Journal of Infectious Diseases
Volume 203 Issue 11 June 1, 2011
http://www.journals.uchicago.edu/toc/jid/current
Mark R. Schleiss

Editor’s Choice: Could Therapeutic Vaccination of Cytomegalovirus-Seropositive Persons Prevent Reinfection and Congenital Virus Transmission?
J Infect Dis. (2011) 203(11): 1513-1516 doi:10.1093/infdis/jir144

Extract
In the developed world, cytomegalovirus (CMV) is the most common congenital viral infection, with an overall birth prevalence of ∼0.6% [ 1]. Approximately 10% of congenitally infected infants have signs and symptoms of disease at birth, and these symptomatic infants have been reported to have a 40%–90% risk of subsequent neurologic sequelae, including mental retardation, microcephaly, development delay, seizure disorders, and cerebral palsy [ 2– 4]. Seven percent –to 20% of asymptomatically infected newborns will also demonstrate sequelae, particularly sensorineural hearing loss [ 5– 7]. The public health impact of congenital CMV infection is substantial and underrecognized; although more children suffer from long-term neurodevelopmental handicaps as a result of congenital CMV infection than either Down syndrome or fetal alcohol syndrome [ 8], awareness unfortunately remains low, particularly among women of childbearing age [ 9, 10]. An effective vaccine could, by preventing neurological sequelae and other disabilities, provide a newborn with a lifetime of benefit. For that reason, a report from the Institute of Medicine (IOM) of the National Academy of Sciences placed CMV in its highest priority category for vaccine development, concluding that a vaccine would be strongly cost saving [ 11, 12].

Among the various CMV vaccine candidates currently in clinical trials [ 13], the most encouraging results to date have been observed in studies of a vaccine based on the immunodominant envelope glycoprotein B (gB). Several clinical trials have been performed using a recombinant form of this protein expressed in Chinese hamster ovary cells, purified and combined with an oil-in-water adjuvant known as MF59 [ 14– 17]. Pass et al recently reported the results of a seminal phase II efficacy trial of the gB-MF59 …

Journal of Infectious Diseases
Volume 203 Issue 11 June 1, 2011
http://www.journals.uchicago.edu/toc/jid/current

VIRUSES
Sanny Y. Chen, Shoana Anderson, Preeta K. Kutty, Francelli Lugo, Michelle McDonald, Paul A. Rota, Ismael R. Ortega-Sanchez, Ken Komatsu, Gregory L. Armstrong, Rebecca Sunenshine, and Jane F. Seward
Editor’s Choice: Health Care–Associated Measles Outbreak in the United States After an Importation: Challenges and Economic Impact
J Infect Dis. (2011) 203(11): 1517-1525 doi:10.1093/infdis/jir115

[Free full text]
Abstract
(See the editorial commentary by Ostroff, on pages 1507–9.)

Background. On 12 February 2008, an infected Swiss traveler visited hospital A in Tucson, Arizona, and initiated a predominantly health care–associated measles outbreak involving 14 cases. We investigated risk factors that might have contributed to health care–associated transmission and assessed outbreak-associated hospital costs.

Methods. Epidemiologic data were obtained by case interviews and review of medical records. Health care personnel (HCP) immunization records were reviewed to identify non–measles-immune HCP. Outbreak-associated costs were estimated from 2 hospitals.

Results. Of 14 patients with confirmed cases, 7 (50%) were aged ≥18 years, 4 (29%) were hospitalized, 7 (50%) acquired measles in health care settings, and all (100%) were unvaccinated or had unknown vaccination status. Of the 11 patients (79%) who had accessed health care services while infectious, 1 (9%) was masked and isolated promptly after rash onset. HCP measles immunity data from 2 hospitals confirmed that 1776 (25%) of 7195 HCP lacked evidence of measles immunity. Among these HCPs, 139 (9%) of 1583 tested seronegative for measles immunoglobulin G, including 1 person who acquired measles. The 2 hospitals spent US$799,136 responding to and containing 7 cases in these facilities.

Conclusions. Suspecting measles as a diagnosis, instituting immediate airborne isolation, and ensuring rapidly retrievable measles immunity records for HCPs are paramount in preventing health care–associated spread and in minimizing hospital outbreak–response costs.

The Lancet  
May 21, 2011  Volume 377  Number 9779  Pages 1719 – 1806
http://www.thelancet.com/journals/lancet/issue/current

Editorial
HIV treatment as prevention—it works
The Lancet

Preview
Last week any doubts around treatment as an approach to halt the spread of the HIV epidemic were allayed. An international study showed that antiretroviral treatment can prevent the sexual transmission of HIV among heterosexual couples in whom one partner is HIV-infected and the other is not. UNAIDS described the result as a “serious game changer” for HIV prevention.

The Lancet  
May 21, 2011  Volume 377  Number 9779  Pages 1719 – 1806
http://www.thelancet.com/journals/lancet/issue/current

Articles
Long-term protection against malaria after experimental sporozoite inoculation: an open-label follow-up study
Meta Roestenberg, Anne C Teirlinck, Matthew BB McCall, Karina Teelen, Krystelle Nganou Makamdop, Jorien Wiersma, Theo Arens, Pieter Beckers, GeertJan van Gemert, Marga van de Vegte-Bolmer, André JAM van der Ven, Adrian JF Luty, Cornelus C Hermsen, Robert W Sauerwein

Preview
Artificially induced immunity lasts longer than generally recorded after natural exposure; providing a new avenue of research into the mechanisms of malaria immunity.

Pharmacoeconomics
June 1, 2011 – Volume 29 – Issue 6  pp: 455-547
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Review Articles
Health Technology Funding Decision-Making Processes Around the World: The Same, Yet Different
Stafinski, Tania; Menon, Devidas; Philippon, Donald J.; McCabe, Christopher
Pharmacoeconomics. 29(6):475-495, June 1, 2011.
doi: 10.2165/11586420-000000000-00000

Abstract:
All healthcare systems routinely make resource allocation decisions that trade off potential health gains to different patient populations. However, when such trade-offs relate to the introduction of new, promising health technologies, perceived ‘winners’ and ‘losers’ are more apparent. In recent years, public scrutiny over such decisions has intensified, raising the need to better understand how they are currently made and how they might be improved. The objective of this paper is to critically review and compare current processes for making health technology funding decisions at the regional, state/provincial and national level in 20 countries.

A comprehensive search for published, peer-reviewed and grey literature describing actual national, state/provincial and regional/institutional technology decision-making processes was conducted. Information was extracted by two independent reviewers and tabulated to facilitate qualitative comparative analyses. To identify strengths and weaknesses of processes identified, websites of corresponding organizations were searched for commissioned reviews/evaluations, which were subsequently analysed using standard qualitative methods.

A total of 21 national, four provincial/state and six regional/institutional-level processes were found. Although information on each one varied, they could be grouped into four sequential categories: (i) identification of the decision problem; (ii) information inputs; (iii) elements of the decision-making process; and (iv) public accountability and decision implementation. While information requirements of all processes appeared substantial and decision-making factors comprehensive, the way in which they were utilized was often unclear, as were approaches used to incorporate social values or equity arguments into decisions.

