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CME/CE

Vaccine Safety: What Does Experience Tell Us? Part 2

  • Authors: David Salisbury, MB, FRCP, FRCPH, MFPHM; Paul A. Offit, MD
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Target Audience and Goal Statement

This activity is designed to meet the continuing education needs of pediatricians and pediatric nurses.

To demonstrate how information gathered through long-term experience is used to monitor and enhance vaccine safety and increase confidence.

On completion of this CME offering, participants will be able to:

  1. Demonstrate the impact of public confidence and the global challenge that providers face in maintaining this confidence to ensure the success of immunization programs.

  2. Describe the extensive pre- and postlicensure monitoring and surveillance techniques used to ensure vaccine safety.

  3. Demonstrate an international perspective of safety concerns with regards to particular vaccines.

  4. Summarize the resources available and the communication techniques required to meet the needs of differing patient types who may require multiple sources of information.

  5. Review case examples, including measles, mumps, and rubella, as models to explain the impact of public confidence and the experience gained through monitoring and surveillance.

  6. Explain the significant impact vaccines have made on the morbidity and mortality of common childhood diseases.


Author(s)

  • Paul A. Offit, MD

    Chief of the Section of Infectious Diseases, Children's Hospital of Philadelphia; Henle Professor of Immunologic and Infectious Diseases, University of Pennsylvania School of Medicine, both in Philadelphia, Pennsylvania.

    Disclosures

    Disclosure: Dr. Offit has received honoraria related to specific research activities and product royalty/licensing fees from Merck & Co., Inc.

  • David Salisbury, MD

    Principal Medical Officer, Department of Health, London, United Kingdom

    Disclosures

    Disclosure: Dr. Salisbury has received no honoraria related to formal advisory activities, development of educational materials, speakers' bureau activities, or specific research.


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CME/CE

Vaccine Safety: What Does Experience Tell Us? Part 2: Addressing Vaccine Safety Concerns

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Addressing Vaccine Safety Concerns, Presented by Paul A. Offit, MD

How Do You Define "Safe"?

  • What I thought I would do briefly in my time is try and answer this question, Are Vaccines Safe by using two specific examples; one, the poliovirus vaccine story, and two, the rotavirus vaccine story. Before we can answer the question, we have to define what we mean by the word safe, and if you look at the Oxford English Dictionary, there are actually 10 definitions of the adjective safe, two of which are included on this slide. The first is unhurt, uninjured or unharmed, and the second is having been preserved from a real or apprehended danger. If we use the first definition, unhurt, uninjured or unharmed, I think we can say then that no vaccine is safe because all vaccines have mild adverse reactions, and some have more severe adverse reactions.

  • Definition of Safe

    Slide.

    Definition of Safe

    (Enlarge Slide)
  • But I think that if you look at that definition, it would be impractical to use that really for anything, because even in routine daily activities such as taking a bath or showering, we know that 350 people die a year, eating solid food is also unsafe, and 200 people die a year, hopefully, it won't be one of you, and walking outside on a rainy day, we know that 100 people die every year in the United States from being struck by lightening. So that's not a fair definition.

  • Defining Safe as "Unharmed or Free From Harm"

    Slide.

    Defining Safe as "Unharmed or Free From Harm"

    (Enlarge Slide)
  • I think a more reasonable definition is the second, having been preserved from real danger, or said another way, that immunizations provide safety; therefore, the danger or disease must be significantly greater than the means of protecting against the danger, the vaccine, or said another way, that the benefits of vaccines must clearly and definitively outweigh the risk.

  • Defining Safe As "Having Been Preserved From Real...Danger"

    Slide.

    Defining Safe As "Having Been Preserved From Real...Danger"

    (Enlarge Slide)
  • Now the Food and Drug Administration also has a definition of safety which is shown here. The word safety means the relative freedom from harmful effects, meaning that it compares to something else, in this case, the risks of the disease that the vaccine is preventing.

  • FDA Definition of Safety

    Slide.

    FDA Definition of Safety

    (Enlarge Slide)

Poliovirus and the Polio Vaccine

  • So let's go through the polio vaccine story because I think there's a lot of twists and turns in the story that makes it interesting in our attempts to define what we mean by the word safe. Polio, in the 40s and 50s in the United States, was highly contagious and occasionally devastating infection. In the early 50s there were 58,000 cases of paralytic polio reported. More than half of those cases occurred in previously healthy young children, and 90% of adults and 100% of children living in a home with someone with polio seroconverted.

