered more often, increasing from 15% of patients in 2006 to 73% in 2011.
1. The study analyzed treatment patterns over time in patients receiving first-line chemotherapy for advanced or metastatic esophageal or gastric cancer based on data from 2,808 patients documented in Therapiemonitor from 2006-2013.
2. Treatment intensity increased over time, with 49.3% of patients receiving triplet chemotherapy in 2013 compared to just 10.1% in 2006. HER2 testing rates increased from 49.1% in earlier studies to 79.1% in 2012-2013, though testing was still not always performed according to guidelines.
3. Usage of fluoropyrimidine/cisplatin combinations with trastuzumab declined from 67% in 2010-2011 to 50% in 2012-2013
Treatment (tx) intensity for patient groups by predefined tx aims and clinical characteristics in the management of patients (pts) with metastatic colorectal cancer (MCRC): Findings from TherapyMonitor mCRC 2009 in Germany
1. The document analyzes changes in treatment strategies for metastatic colorectal cancer in Germany between 2005-2007 based on data from large population surveys. It finds that results from clinical trials showing increased effectiveness of new drugs like oxaliplatin and irinotecan were quickly implemented in clinical practice.
2. The treatment objective of achieving secondary resection of metastases after chemotherapy increased significantly from 18% to 27% during this period, as clinical trials showed biologicals improving resectability rates. Biologicals were used more often when secondary resection was the goal compared to other objectives.
3. A multivariate analysis found that while many factors influenced treatment choices, the objective of secondary resection and patient age had the most significant impact
1. Comparative Effectiveness of Pomalidomide
Plus Low-Dose Dexamethasone (POM+LoDEX)
in Relapsed and Refractory Multiple Myeloma:
Use of Real-World Data in the Absence of Head-
to-Head Studies
Hartmut Goldschmidt,1 Rebecca Harvey,2
Dawn Lee,2 Sujith Dhanasiri,3 Pellegrino Musto,4 Sergio Storti,5 Lucia
Pantani,6 Lenka Kellermann,7 Brigitte Kolb,8 Gordon Cook9
1University of Heidelberg, Heidelberg, Germany; 2BresMed Health Solutions, Sheffield, South Yorkshire, United
Kingdom; 3Celgene International Sàrl, Boudry, Switzerland; 4IRCCS-CROB, Referral Cancer Center of Basilicata,
OECI Clinical Cancer Center, Basilicata, Italy; 5University Cattolica del Sacro Cuore, Campobasso, Italy; 6Seràgnoli
Institute of Hematology, Bologna University School of Medicine, Bologna, Italy; 7OncologyInformationService,
Freiburg, Germany; 8Hématologie Clinique, Centre Hôpitalier Universitaire de Reims, Paris, France; 9St James's
Institute of Oncology, St James's University Hospital, Leeds, United Kingdom.
P8
2. Disclosures
• HG: Has received research support from Celgene, Janssen, Chugai, Novartis, BMS,
Millennium, Served on the advisory boards at Celgene, Janssen, Novartis, Onyx,
Amgen, Takeda, BMS and received honoraria from Celgene, Janssen, Novartis,
Chugai, Onyx, Millennium
• DL, RH: Consultant/advisor for Celgene
• SD: Employment by and equity ownership of Celgene
• PM: Received honoraria from Celgene
• SS: Has no relevant conflicts of interest to declare
• LP: Has no relevant conflicts of interest to declare
• LK: Received grants for research projects from Amgen, BMS, Celgene, Janssen,
Novartis, Roche, Sanofi, Takeda
• B.K. has received travel accommodations/expenses from Celgene
• GC: Disclosures have been requested
3. Background
• The MM-003 study demonstrated a clinically and statistically significant survival
benefit with POM+LoDEX vs high-dose dexamethasone (HiDEX) in relapsed
and refractory multiple myeloma (RRMM) following prior treatment with both
bortezomib (BORT) and lenalidomide (LEN)1,2:
– Median increase 4.6 months overall survival (OS) unadjusted for crossover (12.7 vs 8.1
months; HR 0.74 [95% CI, 0.56-0.97])1 based on the March 2013 data cut
– Median increase 7.0 months OS adjusted for crossover (12.7 vs 5.7 months; HR 0.52
[95% CI, 0.39-0.68])2 based on the March 2013 data cut
– Median increase 5.0 months OS unadjusted for crossover (13.1 vs 8.1 months; HR 0.52
[95% CI, 0.39-0.68])3 based on the September 2013 data cut
• Increasingly, access to innovative medicines requires a demonstration of
increased benefit vs current care by reimbursement bodies
• Although HiDEX was standard of care when MM-003 was designed, in the
treatment setting immediately following BORT and LEN, DEX is now mostly
used with palliative intent or as an add-on to other treatments
• Current European standard of care in this setting primarily comprises
combinations including bendamustine (BEN), BORT retreatment, or LEN
retreatment
4. Objectives
• The objective of this study was to estimate the comparative effectiveness of
POM+LoDEX vs other active treatments in patients with RRMM who had
previous failure of LEN and BORT treatment using statistical analyses
performed on time-to-event individual patient data (IPD)
• A secondary objective was to estimate long-term OS outcomes based on
standard extrapolation methods
5. Inclusion/Exclusion Criteria
• IPD for current care treatments was sourced from 5 EU countries (United Kingdom, France, Spain,
Italy, Germany) using the following inclusion/exclusion criteria to allow for appropriate comparisons
• However, for the current analysis and results, only the UK data was available to report
Inclusion Criteria Exclusion Criteria
Subsequent therapy received following previous treatment with
both BORT and LEN
Missing OS
information
Information collected on the following potentially prognostic
covariates:
- Age
- Disease duration
- ISS stage
- Receipt of prior SCT
- Receipt of prior thalidomide
- Treatment regimen received post BORT and LEN
- Refractoriness to BORT and LEN
Missing covariate
information
Subsequent POM
received
Table 1. Inclusion/Exclusion Criteria
ISS, International Staging System; SCT, stem cell transplant.