A comprehensive inventory of approaches to implementing the four main components of all technology funding decision-making processes was compiled, from which areas for future work or research aimed at improving the acceptability of decisions were identified. They include the explication of decision criteria and social values underpinning processes

Vaccine
Volume 29, Issue 24  pp. 4079-4182 (31 May 2011)
http://www.sciencedirect.com/science/journal/0264410X

Short Communications
Patent data mining: A tool for accelerating HIV vaccine innovation
Pages 4086-4093
K. Clark, J. Cavicchi, K. Jensen, R. Fitzgerald, A. Bennett, S.P. Kowalski

Abstract
Global access to advanced vaccine technologies is challenged by the interrelated components of intellectual property (IP) management strategies, technology transfer (legal and technical) capabilities and the capacity necessary for accelerating R&D, commercialization and delivery of vaccines. Due to a negative association with the management of IP, patents are often overlooked as a vast resource of freely available, information akin to scientific journals as well as business and technological information and trends fundamental for formulating policies and IP management strategies. Therefore, a fundamental step towards facilitating global vaccine access will be the assembly, organization and analysis of patent landscapes, to identify the amount of patenting, ownership (assignees) and fields of technology covered. This is critical for making informed decisions (e.g., identifying licensees, building research and product development collaborations, and ascertaining freedom to operate). Such information is of particular interest to the HIV vaccine community where the HIV Vaccine Enterprise, have voiced concern that IP rights (particularly patents and trade secrets) may prevent data and materials sharing, delaying progress in research and development of a HIV vaccine. We have compiled and analyzed a representative HIV vaccine patent landscape for a prime-boost, DNA/adenoviral vaccine platform, as an example for identifying obstacles, maximizing opportunities and making informed IP management strategy decisions towards the development and deployment of an efficacious HIV vaccine.

Vaccine
Volume 29, Issue 24  pp. 4079-4182 (31 May 2011)
http://www.sciencedirect.com/science/journal/0264410X

Addressing the needs and gaps in safety assessment of vaccines during clinical trials in resource limited countries
Pages 4173-4174
Agnes Kisser, Ulrich Heininger, Vasee S. Moorthy, Bartholomew D. Akanmori, Odile Lero

[No abstract]

Vaccine
Volume 29, Issue 24  pp. 4079-4182 (31 May 2011)
http://www.sciencedirect.com/science/journal/0264410X

Regular Papers
Economic burden of rotavirus disease in children under 5 years in Kazakhstan
Pages 4175-4180
Renat Latipov, Aynagul Kuatbaeva, Olga Kristiansen, Saltanat Aubakirova, Ulbosin Akhanaeva, Ivar Sønbø Kristiansen, Elmira Flem

Abstract
Background
We aimed to estimate the societal costs of rotavirus cases among children less than 5 years in Kazakhstan, an upper-middle income country in Central Asia.

Methods
Data on medical, non-medical and indirect costs were collected for 190 patients less than 5 years, hospitalized with severe diarrhea in 2009 in two pediatric hospitals. Data on resource use for moderate and mild diarrhea cases were obtained from published sources. A probabilistic sensitivity analysis was performed to explore uncertainty in cost estimates.

Reults
Approximately 4,000 severe, 30,700 moderate, and 122,900 mild rotavirus cases were estimated annually in children <5 years old. The mean societal cost of a severe, moderate and mild rotavirus case was estimated at US$ 454, 82, and 21, respectively. The total annual cost of rotavirus disease was $37.53 million or on average $107.36 for a child under 5 years old in Kazakhstan. Ninety-four percent of total costs (35.13 million) are indirect costs (productivity losses) from fatal cases and parents’ job absenteeism, while direct medical costs account for 2.04 million (5.4%), and direct non-medical for 0.46 million (1.2%).

Conclusions
Rotavirus-associated diarrhea represents a significant economic burden in Kazakhstan, largely due to indirect costs. The costs of rotavirus infections should be considered when planning further preventive actions, including the introduction of rotavirus vaccination.

Art Caplan, Ph.D., Director of the Penn Center for Bioethics, addressed the symposium’s opening dinner (2 May 2011) attendees. His keynote is titled: Vaccination: Personal Responsibility; Community Imperative.

Video: Part I, Part II

Symposium – Global Vaccines 202X: Access, Equity, Ethics

Center for Vaccine Ethics and Policy

2-4 May 2011
The Franklin Institute Science Museum
Philadelphia

Global Vaccines 202X: Access, Equity, Ethics was a three-day symposium gathering approximately 100 leaders from global public health, government, academia, foundations and the NGO community to assess key issues and lay the foundation for an effective policy framework focused on access, equity and ethics for the decade-plus ahead.

Please find the final agenda and video documentation of the keynotes and presentations here.

More on the Global Vaccines 202X Symposium at: http://globalvaccines202xsymposium.wordpress.com/

PATH CEO Chris Elias addressed symposium participants during dinner in the Benjamin Franklin National Memorial on Day 2 of the meeting. The keynote is titled: “Global Vaccine Access — Why Now?”

[Video: Part I, Part II ]

.

Symposium – Global Vaccines 202X: Access, Equity, Ethics

Center for Vaccine Ethics and Policy

2-4 May 2011
The Franklin Institute Science Museum
Philadelphia

Global Vaccines 202X: Access, Equity, Ethics was a three-day symposium gathering approximately 100 leaders from global public health, government, academia, foundations and the NGO community to assess key issues and lay the foundation for an effective policy framework focused on access, equity and ethics for the decade-plus ahead.

Please find the final agenda and video documentation of the keynotes and presentations here.

More on the Global Vaccines 202X Symposium at: http://globalvaccines202xsymposium.wordpress.com/

Vaccines: The Week in Review  16 May 2011 pdf version, comprising all the psost below for this date: Vaccines_The Week in Review_16 May 2011

The Sixty-fourth World Health Assembly convenes 16–24 May 2011 in Geneva. Provisional agenda and meeting documentation available here: http://www.who.int/mediacentre/events/2011/wha64/en/index.html

Twitter updates by whonews and tags #worldhealthassembly #globalhealth

PAHO reported that Haiti “finalized a plan to ensure immunization against the country’s most prevalent childhood diseases for at least 90 percent of children under 1 by 2015.” The plan was said to reflect the Haitian Ministry of Public Health and Population’s “determination to re-launch routine vaccination efforts, which were lagging—relative to other countries of the Americas—even before the earthquake.”

PAHO said the plan’s specific goals include:

– increasing immunization coverage from around 60 percent to 90 percent among children under 1;
– maintaining the country free of polio, measles, and rubella;

– eliminating maternal and neonatal tetanus by 2015;

– introducing new rotavirus and pneumococcal vaccines, as well as the pentavalent vaccine which protects against diphtheria, pertussis (whooping cough), tetanus, Hepatitis B and Haemophilus influenzae type b (Hib), which is a bacteria responsible for some types of meningitis and pneumonias; and

– improving immunization surveillance for the early detection of vaccine-preventable diseases.

PAHO’s Deputy Director Dr. Jon Andrus commented, “When Haiti is well supported, its people can do incredible things. The earthquake and cholera outbreak have focused international support, providing an opportunity to help the country catch up in some areas and hopefully leap forward in others.” http://new.paho.org/hq/index.php?option=com_content&task=view&id=5406&Itemid=1

     “Men and women infected with HIV reduced the risk of transmitting the virus to their sexual partners by taking oral antiretroviral medicines when their immune systems were relatively healthy,” according to findings from a large-scale clinical study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The clinical trial, known as HPTN 052, was slated to end in 2015 but NIH said the findings are being released early as the result of a scheduled interim review of the study data by an independent data and safety monitoring board (DSMB). The DSMB “concluded that it was clear that use of antiretrovirals by HIV-infected individuals with relatively healthier immune systems substantially reduced transmission to their partners. The results are the first from a major randomized clinical trial to indicate that treating an HIV-infected individual can reduce the risk of sexual transmission of HIV to an uninfected partner.” NIAID Director Anthony S. Fauci, M.D commented, “Previous data about the potential value of antiretrovirals in making HIV-infected individuals less infectious to their sexual partners came largely from observational and epidemiological studies. This new finding convincingly demonstrates that treating the infected individual—and doing so sooner rather than later—can have a major impact on reducing HIV transmission.”

http://www.nih.gov/news/health/may2011/niaid-12.htm

The GAVI Alliance said it committed US$100 million “to help tackle meningitis A in Cameroon, Chad, and Nigeria as part of a strategy to save tens of thousands of lives in Africa with a new life-saving vaccine, MenAfriVac.” Helen Evans, interim GAVI CEO, said,  “We accelerated our approvals process so that we can ensure this vaccine is available in Cameroon, Chad, and Nigeria, before next year’s epidemic season due to start in December. This is a breakthrough vaccine in the fight against meningitis A. If GAVI is fully funded for our 2011-2015 programme, this vaccine could save many lives and avoid the other terrible consequences of epidemics.” http://www.gavialliance.org/media_centre/press_releases/meningitis_a_funding.php