  • Poliovirus in the US: The 1950s

    Slide.

    Poliovirus in the US: The 1950s

    (Enlarge Slide)
  • This is a slide showing lower limb paralysis in adults with polio.

  • Slide.

    (Enlarge Slide)
  • And this is a slide showing at the University of Michigan these negative pressure ventilators or iron lungs where children who had cranial nerves affected by poliovirus were unable to breathe on their own, and therefore required these ventilators, and most of these children died of aspiration pneumonia.

  • Slide.

    (Enlarge Slide)
  • So there was a tremendous effort in the United States to develop a vaccine to prevent this disease, and at the heart of this effort was this man, a man who won the Nobel Prize for the development of that vaccine. He won it in 1954. Anybody know his name?

  • Slide.

    (Enlarge Slide)
  • John Enders. Right. With John Enders-and actually he won it with his two graduate students, Weller and Robbins-and what he figured out was he figured out how to grow poliovirus in non-neural cell culture, which then allowed one to grow up that virus in cell culture, and one could then either inactivate it as Jonas Salk did, or attenuate it via serial pathogen culture as Albert Sabin did, and that's just purified poliovirus.

  • Poliovirus

    Slide.

    Poliovirus

    (Enlarge Slide)
  • The work is done by this man on the left, Jonas Salk, and what Jonas Salk did was he figured out how to inactivate poliovirus. He figured the conditions under which a certain amount of formaldehyde and heat and pH allow for a complete inactivation of that virus, so that one can retain immunogenicity, but eliminate pathogenicity or virulence.

  • Slide.

    (Enlarge Slide)
  • And so there was a huge field trial that was conducted or headed by Thomas Francis out of the University of Michigan. It was done in 1954, and it was sponsored by the National Foundation for Infantile Paralysis or March of Dimes.

  • Slide.

    (Enlarge Slide)
  • It was at that time, and remains today, the largest field trial in the history of vaccines, I think to my knowledge. It was three doses of inactivated polio vaccine given to 420,000 children. Controls included 200,000 placebo recipients and 1.2 million uninoculated children, and the vaccine was found to be about 90% effective in preventing type 2 and 3 disease, and about 70% effective in preventing type 1 disease. It was a trial that cost about $6 million at that time, which would work out to maybe $100 million today. But there were tremendous numbers of volunteers that contributed to this private organization, the March of Dimes, to get this done. I think pharmaceutical companies had trouble getting people to volunteer their time to contribute to it. Maybe that's why it's a little more expensive then.

  • The "Francis Field Trial": 1954

    Slide.

    The "Francis Field Trial": 1954

    (Enlarge Slide)
  • But the vaccine was then released for licensure on April 12, 1955. There were five companies that made the vaccine in the United States at that time, and within 2 weeks really of the release of that vaccine, this headline appeared in the New York Times, One Firm's Vaccine Barred, Six Polio Cases are Studied. I mean this was April in the United States. This was before we really started to see polio, which was primarily a summer disease, but what was seen was essentially a point source outbreak of polio associated with the administration of this vaccine, and it was traced, at least in the early cases, were traced to a vaccine that was made by one laboratory in Berkeley California called Cutter Laboratories, and Cutter Laboratory vaccine was withdrawn. The Cutter vaccine was withdrawn from the market within 24 hours of those cases being reported, and the United States Public Health Service then went on to investigate all of the companies that made that vaccine.

  • The Polio Vaccine: April 1955

    Slide.

    The Polio Vaccine: April 1955

    (Enlarge Slide)
  • They found something that surprised them. I should take a step back and say that when we looked at what the incidence of disease was in people who received the polio vaccine, and compared that with the number of cases, we would have expected in those people who received polio vaccine, we found really for almost all of these companies, that there were a greater number of cases in the vaccinated than in the unvaccinated group.

  • "The Cutter Incident": April 1955

    Slide.

    "The Cutter Incident": April 1955

    (Enlarge Slide)
  • And when the United States Public Health Service looked at the records of these companies to try and determine whether or not there was any hint that there were difficulties inactivating the poliovirus for the purpose of vaccine. They found that all companies had at least some percent of lots that contained live virulent poliovirus, and then these lots weren't used, but we had a relatively insensitive measure of an inactivation at that time. So it certainly warned of a big problem, and the Poliovirus Program was shut down in this country between May 7, 1955, and May 14, 1955.