6. Methods
• IPD for POM+LoDEX was sourced from the MM-002 and MM-003 trials
• Available data were included in a time-to-event regression model, adjusting
for 8 covariates selected based on prognostic value in the MM-003 trial and
clinician advice
– Age (years)
– Disease duration (years)
– ISS stage (1/2/3)
– Receipt of prior thalidomide (yes/no)
– Receipt of prior stem cell transplant (yes/no)
– Refractory to BORT (yes/no)—defined as progression on or within 60 days of
treatment
– Refractory to LEN (yes/no)—defined as progression on or within 60 days of
treatment
– Treatment (POM+LoDEX/other active treatments)
• OS and progression-free survival (PFS) were measured from the start of the
treatment line of interest to the analysis, ie, the first line of therapy post
BORT and LEN
7. Data Analysis
• As a large proportion of patients in this setting received treatment with BEN,
the difference in survival with POM+LoDEX vs BEN vs other therapies was
investigated using Cox regression analysis
• Adjusted Kaplan-Meier plots stratified by treatment were then generated for:
– OS
– PFS
– Time to treatment failure (TTF)
• Five parametric curves (exponential, Weibull, log-logistic, log-normal and
extreme value) were fitted to the adjusted Kaplan-Meier data to predict long-
term survival
• Goodness of fit was assessed in accordance with NICE Decision Support
Unit guidance4 based on statistical goodness of fit (Akaike Information
Criteria [AIC], Bayesian Information Criteria [BIC]), visual fit, and clinical
validity
8. Summary of Trial Design for Datasets
THAL, thalidomide.
Dataset
Number of
Relevant
Patients
Trial Design Dates of Data Datasets Considered Inclusion Criteria
Included in This
Analysis?
CurrentCare
Gooding
et al5 30
Retrospective chart review using
pharmacy-generated lists of
sequential LEN recipients
Jan 2011 to
Jul 2013
BEN containing
BORT containing
DT-PACE
LEN containing
No treatment
Progressive or refractory disease
following receipt of BORT and LEN
Y
Tarant
et al7 26
Jan 2007 to
Sep 2012
BEN containing
BORT containing
LEN containing
Clinical trials
Other chemotherapies
Progressive disease following receipt
sequentially THAL, BORT, then LEN
Y
Musto
et al6 41
Retrospective, real-life analysis of
Italian patients with RRMM who had
received salvage therapy with BEN
as single agent or in combination
with other drugs, within a national,
compassionate- use program
(18 centers)
Jan 2011 to 2014
BEN containing Progressive disease following receipt
of THAL, BORT, and LEN
N—missing
covariate
information
Used for validation
EU Therapy
Monitor
≈ 200
Retrospective chart review via
survey of European centers (≈ 20
per country) in France, Germany,
Italy and Spain
Jan 2012 to 2014
POM containing
BEN containing
Other active
treatment
Receipt of BORT and LEN
Died in 2015 from MM
N—planned for
inclusion in future
analysis
Pomalidomide
MM-0028 113
Randomized open-label Phase II
study
18 centers in the USA and Canada
Dec 2009 to
Feb 2013
POM+LoDEX arm
Progressive disease following ≥ 2
cycles of LEN and ≥ 2 cycles of BORT
Y
MM-0031 302
Randomized open-label Phase III
study
93 centers in Europe, Russia,
Australia, Canada, and the USA
Mar 2011 to
Sep 2013
POM+LoDEX arm
Progressive or refractory disease
following ≥ 2 cycles of LEN and ≥ 2
cycles of BORT
Progressive disease ≤ 6 months after
achieving partial response to BORT or
intolerance of BORT
≥ 6 cycles of alkylator treatment, or
progressive disease after ≥ 2 cycles
of alkylator treatment
Y
Table 2. Provides a summary of the trial design for datasets
9. Summary of Patient Characteristics in
Datasets Included in This Analysis
• In Table 3, the datasets available for current care include patients with a
similar age and number of prior therapies to the patients from the trials for
POM+LoDEX, however, substantially fewer patients in the current care trials
were refractory to either BORT or LEN
* Includes only patients meeting the study inclusion/exclusion criteria.
