The WHO continues to issue regular updates on both A/(H1N1) and A/(H5N1) posted on the WHO main page, as well as other advisories linked from that page. Here are the current updates:

– Pandemic (H1N1) 2009 – update 58
6 July 2009 – The title of this update has now evolved to “Pandemic (H1N1) 2009.” WHO notes 94,512 officially reported cases of influenza A(H1N1) infection (up from 59,814 a week ago and 44,287 a week earlier), including 429 deaths (up from 263 a week ago and 180 a week earlier).
http://www.who.int/csr/don/2009_07_06/en/index.html
WHO has included an interactive “timeline of all cases” (requires Flash player) at:
http://gamapserver.who.int/h1n1/atlas.html?select=ZZZ&filter=filter4,confirmed

– Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO
2 June 2009  [No update since 2 June 2009]
The published tabular chart reports 436 confirmed cases (up from 433 cases reported as of 2 June 2009) and 262 deaths (unchanged from the 2 June 2009 report).
http://www.who.int/csr/disease/avian_influenza/country/cases_table_2009_06_02/en/index.html

The Weekly Epidemiological Record (WER) for 3 July 2009, vol. 84, 27 (pp 261–280) includes: Human infection with new influenza A (H1N1) virus: WHO Consultation on suspension of classes and restriction of mass gatherings to mitigate the impact of epidemics caused by influenza A (H1N1), May 2009; Progress towards the 2012 measles elimination goal in WHO’s Western Pacific Region, 1990–2008, and Monthly report on dracunculiasis cases, January– May 2009

http://www.who.int/wer/2009/wer8427.pdf

The White House announced that it will host an all-day H1N1 Flu Preparedness Summit with states to further prepare this nation for the possibility of a more severe outbreak of H1N1 flu. Health and Human Services Secretary Kathleen Sebelius, Homeland Security Secretary Janet Napolitano, Education Secretary Arne Duncan, and Homeland Security Advisor John Brennan will lead the Summit, to be held on July 9, 2009 at the Natcher Conference Center at the National Institutes of Health in Bethesda, Maryland. Secretary Sebelius said, “Scientists and public health experts forecast that the impact of H1N1 may well worsen in the fall – when the regular flu season hits, or even earlier, when schools start to open – which is only five or six weeks away in some cases. The goal of the Summit is to launch a national influenza campaign by bringing federal, state and local officials, emergency managers, educators and others together with the nation’s public health experts to build on and tailor states’ existing pandemic plans, share lessons learned and best practices during the spring and summer H1N1 wave, and discuss preparedness priorities.”

http://www.cdc.gov/media/pressrel/2009/a090702.htm

HHS Secretary Kathleen Sebelius announced that the United States will provide 420,000 treatment courses of Tamiflu (Oseltamavir) to the Pan-American Health Organization (PAHO) to fight the novel H1N1 influenza in Latin America and the Caribbean. Secretary Sebelius commented, “The U.S. is committed to supporting and enhancing the health security in the region by reducing transmission and severity of illness. Viruses know no borders. The U.S. recognizes that a novel virus such as the H1N1 is a burden borne by all nations, and all of us have a responsibility to help support one another in the face of this challenge.”  HHS said that on June 23 it received a request from PAHO to partner with the U.S. government to increase the PAHO stockpile of Tamiflu in the regional stockpile available for Latin America and the Caribbean countries. PAHO is working to ensure that its member countries have the capacity and resources to respond to outbreaks of H1N1. HHS holds approximately 50 million courses of antiviral medications in the Strategic National Stockpile (SNS). In April, HHS deployed 11 million treatment courses from the SNS to the states across the country to fight the H1N1 influenza. Since then, HHS has purchased antiviral drugs to replenish the SNS along with an additional 2 million treatment courses.

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20090702005463&newsLang=en

JAMA
Vol. 302 No. 1, pp. 7-108, July 1, 2009
http://jama.ama-assn.org/current.dtl

The Obligation to Participate in Biomedical Research
G. Owen Schaefer, BA; Ezekiel J. Emanuel, MD, PhD; Alan Wertheimer, PhD

The current prevailing view is that participation in biomedical research is above and beyond the call of duty. While some commentators have offered reasons against this, we propose a novel public goods argument for an obligation to participate in biomedical research. Biomedical knowledge is a public good, available to any individual even if that individual does not contribute to it. Participation in research is a critical way to support an important public good. Consequently, all have a duty to participate. The current social norm is that individuals participate only if they have a good reason to do so. The public goods argument implies that individuals should participate unless they have a good reason not to. Such a shift would be of great aid to the progress of biomedical research, eventually making society significantly healthier and longer lived.

