This pdf format includes all the posts for this date below:

Vaccines_The Week in Review_28 February 2011

The U.S. Supreme Court decided 6-2 to affirm a lower court ruling upholding the National Childhood Vaccine Injury Act. The Act prevents civil suits against manufacturers of FDA-approved childhood vaccines “based on a claim that a particular vaccine should have been designed differently.” The opinion of the Court in the case – Bruesewitz v. Wyeth – stated that “[The Vaccine Act] reflects a sensible choice to leave complex epidemiological judgments about vaccine design to the FDA and the National Vaccine Program rather than juries.”  In an amicus brief, the American Academy of Pediatrics and over 20 other professional and public health organizations argued that a ruling against Wyeth could “precipitate the same crisis that Congress sought to avert in passing the Vaccine Act: ‘the very real possibility of vaccine shortages, and, in turn increasing numbers of unimmunized children, and, perhaps, a resurgence of preventable diseases.’” The court’s opinion is available at: http://www.supremecourt.gov/opinions/10pdf/09-152.pdf.

The International Vaccine Institute (IVI) and Sanofi Pasteur announced “their intent to work together towards creating the conditions to make a dengue vaccine widely accessible to countries where this disease is endemic.” Dr. Ragnar Norrby, Chairman of the IVI Board of Trustees, said, “A dengue vaccine represents the most viable prevention tool in our quest to reduce the growing number of dengue infections occurring globally each year. We thank Sanofi Pasteur for their commitment to reducing the considerable burden placed on communities and health systems around the world due to dengue and dengue hemorrhagic fever.“ Earlier this month, the IVI announced the launch of the Dengue Vaccine Initiative, in collaboration with the Sabin Vaccine Institute, the Johns Hopkins University, and the World Health Organization. Through a $6.9 million grant from the Bill & Melinda Gates Foundation, DVI “will accelerate the availability and utilization of safe, affordable and broadly protective vaccines to combat dengue.”

http://www.ivi.org/event_news/news_view.asp?enid=118

WHO released the priorities for vaccine evaluations for prequalification for 2011-2012. The prioritization list below “is a tool published every two years by the WHO by the prequalification programme to guide decisions as to the vaccines on which to focus resources.” Vaccines are categorized in four groups: high, medium, low and no priority. The priority list was developed by consultation between WHO and the two United Nations purchasing agencies (UNICEF and the Pan American Health Organization Revolving Fund) which use the prequalification service for vaccines. The prioritization exercise takes into account needs from WHO programmes (e.g. polio, measles, rabies) and the International Health Regulations, as well as vaccines defined globally as priority for accelerated introduction.

WHO said that in the consultation process for the current list, vaccines were considered if, based on information available to the UN purchasing agencies and WHO, they were already available in the market or were expected to become available during the biennium 2011-2012. The criteria used to assign priorities include:

a) Demand in the respective UN-supplied markets, with consideration given to plans for introduction;
b) WHO programmatic needs;
c) recommendations of WHO’s Strategic Advisory Group of Experts (SAGE) on immunization ; and
d) security of supplies: number, diversity, and production capacity of suppliers in the market.

Vaccines prequalification priority list 2011-12

– High priority vaccines

– Bivalent oral polio (bOPV1+3)

– DTwP based pentavalent combination (fully liquid DTwP-Hep B-Hib)

– Inactivated polio (IPV)

– Meningococcal A-containing conjugate

– Meningoccocal AC-containing polysaccharide

– Meningococcal W-containing polysaccharide

– Meningococcal W-containing conjugate

– Pneumococcal conjugate

– Rotavirus

– Trivalent oral polio (tOPV)

– Yellow fever

Vaccines of high programmatic interest but not available for supply in January 2011 (e.g. dengue; malaria; and new formulations of current vaccine types with enhanced stability outside of the currently accepted storage conditions) may be considered as high priority if they become available before the end of the period for which the list is in force.

http://www.who.int/immunization_standards/vaccine_quality/pq_priorities/en/index.html

WHO released the newest issue of Global Immunization News (25 February 2011) http://www.who.int/entity/immunization/GIN_February_2011.pdf Included in this issue:

ANNOUNCEMENTS FROM THE SIVAC INITIATIVE

25/02/2011 from Julia Blau, AMP

The briefing described below is available in the Center of Expertise on the NITAG Resource

– The “Introduction to Health Economic Evaluations for NITAG members briefing” is an e-learning tool that provides NITAG members with a basic background on health economic evaluations applied to immunization. It contains 4 modules of 10 to 40 minutes each:

– Module 1: The usefulness of economic evaluations for public health

– Module 2: The different types of economic evaluations

– Module 3: The main methodological issues of an economic evaluation

– Module 4: Interpretation of cost-effectiveness ratios

http://www.nitag-resource.org/en/training/rapid-briefing.php

Twitter Watch

A selection of items of interest this week from a variety of twitter feeds from NGOs and other sources

SingerPeter Peter Singer
Great photo of polio vaccination @gatesfoundation! Is there an ethical obligation to complete polio eradication? Yes! http://bit.ly/dfbjT2
26 Feb

CDCgov CDC.gov
Protect your child against #rotavirus. #Vaccinate beginning at 2 months of age. http://go.usa.gov/g7A
25 Feb

USAID USAID
Podcast of Deputy Assistant Admin for Global Health Amie Batson on the importance of #vaccines: @GLOBALHEALTHorg http://tinyurl.com/643gtse
24 Feb

MalariaVaccine PATH MVI
RT @PATHtweets: RTS,S is the first malaria vaccine candidate to ever reach large-scale Phase 3 clinical testing. http://ow.ly/3XFed
22 Feb

British Medical Bulletin
Volume 96 Issue 1 December 2010
http://bmb.oxfordjournals.org/content/current

Articles
Sarah J. Whitehead and Shehzad Ali

Health outcomes in economic evaluation: the QALY and utilities
Br Med Bull (2010) 96(1): 5-21 first published online October 29, 2010 doi:10.1093/bmb/ldq033

Abstract
The quality-adjusted life year (QALY) is routinely used as a summary measure of health outcome for economic evaluation, which incorporates the impact on both the quantity and quality of life. Key studies relating to the QALY and utility measurement are the sources of data. Areas of agreement include the need for a standard measure of health outcome to enable comparisons across different disease areas and populations, and the methods used for valuing health states in utility measurement. Areas of controversy include the limitation of the QALY approach in terms of the health benefits it can capture, its blindness towards equity concerns, the underlying theoretical assumptions and the most appropriate generic preference-based measure of utility. There is growing debate relating to whether a QALY is the same regardless of who accrues it, and also the issue as to who should value health states. Research is required to further enhance the QALY approach to deal with challenges relating to equity-weighted utility maximization and testing the validity of underlying assumptions. Issues around choosing between condition-specific measures and generic instruments also merit further investigation.

British Medical Journal
26 February 2011 Volume 342, Issue 7795
http://www.bmj.com/content/current

Editorials
Pandemic influenza vaccines
John M Watson, Richard G Pebody
BMJ 342:doi:10.1136/bmj.d545 (Published 8 February 2011

Extract
Are protective, but are limited by delays in availability

Almost as soon as the new influenza A/H1N1 2009 virus was identified in April 2009, its pandemic potential was realised. 1 Immediate steps were taken by vaccine manufacturers, working with the World Health Organization’s network of influenza reference laboratories, and with regulatory and standardisation authorities, to develop a pandemic specific vaccine and manufacture enough to meet global needs. To make best use of the H1N1 antigen, low dose monovalent vaccines were developed with the addition of adjuvant to enhance immunogenicity. These vaccines became available towards the end of 2009. The first of several studies to assess the effectiveness of these pandemic influenza A/H1N1 vaccines, including the linked study (doi: 10.1136/bmj.c7297 ) by Skowronski and colleagues, 2 are now being published.

