text:
Culture Plan 2008-2018
Theatres and performance spaces
Art and cultural activities
Culture|Shift
Find a performance or exhibit space
Fieldhouse programs in parks
Making space for arts and culture
Vancouver Music Strategy
Culture Plan for Vancouver 2008-2018
Envisioning a future with culture at the centre
The vibrancy of Vancouver's arts and culture scene is a priceless benefit to its citizens and visitors.
In 2008, City Council affirmed its commitment to a diverse and healthy creative sector through the adoption of the Cultural Plan for Vancouver 2008 – 2018.
Created through an inclusive community process, it is our guide for the City's ongoing and future role in arts and culture.
Vancouver's Culture Plan vision is to develop, enliven, enhance, and promote arts, culture, and cultural diversity in our city in ways that benefit our citizens, creative community, businesses, and visitors.
Phase 2 Implementation
Creating cultural and performance spaces
Culture|Shift: Blanketing the city in arts and culture
Learn more about Vancouver's new Culture Plan for 2020-2029
Strategic themes
February 3, 2017 - Help shape the future of Vancouver's arts and culture spaces. Take the Making Space for Art Survey.
We have commissioned a study on arts and cultural spaces in Vancouver. As part of the research, we need input from arts and cultural organizations and individual artists to understand current and future programming activity, space use and facility needs. This information will be used to help inform future support for arts and cultural spaces in Vancouver. It is critical that we gather meaningful input from the arts and culture community.
The survey takes about 15 minutes, and is being conducted by AMS Planning and Research. (If your organization receives support from us, you may have already received an invitation to participate.)
Deadline: Friday, February 24, 2017
If you have any questions about the survey, please contact Kristen Lambertson, Cultural Planner at kristen.lambertson@vancouver.ca or Bill Blake, AMS Planning and Research at bblake@ams-online.com.
Take the Making Space for Art Survey
Public art update and signature opportunities
June 1, 2016 – Vancouver's Public Art Program is celebrating it's 25th Anniversary in 2016. The program has enabled over 400 pieces of public art and community art installations in the city.
As reported to City Council, this year the program will launch over 25 temporary and permanent artworks to be built and installed over the next several years.
In addition, the program plans to launch three signature public artworks with substantive budgets in key Vancouver locations. These will include:
Major artworks by local First Nations
A contemporary City of Reconciliation artwork
A commission in which an artist of international calibre will be invited to create a major artwork for Vancouver
View the staff presentation to Council (3.5 MB) and meeting video
Read the 25th Anniversary Retrospective blog
Community Arts Grants 2016
June 1, 2016 – Vancouver City Council approved grant allocations totalling $464,650 to a record 82 organizations representing the full spectrum of amateur to professional art practices.
Through the Community Arts Grants program, the Council-adopted Culture Plan vision to invest in Vancouver's vibrant and creative neighbourhoods is clearly accomplished. Additionally, it delivers on the City's Health City Strategy goals of supporting creative expression, cultivating social connections, and lifelong learning through unique artist and community collaborations, leading to healthier communities.
Read the Council report (900 KB)
Add to our cultural spaces map
June 1, 2016 - Cultural spaces are where people come together to express themselves through art and culture. We're looking to those who know the landscape to be a part of the illustrating Vancouver's evolving cultural spaces story. Now until the end of June 2016, we're opening up a simple online survey for adding spaces and providing updates. The goal of this ongoing open data project is to improve the information we publish and make it available in fall 2016 for anyone to use.
Are the cultural spaces you value on the map? Help make sure that the data is correct and complete.
View and add to the map
Cultural spaces update
June 1, 2016 - We updated Vancouver City Council on the six ways we're working to support the local facility needs of artists:
Partner to develop new spaces
Major capital funding to acquire and renovate
Renting out City of Vancouver spaces (both nominal and market rates)
Infrastructure grants
View the staff presentation to Council (2.5 MB)
Vancouver Civic Theatres update
June 1, 2016 - Vancouver Civic Theatres oversees five City-owned performance venues: The Orpheum, The Annex, Vancouver Playhouse, Queen Elizabeth Theatre and Queen Elizabeth Plaza.
This report to Vancouver City Council presents an update on priorities, business planning, and a study underway to identify gaps in performing arts space in the city.
View the presentation (1.1 MB)
Giving public art a boost
May 31, 2016 - The City of Vancouver unanimously adopted a motion that recommends significantly expanding the City's Public Art Program through a "public art boost".
Read the Council motion (20 KB)
Help us map Vancouver's cultural spaces
June 3, 2014 – Cultural spaces are places where people express themselves through art and culture. The City is sharing information on cultural spaces and we need your help. We know there are many valuable cultural spaces not currently on our list, and we're checking with you to identify those which we may have missed.
Use Google Chrome, Mozilla Firefox, or Safari to follow this link:
Add to the map
Culture Plan strategic directions presented
October 23, 2013 – Council received the new Culture Plan strategic directions that will guide cultural planning in Vancouver over the next five years.
Read the Culture Plan strategic directions (1.6 MB)
Creative SpaceMaking Vancouver
May 9, 2013 – On June 12 and 13, join artists, architects, art and cultural organizations, business and community leaders, in a series of workshops and events on creative space in Vancouver. Creative SpaceMaking Vancouver is part celebration, part learning and part crafting a new roadmap for the sustainable creation and operation of cultural spaces in our city.
Learn more about Creative SpaceMaking and sign up
Civic Theatres Business Review and Strategic Planning
May 15, 2012 – Following the renovation and renewal of Vancouver's Civic Theatres and the implementation of Vancouver's Culture Plan, the City is undertaking a comprehensive review of our Civic Theatre operations.
Organizational and Leadership Development
March 30, 2012 – Partnering with Vantage Point to further learning and capacity within the arts and cultural sector the City is offering creative learning opportunities for leaders in the non-profit community.
Arts and culture grants
Arts and Culture Policy Council
February 28, 2012 – City Council has established an Arts and Culture Policy Council which will advise Council and staff on civic arts and cultural issues, programs, and services.
Cultural Grants
November 21, 2011 – Changes to cultural grants have included streamlining programs, increased grant budget, and expanded eligibility requirements, which include artist residencies, mentorships, and convergences.
2011 Mayor's Arts Awards
October 6, 2011 – Since 2008, in partnership with the Alliance for Arts and Culture, the City honours local artists and community members for making significant contributions to the creative life of Vancouver.
Mayor's Arts Awards
Artist Studio Regulatory Review
June 29, 2011 – The City has been conducting roundtables with artists and City staff to improve opportunities for artist studio creation, presentation and operation.
Public Art Program
April 11, 2012 – The City has expanded the Private Sector Program, appointed an artist to the Urban Design Panel, developed artist-initiated projects, created opportunities for temporary 2D artwork, partnered with the Canada Line, and developed Art Plans for South East False Creek, Knight Street, and Carroll Street.
Live Performance Venue Regulatory Review
January 15, 2011 – The City is working to improve the regulations to enable live performance venues for music, theatre, dance, media, interdisciplinary, festival, performance arts events and activities.
Great Beginnings in the Downtown Eastside
December 17, 2010 – Art and culture activities, celebrations and street festivals are just the beginning.
Culture Plan for Vancouver 2008 – 2018
Culture Plan for Vancouver 2008 – 2018 detailed (211 KB)
Culture Plan for Vancouver 2008 – 2018 final (30 MB)
Culture Plan Strategic Directions – 2014 to 2018 (1.6 MB)
The central vision of this ten-year Culture Plan is to promote and enhance the culture and creative diversity of the City of Vancouver to the benefit of our citizens, our creative community, and our visitors. We will build upon Vancouver's current diverse and plentiful artistic and entertainment offerings to create a new dynamism and pride in our cultural life.
Creative City Profile
Creative City Profile 2003 (3.88 MB)
Creative City Profile 1999 (15.4 MB)
Annual Review 2005 (1.04 MB)
Annual Review 2004 (925 KB)
Vancouver Special Events Sampler 2004 (2.04 MB)
Arts Report 1997 (2.48 MB)
Phase 1 Implementation action plans
Cultural grant programs
Culture Plan Implementation Phase 1: Review of Grant Programs (913 KB)
Cultural Grants Evaluation (1.1 MB)
Cultural Plan Implementation Phase 1: Public Art Program Revisions and Plan (420 KB)
Public Art Review Plan (257 KB)
Facilities priority plan
Culture Plan Implementation Phase 1: 2008 – 2023 Cultural Facilities Priorities Plan (1.3 MB)
City of Vancouver Cultural Facilities Priorities Plan, Final Report (May 2008) (3.6 MB)
Cultural Facility Planning and Development: Self-Assessment Checklist (44 KB)
Cultural tourism strategy
Culture Plan Implementation Phase 1: Cultural Tourism Strategy (1.3 MB)
1. Innovation
Recognize Vancouver – locally, nationally and internationally – as a city of creative ideas and innovation, with unique, diverse and authentic voices, and a young and growing cultural community on the leading edge.