Journal of Infectious Diseases
1 August 2009  Volume 200, Number 3
http://www.journals.uchicago.edu/toc/jid/current

EDITORIAL COMMENTARY
A Malaria Vaccine for Control: More Progress

Joel G. Breman1 and
Christopher V. Plowe2,3

1Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, and 2Howard Hughes Medical Institute and 3Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore

Journal of Infectious Diseases
1 August 2009  Volume 200, Number 3
http://www.journals.uchicago.edu/toc/jid/current

Perspective
“Prepandemic” Immunization for Novel Influenza Viruses, “Swine Flu” Vaccine, Guillain-Barré Syndrome, and the Detection of Rare Severe Adverse Events
David Evans, Simon Cauchemez, and Frederick G Hayden

The availability of immunogenic, licensed H5N1 vaccines and the anticipated development of vaccines against “swine” influenza A(H1N1) have stimulated debate about the possible use of these vaccines for protection of those exposed to potential pandemic influenza viruses and for immunization or “priming” of populations in the so‐called “prepandemic” (interpandemic) era. However, the safety of such vaccines is a critical issue in policy development for wide‐scale application of vaccines in the interpandemic period. For example, wide‐scale interpandemic use of H5N1 vaccines could lead to millions of persons receiving vaccines of uncertain efficacy potentially associated with rare severe adverse events and against a virus that may not cause a pandemic. Here, we first review aspects of the 1976 National Influenza Immunization Programme against “swine flu” and its well‐documented association with Guillain‐Barré syndrome as a case study illustration of a suspected vaccine‐associated severe adverse event in a mass interpandemic immunization setting. This case study is especially timely, given the recent spread of a novel influenza A(H1N1) virus in humans in Mexico and beyond. Following this, we examine available safety data from clinical trials of H5N1 vaccines and briefly discuss how vaccine safety could be monitored in a postmarketing surveillance setting.

Journal of Infectious Diseases
1 August 2009  Volume 200, Number 3
http://www.journals.uchicago.edu/toc/jid/current

Major Articles and Brief Reports
Parasites
Long–Term Safety and Efficacy of the RTS,S/AS02A Malaria Vaccine in Mozambican Children

Jahit Sacarlal, Pedro Aide, John J. Aponte, Montse Renom, Amanda Leach, Inácio Mandomando, Marc Lievens, Quique Bassat, Sarah Lafuente, Eusébio Macete, Johan Vekemans, Caterina Guinovart, Betuel Sigaúque, Marla Sillman, Jessica Milman, Marie-Claude Dubois, Marie-Ange Demoitié, Joelle Thonnard, Clara Menéndez, W. Ripley Ballou, Joe Cohen, and Pedro L. Alonso

Background.We previously reported that the RTS,S/AS02A vaccine had an acceptable safety profile, was immunogenic, and demonstrated efficacy against Plasmodium falciparum malaria disease for 21 months.

Methods.We conducted a randomized, controlled, phase 2b trial of RTS,S/AS02A in 2022 Mozambican children aged 1–4 years. We now report safety results for all randomized subjects and vaccine efficacy (VE) findings for children in the Manhiça area over the 45-month surveillance period.

Results.During the surveillance period, the VE(2.5–45) (VE over months 2.5–45 of surveillance) against a first or only episode of clinical malaria disease was 30.5% (95% confidence interval [CI], 18.9%–40.4%; ), and the VE(2.5–45) against all episodes was 25.6% (95% CI, 11.9%–37.1%; ). When the same period was considered, the VE(2.5–45) for subjects protected against severe malaria was 38.3% (95% CI, 3.4%–61.3%; ). At study month 45, the prevalence of P. falciparum was 34% lower in the RTS,S/AS02A group than in the control group (66 [12.2%] of 541 patients vs 101 [18.5%] of 547 patients) ( ).

Conclusion.These results show evidence that RTS,S/AS02A maintained protection during the 45‐month surveillance period, and they highlight the feasibility of developing an effective vaccine against malaria. In combination with other malaria‐control measures, such a vaccine could greatly contribute to reducing the intolerable global burden of this disease.

Trial registration.ClinicalTrials.gov identifiers NCT00197041 and NCT00323622.