On the basis of the emerging epidemiological picture, pandemic vaccines were given to subsets of the population at higher risk of infection and severe disease according to national immunisation policies. In the United Kingdom, people with underlying health conditions that place them at increased risk from the complications of influenza, including those aged 65 years and over …

The Lancet
Feb 26, 2011  Volume 377  Number 9767  Pages 691 – 782
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Better spending needed for neglected diseases
The Lancet

Preview
Over the past decade, there has been a concerted effort, mainly by public and philanthropic organisations, to counter the neglect of developing world diseases by increasing funding for research and development. The Global Funding of Innovation for Neglected Diseases (G-FINDER) survey, now in its third year, does the valuable job of tracking this global investment. The latest survey covers 31 neglected diseases, including HIV, malaria, and tuberculosis as well as conditions such as leprosy and trachoma.

The Lancet
Feb 26, 2011  Volume 377  Number 9767  Pages 691 – 782
http://www.thelancet.com/journals/lancet/issue/current

Series
Towards achievement of universal health care in India by 2020: a call to action
K Srinath Reddy, Vikram Patel, Prabhat Jha, Vinod K Paul, AK Shiva Kumar, Lalit Dandona, for The Lancet

Preview
To sustain the positive economic trajectory that India has had during the past decade, and to honour the fundamental right of all citizens to adequate health care, the health of all Indian people has to be given the highest priority in public policy. We propose the creation of the Integrated National Health System in India through provision of universal health insurance, establishment of autonomous organisations to enable accountable and evidence-based good-quality health-care practices and development of appropriately trained human resources, the restructuring of health governance to make it coordinated and decentralised, and legislation of health entitlement for all Indian people.

PLoS Medicine
(Accessed 27 February 2011)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&document_count=1533&ct=1&SESSID=aac96924d41874935d8e1c2a2501181c#results

Dengue Vaccines Regulatory Pathways: A Report on Two Meetings with Regulators of Developing Countries
Richard Mahoney, Liliana Chocarro, James Southern, Donald P. Francis, John Vose, Harold Margolis Policy Forum, published 22 Feb 2011
doi:10.1371/journal.pmed.1000418

Summary Points
– Because a dengue vaccine should be tetravalent in nature and provide protection against all four dengue serotypes, regulatory agencies need to address additional issues associated with multi-valent vaccines such as interference between the vaccine serotypes.

– Safety assessment needs to account for the potential risk of inducing antibody-enhanced diseases (antibody-dependent enhancement).

– Because of the varying epidemiology and disease impact in different countries and regions, dengue vaccines will likely need to be evaluated in diverse populations initially in both the Americas and the Asia Pacific region.

– Several national regulatory authorities (NRAs) in endemic developing countries are likely to be engaged in review of both applications for clinical evaluation and for marketing of vaccines and they should receive support as appropriate.

– Manufacturers can submit a dossier to the European Medicines Agency for the Evaluation of Medicinal Products (EMA) for review (Scientific Opinion). This is possible due to the introduction of Article 58 of EMA’s regulation 726/2004 (within which the example of dengue is specifically mentioned). This Opinion could facilitate the review process by NRAs in developing countries. Manufacturers may also obtain scientific advice and protocol assistance from the EMA, which may facilitate later Article 58 review.

– The Developing Countries’ Vaccine Regulators Network recommends that consideration be given to agreements for joint reviews of clinical trial applications by similarly affected NRAs and also the review of applications for licensure in order to accelerate the launch and introduction of dengue vaccines. The NRAs would need to have access to the necessary expertise to review the quality and safety aspects of the license application.

– It is critical that improved standardized tests be introduced as soon as possible for the diagnosis of early infection and for the measurement of immune protection (requiring identification of a correlate of protection). The World Health Organization (WHO), through its Expert Committee on Biological Standardization, can evaluate and standardize such tests; in addition, WHO and its Collaborating Centers may also help ensure availability of necessary standards and reagents for use in the field.

Science
25 February 2011 vol 331, issue 6020, pages 975-1098
http://www.sciencemag.org/current.dtl

EDITORIAL:
Advancing Regulatory Science
Margaret A. Hamburg, Commissioner of the U.S. Food and Drug Administration

Summary
Ensuring the safety and quality of food and medical products has never been more complicated. Societies around the world face increasingly complex challenges that require harnessing the best available science and technology on behalf of patients and consumers. This effort requires a strong field of regulatory science to develop new tools, standards, and approaches that efficiently and consistently assess the safety, efficacy, quality, and performance of products. Yet, despite being a critical component of the scientific enterprise, regulatory science has long been underappreciated and underfunded.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 12 pp. 2227-2348 (9 March 2011)

Regular Papers
Human papillomavirus vaccine initiation among adolescent girls in high-risk communities Original Research Article
Pages 2235-2241
Sarah L. Guerry, Christine J. De Rosa, Lauri E. Markowitz, Susan Walker, Nicole Liddon, Peter R. Kerndt, Sami L. Gottlieb

Abstract
Background
We assessed human papillomavirus (HPV) vaccine uptake among adolescent girls, parents’ intentions to vaccinate daughters, and barriers and facilitators of vaccination in a population at elevated risk for cervical cancer.

Methods
Between October 2007 and June 2008, telephone surveys were conducted with randomly selected parents/guardians of 11–18 year old girls attending public middle and high schools serving economically disadvantaged populations in Los Angeles County.

Results
We surveyed 509 predominantly Hispanic (81%) and African American (16%) parents; 71% responded in Spanish. Overall, 23% reported their daughter had received ≥1 dose of HPV vaccine. Although 93% of daughters had seen a doctor in the past year, only 30% reported that a provider recommended HPV vaccine. Characteristics positively associated with odds of having initiated HPV vaccine were having heard of the vaccine (adjusted odds ratio [aOR] 2.6), belief in vaccine effectiveness (aOR 2.9), and doctor recommendation (aOR 48.5). Negative attitudes toward HPV vaccine (aOR 0.2) and needing more information about it (aOR 0.1) were negatively associated with vaccine initiation. Of those with unvaccinated daughters (n = 387), 62% said they “probably/definitely will” vaccinate within the next year and 21% were undecided or didn’t know; only 11% said they definitely won’t.

Conclusions
About one-quarter of adolescent girls in this at-risk community had initiated HPV vaccine by mid-2008. Provider recommendation was the single most important factor associated with vaccination. Because a substantial proportion of parents remain undecided about HPV vaccine, health care providers can play a key role by providing needed information and offering HPV vaccine to all eligible adolescents.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 11 pp. 2005-2226 (3 March 2011)

Meeting Report
Lessons from smallpox eradication campaign in Bihar State and in India
Pages 2005-2007
Mahendra Dutta, R.N. Basu

Abstract
Following several key breakthroughs during the mid-1960s under the global smallpox eradication programme namely, development of a thermo-stable vaccine, efficient and acceptable technique of it’s delivery by bifurcated needle and evolution of a strategy (in lieu of mass vaccination) of active case search and containment, an intensified campaign of smallpox eradication from India was successfully implemented during 1973–1975. A formidable battle was fought, particularly in Bihar state leading to the occurrence of last indigenous case on 17 May 1975. The rapid achievement of eradication of the scourge from India in a record time was hailed as unprecedented in public health history. The single key factor in the achievement was the sustained efforts of a band of national and international epidemiologists, supported by young medical interns heading mobile containment teams, working under trying field conditions.

Through the campaign several important lessons were learnt and innovations made. Important among these were: (i) need for refinement of tools, techniques, and strategies for attaining the objective; (ii) implementation of a time and target oriented campaign; (iii) support of adequate and dedicated short term personnel to supplement supervision and field activities; (iv) providing of flexible funding and a convenient disbursement procedure; (v) building private-public partnership; (vi) devising of simple innovations, based on feedback from field, to support activities; (vii) development of political commitment; (viii) improved communication from field to higher levels to enable action on recent information; (ix) regular periodic staff meetings at each administrative level to facilitate early recognition and correction of deficiencies; (x) mobilization of support from international community, whenever required.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 11 pp. 2005-2226 (3 March 2011)

Regular Papers
Vaccine eligibility and acceptance among ambulatory obstetric and gynecologic patients Original Research Article
Pages 2024-2028
Wendy S. Vitek, Aletha Akers, Leslie A. Meyn, Galen E. Switzer, Bruce Y. Lee, Richard H. Beigi

Abstract
Objective
To assess vaccine eligibility and factors associated with vaccine acceptance among ambulatory obstetric and gynecologic patients.