WHO released World Health Statistics 2011, noting that “an increasing number of countries are facing a double burden of disease as the prevalence of risk factors for chronic diseases such as diabetes, heart diseases and cancers increase and many countries still struggle to reduce maternal and child deaths caused by infectious diseases.”  The report identifies that “noncommunicable diseases such heart diseases, stroke, diabetes and cancer, now make up two-thirds of all deaths globally, due to the population aging and the spread of risk factors associated with globalization and urbanization. The control of risk factors such as tobacco use, sedentary lifestyle, unhealthy diet and excessive use of alcohol becomes more critical. The latest WHO figures showed that about 4 out of 10 men and 1 in 11 women are using tobacco and about 1 in 8 adults is obese.” Ties Boerma, Director of WHO’s Department of Health Statistics and Informatics, said, “This evidence really shows that no country in the world can address health from either an infectious disease perspective or a noncommunicable disease one. Everyone must develop a health system that addresses the full range of the health threats in both areas.” says

http://www.who.int/mediacentre/news/releases/2011/health_statistics_20110513/en/index.html

Gates Foundation blog
http://www.gatesfoundation.org/foundationnotes/Pages/margaret-chan-saving-lives-immunization.aspx

Posted by Margaret Chan on May 11, 2011

Saving Lives With Immunization
I am a believer in human ability and ingenuity. I believe it is our duty to try our best to make the health of each successive generation better.

As a public health expert, I reflect often on how this can be done. Diseases have plagued mankind for millennia but the human race has fought back with ingenuity. It was Edward Jenner’s innovation in 1796 that gave us the strongest public health tool that we have ever possessed: the vaccine.

New technology in the middle of the last century led to the development of vaccines for polio, measles, mumps, rubella, typhoid and tuberculosis. More recently we have developed vaccines for influenza, hepatitis B, meningitis and yellow fever. We are pushing forward in our quest to find vaccines for HIV and malaria. The time lag from discovery to delivery is getting shorter and more countries are receiving good quality vaccines that they can afford.

Today, four out of five children now receive routine vaccines and are protected from death, disease and disability. The numbers of people with polio are down 99 percent, and measles deaths in Africa are down 90percent. Immunization is estimated to save between 2and 3million lives each year, and the prevention of these childhood diseases is one of the greatest success stories in global public health.

But how did we get from a great idea to great results?

Thirty seven years ago, a World Health Assembly (WHA) resolution set an ambitious agenda for humanity. The Expanded Programme on Immunization (EPI) tasked the World Health Organization (WHO) with supporting immunization programmes in developing countries to increase vaccination coverage and help them obtain good quality vaccines at an affordable cost. In 2005, WHO adopted the Global Immunization Vision and Strategy, which took this even further.

But challenges remain. About 23 million infants worldwide are still not protected from life-threatening diseases. Many of them live in developing countries that are proving difficult to reach with vaccines.

Developing vaccines and getting them to every part of the world, regardless of a country’s ability to pay, is a complex and daunting task. Partners are a key part of the world’s machinery against diseases. The WHO and other United Nations agencies, the GAVI Alliance, and the Bill & Melinda Gates Foundation work through dynamic partnership to focus international attention on the importance of immunization.

Immunization can significantly contribute to achieving the health-related Millennium Development Goals (MDGs). With less than four years until the 2015 deadline, I urge countries to realize that vision. We must keep our promises by getting back on track to meet the global goals, and we need to do this together. Everyone – from world leaders to individuals – has a role to play to help save millions of lives in years to come.

It’s time to give more children a shot at life.

Dr. Margaret Chan is the Director-General of the World Health Organization.

    The Board of the Global Fund to Fight AIDS, Tuberculosis and Malaria said it elected Martin Dinham, a former Director General in the United Kingdom’s Department for International Development, as the new Board Chair. Dr. Mphu Ramatlapeng, Health Minister of the Kingdom of Lesotho, was elected Vice-Chair.  The Board also approved “a comprehensive reform agenda to maximise the effectiveness of the Global Fund,” as well as the framework for “an ambitious five-year agenda, which will set the direction and targets for the organization.”  The new five-year strategy (2012-2016) proposes that the Global Fund “should strive towards saving up to 20 million additional lives and averting 200 million infections by 2016. This will require improvements in efficiency”

http://www.theglobalfund.org/en/pressreleases/?pr=pr_110513

The Weekly Epidemiological Record (WER) for 13 May 2011, vol. 86, 20 (pp 189–204) includes: Dracunculiasis eradication – global surveillance summary, 2010; Progress towards interrupting wild poliovirus transmission worldwide: January 2010–March 2011.

http://www.who.int/entity/wer/2011/wer8620.pdf

The Center for Vaccine Ethics and Policy convened Global Vaccines 202X: Access, Equity, Ethics – a three-day symposium held 2-4 May 2011 at The Franklin Institute Science Museum, Philadelphia. The meeting gathered approximately 100 leaders from global public health, government, academia, foundations and the NGO community to assess key issues and lay the foundation for an effective policy framework focused on access, equity and ethics for the decade-plus ahead. Video documentation of the meeting will be posted at the symposium website beginning this week. Upcoming Vaccines: The Week in Review will feature content from symposium sessions. Videos of keynote addresses are available now as below:

– Opening Keynote: Realizing the Promise of Global Vaccines
Seth Berkley, IAVI
Introduction: Phil Johnson, Children’s Hospital of Philadelphia
[video: Part I, Part II, Part III ]

– Keynote: 202X trends and perspectives – Immunization Strategy 
JM Okwo-Bele, WHO IVB
[video: here ]

– Keynote: The Value of Evidence in Immunization
Anne Schuchat, Director, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA, CDC
Introduction: Art Caplan, Penn Center for Bioethics
[video: here ]

– Dinner Keynote: Vaccination: Personal Responsibility; Community Imperative
Art Caplan, Penn Center for Bioethics
[video: Part I, Part II]

– Keynote: WHO’s Immunization Policy Framework: Is it achieving its goal?
Helen Rees, Chairperson, SAGE/WHO
Introduction: Paul Offit, Children’s Hospital of Philadelphia
[video: Part I, Part II ]

– Dinner Keynote: Global Vaccine Access — Why Now?
Chris Elias, CEO, PATH
Introduction: Art Caplan, Penn Center for Bioethics
Benjamin Franklin National Memorial
[video: Part I, Part II ]

– Keynote: Priorities, policies, perceptions & the public
David Salisbury, Department of Health, United Kingdom
Introduction: Art Caplan, Penn Center for Bioethics
[video: Part I, Part II, Part III, Part IV ]

Twitter Watch

A selection of items of interest this week from a variety of twitter feeds. This capture is highly selective and by no means intended to be exhaustive.

