Two important vaccine meetings were held September 11 and 12 at The College of Physicians of Philadelphia. The September 12 meeting entitled Research Integrity Challenges in Vaccine Development and Distribution for Public Health Emergencies was sponsored by the Department of Health and Human Services, the Office of Research Integrity, Drexel University, University of Pennsylvania Center for Bioethics, and The College of Physicians of Philadelphia.
Speakers focused on vaccine development and distribution for biological threats and how the emergency preparedness experiences with A/H1N1 provided lessons that might inform future preparation for similar public health emergencies.
Robin Robinson, PhD, Director of the Biomedical Advanced Research and Development Authority (BARDA), opened the session by outlining risks to research integrity in preparedness and response for biological threats. In particular, he noted the lessons learned during the continuing response to the HIV epidemic and the reactions to the anthrax situation of 2001, the SARS threat of 2003, and the re-emergence of H5N1 bird flu in 2003. Each situation put pressure on vaccine development, which in turn had the potential to influence research integrity. (For example, the determination of endpoints of vaccine clinical trials might be particularly vulnerable to pressures in an emergency.) Robinson suggested measures that could alleviate the pressures and ensure the integrity of research during a public health emergency; these included transparent public/private partnerships in vaccine and drug development and a national review board to approve studies in human subjects (to replace review boards based in the specific institutions that are conducting research). Finally, he stressed the importance in emergency situations of sharing data among various public and private entities, the need for response plans to include vaccine development for known and unknown pathogens, and the need to address special populations (such as the very young, the very old, those who live in rural populations, and minority populations) in response plans.
Robert Nelson, MD, PhD, Senior Pediatric Ethicist, Office of Pediatric Therapeutics, U.S. Food and Drug Administration, described the FDA pathways to vaccine licensure, including the traditional steps under which the 2009 A/H1N1 vaccine was produced. Because production of this vaccine was considered merely a strain change to the already-approved seasonal influenza vaccine, it proceeded through the established steps for influenza vaccine development, research, and release. (Nonetheless, Nelson and others noted that the A/H1N1vaccine underwent testing in excess of the requirements for seasonal influenza vaccine.)
In other situations when a new vaccine is needed, different licensure pathways are available. An accelerated pathway to approval may apply in the case of a life-threatening illness. If a new process will produce a vaccine with meaningful therapeutic benefit over existing options, then the accelerated pathway may be used. In other, more drastic threats, the animal rule may be invoked—if research toward a vaccine or treatment would necessitate exposing humans to a toxic threat, then animal studies may be sufficient for approval. Nelson noted that these two rapid pathways have not been invoked for vaccines to date. More information is available at the FDA’s Critical Path Initiative.
Nelson also discussed U.S. Emergency Use Authorization (EUA) as a tool for pandemic and bioterror response for both civilian and military populations. After a declaration of emergency by the Department of Health and Human Services secretary, this program allows for use of an unapproved medical product (or a product that has been approved but not for the specific use applicable to the situation at hand) that is the best available treatment or prevention for the threat in question. EUAs were issued for antiviral treatments, a respirator, and a PCR diagnostic test during the A/H1N1 pandemic.
During an afternoon talk, Stephen C. Redd, MD, Rear Admiral and Assistant Surgeon General, U.S. Public Health Service, Director of CDC’s Influenza Control Unit, reviewed steps taken to produce and distribute the A/H1N1 vaccine in 2009. The virus was detected in a Californian in mid-April 2009, in a CDC project related to surveillance of a medical device. Investigators first thought the illness might have been an isolated case related to exposure to pigs. But, as further cases were identified, investigators quickly determined the nature of the virus and its ability to be transmitted among humans. The decision to develop a vaccine for the novel virus was made within days, and manufacturers received the seed strain for the vaccine in May.
Redd then outlined possible future changes to pandemic influenza response, which he classified into short-, medium-, and long-term actions. Immediate steps could improve changes to potency testing of vaccines, as well as improvements to the fill and finish process of manufacturing vaccines. In the medium-term, new cell-based methods of producing influenza vaccine viruses might be employed (rather than current methods that rely on incubating virus in chicken eggs). Long-term changes could include the use of recombinant technologies to produce antigen as well as future development of a universal influenza vaccine.