Methods
An anonymous office-based survey was administered to women seeking ambulatory obstetric and gynecologic care at a large women’s hospital from December 2007 to July 2008. Information collected included: demographics, medical and vaccination history, interest in receiving vaccines and attitudes towards vaccine providers. Vaccine eligibility was based on age and/or self-reported risk factors in accord with the 2007–2008 Center for Disease Control and Prevention (CDC) adult immunization schedule. Vaccine eligibility was examined using descriptive statistics, and demographic characteristics were compared using chi-squared analysis. A multivariable logistic regression model was developed to assess factors associated with participants’ willingness to accept vaccines from their obstetrician–gynecologist.

Results
A total of 1441 women completed the survey. The majority of participants (87%) would accept vaccines if recommended by their obstetrician–gynecologist. The primary factors associated with vaccine acceptance were having less than a high school education, being privately insured, currently being pregnant, reporting a history of vaccinations and previously receiving vaccinations from an obstetrician–gynecologist. A significant portion of participants were eligible for the hepatitis B, influenza and HPV vaccines (≥50% for each). The type of vaccine did not influence willingness to accept vaccines from an obstetrician–gynecologist.

Conclusion
A majority of women appear eligible for, and will accept, vaccinations regardless of specific vaccine, if recommended by their obstetrician–gynecologist. These findings justify ongoing efforts to expand immunization services offered by obstetrician–gynecologists.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 11 pp. 2005-2226 (3 March 2011)

From the patient perspective: The economic value of seasonal and H1N1 influenza vaccination Original Research Article
Pages 2149-2158
Bruce Y. Lee, Kristina M. Bacon, Julie M. Donohue, Ann E. Wiringa, Rachel R. Bailey, Richard K. Zimmerman

Abstract
Although studies have suggested that a patient’s perceived cost-benefit of a medical intervention could affect his or her utilization of the intervention, the economic value of influenza vaccine from the patient’s perspective remains unclear. Therefore, we developed a stochastic decision analytic computer model representing an adult’s decision of whether to get vaccinated. Different scenarios explored the impact of the patient being insured versus uninsured, influenza attack rate, vaccine administration costs and vaccination time costs. Results indicated that the cost of avoiding influenza was fairly low (with one driver being required vaccination time). To encourage vaccination, decision makers may want to focus on ways to reduce this time, such as vaccinating at work, churches, or other normally frequented locations.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 11 pp. 2005-2226 (3 March 2011)

Pandemic influenza A/H1N1 vaccination uptake among health care workers in Qatar: Motivators and barriers Original Research Article
Pages 2206-2211
Mohamed Ghaith Alkuwari, Nagah A. Aziz, Zaher A.S. Nazzal, Saad A. Al-Nuaimi

Abstract
Influenza A/H1N1 new vaccine helps control disease spread. Cross-sectional survey was conducted at PHC & Emergency Departments in Qatar to determine influenza A/H1N1 vaccination rate among HCWs and associated factors, 523 HCWs were enrolled. The study showed that 13.4% HCWs received vaccination. Feeling protected strongly influenced vaccination decision (OR = 14.5). Uncertainty about vaccine efficacy and fear of side effects strongly influenced decision to reject the vaccine (OR = 0.3 and 0.2 respectively). Vaccination coverage was very low. The most common barriers were uncertainty about vaccine efficacy and fear of side effects. Health authorities should build message highlighting how the benefit of vaccination outweighs risk.

This is a pdf version compiling all the posts below for this date:

Vaccines_The Week in Review_21 February 2011

The U.S. Department of Health and Human Services released a new National Vaccine Plan to “enhance coordination of all aspects of federal vaccine and immunization activities (and) to ensure that all Americans can access the preventive benefits of vaccines.”  HHS described that new plan as “a wide-ranging guide to innovating the nation’s vaccine system. It addresses such issues as research and development, supply, financing, distribution, safety, global cooperation, and informed decision-making among consumers and health care providers.” This is the first update of the National Vaccine Plan since the original version in 1994.

Bruce Gellin, M.D., M.P.H., Director of the National Vaccine Program Office and Deputy Assistant Secretary for Health, said, “This plan is a 10-year vision for the nation to more effectively prevent infectious diseases and reduce adverse reactions to vaccines. The plan is national in scope. Implementation will require a well-organized effort among stakeholders, including federal, state and local policymakers, health care providers, manufacturers, academia, philanthropic organizations, and the public.” HHS said next steps include “a series of regional meetings with stakeholders in the spring and summer of 2011, which will focus on how to implement the strategies laid out in the National Vaccine Plan. The final implementation plan will be completed by the end of 2011.”

Text of the new National Vaccine Plan: http://www.hhs.gov/nvpo/vacc_plan/.

http://www.businesswire.com/news/home/20110216006036/en/HHS-releases-strategic-plan-advance-vaccine-immunization

The Bill & Melinda Gates Foundation announced that Dr. Tachi Yamada president of the Foundation’s Global Health Program intends to retire from his position after serving for five years. Bill Gates, co-chair of the Gates Foundation, commented, “Tachi has done a great job of focusing our ability to create and deliver vaccines and other interventions to the people who need them the most. He has put our global health programs on a path to success, and we look forward to building on his work.” Dr. Margaret Chan, Director-General of the World Health Organization, said, “Tachi’s leadership has helped keep the global health community focused on results. He has built a long-lasting partnership with the WHO and we look forward to remaining deeply engaged with the Gates Foundation.” The Foundation said Dr. Yamada will remain in his role until June and that a global search for his successor is underway. Dr. Yamada said, “It has been my greatest privilege to be able to impact the lives of so many people in need. I will always cherish the friendship and collaboration of my outstanding colleagues who have been my partners in this endeavor.”

http://www.gatesfoundation.org/press-releases/Pages/tachi-yamada-to-leave-110214.aspx

Dr. Rajiv Shah, Administrator of the United States Agency for International Development (USAID) presented the most recent David E. Barmes Global Health Lecture on Tuesday, 15 February 2011 at NIH in Bethesda, Maryland. In his remarks, Dr. Shah noted USAID is:

– Recommitting to the Millennium Development Goals by building sustainable governance and delivery systems to support healthy and productive lives.

– Investing in country-owned models of inclusive growth and development in a focused set of countries that are well-governed, economically stable, globally connected and market-oriented.

– Developing and delivering scientific and technological breakthroughs.

The recorded videocast of Dr. Shah’s lecture is available here: Addressing Grand Challenges: The Role of Science in Global Health Development [VIDEO] The transcript is available here: Remarks by USAID Administrator Dr. Rajiv Shah

http://www.fic.nih.gov/news/events/barmeslecture.htm

The American Public Health Association adopted 17 policies at its 138th Annual Meeting 6-10 November 2010 in Denver. The newly adopted policies “address a broad range of public health concerns, from environmental health issues and public health education and workforce challenges to oral health prevention strategies and implications of immigration policy on public health outcomes.” Included was:

201014 Influenza vaccination of health workers — Supports implementation of requirements for all health workers to receive an annual influenza vaccination. Urges providers, employers and other organizations to implement comprehensive infection control programs, including vaccination training and education, housekeeping and standard respiratory precautions in keeping with infection control standards. Emphasizes that vaccination of health workers is important for their own protection, not just patient safety.