Collaborate with community partners to realize our full creative potential by fostering innovation in our cultural policies, programs and services to support cultural ideas and expression
2. Learning
Build on Vancouver's reputation as a city of learning that embeds cultural exchange, curiosity and development as part of lifelong learning. Ensure that all citizens have the opportunity to engage with and participate in cultural education throughout their lives and to develop his or her expressive capacities.
Support lifelong learning for all Vancouver citizens by collaborating with community partners to embed cultural awareness, instruction and programming within all our institutions and systems.
3. Connecting People, Ideas and Communities
Take advantage of Vancouver's position as a creative city where connectivity is a hallmark of our cultural system – artists, creative industries, institutions, communities, and neighbourhoods. It is a city engaged in a dynamic ongoing dialogue and exploration that connects people, communities, innovative ideas and programs.
Play a leadership role. With our partners, find practical ways to support a collaborative environment and opportunities for dialogue. Invite citizens to engage and participate in cultural activities.
4. Neighbourhoods
Highlight Vancouver as a city of vibrant creative neighbourhoods by showcasing the talent, enterprise and diversity of our artists, communities and neighbourhoods. Build on the unique identity of our neighbourhoods – engaging local residents, artists and businesses – to ensure that the rich culture, creativity, diversity and innovation of Vancouver lives on and is accessible to all.
Support neighbourhoods to develop cultural plans and seek new partnerships and collaborations. Encourage new initiatives and activities that support neighbourhood cultures as a central facet of Vancouver's cultural life.
5. Valued and Valuable
Ensure that citizens and taxpayers of Vancouver experience in real and concrete ways the value that arts and culture bring to the city and their lives, families and businesses. Promote Vancouver's growing reputation as an international cultural tourism and entertainment destination where culture is vibrant and happening and where we value and celebrate the rich multicultural and intercultural expression that is unique to Vancouver.
Increased public participation means increased financial viability for quality cultural experiences. Work with the non-profit arts and cultural sector, cultural industries, business and public sectors to develop new and innovative ways to highlight and profile the creative sector to the citizens of Vancouver and promote Vancouver's reputation as a Creative City.
Vancouver is poised to establish itself as a city on the cutting edge of art, culture, education, entertainment, and support of the creative industries. The vision and strategy articulated in the Culture Plan provides momentum for the City to move forward over the next ten years by harnessing this creativity for the benefit of all.
City Council approved the terms of reference for the Creative City Task Force, comprised of Councillors, community representatives, and City staff. Their mandate was to consult with stakeholders to identify strategic goals and directions for the City's long-term role in support of arts and culture.
Creative City Conversation: the City's first forum on the power of culture, creativity, and community.
Creation of a long-term Culture Plan to guide the City's role in arts and culture in Vancouver for the next decade.
Contact Cultural Services
Woodward's Heritage Building
501 - 111 West Hastings St
Vancouver, BC V6B 1H4
Vancouver, BC V5Y 1V4
Get arts and culture news
Hours day


The Pine Bluffs Lady Hornets celebrated their 2A State Championship with a pep rally in the high school gym Monday afternoon. See the March 24 issue of the Pine Bluffs Post for a special commemorative insert for more coverage.
Having lost to Southeast the week before at Regionals, the Pine Bluffs Lady Hornets entered the state tournament as a number two seed and with strong determination.
Their season was great as they lost only three times. Twice came by way of Southeast. A fact that is significant.
The girls kicked off their tournament play at 4:30 on Thursday at Casper College. Their opponent was the number three seed out of the West, Kemmerer.


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For the moth genus Sanguesa (moth), see Chrysauginae.
Sangüesa (Basque: Zangoza) is a city in Navarre, Spain, 44.5 kilometers from Pamplona. It lies close to the River Aragon and in 2007 had a population of 5,128. It is located on the Way of Saint James. It has been an important stopping point for pilgrims since the Middle Ages and has preserved its medieval character.
Entrance to Sangüesa
Sangüesa-Zangoza is the historic capital of one of the six merindades into which the old Kingdom of Navarre was divided.
In 1089, a bridge was built here over the River Aragon and Sancho Ramirez located the town to the present location.[1] In 1121, Alfonso el Batallador (Alfonso the Battler) extended the fuero of Jaca to Sangüesa which significantly expanded the opportunities for Frankish merchants to settle here.[2]
1 Religious monuments
2 Civil monuments
Religious monumentsEdit
Church of Santa María la Real, located on Calle Mayor. The oldest part dates from 1131. Its magnificent main façade is particularly remarkable, with its representation of the Final Judgement (built in the 12th to 13th centuries), one of the masterpieces of Navarre and Iberian Romanesque architecture.
Church of Santiago the Elder, (12th to 13th centuries), transitional Romanesque.
Church of San Salvador. Gothic (13th to 14th centuries).
Convent of Saint Francis of Assisi. Founded in 1266 by Teobaldo II, and reformed in the 16th century. Contains an interesting Gothic cloister and chapter room.
Church of the Carmen, first Carmelite convent established in Sangüesa in the 13th century. A Gothic church, it was reformed in the 16th and 17th centuries. Gothic cloister.
Civil monumentsEdit
Palace of the Dukes of Granada de Ega, urban palace of the 15th century.
Palace of the Prince of Viana, former residence of the kings of Navarre, 13th century.
Palace of the marquises of Valle-Santoro, built in the 17th century.
Palace of the Counts of Guendulain, typical baroque palace of the 17th century.
Major House, built in 1570 over part of the former palace of the Kings of Navarre. Sober Renaissance facade.
San Adrián de Vadoluengo, Romanesque building close to Sangüesa, on the way to Sos del Rey Católico.
^ Gitlitz & Davidson, The Pilgrimage Road to Santiago: The Complete Cultural Handbook, 2000, St Martin's Press, ISBN 0-312-25416-4
SANGUESA - ZANGOZA in the Bernardo Estornés Lasa - Auñamendi Encyclopedia (Euskomedia Fundazioa) (in Spanish)
Sangüesa.- Medieval History of Navarre
Coordinates: 42°35′N 1°17′W / 42.583°N 1.283°W / 42.583; -1.283
Retrieved from "https://en.wikipedia.org/w/index.php?title=Sangüesa&oldid=973721853"
This page was last edited on 18 August 2020, at 21:11 (UTC).

redpajama_set_name: RedPajamaCommonCrawl


text:
Dexter Fowler plans rehab Monday; Troy Tulowitzki targets Dodgers series
By Troy E. Renck
Dexter Fowler, Patrick Corbin, Roy Oswalt, Troy Tulowitzki, Walt Weiss
Colorado Rockies third baseman Nolan Arenado, right, celebrates with injured teammate Dexter Fowler after hitting a walk-off game winning single to defeat the San Francisco Giants 2-1 at Coors Field on June 29, 2013. (Andy Cross, The Denver Post)
PHOENIX — Troy Tulowitzki ran, fielded, did agility drills and planned to hit Sunday morning. His fractured right fifth rib has improved dramatically. However, he still feels a dull ache when he swings, which is why he can't say specifically when he will return to the Rockies.
He'd like to be back for the Dodgers series beginning on Thursday in Los Angeles. But he told The Post that he needs to play more than two rehab games to test his injury. So that could mean three appearances for the Sky Sox, and possibly more if a rest day is required. He will begin his rehab assignment this week, possibly playing as soon as Monday. An update will be provided following the game on his schedule, which will be adjusted based on how the injury responds.
The last thing Tulo wants to do is rush it, creating another lengthy absence. He reiterated he would not play in the All-Star Game, where he was voted to start at shortstop, without first playing for the Rockies.
"I want to be back for the Dodgers series. But I have to make sure it's right. I need to see how it responds in a game, and how it feels on a check swing or an awkward swing. The team needs me for the second half. I don't want to come back too quickly because I didn't test everything then get hurt again," Tulowitzki said.
Tulowitzki has not played since June 13. The Rockies are 7-14 without him, missing his power offensively and steady hand defensively (he has committed just one error). However, he couldn't perform baseball activities for nearly two weeks following the injury, so he must continue clearing hurdles in a game situation before rejoining the Rockies.
Dexter Fowler's situation is different. The center fielder said he plans to play Monday and Tuesday in Colorado Springs.
He has never really been shut down because of the bone bruise on his right hand. Though the Rockies took it slowly with him swinging the bat following his injury, Fowler has been shagging flyballs. Swinging left-handed is the challenge for Fowler. He must feel comfortable in those at-bats before returning.
The lineup has not been the same in his absence, and there's no been no consistent answer in center field as Tyler Colvin has struggled defensively.
The Rockies are looking to avoid a sweep against Arizona. The Diamondbacks have outscored them 16-1 in the first two games. Right-hander Roy Oswalt, looking for his first win as a Rockie, faces Patrick Corbin, who has not lost at home this season.