Randomized, Double-Blind, Phase 2a Trial of Falciparum Malaria Vaccines RTS,S/AS01B and RTS,S/AS02A in Malaria-Naive Adults: Safety, Efficacy, and Immunologic Associates of Protection

Kent E. Kester, James F. Cummings, Opokua Ofori-Anyinam, Christian F. Ockenhouse, Urszula Krzych, Philippe Moris, Robert Schwenk, Robin A. Nielsen, Zufan Debebe, Evgeny Pinelis, Laure Juompan, Jack Williams, Megan Dowler, V. Ann Stewart, Robert A. Wirtz, Marie‐Claude Dubois, Marc Lievens, Joe Cohen, W. Ripley Ballou, D. Gray Heppner, Jr., and the RTS,S Vaccine Evaluation Group

Background.To further increase the efficacy of malaria vaccine RTS,S/AS02A, we tested the RTS,S antigen formulated using the AS01B Adjuvant System (GlaxoSmithKline Biologicals).

Methods.In a double‐blind, randomized trial, 102 healthy volunteers were evenly allocated to receive RTS,S/AS01B or RTS,S/AS02A vaccine at months 0, 1, and 2 of the study, followed by malaria challenge. Protected vaccine recipients were rechallenged 5 months later.

Results.RTS,S/AS01B and RTS,S/AS02A were well tolerated and were safe. The efficacy of RTS,S/AS01B and RTS,S/AS02A was 50% (95% confidence interval [CI], 32.9%–67.1%) and 32% (95% CI, 17.6%–47.6%), respectively. At the time of initial challenge, the RTS,S/AS01B group had greater circumsporozoite protein (CSP)–specific immune responses, including higher immunoglobulin (Ig) G titers, higher numbers of CSP‐specific CD4+ T cells expressing 2 activation markers (interleukin‐2, interferon [IFN]–γ, tumor necrosis factor–α, or CD40L), and more ex vivo IFN‐γ enzyme‐linked immunospots (ELISPOTs) than did the RTS,S/AS02A group. Protected vaccine recipients had a higher CSP‐specific IgG titer (geometric mean titer, 188 vs 73 μg/mL; ), higher numbers of CSP‐specific CD4+ T cells per CD4+ T cells (median, 963 vs 308 CSP‐specific CD4+ T cells/ CD4+ T cells; ), and higher numbers of ex vivo IFN‐γ ELISPOTs (mean, 212 vs 96 spots/million cells; ). At rechallenge, 4 of 9 vaccine recipients in each group were still completely protected.

Conclusions.The RTS,S/AS01B malaria vaccine warrants comparative field trials with RTS,S/AS02A to determine the best formulation for the protection of children and infants. The association between complete protection and immune responses is a potential tool for further optimization of protection.

Trial registration.ClinicalTrials.gov identifier NCT00075049.

Pediatrics
July 2009 / VOLUME 124 / ISSUE 1
http://pediatrics.aappublications.org/current.shtml

Continued Impact of Pneumococcal Conjugate Vaccine on Carriage in Young Children
Susan S. Huang, MD, MPHa,b, Virginia L. Hinrichsen, MS, MPHc, Abbie E. Stevenson, BSd, Sheryl L. Rifas-Shiman, MPHc, Ken Kleinman, ScDc, Stephen I. Pelton, MDd, Marc Lipsitch, DPhile,f, William P. Hanage, PhDg, Grace M. Lee, MD, MPHc and Jonathan A. Finkelstein, MD, MPHc,h,i

OBJECTIVES: The goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (PCV7).

METHODS: Nasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to <7 years of age in primary care practices in 16 Massachusetts communities during the winter seasons of 2000–2001 and 2003–2004 and in 8 communities in 2006–2007. Antimicrobial susceptibility testing and serotyping were performed with S pneumoniae isolates.

RESULTS: We collected 678, 988, and 972 specimens during the sampling periods in 2000–2001, 2003–2004, and 2006–2007, respectively. Carriage of non-PCV7 serotypes increased from 15% to 19% and 29% (P < .001), with vaccine serotypes decreasing to 3% of carried serotypes in 2006–2007. The relative contribution of several non-PCV7 serotypes, including 19A, 35B, and 23A, increased across sampling periods. By 2007, commonly carried serotypes included 19A (16%), 6A (12%), 15B/C (11%), 35B (9%), and 11A (8%), and high-prevalence serotypes seemed to have greater proportions of penicillin nonsusceptibility. In multivariate models, common predictors of pneumococcal carriage, such as child care attendance, upper respiratory tract infection, and the presence of young siblings, persisted.