The full text of all policies are available at: http://www.apha.org/advocacy/policy/policysearch/

http://www.apha.org/about/news/pressreleases/2011/2010adoptedpolciesrelease.htm

The Weekly Epidemiological Record (WER) for 18 February 2011, vol. 86, 8 (pp 61–72) includes: Influenza A(H1N1) 2009 virus: current situation and postpandemic recommendations; Safety of rotavirus vaccines: postmarketing surveillance in the WHO Region of the Americas.

http://www.who.int/entity/wer/2011/wer8608.pdf

Twitter Watch
A selection of items of interest this week from a variety of twitter feeds from NGOs and other sources

gatesfoundation Gates Foundation
“We need a higher sense of urgency.” –@BillGates on the fight against #HIV and #AIDS: http://bit.ly/gQvhLj

PATHtweets PATH
“Relenting in the effort to finally defeat #malaria would be an abdication of our responsibility.”~ Dr. Christian Loucq http://ow.ly/3YEjM

CDCgov CDC.gov
Read the vision for vaccine science and policy over the next decade in @HHSgov’s National #VaccinePlan http://bit.ly/wvW0p

PATHtweets PATH
Injections without needles? PATH and partners are bringing “jet injection” to developing-country immunization programs. http://ow.ly/3XGth

EndPolioNow EndPolioNow
A longtime skeptic in the war against polio, Dr. Henderson has changed his mind. #polio http://cot.ag/gIVdm9

TBVI_EU TBVI
by TropMed_IntHlth
How can we eliminate #tuberculosis? Progress in TB vaccine research – New blogs http://tiny.cc/c8ch8

PATHtweets PATH
@MalariaVaccine RTS,S is the first malaria vaccine candidate to ever reach large-scale Phase 3 clinical testing. http://ow.ly/3XFed

WHO_Europe WHO/Europe
by whonews
WHO Epidemiological Brief 12: Importation of Wild Poliovirus and Response Measures in the European Region http://bit.ly/i7m8OY
nytimeshealth NYTimes Health

British Medical Journal
19 February 2011 Volume 342, Issue 7794
http://www.bmj.com/content/current

Features
Vaccines: Global HPV vaccination
Sophie Arie

[Initial article language]
Most deaths from cervical cancer occur in countries without the resources to screen, treat, or vaccinate against the disease. Sophie Arie explores what’s being done to make HPV vaccination available to low income countries

In roughly five years since they arrived on the market, vaccines against human papillomavirus (HPV), which causes cervical cancer, have been rapidly and widely adopted in countries that can afford to do so.

The United States and much of Europe have introduced vaccines for school age girls in addition to existing well established screening programmes for women. The vaccines—Cervarix, made by GlaxoSmithKline (GSK), and Gardasil, made by Merck—protect against the most common types of virus, which cause around 70% of all cervical cancers, but they are among the most expensive of all vaccines. Both companies say their prices reflect a major investment in research and development and relatively complex manufacturing processes. Pricing varies from country to country but the current price in the US for a three dose course of Cervarix is a little under $300 (£187; €222) for government health service providers and close to $360 for private healthcare providers.

In the developing world, however, the situation is very different. Nearly 530 000 women each year develop cervical cancer and 275 000 die from it. 2 More than 85% of those deaths occur in low and middle income countries, where cervical cancer is the most common type of cancer in women, but screening is usually available only to women who can afford it privately, and where there is little or no capacity to treat the disease, let alone the resources to invest in a vaccine.

More than 60% of women who contract the disease in the developing world die of it because of late detection. According to the World Health Organization, if current trends continue, the …

Health Affairs
February 2011; Volume 30, Issue 2
http://content.healthaffairs.org/content/30/2.toc

Policy & Pharmaceuticals
What Are The Respective Roles Of The Public And Private Sectors In Pharmaceutical Innovation?
Bhaven N. Sampat and Frank R. Lichtenberg
Health Aff February 2011 30:2332-339; doi:10.1377/hlthaff.2009.0917

Abstract
What are the respective roles of the public and private sectors in drug development? This question is at the heart of some policy proposals, such as those that would give the government a share of profits from drugs at least partly developed with federal research dollars. This paper provides empirical data on these issues, using information included in the patents on drugs approved between 1988 and 2005. Overall, we find that direct government funding is more important in the development of “priority-review” drugs—sometimes described as the most innovative new drugs—than it is for “standard-review” drugs. Government funding has played an indirect role—for example, by funding basic underlying research that is built on in the drug discovery process—in almost half of the drugs approved and in almost two-thirds of priority-review drugs. Our analyses should help inform thinking about the returns on public research funding—a topic of long-standing interest to economists, policy makers, and health advocates.

JAMA
February 16, 2011, Vol 305, No. 7, pp 645-732
http://jama.ama-assn.org/current.dtl

Commentaries
A Historical Perspective on Clinical Trials Innovation and Leadership: Where Have the Academics Gone?
David L. DeMets, Robert M. Califf
JAMA. 2011;305(7):713-714.doi:10.1001/jama.2011.175

[No abstract; initial article text per JAMA convention]

The randomized controlled trial (RCT), the gold standard for evaluating the balance of risk and benefit in medical therapies, first emerged as a key clinical research tool in the mid-20th century thanks to visionary leadership of agencies such as the US National Institutes of Health (NIH), the UK Medical Research Council, and academic research institutions. Since then, clinical trials activity has shifted from the NIH and academia into the purviews of the medical products industry and regulatory authorities. Recent emphasis on evidence-based medicine, patient-centered outcomes research, 1 and learning 2 and accountable 3 health care systems underscores the fact that most clinical trials fail to provide the evidence needed to inform medical decision making. However, the serious implications of this deficit are largely absent from public discourse, and a better balance between commercial interests and public health is critically needed….

Medical Decision Making (MDM)
January/February 2011; 31 (1)
http://mdm.sagepub.com/content/current

Cost-Effectiveness Analysis: Methods
Steven M. Shechter
Treatment Evolution and New Standards of Care: Implications for Cost-Effectiveness Analysis
Med Decis Making January/February 2011 31: 35-42, first published on March 30, 2010 doi:10.1177/0272989X10364849

Abstract
Background. Traditional approaches to cost-effectiveness analysis have not considered the downstream possibility of a new standard of care coming out of the research and development pipeline. However, the treatment landscape for patients may change significantly over the course of their lifetimes.

Objective. To present a Markov modeling framework that incorporates the possibility of treatment evolution into the incremental cost-effectiveness ratio (ICER) that compares treatments available at the present time.

Design. Markov model evaluated by matrix algebra. Measurements. The author evaluates the difference between the new and traditional ICER calculations for patients with chronic diseases facing a lifetime of treatment. Results. The bias of the traditional ICER calculation may be substantial, with further testing revealing that it may be either positive or negative depending on the model parameters. The author also performs probabilistic sensitivity analyses with respect to the possible timing of a new treatment discovery and notes the increase in the magnitude of the bias when the new treatment is likely to appear sooner rather than later. Limitations. The modeling framework is intended as a proof of concept and therefore makes simplifying assumptions such as time stationarity of model parameters and consideration of a single new drug discovery.

Conclusions. For diseases with a more active research and development pipeline, the possibility of a new treatment paradigm may be at least as important to consider in sensitivity analysis as other parameters that are often considered.

Medical Decision Making (MDM)
January/February 2011; 31 (1)
http://mdm.sagepub.com/content/current

Infectious Disease Modeling
Joseph R. Egan, Ian M. Hall, and Steve Leach
Stamping Out Fires! Controlling Smallpox with Targeted Mass Vaccination
Med Decis Making January/February 2011 31: 69-78, first published on May 18, 2010 doi:10.1177/0272989X10369003

Abstract
Background. More than 30 years have now passed since the last naturally occurring case of smallpox; however, the variola virus still exists in at least 2 locations. The possibility that any clandestine stocks could be used for bioterrorism is a continuing concern for the public health community.

Objective. Mathematical modeling is used to assess the impact of mass vaccination following a smallpox release when either standard public health controls are failing or political/public opinion is urging more comprehensive methods. Two mass vaccination strategies are considered: a blanket nationwide campaign v. an approach targeted only at those geographic areas that experience smallpox cases. The study evaluates which intervention strategy results in the fewest combined disease and vaccine-related deaths.

Results. Outbreaks that go unnoticed until up to 50 cases have occurred are optimally controlled with targeted mass vaccination of the affected administrative districts in the majority of scenarios considered. The number of people vaccinated is approximately two thirds fewer than when implementing a nationwide campaign. Similar results arise when contact tracing is either highly unsuccessful or reduced in favor of reallocating limited resources for a policy of mass vaccination.