Categories: Injuries, Rockies on Deck
Roy Oswalt leaves game Sunday with strained hamstring
VIDEO: Troy Tulowitzki on playing in all-star game, and Michael Cuddyer's deserved recognition
Ep. 13 — 2017 Here We Come
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mtDNA tests as a vehicle for Jewish recognition of Former Soviet Union Israeli citizens: religious and political debate
Nurit Kirsh, Yael Hashiloni-Dolev
Until recently, in rabbinic discourse as well as Israeli state policy, Jewish identity was not reckoned via genetics. While academic studies looked for genetic similarities among Jewish communities, these similarities did not determine Jewishness or state policy. This article is the first study spotlighting the novel use of mtDNA testing in order to determine the Jewishness of Israeli citizens who immigrated to Israel from the Former Soviet Union (FSU) 1990 onward. These tests offered by the Israeli State Rabbinate are accompanied by heated political and religious wrangles, in particular between leaders of the Ultra-Orthodox Jewish community and the political party claiming to represent immigrants from the FSU. We aim to understand this current debate on determining Jewishness by mtDNA. We examine the reciprocal relationship between science, religion, communal identity and state policy, and question the possible social implications. In contrast to claims that the change in Jewish' definition is guided by science and technology, we argue that this change is dictated primarily by specific historical and socio-political circumstances. Furthermore, enthusiasm or rejection of the use of mtDNA for Jewish recognition depends on inclusive or exclusive ideologies, not on the indecisive content of science or religion themselves.
BioSocieties
Accepted/In press - 1 Jan 2021
Jewishness
MtDNA
Dive into the research topics of 'mtDNA tests as a vehicle for Jewish recognition of Former Soviet Union Israeli citizens: religious and political debate'. Together they form a unique fingerprint.
Religion and Science Medicine & Life Sciences 100%
USSR Medicine & Life Sciences 96%
Israeli Social Sciences 62%
citizen Social Sciences 43%
Religion Social Sciences 37%
studies (academic) Social Sciences 27%
Israel Medicine & Life Sciences 26%
Kirsh, N., & Hashiloni-Dolev, Y. (Accepted/In press). mtDNA tests as a vehicle for Jewish recognition of Former Soviet Union Israeli citizens: religious and political debate. BioSocieties. https://doi.org/10.1057/s41292-021-00228-6
Kirsh, Nurit ; Hashiloni-Dolev, Yael. / mtDNA tests as a vehicle for Jewish recognition of Former Soviet Union Israeli citizens : religious and political debate. In: BioSocieties. 2021.
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Kirsh, N & Hashiloni-Dolev, Y 2021, 'mtDNA tests as a vehicle for Jewish recognition of Former Soviet Union Israeli citizens: religious and political debate', BioSocieties. https://doi.org/10.1057/s41292-021-00228-6
mtDNA tests as a vehicle for Jewish recognition of Former Soviet Union Israeli citizens : religious and political debate. / Kirsh, Nurit; Hashiloni-Dolev, Yael.
In: BioSocieties, 01.01.2021.
T1 - mtDNA tests as a vehicle for Jewish recognition of Former Soviet Union Israeli citizens
T2 - religious and political debate
AU - Kirsh, Nurit
AU - Hashiloni-Dolev, Yael
N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
N2 - Until recently, in rabbinic discourse as well as Israeli state policy, Jewish identity was not reckoned via genetics. While academic studies looked for genetic similarities among Jewish communities, these similarities did not determine Jewishness or state policy. This article is the first study spotlighting the novel use of mtDNA testing in order to determine the Jewishness of Israeli citizens who immigrated to Israel from the Former Soviet Union (FSU) 1990 onward. These tests offered by the Israeli State Rabbinate are accompanied by heated political and religious wrangles, in particular between leaders of the Ultra-Orthodox Jewish community and the political party claiming to represent immigrants from the FSU. We aim to understand this current debate on determining Jewishness by mtDNA. We examine the reciprocal relationship between science, religion, communal identity and state policy, and question the possible social implications. In contrast to claims that the change in Jewish' definition is guided by science and technology, we argue that this change is dictated primarily by specific historical and socio-political circumstances. Furthermore, enthusiasm or rejection of the use of mtDNA for Jewish recognition depends on inclusive or exclusive ideologies, not on the indecisive content of science or religion themselves.
AB - Until recently, in rabbinic discourse as well as Israeli state policy, Jewish identity was not reckoned via genetics. While academic studies looked for genetic similarities among Jewish communities, these similarities did not determine Jewishness or state policy. This article is the first study spotlighting the novel use of mtDNA testing in order to determine the Jewishness of Israeli citizens who immigrated to Israel from the Former Soviet Union (FSU) 1990 onward. These tests offered by the Israeli State Rabbinate are accompanied by heated political and religious wrangles, in particular between leaders of the Ultra-Orthodox Jewish community and the political party claiming to represent immigrants from the FSU. We aim to understand this current debate on determining Jewishness by mtDNA. We examine the reciprocal relationship between science, religion, communal identity and state policy, and question the possible social implications. In contrast to claims that the change in Jewish' definition is guided by science and technology, we argue that this change is dictated primarily by specific historical and socio-political circumstances. Furthermore, enthusiasm or rejection of the use of mtDNA for Jewish recognition depends on inclusive or exclusive ideologies, not on the indecisive content of science or religion themselves.
KW - DNA
KW - Halakha
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KW - MtDNA
JO - BioSocieties
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Kirsh N, Hashiloni-Dolev Y. mtDNA tests as a vehicle for Jewish recognition of Former Soviet Union Israeli citizens: religious and political debate. BioSocieties. 2021 Jan 1. https://doi.org/10.1057/s41292-021-00228-6


text:
Posted 31/01/2019 από Thanasis Chalikias	Έρευνες/Κλινικές Μελέτες
The 2019 pipeline report: Changing the treatment paradigm
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Big pharma is experiencing something of a blockbuster revival thanks to a wave of acquisitions and the maturation of several novel drug classes. Of the more than 40 novel drugs approved in 2018, nearly a quarter are on their way to becoming major cash cows, prompting firm Clarivate Analytics to dub 2018 "the year of the blockbuster."
While it's unclear if 2019 can smash this year's record, the overall blockbuster market appears to be heating up. Dozens of promising drug candidates are slated to rake in more than $1 billion in sales by 2025, according to Credit Suisse forecasts.
The recent regulatory successes of first-in-class medicines — including Alnylam Pharmaceuticals' RNAi drug Onpattro, Spark Therapeutics' gene therapy Luxturna, and Novartis' CAR-T cell therapy Kymriah — prove these new types of drugs, once considered high-risk, are here to stay.
Next year's would-be blockbusters span the gamut. Some belong to the aforementioned new drug classes, while others are traditional small molecules or antibodies that nevertheless represent a marked improvement over the existing standard of care.
Many of these candidates are carving out a space as "niche-busters," dramatically changing the treatment paradigm in areas of high unmet need. Following its breakout success with Onpattro, Alnylam is developing another RNAi candidate, fitusiran for hemophilia. Elsewhere in the field of blood disorders, Acceleron/Celgene's anemia drug luspatercept and GlaxoSmithKline's anemia candidate daprodustat are generating enthusiasm from patients with few treatment options.
In immunology, Gilead/Galapagos and Bristol-Myers Squibb are moving forward with candidates that are expected to compete in the already crowded markets of rheumatoid arthritis and plaque psoriasis, respectively.
With all the recent failures in Alzheimer's disease, investors appear to be putting all their eggs into Biogen's basket, with valuations of the company's monoclonal antibody hovering around $11.5 billion, according to EP Vantage. For other neurodegenerative diseases, companies are advancing gene therapies, with AveXis/Novartis developing AVXS-101 for spinal muscular atrophy and Sarepta developing microdystrophin for Duchenne muscular dystrophy.
Though oncology has been transformed by recent cell therapy treatments, there's still space for more traditional drug candidates. Daiichi Sankyo delivered promising overall survival data for its small molecule candidate quizartinib in acute myeloid leukemia (AML), while GSK is drumming up excitement for its Phase II multiple myeloma antibody-drug conjugate GSK2857916. Biotech is also heating up in China, where newcomer BeiGene's take on the anti-PD-1 class of oncology drugs is moving into niche cancer indications with promising results.
Looking ahead to 2019, the development landscape is marked by a healthy mix of sure-fire blockbuster medicines, treatments with new mechanisms of action, and niche products that will bring new value to underserved patient populations.
Most-anticipated Products
Luspatercept
Acceleron Pharma/Celgene, Phase III
Indication: Anemia related to myelodysplastic syndromes (MDS) and beta-thalassemia
What the clinical trials found: MDS is a bone marrow disease which often results in anemia. A Phase III trial evaluated luspatercept in patients with low-risk MDS and chronic anemia, finding the patients who received treatment were less likely to need blood transfusions compared to patients who received a placebo.
The drug is also in Phase III trials for beta-thalassemia, a blood disorder that limits the body's ability to produce hemoglobin.
Credit Suisse success probability and inThought comment: 80%, with an expected launch in 2019. "MDS patients have few treatment options. A high portion of [low-risk] patients fail erythropoiesis-stimulating agents [the standard of care], and in those patients anemia is really difficult to treat.
"There's a real need, because anemia is the biggest quality-of-life burden for these patients." — Lisa Kennedy, senior principal, inThought Research
Credit Suisse revenue forecast: $1.21 billion in global annual sales by 2022
What physicians are saying: "Based on the initial data reports, luspatercept will likely be considered transformative for these patient groups and is the first to market to offer a different approach in managing anemias that addresses the delivery of oxygen versus EPO [a blood production hormone], which only focuses on producing more red blood cells.