AIDSvaccine IAVI
World #AIDS #Vaccine Day is Wednesday. Many significant advances are being made in #HIV prevention #research. Help spread the word!

gatesfoundation Gates Foundation
RT ONECampaign: African health ministers from six countries go “on the record” about #vaccines… http://bit.ly/lyx0xq

whonews WHO News
Tweeting on our World Health Assembly 16-25 May 2011? Join the conversation & use #worldhealthassembly http://j.mp/kbSWfw #globalhealth

AIDSvaccine IAVI
IAVI statement on #HPTN052 trial that finds early ARV treatment can reduce #HIV transmission among discordant couples http://bit.ly/ixogmg

USAIDGH USAID
Tempering Fear When the Winds Blow, great meningitis piece from Marc LaForce, Director Meningitis Vaccine Project: http://1.usa.gov/laTsG1

whonews WHO News

Read Dr Chan’s blog post on saving lives through #immunization http://tinyurl.com/6gqna8d #globalhealth

gatesfoundation Gates Foundation
#Polio campaign in the Congo aims to vaccinate 23 million children under five: http://gates.ly/kJrUsv via @UNICEF

AIDSvaccine IAVI
World #AIDS Vaccine Day/ #HIV #Vaccine Awareness Day is May 18. Build your basic knowledge w/IAVI’s VaxLit Toolkit: http://bit.ly/aSTZXA

British Medical Journal
11 May 2011 Volume 342, Issue 7806
http://www.bmj.com/content/current

Research Methods & Reporting
Economic evaluation alongside randomised controlled trials: design, conduct, analysis, and reporting
Stavros Petrou, Alastair Gray
BMJ 2011;342:doi:10.1136/bmj.d1548 (Published 7 April 2011)

Extract
Collecting economic data at the same time as evidence of effectiveness maximises the information available for analysis but requires proper consideration at the design stage

Economic evaluation involves the comparative analysis of the costs and consequences of alternative programmes or interventions. 1 It has increasingly been used to inform decision making about healthcare in the United Kingdom and other industrialised nations. 2 3 4 5 Randomised controlled trials are commonly used as a vehicle for economic evaluations. Indeed, many funders, such as the UK National Institute for Health Research Health Technology Assessment Programme, routinely request that assessments of cost effectiveness are incorporated in the design of randomised trials. This article outlines some of the key issues concerning the design, conduct, analysis, and reporting of economic evaluations based on trials with individual patient data. Economic evaluations that synthesise data from disparate sources using decision analytical models (typically using summary rather than individual patient data) are discussed in an accompanying article…

JAMA   
May 11, 2011, Vol 305, No. 18, pp 1833-1926
http://jama.ama-assn.org/current.dtl

Commentaries
Vaccine Liability in the Supreme Court: Forging a Social Compact
John D. Kraemer, Lawrence O. Gostin
JAMA. 2011;305(18):1900-1901.doi:10.1001/jama.2011.615

[First 150 words per JAMA convention]

On February 22, 2011, the US Supreme Court decided Bruesewitz v Wyeth LLC, 1 holding that the National Childhood Vaccine Injury Act of 1986 (NCVIA) preempts all design defect claims against vaccine manufacturers in which the plaintiff seeks compensation for injury or death caused by a vaccine’s adverse effects. The public health implications are profound because Congress designed the NCVIA to safeguard a social compact—ensuring access to vaccines by preventing the uncertainty of litigation, while also ensuring vaccine safety and effectiveness.

The Challenge of Vaccine Availability

Vaccines are unquestionably among modern public health’s greatest triumphs. In the United States alone, the incidence of vaccine-preventable diseases declined from more than 1 million cases per year at the start of the 20th century to only a few thousand cases per year by its close. 2 Although vaccines remain a cornerstone of public health, they are far less profitable than most biologics, causing only a few manufacturers …

The Lancet  
May 14, 2011  Volume 377  Number 9778  Pages 1625 – 1718
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Fighting fake drugs: the role of WHO and pharma
The Lancet

Preview
Counterfeit medicines pose a serious threat to public health. Up to 15% of all drugs sold worldwide are estimated to be fake. Last year, WHO, at the request of member states at the 2010 World Health Assembly (WHA), convened an intergovernmental working group on counterfeit medicines tasked with deciding the agency’s role in tackling this global scourge. The intergovernmental group was required to make specific recommendations to this year’s 64th WHA (May 16–24). They will, however, fail in this mission.

The Lancet  
May 14, 2011  Volume 377  Number 9778  Pages 1625 – 1718
http://www.thelancet.com/journals/lancet/issue/current

Comment
The cost of dengue control
Eduardo Massad, Francisco Antonio Bezerra Coutinho

Preview
Dengue is thought to be the most important vector-borne disease,1 with about 2·5 billion people (two-fifths of the world’s population) living in regions affected by dengue.2 There are 50–100 million new infections annually.3 According to WHO, the incidence is increasing because of human population growth and wider spread of vector mosquitoes due to climate change (figure).4,5 The total yearly cost of treatment in dengue-endemic areas can reach US$2 billion.3 Without an effective vaccine or specific antiviral treatment, control of the main mosquito vector, Aedes aegypti, is the only option for the prevention and control of dengue,6 at a cost of between $0·207 and $1·008 a head.

The Lancet  
May 14, 2011  Volume 377  Number 9778  Pages 1625 – 1718
http://www.thelancet.com/journals/lancet/issue/current

Sharing information on adverse events
Koichiro Yuji, Hiroto Narimatsu, Tetsuya Tanimoto, Tsunehiko Komatsu, Masahiro Kami

Preview
The communication gap between researchers and the mass media has become a serious problem worldwide. Emotive media reports have amplified people’s distrust in medicine, and have widened the communication gap between medical professionals and patients. Japan recently experienced a case of a misleading media report about a cancer vaccine clinical trial which had a great impact on cancer patients.

The Lancet  
May 14, 2011  Volume 377  Number 9778  Pages 1625 – 1718
http://www.thelancet.com/journals/lancet/issue/current

Dengue vector control strategies in an urban setting: an economic modelling assessment
Paula Mendes Luz, Tazio Vanni, Jan Medlock, A David Paltiel, Alison P Galvani

Summary
Background
An estimated 2·5 billion people are at risk of dengue. Incidence of dengue is especially high in resource-constrained countries, where control relies mainly on insecticides targeted at larval or adult mosquitoes. We did epidemiological and economic assessments of different vector control strategies.

Methods
We developed a dynamic model of dengue transmission that assesses the evolution of insecticide resistance and immunity in the human population, thus allowing for long-term evolutionary and immunological effects of decreased dengue transmission. We measured the dengue health burden in terms of disability-adjusted life-years (DALYs) lost. We did a cost-effectiveness analysis of 43 insecticide-based vector control strategies, including strategies targeted at adult and larval stages, at varying efficacies (high-efficacy [90% mortality], medium-efficacy [60% mortality], and low-efficacy [30% mortality]) and yearly application frequencies (one to six applications). To assess the effect of parameter uncertainty on the results, we did a probabilistic sensitivity analysis and a threshold analysis.

Findings
All interventions caused the emergence of insecticide resistance, which, with the loss of herd immunity, will increase the magnitude of future dengue epidemics. In our model, one or more applications of high-efficacy larval control reduced dengue burden for up to 2 years, whereas three or more applications of adult vector control reduced dengue burden for up to 4 years. The incremental cost-effectiveness ratios of the strategies for two high-efficacy adult vector control applications per year was US$615 per DALY saved and for six high-efficacy adult vector control applications per year was $1267 per DALY saved. Sensitivity analysis showed that if the cost of adult control was more than 8·2 times the cost of larval control then all strategies based on adult control became dominated.

Interpretation
Six high-efficacy adult vector control applications per year has a cost-effectiveness ratio that will probably meet WHO’s standard for a cost-effective or very cost-effective intervention. Year-round larval control can be counterproductive, exacerbating epidemics in later years because of evolution of insecticide resistance and loss of herd immunity. We suggest the reassessment of vector control policies that are based on larval control only.

Funding
The Fulbright Programme, CAPES (Brazilian federal agency for post-graduate education), the Miriam Burnett trust, and the Notsew Orm Sands Foundation.

Nature  
Volume 473 Number 7346 pp123-248   12 May 2011
http://www.nature.com/nature/current_issue.html

Comment
WHO needs change

The World Health Organization needs major reform to regain its leadership as a convener and provider of scientific and technical knowledge, says Barry R. Bloom.

Pediatrics
May 2011, VOLUME 127 / ISSUE Supplement 1
http://pediatrics.aappublications.org/content/127/Supplement_1

Editors’ Introduction: Vaccine Safety Throughout the Product Life Cycle
Daniel A. Salmon, Andrew Pavia, and Bruce Gellin
Pediatrics 2011; 127:S1-S4

The development and widespread use, in the United States and globally, of safe and effective vaccines has been one of the greatest achievements in science, medicine, and public health—saving lives, preventing disabilities, contributing to improvements in life expectancy, and reducing health care costs. Serious and once common childhood infections are increasingly joining the ranks of “vaccine-preventable diseases.” The number of childhood and adolescent diseases prevented by vaccines has increased from 10 to 16 in just the last 10 years. Moreover, we now have vaccines that can prevent the infections that can lead to cervical and liver cancer.

