This literature review summarizes a document on current and future artemisinin-based combination therapy (ACT). It discusses that ACTs have been recognized by the WHO as the most effective treatment for malaria by increasing cure rates and decreasing resistance risk. However, the 2010 WHO guidelines have limitations by only reviewing literature up to 2004, with some exceptions to 2008, and neglecting nearly 400 relevant papers. The vast amount of literature on ACTs requires an international expert group to clarify treatment strategies. The document also discusses China's role in discovering artemisinin and proposes establishing a Malaria Control Task Force to disseminate information on responsible ACT use.

1. Literature Review on
Current and Future
Artemisinin-based
Combination Therapy:
Recent Trends
Dr. Jan-Cedric Hansen
Medico-Marketing European Strategist
StratAdviserLtd
Medical Coordinator at Hopital Asselin-Hedelin
France

2. China and Artemisinin
Known by traditional Chinese Medicine
– since 4th Century
Extracted from “Chinese Absinth”
Key Role of Chinese Researcher Tu Youyou
– 1971 design of a optimal extraction protocol
– 1972 identification of Artemisinin
– 1979 publication in English of first results with
Artemisinin derivatives
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3. Situational Analysis
16 deaths every 10 min worldwide
WHO’s guidelines for the treatment of malaria
– Evidence-based recommendations
– Clear diagnosis criteria
– Safe and effective antimalarial medicines selection
– Therapeutic strategy for given clinical situations
– Referencing point for malaria control programs
Recognition that artemisinin-based combination therapies (ACTs):
1) increase the rates of clinical and parasitological cures
2) decrease the selection pressure (less resistance risk)
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4. Limitation of WHO’s guidelines*
The 2010 second edition literature overview is
– Limited to June 2004
• with the exception of 47 publications released between 2004
and mid 2008
– Promotes Artemether vs Artesunate
• despite no evidence that Artemisinin derivatives differ
• rather than comparing the partner medicines’ influence
– Whilst neglecting nearly 400 papers released on
• “malaria, falciparum/drug therapy” &
"artemisinins/therapeutic use“
* As a recognised Strategic Knowledge Management advisor, StratAdviser has been granted by Sanofi to appraise “WHO’s guidelines for the
treatment of malaria 2nd edition” in an independent manner in order to determine whether there was a bias regarding the fact that the report
opposes Artemether to Artesunate. In order to achieve its assignment, StratAdviser followed a rigorous proprietary methodology.
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5. Literature review
More complex than expected
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6. Methodology
Artemisinin Medline Search Strategy
– Restriction to past 5 years (relevance)
– 2,427 publications on Malaria Drug Therapy between
2006/10 and 2011/10
• 1,421 related to Artemisinin
• 729 dedicated to Artemisinin Malaria Drug Therapy
• 223 clinical trials (163 full access online)
* "malaria/drug therapy"[MeSH Terms] AND "artemisinins"[MeSH Terms] AND (Clinical Trial[ptyp] AND "2006/10/18"[PDat] :
"2011/10/16"[PDat])
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7. Covered Topics
Diagnostic criteria impact on therapeutic success
– RDT, microscopy (Dr vs HW), ...
Enhanced efficacy strategy
– ACT vs ACT, ACT vs others, blood concentration monitoring, adjunctive treatment, galenic
form, pre-referal treatment, ...
Enhanced tolerance strategy
– Intermittent, ACT vs ACT,
Compliance solutions
– Mobile phone alert, ...
Administration route
– IV, IR, PO, ...
Pharmacology within different population
– infant, pregnant, genetic (CP450, G6PD) , ethnic, ...
Delivery model impact
– Retail, health workers, ...
Public health impact
– Curative, preventive, selection pressure, Cost-effectiveness, ...
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8. Homogeneity of published data
Different
– Methodology
• Double blind, Open label, Cohort, Retrospective, Meta Analysis, ...
– Population
• South America, Western Africa, Eastern Africa, Asia, Oceania, ...
– Clinical situations
• Severe, uncomplicated, age groups, ...
– Treatment strategy
• Dosage, Titration, Regimen, ...
– Efficacy Criteria
• Clinical improvement, gametocyte clearance, relapse, ...