CONCLUSIONS: The virtual disappearance of vaccine serotypes in S pneumoniae carriage has occurred in young children, with rapid replacement with penicillin-nonsusceptible nonvaccine serotypes, particularly 19A and 35B. Except for the age group at highest risk, previous predictors of carriage, such as child care attendance and the presence of young siblings, have not been changed by the vaccine.

a Division of Infectious Diseases, University of California, Irvine School of Medicine, Irvine, California
b Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
c Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, Massachusetts
d Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts
Departments of e Epidemiology
f Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
g Department of Infectious Disease Epidemiology, Imperial College, London, England
h Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
i Division of General Pediatrics, Children’s Hospital Boston, Boston, Massachusetts

Vaccine
Volume 27, Issue 33, Pages 4381-4550 (16 July 2009)
http://www.sciencedirect.com/science/journal/0264410X

Cost-effectiveness of infant vaccination with RIX4414 (Rotarix™) in the UK
Pages 4520-4528
A. Martin, A. Batty, J.A. Roberts, B. Standaert
Abstract
This study estimated the cost-effectiveness of infant rotavirus vaccination with Rotarix™ in the UK, taking into account community rotavirus infections that do not present to the healthcare system. A Markov model compared the costs and outcomes of vaccination versus no vaccination in a hypothetical birth cohort of children followed over a lifetime, from a societal perspective and the perspective of the National Health Service (NHS). The model estimated costs and quality-adjusted life-years (QALYs) lost due to death, hospitalisation, general practitioner (GP) consultation, emergency attendance and calls to NHS Direct for rotavirus infection in children aged <5 years. Time lost from work and parents’ travel costs were also included in the societal perspective. The base case cost-effectiveness ratio for vaccination compared with no vaccination was £23,298/QALY from the NHS perspective and £11,459 from the societal perspective. In sensitivity analysis, the most important parameters were hospitalisation cost and number of GP consultations. Addition of Rotarix™ to the paediatric vaccination schedule would be a cost-effective policy option in the UK at the threshold range (£20,000–30,000/QALY) currently adopted by the National Institute for Health and Clinical Excellence.

The WHO continues to issue regular updates on both A/(H1N1) and A/(H5N1) posted on the WHO main page, as well as other advisories linked from that page. Here are the current updates:

– Influenza A(H1N1) – update 51
26 June 2009 — WHO notes 59814 officially reported cases of influenza A(H1N1) infection (up from 44,287 a week ago), including 263 deaths (up from 180 a week ago). http://www.who.int/csr/don/2009_06_26/en/index.html
WHO has included an interactive “timeline of all cases” (requires Flash player) at:
http://gamapserver.who.int/h1n1/atlas.html?select=ZZZ&filter=filter4,confirmed

– Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO
2 June 2009  [No update since 2 June 2009]
The published tabular chart reports 433 confirmed cases and 262 deaths.
http://www.who.int/csr/disease/avian_influenza/country/cases_table_2009_06_02/en/index.html

PATH and China National Biotec Group (CNBG), described as the leading vaccine manufacturer in China, announced a partnership “to speed the development of an effective vaccine at an affordable price to prevent pneumococcal disease.” The partnership involves a three-year project which will be implemented by Chengdu Institute of Biological Products (CDIBP), a subsidiary of CNBG based in Chengdu, Sichuan, with technical and financial support from PATH. The partners noted that current pneumococcal conjugate vaccines approved for use in children “are effective against strains common in the industrialized world and some developing countries, but they do not cover all pneumococcal serotypes, including several strains common in Africa and Asia. They are also expensive, which makes access to vaccines difficult in low-income countries that most urgently need them. More affordable vaccines with broader coverage are needed to ensure global access to vaccines, especially in developing countries.”

PATH’s pneumococcal vaccine development portfolio “includes a number of approaches to improve vaccine affordability and accessibility in the countries that most urgently need them. In addition to supporting the development of novel vaccines, one of PATH’s key strategies is to accelerate the advancement of low-cost vaccines by improving upon already-established technologies.” Dr. Mark Alderson, director of PATH’s Pneumococcal Vaccine Project, commented, “We are delighted to be partnering with CNBG/CDIBP in our efforts to develop a multivalent pneumococcal conjugate vaccine that can meet the needs of the poorest of the poor. Together, we hope to reduce manufacturing costs by pursuing a candidate that combines proven conjugation methods with new technologies developed by CNBG/CDIBP and other PATH partners. Furthermore, the regional and technical expertise of CNBG/CDIBP, which has successfully marketed a 23-valent polysaccharide pneumococcal vaccine in China, can be leveraged throughout this collaboration as we target strains more common in Asia and Africa.”