Ironically, as the threat of disease has been diminished by vaccines, there has been increasing attention on the risks, both real and perceived, from vaccines. When vaccines are used effectively, the incidence of vaccine-preventable diseases declines, and over time, the diseases that vaccines have prevented are less common. The result is that there is a subtle shift in the benefit/risk ratio. With the recent addition of new vaccines to the recommended childhood immunization schedule, an increasing number of parents have raised concerns that their children are receiving more vaccines than they need.    Changes in information technology, such as the Internet, provide more access to information, both accurate and inaccurate.

The safety standards for vaccines are arguably higher than those of any other medical product because vaccines are given to healthy persons to prevent disease, are recommended for near-universal use, and are often required by state laws for school entrance. Nevertheless, no medical product, including vaccines, is risk free.

Similar to other infrastructures, the components of the US vaccine-safety system may not be familiar to many people. Because the quality and transparency of this system are critical to maintaining public confidence in our immunization program, this supplement to Pediatrics has been assembled to help …

This supplement includes articles on two broad thematic areas:
– Vaccine-Safety System and Vaccine-Safety Studies
– Identifying and Addressing Vaccine-Safety Concerns Among Parents

PLoS Medicine
(Accessed 15 May 2011)
http://www.plosmedicine.org/article/browse.action?field=date

The Joint Action and Learning Initiative: Towards a Global Agreement on National and Global Responsibilities for Health
Lawrence O. Gostin, Eric A. Friedman, Gorik Ooms, Thomas Gebauer, Narendra Gupta, Devi Sridhar, Wang Chenguang, John-Arne Røttingen, David Sanders Policy Forum, published 10 May 2011
doi:10.1371/journal.pmed.1001031

Summary Points
– A coalition of civil society organizations and academics are initiating a Joint Action and Learning Initiative on National and Global Responsibilities for Health (JALI) to research key conceptual questions involving health rights and responsibilities, with the goal of securing a global health agreement and supporting civil society mobilization around the human right to health.
– This agreement—such as a Framework Convention on Global Health—would inform post-Millennium Development Goal (MDG) global health commitments.
– Using broad partnerships and an inclusive consultation process, JALI seeks to clarify the health services to which everyone is entitled under the right to health, the national and global responsibilities for securing this right, and global governance structures that can realize these responsibilities and close major health inequities.
– Mutual benefits to countries in the Global South and North would come from a global health agreement that defines national and global health responsibilities.
– JALI aims to respond to growing demands for accountability, and to create the political space that could make a global health agreement possible.

Science Translational Medicine
11 May 2011 vol 3, issue 82
http://stm.sciencemag.org/content/current

Perspective: Infectious Disease
Diagnosing the Individual to Control the Epidemic
Graham F. Medley
11 May 2011: 82ps18

Abstract
When vaccination is not an option, the only way to actively control an epidemic is to identify infectious individuals and “remove” them (by treatment, quarantine, or culling). In a recent Science paper, Charleston et al. present data and an analysis suggesting that clinical diagnosis of foot-and-mouth disease is very closely linked in time to shedding of virus; as such, removal of clinically affected animals might be sufficient to control an epidemic. Although these results are for a veterinary disease, they are very pertinent for all infectious diseases, including those of humans. In this Perspective, we consider the role of experimental research in determining the biology of infection as well as the importance of diagnosis for epidemic control.

Tropical Medicine & International Health
June 2011  Volume 16, Issue 6  Pages 661–772
http://onlinelibrary.wiley.com/doi/10.1111/tmi.2011.16.issue-6/issuetoc

Maternal Health
Relative and absolute addressability of global disease burden in maternal and perinatal health by investment in R&D (pages 662–668)
Nicholas M. Fisk, Martin McKee and Rifat Atun
Article first published online: 7 APR 2011 | DOI: 10.1111/j.1365-3156.2011.02778.x

Summary
Maternal and perinatal disease accounts for nearly 10% of the global burden of disease, with only modest progress towards achievement of the Millennium Development Goals. Despite a favourable new global health landscape in research and development (R&D) to produce new drugs for neglected diseases, R&D investment in maternal/perinatal health remains small and non-strategic. Investment in obstetric R&D by industry or the not-for-profit sector has lagged behind other specialties, with the number of registered pipeline drugs only 1–5% that for other major disease areas. Using a Delphi exercise with maternal/perinatal experts in global and translational research, we estimate that equitable pharmaceutical R&D and public sector research funding over the next 10–20 years could avert 1.1% and 1.9% of the global disease burden, respectively. In contrast, optimal uptake of existing research would prevent 3.0%, justifying the current focus on health service provision. Although R&D predominantly occurs in high-income countries, more than 98% of the estimated reduction in disease burden in this field would be in developing countries. We conclude that better pharmaceutical and public sector R&D would prevent around 1/3 and 2/3, respectively, of the disease burden addressable by optimal uptake of existing research. Strengthening R&D may be an important complementary strategy to health service provision to address global maternal and perinatal disease burden.

Vaccine
Volume 29, Issue 23 pp. 3931-4078 (23 May 2011)
http://www.sciencedirect.com/science/journal/0264410X

Regular Papers
HPV vaccine acceptability in Ghana, West Africa  
Original Research Article  Pages 3945-3950
Maame Aba Coleman, Judy Levison, Haleh Sangi-Haghpeykar

Abstract
Objective
Cervical cancer is a leading cause of cancer-related mortality among women in Ghana. As of this writing no data are available concerning knowledge, attitudes and acceptability of human papillomavirus (HPV) vaccination by women in Ghana.

Methods
Between November and December 2009, a self-administered survey was used to elicit information from 264 Ghanaian women, ages 18–65.

Results
Overall, 40% had heard about HPV vaccine and 94% were willing to vaccinate themselves or their daughters. Ideal age for vaccination was 12.7 years. Most women (75%) thought the vaccine should be received regardless of one’s number of sex partners. The most prevalent concerns were whether the vaccine would be administered safely using clean needles (82%), and possible future side effects (77%). Concerns about cost and vaccine encouraging earlier sex were reported by nearly half. Significant barriers to vaccine acceptance were women’s lack of knowledge about the gravity of cervical cancer in Ghana and utility of Pap test in detecting it, low perceived risk for cervical cancer, low social support to vaccine use, and low self-efficacy to find a doctor or clinic to get vaccinated (p < 05). About 55% of the women did not know the vaccine only works among those who are not yet infected with HPV. Schools and television were the most preferred methods of educating the public and cervical cancer prevention ranked as the ideal message (80%). Most respondents believed the decision to vaccinate their daughter should be made by both parents (34%) or in conjunction with the daughter (37%), as opposed to the government (17%).

Conclusions
Educational programs addressing specific barriers identified in the current study have the potential to significantly improve HPV vaccine uptake in Ghana.

Vaccine
Volume 29, Issue 23 pp. 3931-4078 (23 May 2011)
http://www.sciencedirect.com/science/journal/0264410X

Regular Papers
Ethnic and racial differences in HPV knowledge and vaccine intentions among men receiving HPV test results  Original Research Article
Pages 4013-4018
Ellen M. Daley, Stephanie Marhefka, Eric Buhi, Natalie D. Hernandez, Rasheeta Chandler, Cheryl Vamos, Stephanie Kolar, Christopher Wheldon, Mary R. Papenfuss, Anna R. Giuliano

Abstract
We examined factors associated with HPV vaccine intentions by racial/ethnic group among men participating in a HPV natural history study. HPV knowledge, vaccine intentions and perceived barriers were assessed among non-Hispanic White, non-Hispanic Black and Hispanic men. Men were tested for HPV every 6 months. After receiving test results from their previous visit, participants (N = 477) reported their intentions for HPV vaccination in a computer-assisted survey instrument (CASI). Vaccine intentions were high among all respondents, although differences were found between racial and ethnic groups in awareness and knowledge of HPV and, vaccine intentions and perceived access and barriers to receiving the HPV vaccine. In order to effectively disseminate the vaccine among men, factors that may promote or inhibit vaccine acceptability need to be identified. Identifying these factors related to vaccine intentions among minority and majority men offers an opportunity for addressing barriers to health equity and, in turn, reductions in HPV-related disparities.