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9. Data Handling
The abundant available literature on Artemisinin
derivatives and partner medicines
– Overcomes individual prescribers (field practitioners)
capacity of integration
– Deserves an international consensus regarding
• Both confidence & relevance of available data
• Both respective indications & related therapeutic strategy
• Both therapeutic success & therapeutic failure indicators
The vast amount of information regarding ACTs make it mandatory to clarify
where, to whom, when and how to prescribe
This can only be achieved by an Independent International Expert Group
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10. Call for an international independent expert group
Malaria Control Task Force
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11. Malaria Control Task Force Overview
It is a Therapeutic Strategy Awareness Program dedicated to
the ACTs’ Malaria Control
– clarifies the ACTs’ Malaria Control rational and its related therapeutic
strategy because ACTs are clearly the current gold standard
Its objective is to help field practitioners
– To understand better the proper use of ACTs
– Thanks to a non product specific, accredited education programs
It would be an academic program
– Elicited by its Co-Chairs
– Potentially run by StratAdviserLtd
– Funded by Third Parties
It would be supported by an associative organisation
– “Loi 1901” if housed in France
– “Unincorporated Association” if housed in the UK
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12. Malaria Control Task Force Organisation
Co-Chairs are 3 key Malaria High Profile
KOL who want to promote CRS as a key
issue
Board Members are 10 to 12 Malaria KOL
who are recognised by their peers
Co-Chairs regarding Clinical and/or susceptibility
determine topics
& questions
and/or Pharmacology... (each specialty
being involved in a way or another
Board Members regarding Malaria Control)
elaborate content Supporters are numerous Field
& advocate Malaria Control Practitioners who are interested in
Supporters upgrading their practice skills regarding
disseminate Malaria Control (early adopter profile) –
Malaria Control they are organised as “clubs” in each
messages countries. They will be invited to register to
Followers a CME programme to become “Malaria
adhere to Malaria Control experts”
Control messages
Followers are other KOL, Field
Stakeholders Practitioners and Healthcare Authorities
Representatives that pay attention and
then adhere to the Malaria Control
“package” thanks to the noise generated
by the above mentioned ones
Stakeholders include all of the above plus
sponsors, governments, patient
associations, third parties...
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13. Malaria Control Task Force Methodology
Board members meet once a year
– They have one to two video conferences per year
They liaise in a monthly basis
– Together in order to produce and/or validate the
scientific/educational/informative production of the
group
– With Supporters to disseminate their Output
They designate speakers
– to advocate Malaria Control Task Force outputs during
congresses and conferences
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14. Malaria Control Task Force Outputs
Grading of available literature and guidelines
– EBM approach (AGREE, GRADE, Proprietary ...)
Classification of Malaria Clinical Presentation
– Severity Score, ...
Proposition of relevant therapeutic strategy
– 1st, 2nd, 3rd line treatment ....
Identification of adequate QA indicators
– Artemisinin Resistance Containment ...
The clarification of the responsible use of ACTs calls for a sustained and robust
dissemination program to ensure field prescribers adhesion
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15. Malaria Control Task Force Tools
Media Releases
– written or recorded supports providing stakeholders, via media, with an information subsidy containing the basics needed
to develop a news story regarding Malaria Control Task Force such as scheduled upcoming events, Board Members
promotions, awards, new educational services, accomplishments, etc.
Flyers
– recto-verso folded supports to advertise the existence of Malaria Control Task Force, invite to a CME session, a Malaria
Control seminar, to register to a Malaria Control mailing list, to visit a given website, ...
Pamphlets
– 8 to 16 stitched supports to disseminate interviews of Malaria Control Task Force board members and short messages
links to Malaria Control
Reprints
– duplex supports to allow disseminating original articles with Malaria Control Task Force board members comments printed
over the folder – original articles are selected by board members due to their interest regarding Malaria Control
Congress Abstracts
– “400 to 600” words supports to advocate and disseminate Malaria Control Task Force Therapeutic Strategy backup,
grading scale, guidelines, and related topics
CRS satellite symposia
– Malaria Control Task Force Board Members are welcome to perform lectures regarding ACTs’ Therapeutic Strategy
whenever they are invited to national and international congresses – sponsor may as well organise satellite symposia
dedicated to ACTs
CME programs
– printed or dematerialized supports to allow appropriation of ACTs’ Therapeutic Strategy management
Newsletter
– printed or dematerialized supports to duplicate any of the above to maximize the chances to influence the target audience
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16. ACTs and their environment
Future Trends and Breakthrough
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17. 2010/2011 Proposed Shortlist
Novartis Institute for Tropical Diseases (NITD), Swiss Tropical &
Public Health Institute and Scripps Research Institute
discovery of a next generation treatment for drug resistant
malaria
WHO/Roll Back Malaria 2011 Global Plan for Artemisinin
Resistance Containment (GPARC)
AstraZeneca and Medicines for Malaria Venture (MMV)
collaborative agreement to identify novel candidate drugs for
the treatment of malaria.
Sanofi and Medicines for Malaria Venture (MMV) alliance
agreement to research malaria treatments
Institute for OneWorldHealth, University of California, Berkeley,
Amyris, and Sanofi semisynthetic (Microbially Derived)
Artemisinin Project
GSK malaria vaccine Phase III published results
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18. Thank You
Dr. Jan-Cedric Hansen
Medico-Marketing European Strategist
StratAdviserLtd
Medical Coordinator at Hopital Asselin-Hedelin
France
Jc.hansen@stratadviser.com