Other approaches are focused on targeting defective genes involved in red blood cell production. Luspatercept addresses a high unmet medical need and may also help with improvement of red blood cell supply, because these patients require multiple blood transfusions to function." — Alan Gray, VP, oncology research and advisory services, Ipsos
Fitusiran
Alnylam/Sanofi, Phase III
Indication: Hemophilia A and B
What the clinical trials found: Fitusiran is a subcutaneously injected RNAi therapeutic that was placed on clinical hold in September 2017 when a patient died from a blood clot.
But Alnylam and Sanofi moved swiftly to put new safety precautions in place, prompting the FDA to lift the clinical hold months later.
In the Phase II study, fitusiran reduced levels of a key anticoagulation enzyme by 80%. However, the high-risk, high-reward candidate was also associated with a number of adverse events, including liver enzyme elevation in a patient with hepatitis C and a seizure in a patient with a history of seizures.
Credit Suisse success probability: 40%, with an expected launch in 2021
What physicians are saying: "Fitusiran is really interesting, as it is targeting a new [mechanism of action]. It is an RNAi therapeutic targeting antithrombin and this means, unlike [with] other hemophilia drugs, it is effective in hemophilia A and B and patients with and without inhibitors. It's a one-drug-fits-all approach.
"Additionally, it is being investigated as a once monthly, subcutaneous administration, a huge step forward compared to the dosing burden currently placed on hemophiliacs." — Sarah Brown, research director, global therapy monitors, Ipsos
Daprodustat
GlaxoSmithKline, Phase III
Indication: Anemia
What the clinical trials found: Daprodustat, a small molecule inhibitor meant to promote red blood cell production, is being tested across several Phase III trials in patients with anemia associated with chronic kidney disease. A Phase III Japanese trial met its primary endpoint of non-inferiority to injections of Amgen's Aranesp in patients who depend on hemodialysis, with no new serious adverse events, according to a press release.
In a previous study, patients saw an improvement in hemoglobin levels four weeks after switching from a growth hormone treatment called rhEPO. Promisingly, the effect remained stable at 24 weeks.
What physicians are saying: According to prepared remarks made by GSK's chief scientific officer and president, research and development, Dr. Hal Barron, "anemia is common in patients with chronic kidney disease and can result in symptoms such as weakness and fatigue. The promising data generated from the [Japanese Phase III study] is an important step in the development of daprodustat as a potential oral treatment option for these patients."
https://e.infogram.com/5344994d-9164-435e-8659-03dd0946d22c?src=embed
Inclisiran
Alnylam Pharmaceuticals/
The Medicines Company, Phase III
Indication: Hypercholesterolemia
What the clinical trials found: Inclisiran is an RNAi therapeutic that targets PCSK9, a key mechanism in the body's regulation of LDL cholesterol. Unlike the recently approved PCSK9 inhibitors, inclisiran works by shutting down PCSK9 directly in the liver. In a Phase II trial, patients saw an average LDL reduction of at least 50% after 180 days.
Credit Suisse success probability and inThought comment: 75% chance of success, with expected launch in 2021. "Inclisiran has a lot going for it in the management of severe hypercholesterolemia — extended dosing on a monthly, quarterly, or even semiannual basis, at least initial efficacy on par with PCSK9s, modest adverse effect profile, massive statin-intolerant patient subpopulation and an anticipated lower cost of goods versus monoclonals (read: PCSK9s).
"However, whereas a decade or so ago our modeling may have suggested multi-blockbuster status by 2023 given a 2019 regulatory submission, today we're looking at a much tougher slog to reach blockbuster status despite an incredibly large patient population with significant unmet need."
— Dr. Leon Henderson-MacLennan, medical adviser, inThought Research
What physicians are saying: According to physicians interviewed by BioPharm Insight reporters Hamish McDougall and Reynald Castaneda, "The Medicines Company/Alnylam's inclisiran has a good chance for market penetration in hypercholesterolemia with its potential for annual dosing despite a lagged entry behind other PCSK9 inhibitors." In addition, experts added "the companies should look to target statin-intolerant patients in future trials, a large market that has been poorly studied with current PCSK9 inhibitors."
Aprocitentan
Idorsia/Janssen, PHASE III
Indication: Hypertension
What the clinical trials found: In a Phase II dose-finding study, aprocitentan demonstrated statistically significant changes in patients' baseline blood pressure after eight weeks of treatment. Depending on the dose, the reduction in blood pressure ranged from 10.3 to 18.5 millimeters of mercury (a measure of systolic pressure) for the treatment arm, compared to only 7.7 for the placebo group and 12.8 for a group treated with mainstay hypertension drug lisinopril.
Credit Suisse success probability and inThought comment: 50% chance of success, with likely launch in 2021. "Although it is not particularly innovative, it is interesting to use this mechanism of action against systemic as opposed to pulmonary hypertension and to see a new mechanism of action tried as an approach to hypertension. That said, I can only imagine the need for optimal strategic execution once in this market dominated by cheapies."
— Henderson-MacLennan
Credit Suisse revenue forecast: $996 million in global annual sales by 2020
CSL112
CSL Behring, Phase III
Indication: Myocardial infarction
What the clinical trials found: CSL112 is a drug designed to lower the risk of heart attacks in patients who have previously suffered a heart attack. A Phase IIb study met its primary safety endpoint, demonstrating the drug does not impair liver or kidney function. Also, the Phase II study showed a four-fold increase in cholesterol efflux, or the body's ability to remove cholesterol build up and dispose of it in the liver.
Credit Suisse success probability and inThought comment: 30% chance of success, with an expected launch in 2022. "The Phase IIb results are encouraging from the safety perspective, especially as relates to the liver. CSL112 has a chance to be an important drug for early, recurrent cardiovascular events, but it'll take a while for robust data to be generated. We're looking at efficacy go/no-go decisioning around 2021 and completion and filing somewhere in 2022." — Henderson-MacLennan
https://e.infogram.com/24e596d9-eceb-449a-8cf4-71585e0cebe5?src=embed
Bristol-Myers Squibb, Phase III
Indication: Plaque psoriasis
What the clinical trials found: BMS-986165 is a new type of all-oral immunology candidate that inhibits TYK2. The drug made a splash in Phase II, when 12 weeks of treatment resulted in a marked improvement in psoriasis in 67% to 75% of patients, compared to only 7% of patients in the placebo arm. Also, a quarter of patients saw a near-total resolution of psoriasis. The results were published in The New England Journal of Medicine and BMS is forging ahead with its registrational Phase III trial.
inThought comment: "BMS-986165 is the new kid on the block. It's not a JAK inhibitor and it's not an IL-23. It's a new target the field is getting excited about." — Amanda Weyerbacher, senior
analyst, inThought Research
What physicians are saying: "Currently patients with moderate to severe psoriasis have a limited number of oral therapeutic options available, the most notable of which is Celgene's Otezla (apremilast) that has been marketed for just a few years.
"After the successful Phase II results of BMS-986165, it may be a promising oral option to help patients control their psoriasis in the future." — Paul O'Meara, head of syndicated patient real world evidence, Ipsos
Tezepelumab
Amgen/AstraZeneca, Phase III
Indication: Asthma
What the clinical trials found: Tezepelumab is being tested in patients with severe asthma who cannot get relief from an inhaler. It was granted breakthrough status by the FDA in 2018 after Phase II results showed monthly and biweekly injections reduced asthma "exacerbation rates" by 61% to 71%, depending on the dose.
The results were statistically significant relative to the placebo group, but investigators noted three serious adverse events linked to treatment: pneumonia and stroke, which occurred in the same patient, and Guillain-Barré syndrome. Subsequent Phase II results found the drug did a better job at controlling asthma than placebo after one year.
Credit Suisse success probability: 60% chance of success, with an expected launch in 2022
What physicians are saying: According to physicians interviewed by Manasi Vaidya, a reporter at BioPharm Insight, "Tezepelumab's Phase II effect in reducing the asthma exacerbation rate is attractive because the effect was seen across patients irrespective of blood eosinophil count. Furthermore, it is significant that tezepelumab's effect was seen over 52 weeks. A smaller time frame for results, such as 18 to 24 weeks, does not take into account the seasonal variations of asthma."
Filgotinib
Galapagos/Gilead, Phase III
Indication: Rheumatoid arthritis and Crohn's disease
What the clinical trials found: Filgotinib is poised to be the next major blockbuster in the JAK inhibitor class, following the lead of Pfizer's blockbuster Xeljanz. The Galapagos candidate has been tested in more than 1,600 rheumatoid arthritis and Crohn's patients.
Recent Phase III results revealed the drug achieved its primary endpoint and all major secondary endpoints in a tough-to-treat group of patients who couldn't tolerate other biologic drugs.