Conclusions. Reactive nationwide mass vaccination remains a suboptimal strategy for controlling an expanding smallpox outbreak in all but the most extreme circumstances. Rather, targeted mass vaccination of affected areas is likely to result in fewer deaths. The vaccines administered are also likely to be much fewer because they would probably be distributed to a much smaller number of districts, thus relieving pressure on potentially stretched public health systems.

New England Journal of Medicine
February 17, 2011  Vol. 364 No. 7
http://content.nejm.org/current.shtml

Original Articles
Safety of Influenza A (H1N1) Vaccine in Postmarketing Surveillance in China
X.-F. Liang and Others

Background
On September 21, 2009, China began administering vaccines, obtained from 10 different manufacturers, against 2009 pandemic influenza A (H1N1) virus infection in priority populations. We aimed to assess the safety of this vaccination program.
Full Text of Background…

Methods
We designed a plan for passive surveillance for adverse events after immunization with the influenza A (H1N1) vaccine. Physicians or vaccination providers were required to report the numbers of vaccinees and all adverse events to their local Center for Disease Control and Prevention (CDC), which then reported the data to the Chinese CDC through the online National Immunization Information System’s National Adverse Event Following Immunization Surveillance System. Data were collected through March 21, 2010, and were verified and analyzed by the Chinese CDC.
Full Text of Methods…

Results
A total of 89.6 million doses of vaccine were administered from September 21, 2009, through March 21, 2010, and 8067 vaccinees reported having an adverse event, for a rate of 90.0 per 1 million doses. The age-specific rates of adverse events ranged from 31.4 per 1 million doses among persons 60 years of age or older to 130.6 per 1 million doses among persons 9 years of age or younger, and the manufacturer-specific rates ranged from 4.6 to 185.4 per 1 million doses. A total of 6552 of the 8067 adverse events (81.2%; rate, 73.1 per 1 million doses) were verified as vaccine reactions; 1083 of the 8067 (13.4%; rate, 12.1 per 1 million doses) were rare and more serious (vs. common, minor events), most of which (1050) were allergic reactions. Eleven cases of the Guillain–Barré syndrome were reported, for a rate of 0.1 per 1 million doses, which is lower than the background rate in China.
Full Text of Results…

Conclusions
No pattern of adverse events that would be of concern was observed after the administration of influenza A (H1N1) vaccine, nor was there evidence of an increased risk of the Guillain–Barré syndrome.
Full Text of Discussion…

Vaccine
Volume 29, Issue 10 pp. 1855-2004 (24 February 2011)
http://www.sciencedirect.com/science/journal/0264410X

Regular Papers
Emerging and continuing trends in vaccine opposition website content
Original Research Article  Pages 1874-1880
Sandra J. Bean

Abstract
Context
Anti-vaccination websites appeal to persons searching the Internet for vaccine information that reinforces their predilection to avoid vaccination for themselves or their children. Few published studies have systematically examined these sites.

Objectives
The aim of this study was to employ content analysis as a useful tool for examining and comparing anti-vaccination websites for recurring and changing emphases in content, design, and credibility themes since earlier anti-vaccination website content analyses were conducted.

Methods
Between February and May 2010, using a commonly available search engine followed by a deep web search, 25 websites that contained anti-vaccination content were reviewed and analyzed for 24 content, 14 design, and 13 credibility attributes.

Results
Although several content claims remained similar to earlier analyses, two new themes emerged: (1) the 2009 H1N1 epidemic threat was “manufactured,” and (2) the increasing presence of so-called “expert” testimony in opposing vaccination.

Conclusion
Anti-vaccination websites are constantly changing in response to the trends in public health and the success of vaccination. Monitoring the changes can permit public health workers to mount programs more quickly to counter the opposition arguments. Additionally, opposition claims commonly appeal to emotions whereas the supporting claims appeal to reason. Effective vaccine support may be better served by including more emotionally compelling content.

Value in Health
December 2010  Volume 13, Issue 8  Pages 863–1065
http://onlinelibrary.wiley.com/doi/10.1111/vhe.2010.13.issue-8/issuetoc

Policy Analysis
Willingness to Pay for a Quality-Adjusted Life-Year: The Individual Perspective (pages 1046–1055)
Ana Bobinac, N. J. A. Van Exel, Frans F. H. Rutten and Werner B. F. Brouwer
Article first published online: 3 SEP 2010 | DOI: 10.1111/j.1524-4733.2010.00781.x

ABSTRACT
Objective: The aim of this study was to elicit the individual willingness to pay (WTP) for a quality-adjusted life-year (QALY).

Methods: In a Web-based questionnaire containing contingent valuation exercises, respondents valued health changes in five scenarios. In each scenario, the respondents first valued two health states on a visual analog scale (VAS) and expressed their WTP for avoiding a decline in health from the better health state to the worse, using a payment scale followed by a bounded open contingent valuation question.

Analysis: WTP per QALY was calculated for QALY gains calculated using VAS valuations, as well as the Dutch EQ-5D tariffs, the two steps in the WTP estimations and each scenario. Heterogeneity in WTP per QALY ratios was examined from the perspective of: 1) household income; and 2) the level of certainty in WTP indicated by respondents. Theoretical validity was analyzed using clustered multivariate regressions.

Results: A total of 1091 respondents, representative of the Dutch population, participated in the survey. Mean WTP per QALY was €12,900 based on VAS valuations, and €24,500 based on the Dutch EuroQoL tariffs. WTP per QALY was strongly associated with income, varying from €5000 in the lowest to €75,400 in the highest income group. Respondents indicating higher certainty exhibited marginally higher WTP. Regression analyses confirmed expected relations between WTP per QALY, income, and other personal characteristics.

Conclusion: Individual WTP per QALY values elicited in this study are similar to those found in comparable studies. The use of individual valuations in social decision-making deserves attention, however.

This is the pdf version of Vaccines: The Week in Review  14 February 2011, aggregating all the posts for this date as below:

Vaccines_The Week in Review_14 February 2011

WHO announced the introduction of pneumococcal conjugate vaccine by the Government of Kenya with support from WHO and partners. Kenya is the fourth country to include the vaccine into its national immunization programme in the past three months, after Nicaragua, Sierra Leone and Yemen. WHO said the introduction comes less than two years after the same vaccine was introduced in industrialized countries. Dr Margaret Chan, WHO Director-General, commented, “The rapid roll-out of new-generation pneumococcal vaccine shows how innovation and technology can be harnessed, at affordable prices, to save lives in the developing world. The payback, as measured by reduced childhood mortality, will be enormous.”  http://www.who.int/immunization/newsroom/newsstory_new_gen_pneumo_vaccine_feb2011/en/index.html

IVI (International Vaccine Institute) announced the launch of the Dengue Vaccine Initiative (DVI), in collaboration with the Sabin Vaccine Institute, the Johns Hopkins University, and the World Health Organization “to support development of vaccines to control dengue fever, a widespread and expanding hemorrhagic fever that is endemic in most tropical and subtropical regions of the world.” DVI is supported by a US$6.9 million grant from the Bill & Melinda Gates Foundation, and “will accelerate the development and utilization of safe, affordable and broadly protective vaccines to combat dengue, a mosquito-borne infection which causes severe flu-like symptoms, and its potentially lethal complication dengue hemorrhagic fever, characterized by bleeding, plasma fluid leakage, and in severe cases shock and death.” Each year, an estimated 2 million people with dengue hemorrhagic fever require hospitalization representing a significant burden on the fragile healthcare systems of developing and endemic nations.