  • Polyvalent Pools Containing Live Poliovirus by Manufacturer: 1954-1955

    Slide.

    Polyvalent Pools Containing Live Poliovirus by Manufacturer: 1954-1955

    (Enlarge Slide)
  • So was the inactivated polio vaccine made in the United States in April of 1955 safe? I think that's easy. The answer is no. The vaccine actually caused more disease than it prevented, and hence it was withdrawn from the market for that period of time when we tried to figure out how to make a safer polio vaccine.

  • Was the Inactivated Polio Vaccine Made in the United States in April 1955 Safe?

    Slide.

    Was the Inactivated Polio Vaccine Made in the United States in April 1955 Safe?

    (Enlarge Slide)
  • In order to make a safer polio vaccine, what we did was we added an extra filtration step. That made for, what was no doubt, a lower potency inactivated polio vaccine, and that's the vaccine we had in this country in the late 1950s, but the result of this whole episode was some lost faith in the polio immunization program, and that in part resulted in lower immunization rates. But despite a relatively low potency vaccine, if you look at the incidence of reported cases of paralytic polio between 1955 and 1962, there was a dramatic reduction in the incidence of polio,

  • Consequences of "The Cutter Incident"

    Slide.

    Consequences of "The Cutter Incident"

    (Enlarge Slide)
  • such that by 1962, which was the year that the Sabin vaccine, at least the serotypes 2 and 1 of the Sabin vaccine were licensed for use in this country, we had gone from 28,000 to 900 cases, but there were other problems. If you looked, first of all, the 900 cases reported there represent only about half the states and there was also underreporting, so I think it's still fair to say that there were thousands of cases of wild type or natural polio infection in this country. What was also worrisome was that if you looked at those cases, about 20% of those children had received 2, 3, 4 or even 5 doses of the inactivated polio vaccine, and yet still had been paralyzed by wild type polio. So what we had in this country in 1962 were relatively low immunization rates, we had a vaccine which was certainly not, was fairly far from 100% effective, and although this lower potency inactivated vaccine was never subjected to the same clinical trials that the original vaccine was, and we knew that it certainly had an effect in reducing the incidence of disease, we knew it was far from a perfect vaccine.

  • Reported Cases of Polio in US: 1955-1962

    Slide.

    Reported Cases of Polio in US: 1955-1962

    (Enlarge Slide)
  • So with all of that information in hand, we made the decision to go to the Sabin or the oral polio vaccine because we know that the OPV was quite effective when administered in three doses, we knew it had the attractive feature of contact immunity, and that 25% of people who just were around those who got the oral polio vaccine would in fact be vaccinated, and it obviated concerns about the decreased potency.

  • The Oral Polio Vaccine (Sabin): 1961

    Slide.

    The Oral Polio Vaccine (Sabin): 1961

    (Enlarge Slide)
  • Now we knew actually as early as 1957, so 5 years before the oral polio vaccine was licensed in this country, that the oral polio vaccine was unique, frankly, among vaccines in its capacity to revert to neurovirulent type. There were three reasons for that. I'll just go through them quickly. One is although the oral polio vaccine was attenuated for growth in the central nervous system, it was not particularly attenuated for growth in the intestinal tract, so it really still replicated well in the intestinal tract.

  • How VAPP Occurs

    Slide.

    How VAPP Occurs

    (Enlarge Slide)
  • Two, because polio is a single-stranded RNA virus, it is fairly highly immunogenic, meaning there's a base pair change per cycle of replication, so it's not particularly faithful in its replication, unlike say double-stranded DNA viruses. And lastly, if you look at the bottom line here, the type 3 polio was not particularly highly mutated. So not only is it not particularly stable, it wasn't even highly mutated, and when you looked at these cases of vaccine-associated paralysis, virtually all of them were type 3.

  • Polio Vaccine Strains

    Slide.

    Polio Vaccine Strains

    (Enlarge Slide)
  • It's a bad confluence of three events, which is to say a virus which replicates, which is not particularly faithful in its replication, and at least one strain of which was not highly mutated, and the result was that the vaccine did occasionally revert to wild type rarely, but still it really did revert to neurovirulent-type causing vaccine-associated paralysis, which was frankly indistinguishable from clinical wild type polio because, in essence, it was wild type polio.

  • Risk of VAPP

    Slide.

