Vaccines and Lotteries: Part II

In a previous article I talked about how vaccine recipients are in a sense playing a lottery. Most individual receiving a vaccine will benefit, but a few will not mount an adequate immune response and the vaccine will fail. The vaccine lottery, however, has a lot of winners and only a few losers, unlike the Powerball lottery. The only consistent winners in the Powerball lottery are the state governments who win with every ticket sold!

What if you were the lottery's primary beneficiary? Let’s pretend a federal lottery is begun with all profit (several billion dollars per year) to be allocated to the NIH to spend as they see fit. Assume you are in charge of the NIH with the power to distribute these funds for research. You decide to focus the funding from this windfall in a single area-influenza. Following is a list of options for that area prepared for you by your staff. Which do you think would provide the most benefit?  There’s no single “correct” answer here, but in my opinion, some choices are better than others.

[[{"type":"media","view_mode":"media_crop","fid":"46779","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_5102416450697","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5451","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right; width: 310px; height: 260px;","title":"©Volt Collection/Shutterstock.com","typeof":"foaf:Image"}}]]Imaginary Influenza Programs to Receive Federal Lottery Payout

A. Influenza remains a huge problem for the US with tens of thousands of excess deaths per year, mostly in the over-65-years-of-age cohort. You will use the funding to boost the influenza vaccination rate in this age group with advertising, free home visits, vaccine clinics in retirement areas, etc. You will also mandate use of the “high-dose” vaccine which has been documented to be more effective than the regular flu shot.

B. The efficacy of the influenza vaccine leaves a lot to be desired. You decide to fund research into a better vaccine. Your staff is confident it can get the efficacy up to perhaps 90%.

C. Data from Japan and the US suggest that children are the primary vectors of influenza, giving it to each other at school and then bringing flu home and transmitting it to parents and grandparents. You will use the funding to start an in-school vaccination program. Your staff assures you that the political climate is right for making flu vaccine a required vaccine for school attendance. More than 95% of children would get vaccinated with this option.

For answer and discussion, please click here.

Discussion

Too bad there isn’t an option D, “All of the above.” 

Option A would be my third choice, since this age group (adults older than age 65) already has the highest rate of vaccination, 67% in 2014-15.  Obviously, a higher rate would help reduce mortality and morbidity in this susceptible population.

Option B is enticing.  Flu vaccine effectiveness studies show wildly variable results depending upon how well matched the vaccine strains were in a given year to the circulating flu strains. Other variables include whether the study is looking at the reduction of culture-positive specimens versus the reduction in “influenza-like illness.” Previous randomized controlled trials (RCT) showed effectiveness ranging from 16%-75%.  RCTs can no longer be performed in the US because of the universal recommendation for all persons over the age of 6 months to get the vaccine.  Institution Review Boards overseeing clinical trials would consider a placebo arm unethical.  So, we are stuck with mostly observational studies with their inherent problems with selection bias and confounding factors.

[[{"type":"media","view_mode":"media_crop","fid":"46780","attributes":{"alt":"","class":"media-image media-image-right","height":"349","id":"media_crop_4717155450480","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5452","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"©mathagraphics/Shutterstock.com ","typeof":"foaf:Image","width":"255"}}]]A downside to option B is that a better vaccine won't help persons refusing to get immunized other than through herd immunity which would require a much higher vaccination rate than we now have. In last year's flu season (2015), 59% of children were vaccinated and 44% of all adults over the age of 17 were vaccinated. On the other hand, if we had a better vaccine maybe we could achieve a higher rate. How many times have you heard a patient tell you, “I got the flu shot once and still got the flu, so I don't bother with it anymore.” A Cochrane Library meta-analysis gives a number needed to vaccinate to prevent one case of confirmed influenza as 71. In other words, if you are 70 years old and have gotten a flu vaccine every year of your life, you will, on average, have prevented only 1 case of the flu in yourself. Clearly, we need a better vaccine.

The best data supporting option C comes from a NEJM retrospective, observational article looking at the impact in Japan of mandating flu vaccine in school children. The flu pandemic of 1957 hit Japan hard. Their epidemiologists concluded that attack rates were much higher in areas that kept schools open. They then promoted the routine use of flu vaccine in children and even made flu vaccine mandatory for school children for about 10 years between the mid-1970's and 1980's. Following the improved vaccination rate in children, the excess death rate in adults during the flu season plummeted even though adult flu vaccine rates did not change. 

In the late 1980's, Japan stopped giving DPT shots due to concerns over safety which unfortunately lead to the mandatory flu vaccine program cancellation and the vaccine rate dropped by a huge amount. Over the next several years, the excess death rate during influenza season climbed back up to the rates seen before the mandatory vaccine program. The authors estimated that for every 571 children vaccinated, 1 adult death was prevented.  Throughout the entire period, adult vaccine rates remained low suggesting a strong impact of herd immunity in children. A number of studies have been done in the US promoting flu vaccine to children in some school districts and not others in the same area with significant reductions in adult flu cases in areas with higher child vaccination rates.

In the long run, I think option B (if achievable) would be the best. Option C could be done right now if someone had the political willpower to advance the agenda.

Resources

This breaks down the vaccination rate by age, race, sex, etc.
http://www.cdc.gov/flu/fluvaxview/coverage-1415estimates.htm

This is the Cochrane database analysis of influenza vaccine effectiveness. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001269.pub5/abstract. 

This is the article looking at the power of herd immunity in children on adult flu deaths http://www.nejm.org/doi/full/10.1056/NEJM200103223441204