The pdf version of Vaccines: The Week in Review  9 May 2011 comprises all the pots for this date below:

Vaccines_The Week in Review_9 May 2011

Documentation supporting the Sixty-fourth World Health Assembly, 16–24 May 2011, Geneva, Switzerland was published at http://apps.who.int/gb/e/e_wha64.html
including:

A64/1 – Provisional agenda

A64/8 – Pandemic influenza preparedness: sharing of influenza viruses and access to vaccines and other benefits

A64/10 – Implementation of the International Health Regulations (2005). Report of the Review Committee on the Functioning of the International Health Regulations (2005) in relation to Pandemic (H1N1) 2009

A64/14 – Global immunization vision and strategy

A64/17 – Smallpox eradication: destruction of variola virus stocks

The Global immunization vision and strategy document above (A64/14) includes an overview of the Decade of Vaccines Collaboration and its status, reproduced in full text below. The paragraph numeration continues from a more general update on GIVS earlier in the document:

“THE DECADE OF VACCINES, 2011–2020: A COMPREHENSIVE VENTURE TO ADVANCE IMMUNIZATION

19. The Decade of Vaccines envisages a world in which children, families and communities enjoy lives free from the fear of vaccine-preventable diseases. Its goal is to extend the full benefits of immunization to all people, regardless of where they live. This goal reflects the perspective that access to safe and effective vaccines is a human right that is not currently enjoyed by all people, particularly in low- and middle-income countries.

20. Achieving this goal will require full engagement of the diverse stakeholders needed to facilitate the discovery, development and delivery of vaccines, including donor governments, policy-makers, industry, researchers, the private sector and civil society, philanthropic bodies, and health workers in the countries where most vaccine-preventable diseases currently occur.

21. The planned activities of the decade build on and apply the lessons learnt from the work done so far in implementing the Global Immunization Vision and Strategy, and extend the base and time period of the strategy’s framework. WHO, UNICEF, the Bill & Melinda Gates Foundation and other partners are beginning a 12-month collaborative process to draft together a global vaccine action plan for consideration by the Sixty-fifth World Health Assembly. Such a plan should enable greater coordination between all stakeholders, outline the steps necessary to achieve the vision and goals outlined above, and identify gaps that must be filled in order to realize the potential of vaccines by

2020 and beyond. The action plan will comprise four essential components:

(i) establishing and sustaining broad public and political support for the use of vaccines and the financing of immunization services,

(ii) strengthening the equitable delivery of immunization services so as to achieve universal coverage of safe and effective vaccines by 2020 in order to prevent, control, eliminate or eradicate vaccine-preventable diseases,

(iii) cultivating a robust scientific environment for innovation in the discovery and development of new and improved vaccines and associated technologies for high-priority diseases,

(iv) creating the right market incentives to ensure an adequate and reliable supply of affordable vaccines.

Delivering immunization services in the next decade

22. Initial discussions on the strategies and key actions needed to improve delivery of immunization services have been held with stakeholders and country representatives, under the joint coordination of WHO and UNICEF. The ensuing programme of work recognizes the centrality of demand-driven, country-led approaches and action, based on equity, responsibility and accountability and a spirit of national self-reliance and gradual self-sufficiency to achieve commonly-shared global immunization goals.

23. The overall goal is to prevent, eliminate or eradicate diseases by means of achieving high and equitable coverage with effective and safe immunization along with other essential health-care interventions throughout the life course.

24. The proposed delivery strategy comprises five overarching objectives:

Objective 1. To uphold immunization as a human right: creating, increasing and sustaining community trust in immunization and awareness of this right; and focusing on underserved and marginalized communities by shifting the current emphasis on “Reaching Every District” to “Reaching Every Community”.

Objective 2. To achieve equity in the use of vaccines: reaching every community with vaccination through complementary delivery methods that engage all appropriate health service providers in the public, private and nongovernmental sectors, thereby ensuring that vaccination covers the poorest and least-served as well as all persons at risk and not just children; building demand for the wider use of new vaccines; and strengthening the efforts to eradicate poliomyelitis and eliminate measles and maternal and neonatal tetanus.

Objective 3. To seek synergies with other programmes and re-establish immunization as a core component of primary health care: putting increased emphasis on reducing the disease burden; coordinating the multiplicity of interventions needed to achieve this reduction with vaccination as an entry point or a complement to other interventions; and participating in collaborative efforts to renovate and strengthen health systems overall.

Objective 4. To develop immunization systems able to meet the challenges posed by the ambitious new goals: improving systems and tools for generating evidence, the monitoring of programme performance and the use of data for action; training, deploying and supporting adequate human resources for programme management and implementation; and building, maintaining and sustaining systems for regular procurement, delivery and effective supply of vaccines.

Objective 5. To bolster national self reliance and partnerships: strengthening structures and processes for countries to develop immunization policies, strategies and best practices; promoting greater ownership, political commitment, accountability and self-reliance of national immunization programmes; enabling formation of collaborative endeavours and engaging actors with diverse expertise across different sectors; achieving sustainable financing of immunization and sound financial management; and establishing national structures and enforcing processes for accountability.

NEXT STEPS

25. The process for preparing the global vaccine action plan will include extensive consultations with Member States and engage various stakeholders, including civil society organizations, professional societies and the private sector, and will provide an opportunity to estimate the costs of implementing the action plan. The Decade of Vaccines secretariat will ensure the overall oversight and coordination of the collaborative project (see paragraph 21) with working groups corresponding to each of the four proposed components undertaking detailed planning.”

The Global Fund announced completion of the selection of the panel that will review its financial safeguards. The panel’s co-chairs – Festus Mogae and Michael O. Leavitt – “selected the group of eminent persons and experts who will jointly conduct the assessment” and agreed on the scope and timeline of the review, which is scheduled to be concluded by 15 September 2011. The members selected to complete the high-level panel are:

– Zeinab Bashir El Bakri, Director, Office of His Highness the Prime Minister of Kuwait and former Vice-President Sector Operations of the African Development Bank;

– Norbert Hauser, Germany’s Vice-President of the Federal Court of Audit;

– Gabriel Jaramillo, Chairman of the Sovereign Bank Board and Special Advisor at the United Nations Secretary-General Office of the Special Envoy for Malaria;

– The Honourable Barry O’Keefe, Consultant, Clayton UTZ Sydney and former Justice of the Supreme Court of New South Wales (Australia); and

– Claude Rubinowicz, Chief Executive for France’s Agence du patrimoine immatériel de l’État (APIE, Agency for Public Intangibles of France) and former Inspecteur Général des Finances.

The panel “is assessing the risk of fraud and misappropriation in the current Global Fund portfolio, and the systems and controls in place which seek to ensure that the resources reach beneficiaries and are used for their intended purposes. To perform the assessment, the members of the panel will examine a representative sample of grants in countries in different risk categories, drawing conclusions and making recommendations, as appropriate.”

http://www.theglobalfund.org/en/pressreleases/?pr=pr_110504

The Weekly Epidemiological Record (WER) for 6 May 2011, vol. 86, 19 (pp 177–188) includes: Second meeting of the GPEI  (Global Polio Eradication Initiative) Independent Monitoring Board; 180 Progress towards meeting the 2012 hepatitis B control milestone: WHO Western Pacific Region, 2011 http://www.who.int/entity/wer/2011/wer8619.pdf

 Twitter Watch

A selection of items of interest this week from a variety of twitter feeds. This capture is highly selective and by no means intended to be exhaustive.