    Risk of VAPP

    (Enlarge Slide)
  • So was the oral polio vaccine safe in 1962? I think the answer to that question is yes. Although we knew the vaccine-associated paralysis occurred, we also knew that we had thousands of cases of polio in this country, we knew that we had a vaccine, the OPV, which worked, and we knew that we had low immunization rates, which was obviated at some level by a vaccine that had contact immunity. So we chose the oral polio vaccine in 1962,

  • Was the Oral Polio Vaccine Safe in 1962?

    Slide.

    Was the Oral Polio Vaccine Safe in 1962?

    (Enlarge Slide)
  • and I think in retrospect, that was the right choice because what we found was within 17 years or so, by 1979, we had eliminated wild type polio from this country. But what we hadn't eliminated was polio because subsequent to 1979, all the polio that was seen in this country was that which was caused by the oral polio vaccine. We'd see about roughly six to eight cases a year.

  • Reported Cases of Polio in the US: 1964-1998

    Slide.

    Reported Cases of Polio in the US: 1964-1998

    (Enlarge Slide)
  •  
  • Was the Oral Polio Vaccine Safe in 1979?

    Slide.

    Was the Oral Polio Vaccine Safe in 1979?

    (Enlarge Slide)
  • So was the oral polio vaccine safe in 1979? I'm not sure I know the answer to that question. I'll give you my opinion. I think it wasn't. I think that although the inactivated polio vaccine was not a great vaccine in the absence of having any natural infection in the United States, and knowing also that Scandinavian countries, certain provinces in Canada, were able to essentially eliminate epidemic and largely endemic polio in their countries using only the inactivated polio vaccine, I think that we probably could have gone to an inactivated polio vaccine in 1979 safely. I do think that the point I'm trying to make here is that the equation changed. Remember our initial hypothesis statement was that in order to define safety, one has to consider the risks and the benefits of vaccine as compared to disease. In the absence of disease then, I think the burden is to have a safer vaccine. So I think that one could reasonable say that we could have gone to an inactivated vaccine in 1979.

  • Why Did ACIP Change Their Recommendation?

    Slide.

    Why Did ACIP Change Their Recommendation?

    (Enlarge Slide)
  • But what happened was as the due advances in protein chemistry and ion exchange chromatography, we were able to make a better inactivated polio vaccine, and we knew that this vaccine was highly immunogenic, and in studies was also quite effective after three doses.

  • Why Did ACIP Change Their Recommendation?

    Slide.

    Why Did ACIP Change Their Recommendation?

    (Enlarge Slide)
  • And so was the oral polio vaccine safe in 1995? I think the answer to that question was clearly no because now we had an acceptable alternative that we knew worked quite well, and hence we moved to the inactivated polio vaccine.

  • Was the Oral Polio Vaccine Safe in 1995?

    Slide.

    Was the Oral Polio Vaccine Safe in 1995?

    (Enlarge Slide)
  • So this just summarizes what I said before that when one considers factors determining safety, one needs to consider the incidence of disease or benefits and the incidence of adverse events of the vaccine or risks, and that much also goes into that formula, such as what are the immunization rates in your particular country. You can argue that in Africa right now, the oral polio vaccine is safe because there's still a fair amount of natural infection, there is a fairly low immunization rate, and one needs to depend on contact immunity. So although the oral polio vaccine, I think, it's not safe in the United States, I think it is safe in Africa or Southeast Asia or India.

  • Factors Determining Vaccine Safety

    Slide.

    Factors Determining Vaccine Safety

    (Enlarge Slide)

Rotavirus Disease and the Rotavirus Vaccine

  • We'll conclude with just the rotavirus vaccine. We know that in the United States, there's about 550,000 doctor visits and 50,000 hospitalizations a year, meaning that 1 of every 75 children born in the United States is hospitalized with rotavirus-induced dehydration, and there's 20 to 40 deaths from dehydration every year.

  • Burden of the Rotavirus Disease: United States

    Slide.

    Burden of the Rotavirus Disease: United States

    (Enlarge Slide)
  • In developing countries, the disease is devastating. There is roughly 600 to 800,00 deaths per year from rotavirus-induced hydration, meaning that one child every minute dies from rotavirus infection, or said another way, 2,000 children die a day from rotavirus infection in developing countries. Therefore, as a single agent, rotavirus kills more infants and young children than any other infectious disease.

