Flu Shots

[Acleron]

The benefits of flu vaccination appear unclear.

The most recent Skeptics Guide to the Universe podcast features an interview with Dr Mark Crislip, an infectious diseases specialist. He debunked many myths about the flu vaccine and concluded it was safe and effective.

However the Lancet Infectious Diseaseshas a recently published paper calling into doubt the benefits of vaccination for the over 65's. This group is the main focus of many vaccination programs, certainly in the UK.

Sorry the link is not directly to the Lancet

 

[fls]

In the elderly, the same systematic reviews said a lot of it had to be due to selection bias, right?
Have you seen the new Simonsen study from a month or two ago?

No. They concluded the vaccines were effective and added there may be some effect from selection bias (i.e. healthy vacinee bias). Studies that have specifically looked at this selection issue (such as the Nichols study) find that adjustments in group characteristics do account for this bias, and that the measured affect is fairly robust.

Yes. The Simonsen study shows that comparing apples and oranges on the basis of colour shows greater differences than comparing them on the basis of 'fruit'. It shows that the portion of deaths related to influenza in a study population should not be assumed to be comparable to the portion of deaths related to influenza in the general population. While it may be reasonable to expect to find that about 5 percent of deaths in an average time period are due to influenza in a sample drawn from a general population, it is not reasonable to assume that 5 percent of deaths during a virulent influenza outbreak drawn from a sample of the frail elderly will be found to be due to influenza. And that the number of excess deaths is sensitive to the method used to measure excess deaths.

Vaccinate all the babies now, figure out if it's safe and effective later.
Got it.

That's the point of expert review. There aren't simple answers to questions such as how much confidence we need before acting - the answer depends on the details. We already have information about safety and effectiveness in babies, and knowledgeable and experienced people have weighed these issues and provided an opinion, which includes the recommendation that better information should continue to be obtained.

Linda

 

[fls]

Link?

The links are in the reference I provided here.

Linda

 

[fls]

So, would you agree that there appears to be something very, very wrong with studies like the Nichol one?

No. It simply shows that studies like the Nichol one are necessary. And that randomized clinical trials would provide useful information. Careful attention must be paid to the validity of generalization.

There are several types of selection bias that are relevant. The first is that of the healthy-vacinee - people who get vaccines are different in important ways from those who don't in ways that will influence outcomes. Another type of selection bias is that of the population from which the sample is selected. And this is of more relevance to external validity and generalizing the study conclusions to a larger population.

Linda

 

[Ivor the Engineer]

For those who can't be bothered to search:

Ref. 17 in Linda's link:

http://www.ncbi.nlm.nih.gov/sites/e...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

BACKGROUND: In children and adults the consequences of influenza are mainly absences from school and work, however the risk of complications is greatest in children and people over 65 years old. OBJECTIVES: To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children; assess vaccine efficacy (prevention of confirmed influenza) and effectiveness (prevention of influenza-like illness) and document adverse events associated with receiving influenza vaccines. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005); OLD MEDLINE (1966 to 1969); MEDLINE (1969 to December 2004); EMBASE (1974 to December 2004); Biological Abstracts (1969 to December 2004); and Science Citation Index (1974 to December 2004). We wrote to vaccine manufacturers and a number of corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised controlled trials (RCTs), cohort and case-control studies of any influenza vaccine in healthy children under 16 years old. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: Fifty-one studies involving 263,987 children were included. Seventeen papers were translated from Russian. Fourteen RCTs and 11 cohort studies were included in the analysis of vaccine efficacy and effectiveness. From RCTs, live vaccines showed an efficacy of 79% (95% confidence interval (CI) 48% to 92%) and an effectiveness of 33% (95% CI 28% to 38%) in children older than two years compared with placebo or no intervention. Inactivated vaccines had a lower efficacy of 59% (95% CI 41% to 71%) than live vaccines but similar effectiveness: 36% (95% CI 24% to 46%). In children under two, the efficacy of inactivated vaccine was similar to placebo. Thirty-four reports containing safety outcomes were included, 22 including live vaccines, 8 inactivated vaccines and 4 both types. The most commonly presented short-term outcomes were temperature and local reactions. The variability in design of studies and presentation of data was such that meta-analysis of safety outcome data was not feasible. AUTHORS' CONCLUSIONS: Influenza vaccines are efficacious in children older than two years but little evidence is available for children under two. There was a marked difference between vaccine efficacy and effectiveness. That no safety comparisons could be carried out emphasizes the need for standardisation of methods and presentation of vaccine safety data in future studies. It was surprising to find only one study of inactivated vaccine in children under two years, given recent recommendations to vaccinate healthy children from six months old in the USA and Canada. If immunisation in children is to be recommended as public-health policy, large-scale studies assessing important outcomes and directly comparing vaccine types are urgently required.