Dr. John Clemens, Director-General of IVI, commented, “We are extremely grateful for the Gates Foundation’s continued support of our critical work to promote the development of life-saving dengue vaccines and ensure their effective introduction. Dengue is an infection whose burden has increased sharply around the world. The global dengue community is on the eve of many important breakthroughs in dengue research and development, and I believe that we’ll make significant progress in controlling dengue within the decade.”

http://sabin.org/news-resources/releases/2011/02/10/dengue-vaccine-initiative-launched-raise-profile-dengue-and-promo

IFPMA “expressed the research-based pharmaceutical industry’s support for calls to extend the deadline for Least-Developed Countries to comply with the provisions of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS).” Mr. David Brennan, President of the IFPMA (International Federation of Pharmaceutical Manufacturers & Associations) and CEO of AstraZeneca, said, “We recognize the significant development challenges experienced by Least-Developed Countries and believe that an extension would be useful to allow for effective TRIPS implementation. Such an extension should be used to align implementation across all areas of technology, to ensure a consistent approach. Our industry continues to believe that effective Intellectual Property Rights are a crucial component of long-term economic development within these countries, and international organizations and national bodies should continue to provide technical assistance, based on specific in-country needs.”

http://www.ifpma.org/News/NewsReleaseDetail.aspx?nID=13819

The Weekly Epidemiological Record (WER) for 11 February 2011, vol. 86, 7 (pp 53–60) includes:

Meeting of the International Task Force for Disease Eradication – October 2010

http://www.who.int/entity/wer/2011/wer8607.pdf

GAVI’s Phase III (2011-15) Strategic Plan is posted. GAVI notes that the plan  has four goals, each supporting GAVI’s overall mission:

– Strategic goal 1: accelerate the uptake and use of underused and new vaccines;

– Strategic goal 2: contribute to strengthening the capacity of integrated health systems to deliver immunisation;

– Strategic goal 3: increase the predictability of global financing and improve the sustainability of national financing for immunisation;

– Strategic goal 4: shape vaccine markets.

The strategy also includes two cross-cutting areas: Monitoring and Evaluation, and Advocacy, Communication and Public Policy.

In November 2010, the GAVI Board approved a business plan designed to implement the strategy and ensure that GAVI’s day-to-day activities deliver on its overall mission. The 2011-15 business plan includes:

– defined targets and goal-level indicators;

– 26 programme objectives with measurable deliverables;

– detailed activities and 2011-2012 budgets.

Strategy Table: http://www.gavialliance.org/resources/Strategy_2011_2015_Table.pdf

Business Plan: http://www.gavialliance.org/resources/Business_Plan_2011_2015.pdf

http://www.gavialliance.org/vision/strategy/phase3/index.php

Twitter Watch
A selection of items of interest this week from a variety of twitter feeds from NGOs and other sources.

GAVIAlliance GAVI Alliance
T-1: 1 million children could be saved every year by fighting pneumonia. Find Out How: http://ht.ly/3VDEy

sabinvaccine Sabin Vaccine Inst.
#Dengue Vaccine Initiative formed 2 develop vaccines against infection which impacts 55% of the world: http://bit.ly/gAPEED

gatesfoundation Gates Foundation
Contest: Raise awareness on #vaccines & win $5K from @GOOD. Sky is the limit–start thinking now: http://bit.ly/dEuhIM

AIDSvaccine IAVI
Saddened by passing of HIV prevention advocate Matilda Mogale of Soweto. We honor her commitment to find an HIV vaccine http://bit.ly/h9dGoO

CDCgov CDC.gov
Be part of the U.S. polio success story: immunize & protect against polio. http://go.usa.gov/gli

malariaday2011 World Malaria Day
by FightingMalaria
#WorldMalariaDay2011 WHO Focus is capturing results achieved by all partners in the fight against #malaria http://bit.ly/g4M16f

British Medical Journal
12 February 2011 Volume 342, Issue 7793
http://www.bmj.com/content/current

Editorials
Postmarketing studies of drug safety
Sebastian Schneeweiss, Jerry Avorn

A European initiative could help bring more transparency and rigour to pharmacoepidemiology

In the early days of randomised clinical trials, their results could be manipulated in several ways—protocols could be altered in light of early findings, sponsors could exert undue influence over what could be published, and some “unfavourable” results could be suppressed entirely. In the United States, the creation of the government clinical trials website ( http://www.clinicaltrials.gov ) greatly contributed to minimising these threats to honest science. 1 But requiring similar consistency, rigour, and transparency has been more difficult with observational studies, because any person or company with modest resources can purchase a large database of health insurance claims and perform a variety of epidemiological analyses with little or no accountability for the transparency, rigour, or visibility of such work ⇓ .

In 2006, the European Medicines Agency took on this problem by creating the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) to provide registration, standardisation, and quality assurance for observational studies of the effects of drugs ( http://www.encepp.eu/ ). To qualify for the “ENCePP seal,” study organisers must agree to a code of conduct and transparency, meet a checklist of methodological standards, and agree to publicly post the study protocol as well as its results. 2

“Best practices” for the conduct of epidemiological studies of the safety of drugs are less well standardised than those developed over the …

JAMA
February 9, 2011, Vol 305, No. 6, pp 535-634
http://jama.ama-assn.org/current.dtl

Original Contributions
Maternal HIV Infection and Antibody Responses Against Vaccine-Preventable Diseases in Uninfected Infants
Christine E. Jones, Shalena Naidoo, Corena De Beer, Monika Esser, Beate Kampmann, Anneke C. Hesseling
JAMA. 2011;305(6):576-584.doi:10.1001/jama.2011.100

Abstract
Context
Altered immune responses might contribute to the high morbidity and mortality observed in human immunodeficiency virus (HIV)−exposed uninfected infants.

Objective
To study the association of maternal HIV infection with maternal- and infant-specific antibody levels to Haemophilus influenzae type b (Hib), pneumococcus, Bordetella pertussis antigens, tetanus toxoid, and hepatitis B surface antigen.

Design, Setting, and Participants
A community-based cohort study in Khayelitsha, Western Cape Province, South Africa, between March 3, 2009, and April 28, 2010, of 109 HIV-infected and uninfected women and their infants. Serum samples from 104 women and 100 infants were collected at birth and samples from 93 infants were collected at 16 weeks.

Main Outcome Measure
Level of specific antibody in mother-infant pairs at delivery and in infants at 16 weeks, determined by enzyme-linked immunosorbent assays.

Results
At birth, HIV-exposed uninfected infants (n = 46) had lower levels of specific antibodies than unexposed infants (n = 54) did to Hib (0.37 [interquartile range {IQR}, 0.22-0.67] mg/L vs 1.02 [IQR, 0.34-3.79] mg/L; P < .001), pertussis (16.07 [IQR, 8.87-30.43] Food and Drug Administration [FDA] U/mL vs 36.11 [IQR, 20.41-76.28] FDA U/mL; P < .001), pneumococcus (17.24 [IQR, 11.33-40.25] mg/L vs 31.97 [IQR, 18.58-61.80] mg/L; P = .02), and tetanus (0.08 [IQR, 0.03-0.39] IU/mL vs 0.24 [IQR, 0.08-0.92] IU/mL; P = .006). Compared with HIV-uninfected women (n = 58), HIV-infected women (n = 46) had lower specific antibody levels to Hib (0.67 [IQR, 0.16-1.54] mg/L vs 1.34 [IQR, 0.15-4.82] mg/L; P = .009) and pneumococcus (33.47 [IQR, 4.03-69.43] mg/L vs 50.84 [IQR, 7.40-118.00] mg/L; P = .03); however, no differences were observed for antipertussis or antitetanus antibodies. HIV-exposed uninfected infants (n = 38) compared with HIV-unexposed infants (n = 55) had robust antibody responses following vaccination, with higher antibody responses to pertussis (270.1 [IQR, 84.4-355.0] FDA U/mL vs 91.7 [IQR, 27.9-168.4] FDA U/mL; P = .006) and pneumoccocus (47.32 [IQR, 32.56-77.80] mg/L vs 14.77 [IQR, 11.06-41.08] mg/L; P = .001).

Conclusion
Among South African infants, antenatal HIV exposure was associated with lower specific antibody responses in exposed uninfected infants compared with unexposed infants at birth, but with robust responses following routine vaccination.