  • Burden of the Rotavirus Disease: Developing Countries

    Slide.

    Burden of the Rotavirus Disease: Developing Countries

    (Enlarge Slide)
  • So there was, like for polio, a tremendous interest, and both the public and private sector, well, certainly the private sector, in developing a vaccine to stop this. The Rotashield Vaccine was licensed in August of 1998, and had it, as its backbone, a simian strain, RRV, or Rhesus Rotavirus into which, at least for three of the strains was cloned an individual gene which coded for one of the outer caps and surface proteins (cannot confirm underscore), so that represented in that vaccine were the four human serotypes that cause disease in the United States.

  • Rotashield® Vaccine

    Slide.

    Rotashield® Vaccine

    (Enlarge Slide)
  •  
  • Safety of RRV Reassortant Vaccine: Dose 1

    Slide.

    Safety of RRV Reassortant Vaccine: Dose 1

    (Enlarge Slide)
  • Pre-licensure - we knew that this vaccine had a first-dose side-effect problem of low-grade, and to a lesser extent, high-grade fever, and then some behavioral disturbances after dose 1. We also knew that there was, to a lesser extent, mild or low-grade fever after dose 2, but nothing after dose 3.

  • Safety of RRV Reassortant Vaccine: Dose 2

    Slide.

    Safety of RRV Reassortant Vaccine: Dose 2

    (Enlarge Slide)
  • We also knew pre-licensure of these data, which is actually, I think more accurately, this would be 2 of 8,000 cases of intussusception occur in the group that received the vaccine that was the final formulation, this quadrivalent vaccine as compared to 1 in 4,600, which was not statistically significantly different. Also, there was no intussusception noted after dose 1, which made people think that because this wasn't statistically significant, because there was no dose 1-associated disease here, that this was likely not to be a coincidence, but rather it was more likely subsequent. However, despite this, this phenomenon was noted in the AAP statement, it was noted in the ACIP statement, it was noted in the package insert, and the company was required to do post marketing surveillance following the release of this vaccine.

  • Rotashield® - Pre-licensure

    Slide.

    Rotashield® - Pre-licensure

    (Enlarge Slide)
  • The vaccine, as I said, was released at the end of August in 1998. It was temporary suspended in July of 1999 because of data that were generated by the Vaccine Adverse Events Reporting System, and what was seen that was worrisome to people was a few things. First of all, 13 to 15 cases reported did occur after the first dose. Most of those occurred within a week of the first dose, and also a significant percentage occurred in young children, which worried people because intussusception was primarily a disease frankly of the 5- to 9-month-old. It was an unusual disease in the 2- to 3-month-old, so this confluence of events worried health officials enough that they temporarily suspended the vaccine while a retrospective case control analysis was performed by the CDC to determine whether or not it really was cause and effect.

  • Rotashield® - VAERS

    Slide.

    Rotashield® - VAERS

    (Enlarge Slide)
  • And in short, it was. This slide shows the relative risk of intussusception by age after dose 1, and you can see that what was seen actually in that VAERS data didn't really hold up in this case control series because independent of really what age you got your first dose at, you were at fairly high relative risk within a week of that first dose of having intussusception. It wasn't really a phenomenon of the young infant,

  • Relative Risk (RR) of Intussusception by Age After Dose 1

    Slide.

    Relative Risk (RR) of Intussusception by Age After Dose 1

    (Enlarge Slide)
  • and that one was at greatest risk after dose 1, lesser risk after dose 2, and essentially no risk after dose 3. So you could immunize yourself against intussusception by getting the Rotashield vaccine. It's a small consolation for those who got intussusception, but that is true.

  • Relative Risk (RR) of Intussusception by Dose

    Slide.

    Relative Risk (RR) of Intussusception by Dose

    (Enlarge Slide)
  •  
  • Was the Rotashield Vaccine Safe?

    Slide.

    Was the Rotashield Vaccine Safe?