As part of a global access commitment, PATH and CNBG/CDIBP said they will design their pneumococcal vaccine candidate to meet the Advance Market Commitment (AMC) requirements, a financing mechanism established by the GAVI Alliance and the World Health Organization. PATH and CNBG/CDIBP said they “acknowledge that challenges lie ahead, particularly related to the complex process of conjugate vaccine development, but potential payoffs could be considerable. A successful outcome could provide broad protection and lead to low-cost mass production capabilities that could substantially increase global access to vaccines and save lives in millions from pneumococcal disease in countries where need is greatest.”

22 June 2009: http://www.path.org/news/pr090622-cdibp.php

GAVI said that the International Finance Facility for Immunisation Company (“IFFIm”) raised US$130 million for health and immunisation programmes through vaccine bonds offered to Japanese retail investors. This most recent offering of vaccine bonds by the International Finance Facility for Immunisation Company (“IFFIm”) “demonstrates Japanese investors’ continued support for IFFIm and its humanitarian purpose.” IFFIm raises funds that are used by the GAVI Alliance for health and immunisation programmes in 70 developing countries to protect millions of children against preventable diseases. This vaccine bond offering was arranged by HSBC Securities (Japan) Limited. For the first time, the bonds were sold through a group of 19 securities distributors and offered to retail investors online, enabling IFFIm to broaden its investor base, the media release noted.

http://www.gavialliance.org/media_centre/press_releases/2009_06_24_iffim_japan_strong_support.php

The GAVI Alliance, which has been hosted by UNICEF since it was launched in 2000, said it has GAVI  – the first organisation to receive such recognition under the new Swiss Host State Act. GAVI said the headquarters agreement allows the GAVI Alliance to “enjoy privileges and immunities similar to those enjoyed by other intergovernmental organisations in Switzerland.” Dr Julian Lob-Levyt, CEO of GAVI, said, “Through this recognition, Switzerland has shown its full support for our mission to save children’s lives and protect people’s health by increasing access to immunisation in the world’s poorest countries.”

Public-private partnership

http://www.gavialliance.org/media_centre/press_releases/2009_06_23_swiss_foundation.php

The Lancet
Jun 27, 2009   Volume 373  Number 9682  Pages 2171 – 2258
http://www.thelancet.com/journals/lancet/issue/current

Judicialisation of the right to health in Brazil
João Biehl, Adriana Petryna, Alex Gertner, Joseph J Amon, Paulo D Picon

Preview
Across Brazil, patients are turning to courts to access prescribed drugs. Brazil is one of at least 115 countries that recognise a constitutional right to health.1 An important part of this right is access to pharmaceutical drugs.2 Although Brazil has the developing world’s most advanced HIV/AIDS programme, many of its citizens still go to local pharmacies only to find that essential medicines are out of stock. Brazil is also one of the fastest growing pharmaceutical markets in the world. Doctors increasingly prescribe and patients demand new drugs, some of questionable benefit.

The Lancet
Jun 27, 2009   Volume 373  Number 9682  Pages 2171 – 2258
http://www.thelancet.com/journals/lancet/issue/current

Is disease eradication ethical?
Arthur L Caplan

Preview
For many in the field of public health, the eradication of smallpox was one of the greatest triumphs of 20th-century medicine. This astounding achievement has influenced national and international organisations to mount or consider efforts to eradicate many other infectious diseases, including measles, Guinea worm disease, Chagas’ disease, polio, and malaria. Eradication may well be public health’s greatest rhetorical weapon in the battle against dread diseases. Indeed, the ability to command funding, popular support, the attention of politicians, and positive media coverage by talk of disease eradication is unparalleled.