The Lancet
Feb 12, 2011   Volume 377  Number 9765  Pages 527 – 610
http://www.thelancet.com/journals/lancet/issue/current

Series
Emerging infectious diseases in southeast Asia: regional challenges to control
Richard J Coker, Benjamin M Hunter, James W Rudge, Marco Liverani, Piya Hanvoravongchai

Summary
Southeast Asia is a hotspot for emerging infectious diseases, including those with pandemic potential. Emerging infectious diseases have exacted heavy public health and economic tolls. Severe acute respiratory syndrome rapidly decimated the region’s tourist industry. Influenza A H5N1 has had a profound effect on the poultry industry. The reasons why southeast Asia is at risk from emerging infectious diseases are complex. The region is home to dynamic systems in which biological, social, ecological, and technological processes interconnect in ways that enable microbes to exploit new ecological niches. These processes include population growth and movement, urbanisation, changes in food production, agriculture and land use, water and sanitation, and the effect of health systems through generation of drug resistance. Southeast Asia is home to about 600 million people residing in countries as diverse as Singapore, a city state with a gross domestic product (GDP) of US$37 500 per head, and Laos, until recently an overwhelmingly rural economy, with a GDP of US$890 per head. The regional challenges in control of emerging infectious diseases are formidable and range from influencing the factors that drive disease emergence, to making surveillance systems fit for purpose, and ensuring that regional governance mechanisms work effectively to improve control interventions.

Nature
Volume 470 Number 7333 pp139-300  10 February 2011
http://www.nature.com/nature/current_issue.html

World View
Pharmaceutical industry must take its medicine

To fix the drug pipeline, governments must take on drug-makers instead of capitulating to their every demand, says Colin Macilwain.

New England Journal of Medicine
February 10, 2011  Vol. 364 No. 6
http://content.nejm.org/current.shtml

Perspective
Developing the Sentinel System — A National Resource for Evidence Development
R.E. Behrman and Others

[Free Full-Text]
The Food and Drug Administration (FDA) now has the capacity to “query” the electronic health information of more than 60 million people, posing specific questions in order to monitor the safety of approved medical products. This pilot program, called Mini-Sentinel, uses a distributed data network (rather than a centralized database) that allows participating health plans and other organizations to create data files in a standard format and to maintain possession of those files. These organizations perform most analyses of their own data by running computer programs distributed by a coordinating center, and they provide consistent summarized results for the FDA’s review.1 The principles and practices involved in this effort to improve the safety of medical products can inform other uses of electronic health information to answer additional important questions about health and health care.

When the FDA announced the Sentinel Initiative in May 2008, it established a vision and objectives for the program, including the development of the Sentinel System, which will eventually be able to search the electronic health data of a minimum of 100 million patients.2 Laying the groundwork for that system has required an extraordinary range of input from public and private organizations. Under a cooperative agreement with the FDA, the Engelberg Center for Health Care Reform at the Brookings Institution has been convening an ongoing series of discussions among stakeholders to address the near- and long-term challenges inherent in implementing the Sentinel System.3 In 2009, the FDA gave the Harvard Pilgrim Health Care Institute the lead role in fulfilling a 5-year contract to establish a system — the Mini-Sentinel — for developing and testing approaches and methods that could be used to inform the structure and operations of the full Sentinel System. The institute is now leading a diverse partnership of approximately 200 epidemiologists, clinical content experts, statisticians, and data specialists from 27 institutions that are participating in this pilot system (www.minisentinel.org).

Through the Mini-Sentinel, capabilities are being developed for actively monitoring the safety of approved medical products using the electronic health information in claims systems, inpatient and outpatient medical records, and patient registries. The Mini-Sentinel builds on the work of the Vaccine Safety Datalink project (managed by the Centers for Disease Control and Prevention), the HMO Research Network, the Population Medicine Distributed Research Network (PopMedNet, funded by the Agency for Healthcare Research and Quality), and the Observational Medical Outcomes Partnership, among others.4

In the first year of the Mini-Sentinel project, its leaders established a network of data partners and a system with robust patient-privacy policies that could be used in querying the network’s databases. The initiative’s distributed data network allows each data partner to maintain physical and operational control over its own patient-level data, while providing the aggregated information needed to address the FDA’s questions. Source data reside behind the data partners’ institutional firewalls, where they are transformed into a standard format. This approach allows each data partner to answer the FDA’s queries by executing standardized computer programs distributed by the Mini-Sentinel Operations Center. A typical result might include the number of new users of a product who experience a particular outcome, grouped according to age, sex, other treatments, and health status. This use of distributed analysis — whenever possible — eliminates or greatly reduces the exchange of protected health information. The data partners can obtain full-text medical records when necessary to confirm diagnoses or exposures and to determine the existence or severity of risk factors.

The initial focus of Mini-Sentinel has been on developing the ability to use claims data. In the next year, laboratory-test results and vital signs, derived from electronic health records and clinical laboratory records, will be added. The partnership is also evaluating procedures whereby Mini-Sentinel data partners will be able to link to data held by other organizations, such as state immunization registries and device registries.

The FDA will soon begin to actively monitor the data, seeking answers to specific questions about the performance of medical products, such as the frequency of myocardial infarction among users of oral hypoglycemic agents (a topic selected because it has been difficult to identify drug-induced myocardial infarction through existing prospective surveillance mechanisms). The FDA will also monitor the occurrence of adverse events associated with select routinely administered vaccines. Using the Mini-Sentinel system, the FDA will also be able to obtain rapid responses to new questions about medical products and, eventually, to evaluate the health effects of its regulatory actions. This monitoring portfolio will expand as the FDA and its collaborators acquire experience and develop operational efficiencies and as additional data resources become available.

The distributed-database-and-analysis model and the infrastructure of the Mini-Sentinel data network can be extended to other forms of evidence development. Provisions in the economic stimulus and health care reform legislation, and a recent report from the President’s Council of Advisors on Science and Technology,5 envision expanded use of electronic health information for other types of public health surveillance, quality measurement, comparative effectiveness research, and biomedical research — all of which are essential to improving the country’s health and health care delivery system.

Issues relevant to other secondary uses of electronic health information include recruitment of appropriate data partners, development and refinement of analytic methods, implementation of standards to ensure that analytic methods are consistent across the data sources, and above all, protection for the rights and privacy of patients. Data privacy and security are top priorities that were key considerations in the decision to build Mini-Sentinel as a system that uses a distributed data system and distributed analysis whenever possible. The committed collaboration among representatives of patients and consumers, health care professionals, Mini-Sentinel’s data partners and safety scientists, and the medical-products industry has been essential to the Sentinel Initiative’s progress.

It is particularly challenging to establish appropriate governance for a distributed data network that can support multiple secondary uses for health information. The current infrastructure is supported by a single federal agency, the FDA, and all the data are provided by private organizations, yet potential users of such a system reside not only broadly in government but also in academia, the private sector, and other user communities. To facilitate the development of this infrastructure into a national resource, this distributed system may ultimately be best managed by a consortium of interested parties operating as a public–private partnership. For example, specialized network-coordinating centers might rely on a consistent infrastructure to use the same sources of health information for various purposes, including public health uses, effectiveness research, quality measurement, and health services research.

The envisioned Sentinel System will build on the knowledge, partnerships, data resources, privacy protections, and technical capabilities that are being developed in the Mini-Sentinel program. Success in the form of improved safety of medical products will depend on the continued engagement of all concerned stakeholders and on ensuring that patients, consumers, and health care providers understand that all medical products pose risks and that postmarketing surveillance is critical to expanding the limited evidence base that exists when products are approved. Success also depends on the continued development of surveillance methods and on increasing the workforce of scientists who are trained to develop and interpret this evidence effectively.

Health care data represent a precious resource that must be used to the fullest possible extent to promote the public health, while the rights of patients and consumers are protected. As an early working model for secondary uses of data produced in the routine delivery of health care, the Sentinel System can and should become a national resource for evidence development and a cornerstone of a learning health care system.

This article (10.1056/NEJMp1014427) was published on January 12, 2011, at NEJM.org.