    (Enlarge Slide)
  • So because of these data, the Centers for Disease Control recommended the withdrawal of the rotavirus vaccine recommendation. So was the Rotashield vaccine safe? One cannot consider safety as an absolute term. One has to consider safety by comparing the risk of the vaccine associated with the risk of getting actual infection. In the case of rotavirus, which is ubiquitous infection, an infection which will affect every child in this country for the most part by 3 years of age, the choice not to get a rotavirus vaccine is simply a choice to get rotavirus disease. So what does that choice mean? Well, let's just go through the numbers. We should have final data by February, but if one assumes a risk of intussusception in 1 in 12,274 vaccine recipients, we can break it down this way. We knew that roughly a million children got vaccinated. If you look at those who got vaccine, we know that the rotavirus vaccine is about 80% effective or so at reducing moderate to severe disease. So therefore one can expect that for one million children who did get the vaccine, about 29,000 would visit their doctor with the rotavirus illness, and 143,000 who didn't get the vaccine would visit their doctor. Similarly, because the vaccine is essentially 100% effective at protecting against severe rotavirus disease, we know that those who got the vaccine wouldn't be hospitalized with rotavirus, but that about 16,000 would be hospitalized with rotavirus that didn't get the vaccine. If you look at intussusception, we know that we would increase the rate of intussusception per million children by about 95 children, and we know that one child dies of intussusception from getting the rotavirus vaccine. So one of a million children died from rotavirus, from intussusception caused by the Rotashield vaccine. We also know that 6 to 12 will die that didn't get the vaccine. So there's some assumptions that were made I think that aren't correct. For example, I think some children who will die from rotavirus disease will die at less than 6 months of age prior to being fully immunized, and one could also argue that now that we know of the risks of intussusception, or risk which occurs, quite frankly soon after vaccine, you can also argue that with that knowledge, and also knowing that when children are hospitalized or die from intussusception, it's because of a failure to recognize that as a problem, that we may not see any deaths from intussusception or from Rotashield vaccine. But in either case, I think it's fair to say that roughly 5 to 10 times more children will die from the disease than would die from the vaccine.

  • Risks and Benefits of Rotashield in US

    Slide.

    Risks and Benefits of Rotashield in US

    (Enlarge Slide)

Defining Safety in 2000 And Beyond

  • We never had this discussion at the ACIP. You know we simply recognize the fact that this was a clear consequence of the vaccine. I mean whatever number you pick, even if it's 1 in 10,000, I think it's fair to say it was a rare consequence of the vaccine, and I think what we didn't do is we didn't represent those children, who will this year be hospitalized and killed by rotavirus disease. And although I think we would have come up with the same conclusion, I think that by not having the discussion we did fail those children who will suffer this disease. Remember that the decision not to give a vaccine is not a medically or morally neutral decision, it's simply a choice in the case of rotavirus to get the disease, and really that's true for any of the common or ubiquitous infections. I'll close with the last two slides.

  • Definition of Safety: 2000

    Slide.

    Definition of Safety: 2000

    (Enlarge Slide)
  • What I found when I give grand rounds these days is that a number of people, physicians will come up and say, you know, after that Rotashield experience, I really want to take a "wait and see" approach on the new pneumococcal vaccine, which I think is kind of a dangerous attitude for this reason. We certainly know the streptococcus pneumoniae is an important cause of meningitis and bloodstream infections, and pneumonia in the United States. There's 1,400 cases of meningitis in the less than 5-year-old every year, there's 17,000 cases of bloodstream infections, and about 70,000 cases of pneumonia. That we know. We also know, for a fact, that the pneumococcal vaccine will prevent about 80 to 85% of serious invasive bacteria infections in that young age group. We also know that we've done a trial of 40,000 children in a controlled trial with those who got pneumococcal vaccine or got another vaccine, and found that the vaccine was safe, and in addition, we know that we have a similar vaccine, meaning a conjugated polysaccharide vaccine in Hib that has about 10 years of experience and a good record of safety. So I think to say I want to take a "wait and see" approach is to say that you want to substitute a theoretical risk for a real risk, and knowing that we're going to have X number of children that are permanently disabled or killed by pneumococcus while we're waiting to see whether this theoretical risk holds up, and I think that's just not good thinking.

  • Taking a "Wait and See" Approach on the Conjugate Pneumococcal Vaccine

    Slide.

    Taking a "Wait and See" Approach on the Conjugate Pneumococcal Vaccine

    (Enlarge Slide)
  • And lastly I'll close with this slide, which is this moral dilemma in a sense. We know that RSV causes about 90,000 hospitalizations and 5,000 deaths per year. Would an RSV vaccine that prevented 90% of severe and fatal illness, but caused five deaths per year, be considered safe?

  • Definition of Safety: 2000

    Slide.

    Definition of Safety: 2000

    (Enlarge Slide)