Ref. 18:

http://www.ncbi.nlm.nih.gov/sites/e...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

BACKGROUND: Two systematic reviews evaluating influenza vaccine efficacy in healthy children have recently been published. Although quantitative summary estimates were similar, authors' conclusions were quite contrasting. We carried out another meta-analysis reevaluating study inclusion criteria and using metaregression techniques in addition to sensitivity and subgroups analyses to evaluate potential sources of heterogeneity of efficacy estimates, including methodologic quality of studies. METHODS: Only randomized clinical studies assessing the efficacy of influenza vaccine in healthy children/adolescents (age < or =18 years) for preventing naturally occurring influenza and/or acute otitis media cases were included. Summary estimates of effect were obtained using a random effects model. The methodologic quality of each study was assessed using 3 systems: Chalmers scale, Jadad scale and Schulz components (randomization, allocation concealment and double-blinding). RESULTS: The overall vaccination efficacy was 36% (95% confidence interval: 31-40%) against clinically diagnosed illnesses (evaluated by 19 randomized clinical studies for a total of 247,517 children); 67% (51-78%) against laboratory-confirmed cases (18 trials, n = 8574); and 51% (21-70%) against acute otitis media (11 trials, n = 11,349). Significant sources of between-study heterogeneity were participants' age and study quality both directly correlated with the efficacy. When the analysis was performed excluding USSR studies, the overall efficacy of the vaccine in preventing clinical cases substantially increased (from 36% to 61%). CONCLUSIONS: These findings may indicate that the vaccine efficacy might be greater than the overall estimates. Although no safety and cost considerations are addressed in this analysis, the present findings support vaccination as a possible option for the prevention of influenza in healthy children and adolescents.

Ref. 19:

http://www.ncbi.nlm.nih.gov/sites/e...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

We conducted a meta-analysis of 13 randomised clinical trials evaluating the efficacy of influenza vaccine in healthy children. Against culture-confirmed influenza the overall efficacy was 74% (95% confidence interval, CI, 57%-84%), 65% for inactivated and 80% for live-attenuated vaccine. Corresponding figures were 59% (95% CI 43%-71%), 63% and 54% for serologically-confirmed influenza, and 33% (95% CI 29%-36%), 33% and 34% for clinical illness. Influenza vaccine is effective in preventing laboratory-confirmed and clinical influenza in healthy children, with no clear difference between inactivated and live-attenuated vaccine. Data on infants and younger children were too scanty to allow separate assessment.

Ref. 67:

http://www.ncbi.nlm.nih.gov/sites/e...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

BACKGROUND: The efficacy of influenza vaccines may decline during years when the circulating viruses have antigenically drifted from those included in the vaccine. METHODS: We carried out a randomized, double-blind, placebo-controlled trial of inactivated and live attenuated influenza vaccines in healthy adults during the 2004-2005 influenza season and estimated both absolute and relative efficacies. RESULTS: A total of 1247 persons were vaccinated between October and December 2004. Influenza activity in Michigan began in January 2005 with the circulation of an antigenically drifted type A (H3N2) virus, the A/California/07/2004-like strain, and of type B viruses from two lineages. The absolute efficacy of the inactivated vaccine against both types of virus was 77% (95% confidence interval [CI], 37 to 92) as measured by isolating the virus in cell culture, 75% (95% CI, 42 to 90) as measured by either isolating the virus in cell culture or identifying it through real-time polymerase chain reaction, and 67% (95% CI, 16 to 87) as measured by either isolating the virus or observing a rise in the serum antibody titer. The absolute efficacies of the live attenuated vaccine were 57% (95% CI, -3 to 82), 48% (95% CI, -7 to 74), and 30% (95% CI, -57 to 67), respectively. The difference in efficacy between the two vaccines appeared to be related mainly to reduced protection of the live attenuated vaccine against type B viruses. CONCLUSIONS: In the 2004-2005 season, in which most circulating viruses were dissimilar to those included in the vaccine, the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic illnesses from influenza in healthy adults. The live attenuated vaccine also prevented influenza illnesses but was less efficacious. (ClinicalTrials.gov number, NCT00133523.) 2006 Massachusetts Medical Society