New England Journal of Medicine
February 10, 2011  Vol. 364 No. 6
http://content.nejm.org/current.shtml

Special Article
The Role of Public-Sector Research in the Discovery of Drugs and Vaccines
A.J. Stevens and Others

Background
Historically, public-sector researchers have performed the upstream, basic research that elucidated the underlying mechanisms of disease and identified promising points of intervention, whereas corporate researchers have performed the downstream, applied research resulting in the discovery of drugs for the treatment of diseases and have carried out development activities to bring them to market. However, the boundaries between the roles of the public and private sectors have shifted substantially since the dawn of the biotechnology era, and the public sector now has a much more direct role in the applied-research phase of drug discovery.
Full Text of Background…

Methods
We identified new drugs and vaccines approved by the Food and Drug Administration (FDA) that were discovered by public-sector research institutions (PSRIs) and classified them according to their therapeutic category and potential therapeutic effect.
Full Text of Methods…

Results
We found that during the past 40 years, 153 new FDA-approved drugs, vaccines, or new indications for existing drugs were discovered through research carried out in PSRIs. These drugs included 93 small-molecule drugs, 36 biologic agents, 15 vaccines, 8 in vivo diagnostic materials, and 1 over-the-counter drug. More than half of these drugs have been used in the treatment or prevention of cancer or infectious diseases. PSRI-discovered drugs are expected to have a disproportionately large therapeutic effect.
Full Text of Results…

Conclusions
Public-sector research has had a more immediate effect on improving public health than was previously realized.

The Pediatric Infectious Disease Journal
March 2011 – Volume 30 – Issue 3  pp: A9-A10,187-272,e38-e55
http://journals.lww.com/pidj/pa     ges/currenttoc.aspx

Commentary
Anthroposophy: A Risk Factor for Noncompliance With Measles Immunization
Ernst, Edzard
Pediatric Infectious Disease Journal. 30(3):187-189, March 2011.
doi: 10.1097/INF.0b013e3182024274

[No abstract available]

The Pediatric Infectious Disease Journal
March 2011 – Volume 30 – Issue 3  pp: A9-A10,187-272,e38-e55
http://journals.lww.com/pidj/pa     ges/currenttoc.aspx

Measles in the United States During the Postelimination Era: Fiebelkorn AP, et al. J Infect Dis. 2010;202: 1520–1528
Pediatric Infectious Disease Journal. 30(3):226, March 2011.
doi: 10.1097/INF.0b013e31820b93c0

The Pediatric Infectious Disease Journal
March 2011 – Volume 30 – Issue 3  pp: A9-A10,187-272,e38-e55
http://journals.lww.com/pidj/pa     ges/currenttoc.aspx

Primary Care Pediatricians’ Perceptions of Vaccine Refusal in Europe
Grossman, Zachi; van Esso, Diego; del Torso, Stefano; Hadjipanayis, Adamos; Drabik, Anna; Gerber, Andreas; Miron, Dan
Pediatric Infectious Disease Journal. 30(3):255-256, March 2011.
doi: 10.1097/INF.0b013e3181faaaa3

Abstract:
An electronic survey assessing primary care pediatricians’ estimations and practices regarding parents’ vaccination refusal was sent to 395 members of the European Academy of Pediatrics Research in Ambulatory Setting network, with a response rate of 87%. Of respondents who vaccinate in the clinic, 93% estimated the total vaccine refusal rate as <1%. Of all respondents, 69% prefer a shared decision-making approach to handle refusing parents.

Pharmacoeconomics
March 1, 2011 – Volume 29 – Issue 3  pp: 173-268
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Commentary
Including Indirect Medical Care Costs from Survivor Years of Life in Economic Evaluations
Nyman, John A.; Jalal, Hawre J.
Pharmacoeconomics. 29(3):173-174, March 1, 2011.
doi: 10.2165/11588790-000000000-00000

Leading Article
Standardizing the Inclusion of Indirect Medical Costs in Economic Evaluations
van Baal, Pieter H.M.; Wong, Albert; Slobbe, Laurentius C.J.; Polder, Johan J.; Brouwer, Werner B.F.; de Wit, G. Ardine
Pharmacoeconomics. 29(3):175-187, March 1, 2011.
Abstract

A shortcoming of many economic evaluations is that they do not include all medical costs in life-years gained (also termed indirect medical costs). One of the reasons for this is the practical difficulties in the estimation of these costs. While some methods have been proposed to estimate indirect medical costs in a standardized manner, these methods fail to take into account that not all costs in life-years gained can be estimated in such a way. Costs in life-years gained caused by diseases related to the intervention are difficult to estimate in a standardized manner and should always be explicitly modelled. However, costs of all other (unrelated) diseases in life-years gained can be estimated in such a way.

We propose a conceptual model of how to estimate costs of unrelated diseases in life-years gained in a standardized manner. Furthermore, we describe how we estimated the parameters of this conceptual model using various data sources and studies conducted in the Netherlands. Results of the estimates are embedded in a software package called ‘Practical Application to Include future Disease costs’ (PAID 1.0). PAID 1.0 is available as a Microsoft® Excel tool (available as Supplemental Digital Content via a link in this article) and enables researchers to ‘switch off’ those disease categories that were already included in their own analysis and to estimate future healthcare costs of all other diseases for incorporation in their economic evaluations.

We assumed that total healthcare expenditure can be explained by age, sex and time to death, while the relationship between costs and these three variables differs per disease. To estimate values for age- and sex-specific per capita health expenditure per disease and healthcare provider stratified by time to death we used Dutch cost-of-illness (COI) data for the year 2005 as a backbone. The COI data consisted of age- and sex-specific per capita health expenditure uniquely attributed to 107 disease categories and eight healthcare provider categories. Since the Dutch COI figures do not distinguish between costs of those who die at a certain age (decedents) and those who survive that age (survivors), we decomposed average per capita expenditure into parts that are attributable to decedents and survivors, respectively, using other data sources.

Pharmacoeconomics
March 1, 2011 – Volume 29 – Issue 3  pp: 173-268
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Review Article
Cost Effectiveness of Pneumococcal Conjugate Vaccination against Acute Otitis Media in Children: A Review
Boonacker, Chantal W.B.; Broos, Pieter H.; Sanders, Elisabeth A.M.; Schilder, Anne G.M.; Rovers, Maroeska M.
Pharmacoeconomics. 29(3):199-211, March 1, 2011.
doi: 10.2165/11584930-000000000-00000

Abstract:
While pneumococcal conjugate vaccines have shown to be highly effective against invasive pneumococcal disease, their potential effectiveness against acute otitis media (AOM) might become a major economic driver for implementing these vaccines in national immunization programmes. However, the relationship between the costs and benefits of available vaccines remains a controversial topic. Our objective is to systematically review the literature on the cost effectiveness of pneumococcal conjugate vaccination against AOM in children.

We searched PubMed, Cochrane and the Centre for Reviews and Dissemination databases (Database of Abstracts of Reviews of Effects [DARE], NHS Economic Evaluation Database [NHS EED] and Health Technology Assessment database [HTA]) from inception until 18 February 2010. We used the following keywords with their synonyms: ‘otitis media’, ‘children’, ‘cost-effectiveness’, ‘costs’ and ‘vaccine’. Costs per AOM episode averted were calculated based on the information in this literature.

A total of 21 studies evaluating the cost effectiveness of pneumococcal conjugate vaccines were included. The quality of the included studies was moderate to good. The cost per AOM episode averted varied from €168 to €4214, and assumed incidence rates varied from 20 952 to 118 000 per 100 000 children aged 0–10 years. Assumptions regarding direct and indirect costs varied between studies. The assumed vaccine efficacy of the 7-valent pneumococcal CRM197-conjugate vaccine was mainly adopted from two trials, which reported 6–8% efficacy. However, some studies assumed additional effects such as herd immunity or only took into account AOM episodes caused by serotypes included in the vaccine, which resulted in efficacy rates varying from 12% to 57%. Costs per AOM episode averted were inversely related to the assumed incidence rates of AOM and to the estimated costs per AOM episode. The median costs per AOM episode averted tended to be lower in industry-sponsored studies.

Key assumptions regarding the incidence and costs of AOM episodes have major implications for the estimated cost effectiveness of pneumococcal conjugate vaccination against AOM. Uniform methods for estimating direct and indirect costs of AOM should be agreed upon to reliably compare the cost effectiveness of available and future pneumococcal vaccines against AOM.