The following day, September 13, the National Vaccine Plan Stakeholders Meeting was sponsored by the Department of Health and Human Services, the National Vaccine Program Office, the Drexel University School of Public Health, and the University of Pennsylvania Center for Bioethics.
Virginia Caine, MD, the Marian, Indiana County Health Director, discussed ethnic disparities in immunization rates. While the gaps in coverage among different ethnicities have improved in children, disparities among adults remain higher. Caine highlighted several barriers to immunization among different minority populations. In particular, she noted that health care providers may fail to use proven office-based strategies in encouraging vaccination, including patient calls and reminder systems, standing orders for vaccines, and electronic medical records.
Some of these issues are particularly prevalent in low-income communities, and are compounded there by low reimbursement rates for vaccine administration, so that clinics avoid filling up time slots with vaccine appointments in favor of appointments for which they will receive higher reimbursements. In a similar vein, Caine noted that the absence of an adult version of the national Vaccines For Children program (VFC), which provides free vaccines for children whose families cannot afford them, leaves some poor adults without a way to receive immunizations.
Caine also noted that among older African Americans, resistance to vaccines may be rooted in long-standing distrust of the medical establishment or the government stemming from events like the infamous Tuskegee study. In such cases, Caine suggested that taking the time to directly address concerns gives health care providers the opportunity to build trust with patients, and thereby provide crucial information that patients would otherwise not receive.
In a related talk, James Lutz, MPA, from the Philadelphia Department of Health’s Immunization Program, discussed the steps that Philadelphia has taken to close ethnic gaps in vaccination rates among children. KYW newsradio briefly covered Lutz’s talk here.
Margaret Trexler Hessen, MD, Fellow of the American College of Physicians, discussed barriers to immunization in adults and highlighted three main challenges: Tdap boosters, Herpes zoster (shingles) vaccine, and seasonal influenza vaccine.
With Tdap – the combination booster vaccine that provides protection against tetanus, diphtheria, and pertussis – Trexler cited issues with insurance providers paying claims for the vaccine’s use. When a Tdap claim is made for wound management – that is, to prevent tetanus after an injury – claims are typically paid. If the vaccine is given to prevent pertussis, however, claims are often denied. This is a particular issue given that grandparents are often advised to receive a Tdap booster to prevent spreading pertussis to young grandchildren.
The herpes zoster (shingles) vaccine is problematic because it is expensive – about $250 – and insurance coverage for the vaccine is highly varied. An additional challenge is availability: the vaccine is often unavailable at doctors’ offices but is available at pharmacies, yet pharmacists may be unable to administer it. Patients who want to receive the vaccine may then have to get a prescription from their doctors, obtain the vaccine from a pharmacy, and bring it back to the doctor’s office. This may be difficult for older patients with limited transportation options – especially since the vaccine must be kept frozen until it is used.
Finally, while seasonal influenza immunization rates are generally good among the 65+ age group, rates for other adults are less impressive. Hessen cited numerous challenges in improving coverage against seasonal flu, including confusion about recent changes in indication for the vaccine. The CDC recommendation that everyone older than six months of age receive a seasonal flu vaccine is relatively new; adults may wonder why they are advised to receive a flu shot now when they were never advised to do so before.
Additionally, realistic expectations of the vaccine are a problem. The efficacy of the flu vaccine varies depending on the strains selected; if the strains that circulate in a given flu season differ from those selected for the vaccine, it may not work well in preventing the flu. This and other factors (such as misconceptions about influenza in general) must be related clearly to patients, to address the “I got a flu vaccine and got the flu anyway, so it’s not worth it” sentiment that is sometimes expressed.
Finally, Hessen noted, primary care physicians need providie information about flu vaccination in the first place; if the vaccine is not available and discussed in a patient’s “medical home,” they may not seek it out.
The NVPO will incorporate dIscussion and comments from the September 12 meeting into the implementation plan for the 2010 National Vaccine Plan. This information should be available on the NVPO website by the end of 2011, after completion of the regional stakeholder meetings.