Ref. 68:

During the 2003-2004 influenza season, we conducted a case-control study of influenza vaccine effectiveness (VE) among Colorado residents aged 50-64 years. Cases (n=330) were identified from laboratory-confirmed influenza reports to the Colorado Department of Public Health and Environment (CDPHE). Controls (n=1055) were recruited by random-digit dial telephone survey. VE was 60% (43-72%) and 48% (21-66%) among those without and with high-risk medical conditions, respectively. VE was 90% (68-97%) and 36% (0-63%) against influenza-related hospitalization for persons without and with high-risk conditions, respectively.

ETA: Ref. 52:

http://www.ncbi.nlm.nih.gov/sites/e...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

BACKGROUND: Different types of influenza vaccines are currently produced world-wide. Healthy adults are at present targeted only in North America. Despite the publication of a large number of clinical trials, there is still substantial uncertainty about the clinical effectiveness of influenza vaccines and this has a negative impact on their acceptance and uptake. OBJECTIVES: To identify, retrieve and assess all studies evaluating the effects (efficacy, effectiveness and harms) of vaccines against influenza in healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2005) which contains the Cochrane Acute Respiratory Infections Group trials register; MEDLINE (January 1966 to January 2006); and EMBASE (1990 to January 2006). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, no intervention. Live, attenuated, or killed vaccines or fractions of them administered by any route, irrespective of antigenic configuration were assessed. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 16 to 65 years were considered. Comparative non-randomised studies were included if they assessed evidence of the possible association between influenza vaccines and serious harms. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Forty-eight reports were included: 38 (57 sub-studies) were clinical trials providing data about effectiveness, efficacy and harms of influenza vaccines and involved 66,248 people; 8 were comparative non-randomised studies and tested the association of the vaccines with serious harms; 2 were reports of harms which could not be introduced in the data analysis.Inactivated parenteral vaccines were 30% effective (95% CI 17% to 41%) against influenza-like illness, and 80% (95% CI 56% to 91%) efficacious against influenza when the vaccine matched the circulating strain and circulation was high, but decreased to 50% (95% CI 27% to 65%) when it did not. Excluding the studies of the 1968 to 1969 pandemic, effectiveness was 15% (95% CI 9% to 22%) and efficacy was 73% (95% CI 53% to 84%). Vaccination had a modest effect on time off work, but there was insufficient evidence to draw conclusions on hospital admissions or complication rates. Inactivated vaccines caused local tenderness and soreness and erythema. Spray vaccines had more modest performance. Monovalent whole-virion vaccines matching circulating viruses had high efficacy (VE 93%, 95% CI 69% to 98%) and effectiveness (VE 66%, 95% CI 51% to 77%) against the 1968 to 1969 pandemic. AUTHORS' CONCLUSIONS: Influenza vaccines are effective in reducing cases of influenza, especially when the content predicts accurately circulating types and circulation is high. However, they are less effective in reducing cases of influenza-like illness and have a modest impact on working days lost. There is insufficient evidence to assess their impact on complications. Whole-virion monovalent vaccines may perform best in a pandemic.

 

[Professor Yaffle]

How close are we to developing a universal flu vaccine? Is it a strong possibility, or just some slightly promising research that has been Daily Mailed:

http://www.dailymail.co.uk/pages/li...ain.html?in_article_id=425227&in_page_id=1774

 

[fls]

The benefits of flu vaccination appear unclear.

The most recent Skeptics Guide to the Universe podcast features an interview with Dr Mark Crislip, an infectious diseases specialist. He debunked many myths about the flu vaccine and concluded it was safe and effective.