Credit Suisse success probability and inThought comment: 80% chance of success, with an expected launch in 2020. "Filgotinib is a JAK inhibitor with strong Phase II results that demonstrated not only good efficacy, but also a really clean safety profile. This is important because safety has been seen as a big concern among this class." — Weyerbacher
What physicians are saying: According to physicians interviewed by Krystnell Storr and Shuan Sim, reporters at BioPharm Insight, "Gilead's filgotinib has potential to offer first-choice appeal in rheumatoid arthritis if safety profile holds out over Pfizer's Xeljanz."
https://e.infogram.com/bd31ea7a-7c84-4c85-a93c-5e4a9a24b3b4?src=embed
Neurodegenerative disease
Aducanumab
Biogen, Phase III
Indication: Alzheimer's disease
What the clinical trials found: Aducanumab is a monoclonal antibody thought to block the buildup of amyloid proteins in the brain associated with Alzheimer's disease. In a post-hoc analysis of aducanumab's Phase Ib study, patients with mild Alzheimer's improved on cognitive functional scores after 24 months of treatment, as measured by the Clinical Dementia Rating scale. Considering recent high-profile failures of late-stage Alzheimer's disease candidates, regulatory success of aducanumab would launch the drug into blockbuster status.
Credit Suisse success probability and inThought comment: 40% chance of success, with an expected launch in 2020. "It's a unique anti-aggregated and insoluble A-beta construct. Its Phase Ib PRIME data in prodromal and mild Alzheimer's patients were the first to prospectively demonstrate a statistically significant benefit on cognition." — Henderson-MacLennan
Credit Suisse revenue forecast: $1.8 billion in global annual revenue by 2022
What physicians are saying: "There is no cure for Alzheimer's disease nor a way to stop or slow its progression, and current medication options only temporarily address symptoms. [Biogen's Phase III] trials are expected to conclude in 2022 and success could pave the way for encouraging earlier treatment to reduce amyloid plaques, which would offer patients and caregivers the first treatment to slow the progression of Alzheimer's." — Christine Dworkin, director, Ipsos
Microdystrophin gene therapy program
Sarepta Therapeutics, Phase I/II
Indication: Duchenne muscular dystrophy
What the clinical trials found: Sarepta's gene therapy candidate demonstrated promising results in a small trial announced in June. In that study, treatment encouraged production of muscle proteins that help stave off disease progression. Though the therapy has only been tested in a small number of patients, it's generating enthusiasm. In October, Sarepta announced a follow-up analysis which found all four boys in the clinical trial saw improvements in motor function as measured by the North Star Ambulatory Assessment.
inThought comment: inThought's Henderson-MacLennan notes that, if approved, Sarepta's microdystrophin construct could address 60% to 70% of Duchenne patients with mutations between exons 18 and 58. "Sarepta's microdystrophin can be systemically delivered, via an AAV-based vector, to crucial, pathology-ridden skeletal, diaphragm, and cardiac muscle. An update on Sarepta's microdystrophin [in October] revealed continued evidence of promising gene expression."
Market potential: Sarepta's first Duchenne drug, Exondys 51, beat approval and uptake expectations, doubling revenue to bring in $73.5 million by Q3 2018. "For 2017 the global market for Duchenne drugs was $172 million, and for 2018 it showed almost 75% growth. Sarepta is likely to lead the competitive landscape by 2023." — Intellica
What physicians are saying: According to physicians interviewed by BioPharm Insight's McDougall, "All the experts noted there is a great expectation microdystrophin gene therapy could generate significant efficacy in Duchenne."
AVXS-101,
AveXis/Novartis, Phase III
Indication: Spinal muscular atrophy
What the clinical trials found: When Novartis acquired AveXis for $8.7 billion, it inherited a gene therapy called AVXS-101. Its strong efficacy data makes it competitive with a recently approved spinal muscular atrophy candidate from Biogen (Spinraza) and a new candidate from Roche (risdiplam). According to data presented at the World Muscle Society in October, 100% of the children enrolled in the AVXS-101 trial were alive after 24 months and 92% were able to sit independently.
Credit Suisse success probability and inThought comment: 85% chance of success, with an expected launch in 2019. "Novartis is counting on AVXS-101 as one of its two upcoming blockbuster launches, together with BAF312 for MS. Prior studies reveal impressive data at the levels of speed of onset of therapeutic action, survival off ventilator support, swallowing ability, and developmental milestone achievement." — Henderson-MacLennan
What physicians are saying: According to physicians interviewed by McDougall, "AveXis' gene therapy [was] delivered in neonatals without a fully formed immune system," with one neurologist noting high doses of viral vectors have been used to deliver AVXS-101 in spinal muscular atrophy with no safety concerns.
https://e.infogram.com/eaf574f7-6e5d-4dc5-8a25-df93c656b192?src=embed
quizartinib,
Daiichi Sankyo, Phase III
Indication: Acute myeloid leukemia
What the clinical trials found: Daiichi Sankyo's quizartinib, an FLT3 inhibitor, bested salvage chemotherapy treatment in a Phase III trial of patients with relapsed/refractory acute myeloid leukemia who carried a mutation in FLT3-ITD — considered a particularly difficult-to-treat population. Patients in the treatment arm saw "significantly prolonging overall survival" compared to those in the chemotherapy salvage arm, according to a press release. If approved, quizartinib is likely to be the second FLT3 inhibitor on the market, following Novartis' Rydapt (midostaurin).
Credit Suisse success probability and inThought comment: 60% chance of success, with an expected launch in 2019. "Quizartinib is considered a very targeted drug. The sentiment is these data is the first step to realizing quizartinib's potential to be used in combination therapies, and moved into earlier lines of treatment." — Kennedy
Credit Suisse revenue forecast: $462 million in global annual revenue by 2025.
What physicians are saying: "A couple of key questions need to be answered. Will oncologists utilize quizartinib after Rydapt for those patients who relapse on Rydapt? Or will oncologists consider using quizartinib in the front line setting instead of Rydapt, because quizartinib is more targeted against FLT3-ITD and was more effective than salvage chemotherapy for FLT3 ITD patients as a single agent?" — Gray
GSK2857916,
GlaxoSmithKline, Phase I/II
Indication: Multiple myeloma
What the clinical trials found: GSK2857916 is a BCMA antibody-drug conjugate that was granted breakthrough designation by the FDA based on its positive response in heavily pretreated relapsed/refractory multiple myeloma patients. In a dose expansion phase of GSK's Phase I/II trial, the candidate demonstrated a 60% response rate and median progression free survival of 7.9 months.
Credit Suisse probability and inThought comment: 5% chance of success, with an expected launch in 2022. "While GSK2857916 is not a CAR-T therapy, it is also directed against BCMA, so it's expected to compete with Celgene's bb2121. It's got the same [regulatory] timeline as bb2121 and it's possible it would be cheaper. It's possible there could be some patient segments that benefit from CAR-Ts and some that benefit from GSK2857916." — Kennedy
BioPharm Insight revenue forecast: $524 million in global annual revenue by 2025
What physicians are saying: "Current trials have shown it to have an excellent level of activity in patients who have received three or more prior lines of therapy, including an anti-CD38 antibody, and who are refractory to a proteasome inhibitor and an immunomodulatory agent." — Eric Blouin, SVP, oncology, Ipsos
Tislelizumab,
BeiGene/Celgene, Phase III
Indication: Hodgkin's lymphoma
What the clinical trials found: Tislelizumab is an investigational anti-PD-1 that will have to compete in a crowded market. However, Chinese biotech BeiGene is avoiding traditional PD-1 indications such as melanoma and lung cancer. Instead, the company has created an international drug development program for several smaller indications. Furthest along is tislelizumab for relapsed/refractory classical Hodgkin's lymphoma. A Phase II trial demonstrated a 73% overall response rate and a 50% complete response in 70 patients.
inThought comment: "It's going to be the next PD-1 inhibitor because it's being investigated in a number of niche indications." — Weyerbacher
BioPharm Insight revenue forecast: $937 million in global annual sales by 2027
Market potential: "In 2016, the [anti-PD-1 drug] market in the U.S. was valued at $3.97 billion. Deutsche Bank has predicted the total Chinese market for PD-1/PD-L1 will rise to $4 billion in 2025. The drug market for Hodgkin's diseases in [the Asia-Pacific] region will grow at a compound annual growth rate of 7.93%. The market in EMEA is expected to reach $3.68 billion by 2021." — Intellica
What physicians are saying: "BeiGene has Celgene onboard as its ex-Asia development partner. However, the main role this asset will play in this partnership is as a backbone to Celgene's next-gen immuno-oncology pipeline assets." — Blouin
https://e.infogram.com/c6c3eec1-ac32-4204-8304-c369acec8ac1?src=embed
Obeticholic acid
Intercept Pharmaceuticals, Phase III
Indication: Nonalcoholic steatohepatitis (NASH)
What the clinical trials found: With the twin epidemics of obesity and fatty liver disease on the rise, the market for an advanced form of fatty liver disease called NASH is expected to be $20 billion by 2025. And of all the dozens of drug candidates currently in development for NASH, Intercept's obeticholic acid is first in line.