New England Journal of Medicine
Volume 360 — June 25, 2009 — Number 26
http://content.nejm.org/current.shtml

:
Ethical and Scientific Implications of the Globalization of Clinical Research

To the Editor: In their article, Glickman et al. (Feb. 19 issue)1 examine the growing phenomenon of clinical trials being conducted outside the regulatory framework of the developed world. They rightfully point out some of the ethical and scientific pitfalls of these investigations. However, they do not mention that the offshoring of clinical studies can also deprive critically ill patients in the developed world access to some of the latest drugs and devices, the underlying basic research for which was paid for through taxes by these same persons. Perhaps this issue, as opposed to paternalistic concerns about inadequate regulation within the Third World, represents the biggest ethical dilemma we confront in this era of research globalization.
John R. Adler, Jr., M.D.
Stanford University
Stanford, CA 94305
References
Glickman SW, McHutchison JG, Peterson ED, et al. Ethical and scientific implications of the globalization of clinical research. N Engl J Med 2009;360:816-823. [Free Full Text]

To the Editor: Glickman et al. imply that international outsourcing of clinical trials may compromise ethical and scientific integrity, but they fail to acknowledge an important safety net that does exist. The Food and Drug Administration (FDA) reviews results of studies regardless of their country of origin, and regulations require that the supporting clinical investigations performed under investigational-new-drug applications1 be held to the same standards regardless of whether the clinical sites are located in the United States. The FDA Guidance for Industry: Acceptance of Foreign Clinical Studies2 permits acceptance of data from a foreign clinical study “only if the study conforms to the ethical principles contained in the Declaration of Helsinki” or with laws and regulations of the country, whichever provide the greatest ethical protections. Aside from the ethical imperative, what is the economic advantage to the company of collecting poor-quality data that could compromise the final regulatory review? There is always room to improve regulatory capacity and training here and abroad, but this article dwells on potential insufficiencies rather than on the advantages of engaging international researchers to develop global products.
Charla A. Andrews, M.S.
Dale and Betty Bumpers Vaccine Research Center
Bethesda, MD 20892-3011
References
21 C.F.R. 312.23(a)(6)(b).
Guidance for industry: acceptance of foreign clinical studies. Rockville, MD: Food and Drug Administration, March 2001.

The authors reply: Adler points out the important implication that offshoring of clinical studies can deprive critically ill patients in high-income countries access to cutting-edge therapies. Research for these therapies, in particular, requires study designs that incorporate the complex environment of highly developed intensive and emergency care settings.1,2 More broadly, the current emphasis on translational research is based on the concept of bench-to-bedside research.3 This type of research may warrant special consideration in the globalization of clinical trials.

We agree with Andrews on the important safety net that the FDA provides in clinical studies outside the United States. Yet, the FDA has been challenged by “ever-expanding responsibilities in the face of a mostly flat annual budget.”4 Thus, we cannot count on the FDA alone to ensure the ethical underpinnings of the global clinical research process.

Since the publication of our article, we have been made aware of independent investigations into the clinical research process in low- and middle-income countries that have validated many of the concerns we expressed.5 At the same time, some of our colleagues in those countries have expressed concerns that our article calls into question the integrity of their work and our collaborations. This dichotomy underlies our basic concerns about the issues of ethical and research integrity in the globalization of clinical research. Currently, there is neither a global mechanism to identify investigators and institutions who strive to meet the highest ethical and scientific standards for clinical research nor a systematic means of tracking those who have violated these standards.     We believe that implementing the recommendations in our article will help to remedy this situation.

Greater international cooperation among industry sponsors, contract research organizations, and interested governments could be used to further ensure the application of internationally established principles and policies in clinical research.

Seth W. Glickman, M.D., M.B.A.
Charles B. Cairns, M.D.
University of North Carolina
Chapel Hill, NC 27599

Kevin A. Schulman, M.D.
Duke University
Durham, NC 27710

References
Glickman SW, Anstrom K, Li L, et al. Challenges in enrollment of minority, pediatric, and geriatric patients in emergency and acute care clinical research. Ann Emerg Med 2008;51:775-780. [CrossRef][ISI][Medline]

Cobb JP, Cairns CB, Bulger E, et al. The United States Critical Illness and Injury Trials Group: an introduction. J Trauma (in press).

Zerhouni EA. Translational and clinical science — time for a new vision. N Engl J Med 2005;353:1621-1623. [Free Full Text]

Okie S. A to-do list for the new FDA commissioner. N Engl J Med 2009;360:1373-1378. [Free Full Text]

Hundley K. Testing grounds: our medicine at what cost? St. Petersburg Times. December 2008. (Accessed June 4, 2009, at http://www.tampabay.com/specials/2008/reports/india/.)