However the Lancet Infectious Diseaseshas a recently published paper calling into doubt the benefits of vaccination for the over 65's. This group is the main focus of many vaccination programs, certainly in the UK.

Sorry the link is not directly to the Lancet

It's not really calling into doubt the benefits, but rather the extent of the benefit if that makes sense. The link that Kelly provided earlier does a better job of summarizing the paper, I think.

http://www.cidrap.umn.edu/cidrap/content/influenza/general/news/oct0907elderly.html

There is a fairly consistent reduction in mortality of 40 to 50 percent in various studies. The question becomes in what way are those excess deaths related to influenza?

Are they simply related to characteristics of people who are vaccinated vs. those who aren't - the healthy-vacinee selection? That is, have we simply found a way to divide people into groups at higher and lower risk of death for other reasons? Studies taking that into consideration (such as the Nichol study) don't find evidence of this effect, and if it were present wouldn't account for much.

Do they simply reflect the combination of an effective vaccine and the expected number of influenza-related deaths in the general population? I think Simonsen is directing his complaint at the assumption, and I think it is a valid complaint. The expected number of influenza-related deaths in the relevant population is much lower (he mentions 5 percent). This suggests that what happens during the study is much different from what happens in the general population. Some of these differences are obvious - studies showing this difference focus only on the highest risk period where influenza-related deaths are a higher proportion of all deaths. And the study populations are also at a higher risk of their death being related to influenza. So these studies will over-estimate the magnitude of the impact if applied directly to a general population. If you want a better estimate, you need studies that more directly answer that question. The question is whether trying to obtain the answer to that question with RCT's is ethical given that the answer wouldn't change the current recommendations nor the direction of current research towards more immunogenic vaccines and use of anti-viral drugs.

Linda

 

[JEROME DA GNOME]

Jerome, unless you cite a source so we can see if we agree with your interpretation of the facts, no one in this forum is likely to believe what you post.

I did earlier in the thread. I was reiterating the point.

 

[kellyb]

Is this correct or incorrect?

http://archinte.ama-assn.org/cgi/content/full/165/3/265#IOI40800T1

UNADJUSTED NUMBERS OF SEASONAL EXCESS DEATHS, 1968 TO 2001
Excess all-cause mortality was only a small portion of the approximately 500 000 deaths that occur annually among the elderly during winter months, never exceeding 10%

Also..I remember this from a few years ago, when Chiron had the contamination issues and we had a huge national shortage of flu vaccines. It was supposed to be the deadliest circulating flu virus in recent years...

Our results have obvious implications for influenza vaccination policy. For the 2004-2005 season, we face a severe influenza vaccine shortage that will likely result in lower coverage among the elderly, and the effect of this shortfall on mortality is a matter of great interest.37 The present findings, and those of at least 1 other study,35 indicate that the shortage will have little impact, perhaps owing to disparities in vaccination rates33-34 and possibly vaccine failure due to immune senescence.38 Other cohort studies suggest that the shortage will have a tremendous impact on mortality among the elderly.13-19,36 Either way, this vast disconnect between conclusions from different studies must be sorted out.

Who ended up being right there?

And just for fun:

http://www.thelancet.com/journals/lancet/article/PIIS0140673605678841/fulltext

We believe that the vaccine effectiveness estimates derived from cohort studies reporting on mortality, for example, are—literally—unbelievably large. Jefferson and colleagues compile cohort study results for prevention of death from all causes, and find a vaccine effectiveness of 47% in community-dwelling elderly people. But because the periods during which the underlying cohort studies record mortality typically include the entire winter season, this estimate implies that influenza is involved in about half of all winter deaths among elderly people, which in turn would mean that influenza is the leading contributing factor to winter mortality in this age-group. This figure is in stark contrast to the finding from our excess-mortality study, which showed that influenza is associated with an average of about 5% of all winter deaths in this age-group.

 

[kellyb]

In the elderly, the same systematic reviews said a lot of it had to be due to selection bias, right?

No. They concluded the vaccines were effective and added there may be some effect from selection bias (i.e. healthy vacinee bias).

You answered "no" and then went on to explain how the answer is "yes".