The candidate surged to prominence when a Phase II proof-of-concept trial was stopped early because the treatment arm saw a dramatic improvement over the control arm. Since then, side effects such as itchiness and lipid elevation have emerged, but obeticholic acid is still on track to be the first NASH drug to hit the market.
What physicians are saying: "It is estimated 16 million people have NASH in the U.S. alone. Currently, there is no treatment available for this disease, but the pipeline is large.
The Ipsos NASH Therapy Monitor study [478 doctors in U.S. and European Union Five reporting on NASH patients] shows current awareness of [obeticholic acid] to be high, with 50% of U.S. doctors and 40% of doctors in the EU5 aware of obeticholic acid. If the next set of clinical trials manage to demonstrate decrease in fibrosis and the resolution of NASH, it will be a successful drug in helping patients manage their liver disease." — Sabina Heinz, research director, Ipsos
Ubrogepant, Merck/Allergan Phase III
Indication: Migraine
What the clinical trials found: Ubrogepant is a CGRP inhibitor for patients with episodic migraines. It's not the only drug to target the CGRP receptor. Others include Eli Lilly's galcanezumab, Teva's fremanezumab, Amgen's erenumab, and Alder Biopharmaceuticals' eptinezumab. But unlike the others, it's an oral candidate. In a Phase III trial of 1,686 patients, the higher of two doses of ubrogepant was superior to placebo, reaching statistical significance. With 14% of patients given a placebo being pain-free after two hours, compared to 22% of patients given a 50 milligram dose.
What physicians are saying: "Analysts have predicted significant uptake for ubrogepant," note McDougall and Sim.
However, experts this news service interviewed noted available data indicates ubrogepant is somewhat comparable to triptans, which dominate the oral acute migraine treatment space. The drug may see use in certain niche populations such as patients who have cardiovascular comorbidities.
Brolucizumab, Alcon, Phase III
Indication: Wet age-related macular degeneration
What the clinical trials found: In two Phase III head-to-head trials against Regeneron's Eylea (aflibercept), brolucizumab was shown to be noninferior. It met its primary outcome — improving vision — and bested Eylea in secondary endpoints of reducing intra and subretinal fluid and central subfield thickness.
Credit Suisse revenue forecast: $1 billion in global annual revenue by 2024
What physicians are saying: "Due to the less frequent dosing, patients are expected to be more compliant to their treatment (to receive all scheduled injections and have a lower burden of treatment due to less frequent injections and the inconvenience of related visits to their treatment centers). Physicians believe this will lead to better treatment outcomes and long-term prognosis for many of their patients." — Joern Kleebach, global account director, Ipsos
https://e.infogram.com/c2dc0f50-f871-41f3-ac28-76b8a2ce4336?src=embed
Έρευνες/Κλινικές Μελέτες, Επιστημονικά Νέα, Marketing/Managment, News
Acceleron Pharma, acute myeloid leukemia, aducanumab, Alcon, Allergan, Alnylam, Alzheimer, Amgen, Anemia related to myelodysplastic syndromes (MDS, Aprocitentan, Asthma, AstraZeneca, BeiGene, beta thalassemia, Biogen, Bristol Myers Squibb, brolucizumab, Celgene, CGRP inhibitor, Crohn's disease, CSL Behring, Daiichi Sankyo, Daprodustat, Duchenne muscular dystrophy, filgotinib, Fitusiran, FLT3 inhibitor, Galapagos, Gilead, GlaxoSmithKline, Hemophilia, hemophilia A, hemophilia B, Hodgkin's lymphoma, Hypercholesterolemia, Hypertension, Idorsia, Inclisiran, Intercept Pharmaceuticals, Janssen, Luspatercept, Merck, Migraine, Myocardial infarction, NASH, News, nonalcoholic steatohepatitis, obeticholic acid, quizartinib, rheumatoid arthritis, Sanofi, Sarepta Therapeutics, Tezepelumab, tislelizumab, Ubrogepant, Wet age-related macular degeneration
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Intelligence Pharma The 2019 pipeline report: Changing the treatment paradigm


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Physician and patient concordance of report of tobacco cessation intervention in primary care in India
Rajmohan Panda1,
Divya Persai1,
Sudhir Venkatesan2 &
Jasjit S Ahluwalia3
Tobacco cessation interventions by physicians hold promise in improving quit rates. The 5As intervention ('Ask', 'Advise', 'Assess', 'Assist' and 'Arrange') is an evidence-based approach for tobacco cessation. However, little is known about adherence with the tobacco cessation interventions in primary care in India. In the present study we assessed physicians' adherence with the 5As intervention and explored physician and patient concordance on the report of 5As intervention for tobacco cessation.
We used data from two cross-sectional surveys conducted in 12 districts of Andhra Pradesh and Gujarat in India. The surveys were administered simultaneously to both patients attending, and physicians working in health facilities providing primary care. Health facilities were selected by systematic random sampling and patients were recruited by simple random sampling. Common health facilities where both surveys were performed were identified, and individual patients were matched to their physicians through a unique matching code to obtain the two study samples.
Slight agreement was observed between the physician and patient responses on 'Ask' and 'Arrange' component of the 5As intervention. The 'Advise', 'Assess' and 'Assist' components showed low agreement. Slightly higher levels of agreement were seen on all components of the 5As, except 'Advise', for those patients who had made an attempt to quit.
Our study suggests an urgent need for revising current strategies in order to strengthen the 'Advise', 'Assess', and 'Assist' interventions in tobacco cessation in primary care settings. Patient surveys should be used routinely in assessing fidelity and provider adherence for large scale behavioral health programs.
Tobacco use is one of the greatest causes of preventable deaths and disease in human history. According to the World Bank, four‐fifths of the world's 1.1 billion smokers live in low‐income or middle‐income countries [1]. As per GATS India data (2010) there are 275 million adult tobacco users (rural-216 million, urban-59 million) in India [2]. About one million Indians die from smoking alone each year, which is 15% of global death burden attributable to tobacco use [3]. To reduce the economic and health burden from tobacco use, effective tobacco cessation interventions are clearly needed.
Tobacco cessation interventions by healthcare providers hold promise in improving quit rates. Several studies have demonstrated that asking about smoking and offering advice about cessation increases quit rates [4,5]. However, little is known about the extent of adherence with the tobacco cessation interventions in primary care in India. A study by Panda et al. in 2011 among physicians in primary care facilities in India suggests that tobacco cessation interventions were not being offered in primary care clinics to any significant extent and patients were not benefiting from opportunistic counseling advice [6]. No simple empirically validated model captures the broad range of interventions across tobacco but the 5As construct provides a workable framework to report tobacco cessation interventions. The 5As include 'Asking' all patients about tobacco use, 'Advising' tobacco users to quit, 'Assessing' tobacco users' readiness to quit, 'Assisting' patients in their quit attempts, and 'Arrange' follow-up visits and counseling. Although the 5As approach is becoming more widely adopted as a strategy for behavior change counseling in tobacco cessation, practical and standardized assessments of 5As delivery are not widely available in the developing world and this is true also for India [7]. Accurate measures of providers' delivery of tobacco cessation efforts during clinical practice are needed to monitor providers' adherence to the 5As approach and to assess the impact of interventions [8]. Provider treatment of tobacco use can be measured by patient surveys, provider surveys, medical record reviews, and direct observation [9]. We assessed physicians' adherence with the 5As intervention by conducting surveys simultaneously with both physicians and patients respectively. We also assessed the concordance on physicians' and patients' report of the 5As intervention by measuring extent of agreement between physicians and patients report on the 5As intervention. We further explored patients' agreement on 5As intervention in relation to their quitting behavior. The study was conducted in selected health facilities providing primary care.
Study settings and design
We used data from two cross-sectional surveys conducted in 12 districts of Andhra Pradesh and Gujarat in India from June to August 2013. The two surveys were administered simultaneously among both patients as well as physicians working in health facilities providing primary care.
Health facilities providing primary care in India include Primary Health Centers (PHC), Community Health Centers (CHC), and sub-district and district hospitals. Each primary and community health center caters to the population of 20,000-30,000 and 80,000-120,000 respectively hospitals [10]. Primary healthcare in India is provided by a variety of healthcare providers including doctors trained in medicine, and practitioners trained in the indigenous systems of medicine (Ayurveda, Unani, Siddha, and Homeopathic medicine-AYUSH) [11].
Physicians' survey
The health facilities were chosen using systematic random sampling. All the health facilities providing primary care in the district were listed. The first health facility was selected at random and then every fifth health facility was selected for inclusion in the sample. All consenting physicians practicing at the selected facilities were surveyed for inclusion into the study. The physicians' survey included a) Background characteristics, b) Practices in tobacco cessation c) Knowledge of physicians in tobacco cessation interventions, d) Attitude towards tobacco cessation. Responses to the 5As interventions were coded as either 'yes' or 'no'. Physicians who self-reported that they 'Ask' patients about tobacco use and who counseled about tobacco cessation were considered to have fulfilled the criteria for 'Ask' and 'Advise' respectively. 'Assist' was measured by any of the following questions: During the past 12 months, did you suggest nicotine replacement therapy such as a patch or gum? or during the past 12 months, did you perform one time counseling to your patients to help them quit? or have you ever given any printed material to the patient? Information on follow-ups to higher centers for cessation determined the 'Arrange' component of the 5As intervention.