AIDSvaccine IAVI
Seth Berkley sat down with John Donnelly from #GlobalHealth Magazine’s blog for a Q&A about the #AIDS #vaccine field. http://bit.ly/iUSlpN

EndPolioNow EndPolioNow
In 10 years, 15 million more kids are alive because of vaccines. See the vaccine PSA from ONE. http://www.one.org/us/actnow/vaccines2011/

Annals of Internal Medicine
May 3, 2011; 154 (9)
http://www.annals.org/content/current

Original Research
Cholera Epidemic in Haiti, 2010: Using a Transmission Model to Explain Spatial Spread of Disease and Identify Optimal Control Interventions
Ashleigh R. Tuite, Joseph Tien, Marisa Eisenberg, David J.D. Earn, Junling Ma, and David N. Fisman
Ann Intern Med May 3, 2011 154:593-601; published ahead of print March 7, 2011,

Abstract
Background: Haiti is in the midst of a cholera epidemic. Surveillance data for formulating models of the epidemic are limited, but such models can aid understanding of epidemic processes and help define control strategies.

Objective: To predict, by using a mathematical model, the sequence and timing of regional cholera epidemics in Haiti and explore the potential effects of disease-control strategies.

Design: Compartmental mathematical model allowing person-to-person and waterborne transmission of cholera. Within- and between-region epidemic spread was modeled, with the latter dependent on population sizes and distance between regional centroids (a “gravity” model).

Setting: Haiti, 2010 to 2011.

Data Sources: Haitian hospitalization data, 2009 census data, literature-derived parameter values, and model calibration.

Measurements: Dates of epidemic onset and hospitalizations.

Results: The plausible range for cholera’s basic reproductive number (R0, defined as the number of secondary cases per primary case in a susceptible population without intervention) was 2.06 to 2.78. The order and timing of regional cholera outbreaks predicted by the gravity model were closely correlated with empirical observations. Analysis of changes in disease dynamics over time suggests that public health interventions have substantially affected this epidemic. A limited vaccine supply provided late in the epidemic was projected to have a modest effect.

Limitations: Assumptions were simplified, which was necessary for modeling. Projections are based on the initial dynamics of the epidemic, which may change.

Conclusion: Despite limited surveillance data from the cholera epidemic in Haiti, a model simulating between-region disease transmission according to population and distance closely reproduces reported disease patterns. This model is a tool that planners, policymakers, and medical personnel seeking to manage the epidemic could use immediately.

Primary Funding Source: None.

Editorials
Cholera in Haiti: Fully Integrating Prevention and Care
David Walton, Arjun Suri, and Paul Farmer
Ann Intern Med May 3, 2011 154:635-637; published ahead of print March 7, 2011,

British Medical Journal
7 May 2011 Volume 342, Issue 7805
http://www.bmj.com/content/current

Editor’s Choice
Cost is an ethical issue
Fiona Godlee, editor, BMJ

Money is tight, so getting value for money has to be a top priority for all of us in healthcare. As Jim Easton, the man in charge of improvement and efficiency for the NHS, says whenever he speaks, cost is an ethical issue. Why, then, do we have so little information on cost effectiveness?

Teppo Järvinen and colleagues find this especially worrying in the case of drug treatments for prevention (doi:10.1136/bmj.d2175). They say that for major preventive drugs, such as statins, antihypertensives, and bisphosphonates, there are “no valid data” on effectiveness or cost effectiveness. This may come as a surprise to some of you. It did to me. They explain that claims for the cost effectiveness of these and other drugs are based on efficacy data from randomised trials in idealised populations. In the real world of clinical care, true cost effectiveness may be much lower. Malcolm Willett’s cartoon shows a man standing on the bottom “efficacy” rung of a ladder: “This is fine,” he says. “I can see all the evidence I need from here.”

What Järvinen and colleagues urge us to recognise is that we can’t. To really see whether these drugs represent value for money, we need to take two steps up. We need to understand effectiveness and cost effectiveness in real clinical settings. As an example of how to do this, they refer to a 2001 study by Clare Robertson and colleagues (BMJ 2001;322:701, doi:10.1136/bmj.322.7288.701). But they point out that this assessed a non-drug intervention—exercise for preventing falls in older adults. “We wonder at the virtual absence of empirical cost effectiveness data on preventive drugs when drug companies stand to make millions of profit a week if their drugs are shown to reduce important clinical outcomes in the community setting.”

The BMJ has a longstanding policy of publishing cost effectiveness studies alongside or after randomised trials and systematic reviews. This week we apply the policy to the challenge of how best to treat heavy menstrual bleeding. A systematic review and individual patient data meta-analysis published last year found that hysterectomy scores higher (least dissatisfaction among patients) than endometrial ablation or the Mirena coil (BMJ 2010;341:c3929, doi:10.1136/bmj.c3929). Now the same group has done a full cost effectiveness analysis (doi:10.1136/bmj.d2202) and concludes that hysterectomy is likely to be the most cost effective strategy. NICE guidelines currently favour Mirena.

At least we do have NICE. With all its inevitable imperfections, it’s still a national treasure. Spare a thought for those charged with creating something similar in the United States, where the C word can’t be mentioned. Instead of “cost,” the focus is firmly on comparative effectiveness in the form of head to head comparisons. And even then, as Doug Kamerow reports (doi:10.1136/bmj.d2635), the Wall Street Journal snipes “Comparative effectiveness isn’t about informing choices, it’s about taking away options.” But there’s no alternative to comparing one treatment with another if we are to make rational decisions; and whatever your health system, cost is an ethical issue.

British Medical Journal
7 May 2011 Volume 342, Issue 7805
http://www.bmj.com/content/current

Analysis
The true cost of pharmacological disease prevention
Teppo L N Järvinen, Harri Sievänen, Pekka Kannus, Jarkko Jokihaara, Karim M Khan
BMJ 2011;342:doi:10.1136/bmj.d2175 (Published 19 April 2011)

Extract
Despite widespread use of preventive drugs such as statins, antihypertensives, and bisphosphonates, there is no valid evidence that they represent value for money, argue Teppo Järvinen and colleagues

Large randomised clinical trials are considered to represent the strongest form of evidence in assessing whether a particular healthcare intervention works. However, little attention has been paid to the fact that people treated in large multicentre randomised trials may not accurately reflect the population receiving the drug in real world settings.

Recently, van Staa and colleagues assessed the external validity of published cost effectiveness studies of selective cyclo-oxygenase-2 (COX 2) inhibitors by comparing the data used in these studies (typically from randomised trials) with observed clinical data.   2 The trial data suggested that the cost of avoiding one adverse gastrointestinal event by switching patients from conventional non-steroidal anti-inflammatory drugs to COX 2 inhibitors would be about $20 000 (£12 500; €14 000). However, when the same analysis was performed using the UK’s General Practice Research Database, comprising anonymised medical records of general practitioners, the cost of preventing one bleed was fivefold greater ($104 000). 2 The authors concluded that the published cost effectiveness analyses of COX 2 inhibitors neither had external validity nor represented the patients treated in clinical practice. They emphasised that external validity should be an explicit requirement for cost effectiveness analyses that are used to guide treatment policies and practices.

Efficacy versus effectiveness

This striking difference between the results from randomised trials and the real world clinical implications was recognised by Archie Cochrane, the pioneering clinical epidemiologist. Almost 40 years ago, Professor Cochrane introduced a specific hierarchy of evidence required from any healthcare intervention before it can be applied to real life situations (table ⇓ ). Three simple questions summarise Cochrane’s scheme: can it work (efficacy)? does it work (effectiveness)? and is it worth it (cost …

Human Vaccines
Volume 7, Issue 5    May 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/4/

NEWS, POLICY AND PROFILES
Response to Commentaries
Open Access Article
Donald W. Light

Extract
Human Vaccines has assembled a set of high quality, important commentaries on my policy analysis and concerns about the future of GAVI and its Advanced Market Commitment (AMC). Several affirm the value of GAVI in raising funds and playing a key role in immunizing millions more children than before, and I fully agree. The real worries concern their current and upcoming use of donations….