Here's what they said:


http://www.thelancet.com/journals/lancet/article/PIIS0140673605673394/fulltext

We think the residual heterogeneity could be the result of the unpredictable nature of the spread of influenza and influenza-like illness and the bias caused by the non-randomised nature of our evidence base. The findings of the cohort studies that we included are likely to have been affected to a varying degree by selection bias;

A further example of the potential effect of such bias is the apparently counterintuitive effectiveness of the vaccines in elderly individuals living in the community. In this population, the vaccines are apparently ineffective in the prevention of influenza, influenza-like illness, pneumonia, hospital admissions, or deaths from any respiratory disease, but are effective in the prevention of hospital admission for influenza and pneumonia and in the prevention of deaths from all causes. That such differences are the result of a baseline imbalance in health status and other systematic differences in the two groups of participants cannot be discounted. Evidence from randomised controlled trials, in which bias is reduced to a minimum, is scant and badly reported. Unfortunately, because of the global recommendations on influenza vaccination, placebo-controlled trials, which could clarify the effects of influenza vaccines in individuals, are no longer possible on ethical grounds.

 

[dudalb]

The Anti Vaccination woo amazes me because so many people buy into it who should really,really,know better.
Some are diving by paranoia against that all purpose villian "big Pharma",others,on the opposite end of the spectrum,by standard issue "Government is Evil" theories.

 

[fls]

You answered "no" and then went on to explain how the answer is "yes".

I went on to explain that while they mentioned that the presence of a particular type of selection bias wasn't ruled-out, other studies, like the Nichol study, did not find evidence that it had much of an effect.

Here's what they said:

http://www.thelancet.com/journals/lancet/article/PIIS0140673605673394/fulltext

My intention with post #107 was to explain the differences between some types of selection bias and how they were relevant. That explanation would apply here as well.

Linda

 

[fls]

Is this correct or incorrect?

http://archinte.ama-assn.org/cgi/content/full/165/3/265#IOI40800T1

The question is, what kind of biases could be influencing the results and whether they pose a threat to internal or external validity. They appear to be more of a threat to external validity which means that while you can draw conclusions about the effectiveness of the vaccine, there is a disconnect when attempting to estimate the magnitude of the impact in the general population. In particular, I think this quote from the article is relevant - "we conclude, therefore, that there are not enough influenza-related deaths to support the conclusion that vaccination can reduce total winter mortality among the US elderly population by as much as half."

Linda

 

[kellyb]

The question is, what kind of biases could be influencing the results and whether they pose a threat to internal or external validity.

I'd say the question is "Does this implausible/impossible finding suggest that there is some bias here?"
Once that's established (or not) you can move onto figuring out what it might or might not be.

They appear to be more of a threat to external validity which means that while you can draw conclusions about the effectiveness of the vaccine, there is a disconnect when attempting to estimate the magnitude of the impact in the general population.

I'm not following you at all. (I guess).
If there's obviously a bias present in the study, it impacts the findings of the study in the group that was just studied...not just extrapolation to the general population.

In particular, I think this quote from the article is relevant - "we conclude, therefore, that there are not enough influenza-related deaths to support the conclusion that vaccination can reduce total winter mortality among the US elderly population by as much as half."

They also say that a study that finds such a thing must have some serious biases present, which casts doubt on the other findings of the study. That seems to be the opinion of the NIH/NIAID people and the Cochrane Collaboration.

 

[fls]

I'd say the question is "Does this implausible/impossible finding suggest that there is some bias here?"
Once that's established (or not) you can move onto figuring out what it might or might not be.

Okay.

I'm not following you at all. (I guess).
If there's obviously a bias present in the study, it impacts the findings of the study in the group that was just studied...not just extrapolation to the general population.

Not really. There are many different kinds of bias and they affect different kinds of validity differently.

They also say that a study that finds such a thing must have some serious biases present, which casts doubt on the other findings of the study. That seems to be the opinion of the NIH/NIAID people and the Cochrane Collaboration.

Not really. Biases, such as the ones they are considering, have independent effects. For example, if a choose a bunch of basketball players when attempting to find the average height of US males, that my sample is unrepresentative does not mean that their measured height is inaccurate.

Linda

 

[Skeptic Ginger]

No, it is not nonsense at all. It is basic supply and demand. Companies with shareholders are not going to waste money scaling up production facilities and making bucket loads of flu vaccine unless they have a market for it. So how is the demand for flu vaccination being grown?