A situational analysis and literature review was conducted which help developed the questionnaire. Prior formative research was done to determine themes of the questionnaire. The questionnaire was administered by trained interviewers hired from a survey agency. The questionnaire was validated and pilot tested and changes were made. The interviews were conducted in local language. The interviewers established good rapport with the respondents before administrating the questionnaire. To reduce the social desirability bias, respondents' names were kept anonymous and confidentiality was maintained.
Patients' survey
Patients were approached immediately following the patient-physician interaction. The study participants were recruited through simple random sampling by selecting every third patient who registered to see the health service provider on each consulting day during the study period excluding weekends and public holidays. The participant eligibility was determined on the basis of whether the respondent was adult (more than 18 years), sought services from health service providers, and consumed tobacco in some or the other form. The questionnaire was administered by trained interviewers hired from a survey agency. The questionnaire was validated and pilot tested and changes were made. Data collection was done at suitable places near to the vicinity of health facilities away from the consultation rooms. Critically ill patients, those younger than 18 years, and those who did not give consent were excluded from the study. The patients' survey included a) Participant eligibility, b) Socio-demographic information, c) Tobacco use information, d) Tobacco counseling practices by physicians working in health facilities providing primary health care and e) Motivation to quit. Data were collected on patient receipt of the 5As through specific questions. The patient reported 'Ask' variable was measured with the question 'Have you been 'Asked' about your tobacco consumption habit during today's visit?' 'Advise' was assessed with the question 'Did your physician advise you to quit tobacco?' Physician provision of 'Assess' were measured with any of the following questions: Did your physician inform you about different medicines for quitting? or Did your physician suggest ways to quit tobacco use? or Did your physician provide you any printed material?
Survey questions used to capture patients' and physicians' responses on the 5As interventions are summarized in Table 1.
Table 1 Survey questions used to capture data on the 5As
Common health facilities where both surveys were performed were identified, and individual patients were matched to their physicians through a unique matching code to obtain the two study samples. The data collection forms for these assessments compared a common set of interventions based on the structure of the 5A algorithm and agreement between the patient and physician responses was assessed.
The main predictors of interest for the present analysis were patient and physician self-reported 5As intervention in tobacco cessation. Percentage agreement for each component of the 5As was calculated to assess agreement between the physicians' survey and the patients' survey. The analyses were performed using Stata 12.0 (StataCorp, 2011. Stata Statistical Software: Release 12.).
The study was approved by the Public Health Foundation of India, Institutional Ethical Committee (IEC 65/60). Informed consent was taken from both physicians and patients.
Background characteristics
Physicians' characteristics
A total of 345 physicians were interviewed. Out of these 345 physicians, there were 293 physicians who were practicing at the health facilities where physician and patient survey were conducted. The majority of physicians were male (69%) and the survey response rate was 95% (345/384). At the health facilities, physicians had multiple encounters with the patients. The average number of patients seen by physicians per day in both the states was 80. The surveyed health facilities consisted of Primary Health Centers (58%), Community Health Centers (40%) and District Hospitals (2%). About 242 (82.6%) of physicians had a medical degree, 17 were dental graduates (5.8%), 33 had Ayurveda, Unani, Siddha, and Homeopathic medicine (AYUSH) qualification (11.3%) and 1 (0.3%) had a government approved professional certificate. Background characteristics of physicians are summarized in Table 2.
Table 2 Background characteristics of physicians (n = 293)
A total of 867 patients who were tobacco users and made outpatient visit to the health facility providing primary care were recruited for the study. The response rate of the patient survey was 97%. About 46% of patients were smokers, 42% were smokeless tobacco users and 12% of them were dual tobacco users. About 68% of the patients had not made an attempt to quit tobacco in past 12 months, with the remaining having made at least one attempt to quit. Table 3 summarizes the background characteristics of patients.
Table 3 Background characteristics of patients
Physicians' report of 5As intervention in tobacco cessation
Over 90% of physicians self-reported that they 'Ask' patients about tobacco use, 'Assess' readiness to quit, 'Assist' in quitting and 'Arrange' follow-up visits. Only 44% of physicians said that they 'Advise' patients to quit tobacco.
Patients' report of 5As intervention in tobacco cessation
More than two-third of the patients reported that they were 'Asked' about tobacco usage (77%) by the physicians. About half of patients reported they were 'Advised' to quit (51%) and 'Assessed' for their interest in quitting (48%), about a third of patients were offered a follow-up (Arranged) contact (38%).
Concordance between physicians and patients on each component of the 5As intervention in tobacco cessation
Proportions of physicians' and patients' report of the 5As intervention are presented in Table 4. Figure 1 depicts this data graphically. Physicians were seen to have reported consistently higher levels of the 5As than patients reported receiving them except the 'Advise' component which was reported at a slightly higher frequency by patients (51%) when compared to physician (43.7%). 'Ask' and 'Advise' components of the 5As showed the least difference in percentages reported between the groups with 'Assess', 'Assist', and 'Arrange' showing increasingly higher percentage differences.
Table 4 Proportions reporting each component of the 5As
Proportion of patients and physicians reporting each of the 5As.
Percentage agreement between physicians and patients was the highest for 'Ask' (76.36%). The remaining three components of the 5As showed low agreement between the two surveys (Table 5). Our findings indicate that percentage agreement was higher among patients who were smokeless tobacco users as compared to those who were smokers across all the 5As interventions. When the patient population was split into those who had made at least one quit attempt in the past twelve months and those who had not, slightly higher levels of agreement were seen in all components of the 5As, except 'Advise', for those patients who had made an attempt to quit. Conversely, amongst those who had not made an attempt to quit over the past twelve months, slightly lower levels of agreement were seen for all components, except 'Advise'.
Table 5 Agreement between patients and physicians on each component of the 5As
The 5As intervention is an evidence-based approach for tobacco cessation and is feasible to apply in primary care. This study describes adherence with the 5As intervention for tobacco cessation and concordance between patient-provider delivery and receipt of 5As interventions respectively. We captured both patients' and physicians' responses simultaneously without a lag period. Globally, patients' view on quality of behavioral interventions has been captured in previous studies [12,13] however, no studies have assessed physician and patient report of the 5As in tobacco cessation in India.
The findings of the current study are consistent with the findings of previous work [14,15] in which the majority of physicians self-report that they 'Asked' patients about tobacco use. Our finding related to asking patients about tobacco use is also in agreement with the study by Conroy et.al. [16] where 76% of the patients reported that they were asked for tobacco use during their visit to physicians. However, on examining physicians and patients responses we found that there is slight agreement between physicians' and patients' responses regarding the 'Ask' component of 5As intervention. The high percentage reported on 'Asking' component by patients is promising as asking for tobacco use is very often the first step towards a more comprehensive cessation intervention.
Our data suggest that most physicians do not 'Advise' patients to quit. Similar findings were observed in GATS, India (2010) data [2], studies by Thankappan et.al. [17], and Mas et.al. [18], which also found that less than 50% of physicians are routinely advising patients to quit tobacco. When we assessed agreement between physicians and patients report, we found low agreement on 'Advise' component of 5As intervention as has also been reported by Pollak et.al, in 2002 [19]. When patients attend primary health facilities, an enquiry about tobacco exposure by a physician and brief advice to quit can increase the rates of tobacco cessation [20]. Unfortunately, these opportunities were largely missed by physicians in our study.
A recent meta-analysis highlights the effectiveness of 'Assess' intervention and suggests that prior assessment of willingness to quit excludes many tobacco users who would have taken up the offer of assistance if offered directly [21]. However, clinical practice guidelines recommend assessment of willingness as an important step which further provides a roadmap for tobacco cessation treatment [10]. Our findings indicate that though a majority of physicians self-reported that they 'Assess' patient willingness to quit, only a few patients reported being 'Assessed' by physicians. Low agreement on 'Assess' intervention between patients' and physicians' report was observed. Although it is possible that patients underestimated physician assessment, the fact that they did not recall a physicians' assessment strategy is clinically important and suggests the need for more intensive interventions in the primary care setting.
In contrast to physicians' self-reported practices, patients in our study mentioned that only a few physicians 'Assisted' them with their quit attempts. Similar findings were observed in studies conducted in other settings [22,23]. Our findings also indicate low agreement between physicians and patients on the 'Assist' component of 5As. This is a cause for concern as it suggests that physicians are not offering adequate support to help patients quit tobacco despite strong recommendations by national guidelines which give emphasis to assist patients in quitting tobacco [10].
In our study, the majority of physicians self-reported that they 'Arrange' follow-up visits for the patients. However, patient surveys reveal contrasting findings. We found slight agreement on 'Arranging' for follow-up visits and this finding is similar to a study reported by Omole et.al.in South Africa in 2010 [23]. The slight agreement on follow-up support is promising and underscores the need for a pragmatic approach incorporating checklists into system reminders to prompt physicians to provide information on follow-up counseling sessions and support [9].