Human Vaccines
Volume 7, Issue 5    May 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/4/

RESEARCH PAPERS
Projecting the effectiveness of RotaTeq® against rotavirus-related hospitalizations and deaths in 6 Asian countries
Open Access Article
Antoine El Khoury, T. Christopher Mast, Max Ciarlet, Leona Markson and Michelle Goveia

RotaTeq is an oral pentavalent rotavirus vaccine (RV5) that has shown high and consistent efficacy in preventing rotavirus gastroenteritis (RGE) in randomized clinical trials conducted mostly in industrialized countries. We projected the effectiveness of RV5 against RGE-related hospitalizations and deaths in 6 Asian countries by using a simple mathematical model. Model inputs included rotavirus surveillance data collected 2006-2007 in China, 2001-2002 in Hong Kong, 2005-2007 in India, 2005-2007 in South Korea, 2005-2007 in Taiwan, and 2001-2003 in Thailand; the numbers of rotavirus-related deaths in each country; and published rotavirus serotype-specific efficacy of RV5. The model projected an overall effectiveness in the region of 82% to 89% against RGE-related hospitalizations and a substantial reduction in RGE-related deaths, suggesting that RV5 could substantially reduce the burden of rotavirus disease in Asia.

Human Vaccines
Volume 7, Issue 5    May 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/4/

Commentaries
Application of ‘Public Health Epidemiological Logic’ in devising a vaccination policy: A broad public health criteria-for routine Immunization
Rajan R. Patil

There is a need to develop clear cut public health criteria for consideration of new vaccines for use in public health. Most of the vaccines which have become recently available or will soon be available are mostly recommended for use in clinical/office practice. A new vaccine that is highly recommended for use in clinical setting may not be effective at all for larger public health use or may even lack rationale to put it in use for public health. It is stressed that a new vaccine which is proven to be good clinical tool for preventing particular disease at individual level need not necessarily be good public health tool in combating the same disease at community level.
The present paper takes a closer look at the logical basis for use of any vaccine in public health. Rabies vaccine is used as a case study to set the background to scrutinize the criteria for eligibility for considering any new vaccine to be included in routine immunization program A rough & ready algorithm is proposed as a check list for a new vaccine as a likely candidate for inclusion in Universal immunization programme. The suggested new algorithm is basically a public health criteria called as Public Health Epidemiological Logic [PHEL] Criteria.. The public health debate and the arguments against inclusion of Rabies vaccine in routine national immunization programme in India is a argued in the frame work of PHEL criteria in this paper Rabies vaccine to drive home the point, that a vaccine which is a good clinical tool need not always be a good public health tool, where as a vaccine which is proven to be a good public health tool will always invariably be a good clinical tool as well.

JAMA   
May 4, 2011, Vol 305, No. 17, pp 1733-1824
http://jama.ama-assn.org/current.dtl

Brief Report
Availability of Comparative Efficacy Data at the Time of Drug Approval in the United States
Nikolas H. Goldberg, Sebastian Schneeweiss, Mary K. Kowal, Joshua J. Gagne
JAMA. 2011;305(17):1786-1789.doi:10.1001/jama.2011.539

Abstract
Context Comparative effectiveness is taking on an increasingly important role in US health care, yet little is known about the availability of comparative efficacy data for drugs at the time of their approval in the United States.

Objective To quantify the availability of comparative efficacy data for new molecular entities (NMEs) approved in the United States.

Data Sources Approval packages publicly available through the online database of drug products approved by the US Food and Drug Administration (FDA).

Study Selection Identification of efficacy studies that supported approval of each NME approved by FDA between 2000 and 2010.

Data Extraction We determined whether eligible studies were head-to-head active controlled trials and whether the results of such studies were available in the approval packages. We recorded the approved indication, whether the NME was an orphan product, whether the NME had undergone priority review, and whether the control group was a specific active comparator or standard care.

Results Of 197 NMEs identified that met eligibility criteria, 100 (51% [95% confidence interval {CI}, 44%-58%]) met criteria for having comparative efficacy data available at the time of market authorization. After excluding NMEs designated as orphan products (n = 37) and those approved for indications for which no alternative treatments existed (n = 17), this proportion increased to 70% (95% CI, 62%-77%). The proportions of NMEs with available comparative efficacy data varied widely by therapeutic area, from 33% (95% CI, 9%-67%) for hormones and contraceptives to 89% (95% CI, 56%-99%) for diabetes medications.

Conclusion Publicly available FDA approval packages contain comparative efficacy data for about half of NMEs recently approved in the United States and for more than two-thirds of NMEs for which alternative treatment options exist. We did not investigate the extent to which available comparative efficacy information is useful for clinical guidance.

JAMA   
May 4, 2011, Vol 305, No. 17, pp 1733-1824
http://jama.ama-assn.org/current.dtl

Commentaries
What Next for QALYs?
Peter J. Neumann
JAMA. 2011;305(17):1806-1807.doi:10.1001/jama.2011.566

Extract
The quality-adjusted life-year (QALY) has come under fire lately. In the United States, health reform legislation prohibited use of cost-per-QALY thresholds. 1 The United Kingdom has proposed that the National Institute for Health and Clinical Excellence (NICE), which has influenced reimbursement through cost-per-QALY ratios, will not in the future use such information to make yes or no recommendations; instead NICE’s cost-effectiveness assessments would provide an input into price negotiations for technologies. 2 In Germany, the Institute for Quality and Efficiency in Health Care implemented a new system for evaluating the value of medical technologies but rejected the cost-per-QALY model on ethical and methodological grounds. 3 Many countries (including France, Spain, and Italy) have opted for other approaches. Other articles have criticized use of QALYs. 4, 5

The drawbacks of QALYs are well known. QALYs represent health over time as a series of preference-weighted health states, for which the preference …

The Lancet  
May 07, 2011  Volume 377 Number 9777  Pages 1543 – 1624
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Financing HPV vaccination in developing countries
The Lancet

Preview
5 years have passed since the first vaccines against the human papillomaviruses (HPV) that cause cervical cancer came onto the market. At the end of 2010, 33 countries had national HPV immunisation programmes. However, few of these initiatives were in developing countries and none were in Africa.

Nature Medicine
May 2011, Volume 17 No 5
http://www.nature.com/nm/index.html

News
Russia pledges $4 billion for Pharma-2020 plan – p517
Gary Peach
doi:10.1038/nm0511-517

Russia’s biomedical industry is woefully underdeveloped, accounting for only 0.2% of the world market. But plans are afoot to change that. Speaking at the opening of a new birth center in Ryazan on 11 March, for example, Prime Minister Vladimir Putin stated that the government wants to boost Russia’s presence on the world biopharma stage to 3–5% in the next decade. And he emphasized that the country already possesses the necessary academic and research institutions to achieve that. “We need to come up with measures to stimulate demand for Russia-made biotechnological products and remove barriers that often prevent businesses from working,” he said.

To that end, Russian leaders announced in March that they have approved 120 billion rubles ($4 billion) for a strategic investment program aimed at developing the country’s massively import-dependent pharmaceutical and medical supplies industries.

Dubbed Pharma-2020, the program—which was adopted two years ago although financing was only approved by the government last month—will attempt to boost output of local medicines, in gross sales terms, from nearly 25% last year to 50% by 2020. In addition, the program calls for ensuring that 90% of vital medicines are domestically produced, retooling some 160 companies to good manufacturing practice standards, establishing ten research and development centers that will focus on creating innovative products and boosting exports to $100 million.

Like nearly all of Russia’s state-driven initiatives, Pharma-2020 sets seemingly unattainable targets. Still, some insiders believe it is realistic. “Everyone acknowledges that it’s an ambitious program, but, considering the amount of construction work going on right now, and the state funds being allocated, then this task is manageable,” says Nikolai Bespalov, an analyst at Pharmexpert, a Moscow-based market research center.

Others have reservations. “I perceive the program as a document and not much more.      The strategy is written, the concept approved, but there are more acute problems that could be solved today without strategies and concepts, such as the low level of domestic products in state purchases,” says Viktor Dmitriev, director of the Association of Russian Pharmaceutical Manufacturers, based in Moscow.