It would seem by promoting it as more effective than it actually is and making flu sound like it's set to become the next plague. Nice to see those in public health communications have learned something from alternative medicine.

I still don't see why they could not appeal to peoples' rational mind, and explain why having a large manufacturing base for flu vaccine will be essential if many deaths are to be avoided from a future pandemic.

It is rather ironic that you, of all people, should be supportive of a marketing campaign which aims to motivate people by appealing to their irrational mind.

Public health agencies are promoting flu vaccinations and when there wasn't enough vaccine the last couple years, public health also instituted some policies to encourage reluctant manufacturers to produce more vaccine. This year more producers are in the market.

You need to stop putting everything into a single category: drug company profit. Everything medical does not revolve around that concept. Believe it or not, a whole bunch of people in medicine are professionals who gain satisfaction from doing a good job. Some of them are public health officials and practitioners. Public health practitioners recognize the benefit of getting more flu vaccine doses to the public. They recognize the benefit and the barriers. Public health has a mission which includes promoting things like flu vaccination because it benefits public health. I don't know a single provider who has stock in a drug company or makes decisions about their job based on promoting the pharmaceutical industry's profit margin.

Drug companies are not charged with the mission of promoting public health. Of course they don't want to produce vaccine there is no market for. Because flu vaccine is only good for the specific season, production has to be matched to the market. But sometimes the demand changes during the flu season. A couple years ago an increase in pediatric deaths from flu occurred sparking a demand for flu vaccine. But supplies were already used up.

Year before last half the supply was contaminated and had to be tossed. There were only 2 flu vaccine manufacturers producing vaccine for the US market. That was bad.

In order to address these problems, the public health has to guarantee a market for vaccine. We can't expect the manufacturers to over produce but if we need a back up supply then overproduction is called for. So public health has been trying to address these problems.

You seem to think any marketing of something which evidence shows benefits the public health is just a marketing scheme for someone's profit. That is naive.

 

[robinson]

Do flu vaccines still contain Thimerosal?

 

[Skeptic Ginger]

The Anti Vaccination woo amazes me because so many people buy into it who should really,really,know better.
Some are diving by paranoia against that all purpose villian "big Pharma",others,on the opposite end of the spectrum,by standard issue "Government is Evil" theories.

Add to that the, "Natural things are better and vaccines are artificial", and, "The diseases are gone because we have better sanitation, not because of vaccines" myths.

 

[Skeptic Ginger]

Do flu vaccines still contain Thimerosal?

Flu vaccines in multi-dose vials contain thimerosal. Flu vaccines in single dose vials or syringes don't.

But thimerosal is just another boogey man. There has never been any actual observed data linking thimerosal to vaccine side effects despite much research looking for it.

 

[Procida]

Considering the amount of time and effort required to gain approval for a medicine or drug, how can each years new flu vaccines possibly meet the safety and efficiency test before being used?

How can anyone even know if they are safe? And that the vaccine actually works? Where is the science to back up the claims made?

They can't back it up, because of the logistics. The situation which applied in 2003 applies today:

URL broken to allow 'take':

fda.gov /ohrms/dockets/ac /03/transcripts/3922t1.doc

DR. DECKER: Yes, Dr. Royal, let me help answer your question. You caught Sam offguard because he's just focused on manufacturing.

The simple answer is nobody can do anything to address that. Everyone has to take it on faith that the strains selected, if grown properly and inoculated, will produce the relevant antibodies and they will not only work against that strain, but they will, hopefully, work against whatever circulates.

All that has to be taken on faith, because by the time you produce it, there's no time left to do any testing. Were there any time to do testing, there would be no time left to manufacture anything.

So from the manufacturer's point of view, their obligation is to produce whatever this Committee tells them to produce. Whether or not it works has to be based on the faith that the data collected by CDC and FDA and presented to this Committee will be relevant and accurate.

.....And then just further to the clinical side of things, we don't really ever know how immunogenic any particular strain is going to be before a vaccine is manufactured, and there really isn't time to do the kind of clinical trials you would anticipate for any other kind of vaccine. Influenza virus vaccine is different from every other one in that it is changed almost every year and it's a new experience with each one.