Similar to the findings of our study, studies conducted in other South-Asian countries reported discordance between rates of 'Advise', 'Assess', 'Assist' between physicians and patients [24,25]. We reason that this discordance could be because patients often underestimate physicians' interventions. The concern of patients about their personal medical problem may have affected their responses [26].
While many studies report on the issues of concordance, there are few which have examined the relationship of agreement to quitting behavior. We explored the association of agreement on 5As intervention with patients' quit attempts. Our findings are similar to the findings reported by Quinn et al. who suggests that patient who made a quit attempt had higher agreement on receipt of 5As as compared to those patients who did not attempt to quit [26].
Our findings, although insightful, need to be interpreted cautiously as the patient survey was conducted in a subsample of health facilities providing primary care, and thus may not be representative of the overall health care experience in primary care settings. The patients' responses were captured at the time of their visit to the health facility. However, the questionnaire captured physicians' responses and 5As interventions over a period of 12 months. Thus, physicians were more likely to overestimate their practices in the present study. Further, these results are based on reports from patients and do not reflect the notations from the medical record. Ideally, an audit of the physicians' records would better validate findings from the surveys. However, considering that medical records of physicians are not currently maintained in India as in other developing countries, patient interviews are likely to be the best available evidence on the 5As interventions of the physicians.
In conclusion, concordance between physician and patient self-report is slightly higher for 'Ask' and 'Arrange' and low for 'Advise', 'Assess', and 'Assist' interventions. Our study suggests an urgent need for revising current strategies in order to strengthen the 'Advise', 'Assess', and 'Assist' interventions in tobacco cessation in primary care settings. This study helped developed what we believe is the first comparison of behavioral health interventions (5As) in India by using two standard surveys capturing both physician as well as patient responses at the same time.
We propose that patient surveys such as ours should be used routinely in assessing fidelity and provider adherence for large scale behavioral health programs especially in the areas of non-communicable disease program. Further research is needed in order to determine the true rate of tobacco cessation intervention in primary care settings, assess barriers towards provision of tobacco cessation services as well as to verify trends in patient and physician reports in India and other developing countries.
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Pbert L, Adams A, Quirk ME, Hebert JH, Ockene JK, Luippold RS. "The patient exit interview as an assessment of physician-delivered smoking intervention: a validation study". Health Psychol. 1999;18:2.
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Rao M, Mant D. Strengthening primary healthcare in India: white paper on opportunities for partnership. BMJ. 2012;344:351. http://dx.doi.org/10.1136/bmj.e3151.
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Abdullah AS, Zhou J, Huang D, Lu S, Luo S, Pun VC. Smoking status and cessation counseling practices among physicians, Guangxi, China, 2007. Prev Chronic Dis. 2010;7:15. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811510/.
Conroy MB, Majchrzak NE, Silverman CB, Chang Y, Regan S, Schneider LI, et al. Measuring provider adherence to tobacco treatment guidelines: A comparison of electronic medical record review, patient survey, and provider survey. Nicotine Tob Research. 2005;7:35–43. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/16036268.
Thankappan KR, Kumar S, Nitcher M. Doctors' behaviour & skills for tobacco cessation in Kerala. Indian J Medical Res. 2007;129:249–55. Retrieved from: http://icmr.nic.in/ijmr/2009/march/0306.pdf.
Mas FGS, Balcazar HG, Alberola JV, Hsu CE. Correlates of tobacco cessation counseling among Hispanic physicians in the US: A cross-sectional survey study. BMC Public Health. 2008;8:5. doi:10.1186/1471-2458-8-5.
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Omole OB, Ngobale KNW, Yusuf OAA. Missed opportunities for tobacco use screening and brief cessation advice in South African primary health care: a cross-sectional study. BMC Fam Prac. 2010;11:94. doi:10.1186/1471-2296-11-94.
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Daskalakis C, Goldberg R, Ockene JK, Kalan K, Hosmer DW, Pbert L. Comparison of Patients' and their resident Physicians' responses regarding smoking cessation interventions. Acad Med. 1995;68:2.
Quinn VP, Hollis JF, Smith KS, Rigotti NA, Solberg LI, Hu W. Effectiveness of the 5-As tobacco cessation treatments in nine HMOs. J Gen Inter Med. 2008;24:149–54. doi:10.1007/s11606-008-0865-9.
This study is a subset of project funded by Bill and Melinda Gates Foundation. We would like to thank Dr. Puja Myles, Division of Epidemiology and Public Health, University of Nottingham, for her valuable inputs.
Public Health Foundation of India, New Delhi, India
Rajmohan Panda & Divya Persai
Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
Sudhir Venkatesan
Center for Health Equity, University of Minnesota, Minneapolis, MN, USA
Jasjit S Ahluwalia
Rajmohan Panda
Divya Persai
Correspondence to Sudhir Venkatesan.
DP, RP, SV conceptualized and planned the overview of the manuscript. RP was involved in designing and conducting the study as well as the design of the manuscript. DP contributed to the interpretation and writing of the results and discussion. SV led the data analysis. JSA reviewed the manuscript and provided critical inputs relating to quality and content of the manuscript. All authors read and approved the final manuscript.
Panda, R., Persai, D., Venkatesan, S. et al. Physician and patient concordance of report of tobacco cessation intervention in primary care in India. BMC Public Health 15, 456 (2015). https://doi.org/10.1186/s12889-015-1803-5
Primary Care Setting
Nicotine Replacement Therapy


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Home » Snooker » Ace out to trump heavy-favourite O'Sullivan in high-profile semi
Ace out to trump heavy-favourite O'Sullivan in high-profile semi
Ronnie O'Sullivan's steamrollering of the competition at the World Championship has led to an influx of bets backing the Essex-based potsmith to remain perched on his mantle at the summit of the snooker industry.
However, Judd Trump is more than capable of ending the Rocket's reign in their semi-final and go on to claim a maiden world crown himself. Mr Haircut 100 may not be blessed with a good nickname but, at 11/5, he can entitle those punting him to hoist snooker's richest prize come the end of the week to a handsome payout.
Having overcome an 8-3 deficit to break Shaun Murphy's sizeable heart in the quarters, the underdog will be flying and is sure to give Ronnie a sterner test than any potential final adversary.
The 13-12 Crucible classic was, undoubtedly, the match of the tournament thus far and should have filled Trump with the self-belief that he can derail the runaway Rocket bandwagon, despite the 14 years experience between the players.
Trump has bettered O'Sullivan in six of their 11 duels, including the most recent; a 6-2 mauling in the 2012 Masters.
The World Championship semi-final format is unlike any other in which they have squared off before, however, making such a convincing victory an unlikely outcome. Backing over 29 frames to be contested in this best of 33 clash is almost certain to result in payout and, at 10/11, this bet should have plenty of takers.
This clash also promises plenty of big breaks. These two players are recognised for their ability to rack up the big numbers at the felt and they've ran in 13 centuries already in the tournament.
A bet on four or five 100+ breaks enables a windfall to the tune of 4/1 for both outcomes and it's difficult to see the match ton-total falling below this mark.
All odds and markets accurate as of publication's time and date
« Barry Hawkins preparing for a Rocket showdown
Ding set to continue relentless march into record books »
James Middleton
O'Sullivan and Selby tipped to reach Crucible semi finals
World Championship Snooker: Trump semi-final bound
Stevens to reach quarter finals as other leaders should also advance


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Cardi B Jokes That Everybody Wants Her To Be Their Kids' Godmother Now That She's Making Money
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By Sydney Scott	· December 21, 2017 October 24, 2020
Cardi B has the best answer for why she isn't buying everyone Christmas gifts this year.
The rapper recently stopped by The Tonight Show Starring Jimmy Fallon, where she was asked about a recent tweet that read, "I'm not giving NO ADULTS NO Christmas gift."
I'm not giving NO ADULTS NO Christmas gift 😤😤😤
— iamcardib (@iamcardib) December 2, 2017
The fun-loving rapper gave the most Cardi B answer to why when she told Fallon, "Everybody that I know got kids and that's just a lot of kids. And, I got new god kids out of nowhere. Once you start making money everybody wants you to be they kids godmother or something."
Really, who wouldn't want to be on Cardi's Christmas list. The singer has had an amazing 2017. Her hit "Bodak Yellow" the fifth female rapper to ever top the Billboard Hot 100 and the second to do so since Lauryn Hill's "Doo Wop (That Thing)" in 1998. And, the rapper's net worth reportedly rose from $600,000 to $4 million.
But, her rise to fame almost didn't happen. Cardi recently revealed that she thought about leaving hip hop after being kicked off of a song by an unnamed rapper because another rapper didn't think she was big enough to be on the track.
"I did a verse to somebody's song, and other artists were on the song as well," she said during an Instagram Live session. "I was so excited because I felt like my verse was so poppin'. Then, the artist told me that I couldn't be on the song anymore because one of the artists that was on the song felt like I was too small and they were too big for me to be on the same song with them. I was just fresh off Love & Hip Hop and everything, and that shit broke my heart."
Thankfully, the incident didn't derail Cardi's enthusiasm or else we wouldn't have been given the song of the summer. Can you imagine 2017 without "Bodak Yellow"?


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