Trial Treatment
No. of
Pts
ISS stage Prior THAL Prior SCT
Refractory to
BORT
Refractory
to LEN
Age,
(yrs) Disease
Duration
(yrs)
Un-
adjusted
Median
Survival
(mos)
No of Pts
in
Analysis*(% 1,2,3; n) (% yes) (% yes) (% yes) (% yes) (mean)
Gooding
et al5
Current UK
standard of
care
30
21.7, 34.8,
43.5; 23
83.3 46.7 10.0 16.7 67.6 4.5 5.3 21
Tarant
et al7
Current UK
standard of
care
26
58.8, 35.3,
5.9; 17
76.9 65.4 3.8 7.7 64.3 6.3 8.4 15
MM-0028 POM+
LoDEX
113
7.1, 25.7,
67.3; 113
68.1 74.3 72.6 77.0 64.4 6.2 16.5 113
MM-0031 POM+
LoDEX
302
27.9, 40.0,
32.1; 290
57.2 70.9 78.8 94.7 63.6 6.2 13.1 290
10. Survival of BEN vs Other Active Treatments
• Within the current care datasets, no significant difference in survival
prospects was found between BEN and other forms of active treatments
(HR=0.98, 95% CI [0.50, 1.94])
• This led to all active treatments being assessed as a whole rather than by individual
treatment
Figure 1. Kaplan-Meier Curves for BEN vs Other Standard Care Treatments
1.00
0.75
0.50
0.25
0.00
0 6 12 18 24 30 36 42
Time (Months)
Bendamustine Other UK standard care treatments
ProbabilityofSurvival
Bendamustine
Other UK standard care treatments
20 9 5 2 1 1
36 14 4 3 0 0
11. Survival of POM+LoDEX vs Other Active
Treatments
• Once adjusted for baseline patient demographics, POM+LoDEX showed even
greater survival prospects vs other active treatments (Figure 2, HR, 0.33 [95% CI,
0.18-0.59]); median OS was 14.4 and 4.6 months, respectively
UnadjustedAdjusted
100
75
50
25
0
0 21 3 0 21 3
100
75
50
25
0
Time (years) Time (years)
OverallSurvival(%)
OverallSurvival(%)
POM+LoDex
Other Active Rx
415 282 216 45 25 4
56 23 9 1 1 0
89
5
POM+LoDex
Other Active Rx
415 282 216 45 25 4
56 23 9 1 1 0
89
5
Number at risk (pooled data) Number at risk (pooled data)
Other Active Rx
POM+LoDex
Other Active Rx
POM+LoDex
Figure 2. Kaplan-Meier Curves for OS, Stratified by Treatment Arm
12. RESULTS
All curves fitted the adjusted survival data well. The log-
normal curve produced the lowest AIC and BIC values and
yielded a mean OS of 28.7 vs 9.6 months with
POM+LoDEX vs other active treatments respectively
13. Conclusions
• Based on this analysis, POM+LoDEX showed greater OS vs other
active treatments, with the predicted median remaining in line with
published estimates for patients in this hard-to-treat group who have
received prior therapy with both LEN and BORT.4,5,8
• A limitation of this analysis is that randomization is not preserved
due to data arising from different center and studies; however, the
method of covariate adjustment used can account for some
imbalances that arise from the use of different populations.
Additionally, the sample size available for the current analysis is
relatively small. Additional datasets are being sought to validate the
outcomes observed here with a larger sample size.
• Data sourcing is ongoing, and results from any additional datasets
identified will be reported subsequently.
14. References
1. San Miguel J, et al. Lancet Oncol. 2013;14(11):1055-1066.
2. Morgan G, et al. Br J Haematol. 2015;168(6):820-823.
3. Dimopoulos M, et al. ASH 2013 [abstract 408].
4. NICE Decision Support Unit TSD 14. 2011.
5. Gooding S, et al. PLoS One. 2015;10(9):e.0136207.
6. Musto P, et al. Leuk Lymph. 2015;56(5):1510-1513.
7. Tarant J, et al. Blood. 2013;122(21):5380.
8. Richardson PG, et al. Blood. 2014;123(12):1826-1632.
9. Kumar SK, et al. Leukemia. 2012;26:149-157.
15. Acknowledgments
This study was supported by Celgene Corporation. The authors
received editorial and production support in the preparation of
this poster from MediTech Media, funded by Celgene
Corporation. The authors are fully responsible for all content and
editorial decisions for this poster.
Correspondence
Hartmut Goldschmidt –
hartmut.goldschmidt@med.uni-heidelberg.de
16. QR Code
Copies of this poster obtained through the QR Code are for personal use only
and may not be reproduced without permission from the author of this poster.