Vaccine efficacy

Vaccine efficacy is the percentage reduction of disease in a vaccinated group of people compared to an unvaccinated group, using the most favorable conditions.[1] Vaccine efficacy was designed and calculated by Greenwood and Yule in 1915 for the cholera and typhoid vaccines. It is best measured using double-blind, randomized, clinical controlled trials, such that it is studied under "best case scenarios."[2] Vaccine effectiveness differs from vaccine efficacy in that vaccine effectiveness shows how well a vaccine works when they are always used and in a bigger population whereas vaccine efficacy shows how well a vaccine works in certain, often controlled, conditions.[1] Vaccine efficacy studies are used to measure several possible outcomes such as disease attack rates, hospitalizations, medical visits, and costs.

Influenza Vaccine

Vaccine efficacy formulaEdit

The outcome data (vaccine efficacy) generally are expressed as a proportionate reduction in disease attack rate (AR) between the unvaccinated (ARU) and vaccinated (ARV), or can be calculated from the relative risk (RR) of disease among the vaccinated group.[3][4][5]

The basic formula[6] is written as:

 
with
  •   = Vaccine efficacy,
  •   = Attack rate of unvaccinated people,
  •   = Attack rate of vaccinated people.

An alternative, equivalent formulation of vaccine efficacy

 
where   is the relative risk of developing the disease for vaccinated people compared to unvaccinated people.

Testing for efficacyEdit

Vaccine efficacy differs from vaccine effectiveness in the same way that an explanatory clinical trial differs from an intention to treat trial[clarification needed]: vaccine efficacy shows how effective the vaccine could be given ideal circumstances and 100% vaccine uptake; vaccine effectiveness measures how well a vaccine performs when it is used in routine circumstances in the community.[7] What makes the vaccine efficacy applicable is that it shows the disease attack rates as well as a tracking of vaccination status.[jargon][7] Vaccine effectiveness is more easily tracked than the vaccine efficacy considering the difference in environment;[vague] however, the vaccine efficacy is more expensive and difficult to conduct. Because the trial is based on people who are taking the vaccination and those not vaccinated, there is a risk for disease, and optimal treatment is needed for those who become infected.

The advantages of a vaccine efficacy have control for all biases that would be found with randomization, as well as prospective, active monitoring for disease attack rates, and careful tracking of vaccination status for a study population there is normally a subset as well, laboratory confirmation of the infectious outcome of interest and a sampling of vaccine immunogenicity.[7][failed verification] The major disadvantages of vaccine efficacy trials are the complexity and expense of performing them, especially for relatively uncommon infectious outcomes of diseases for which the sample size required is driven up to achieve clinically useful statistical power.[7]

It has been proposed that standardized statements of efficacy be parametrically expanded to include multiple categories of efficacy in a table format. While conventional efficacy / effectiveness data typically shows ability to prevent a symptomatic infection, this expanded approach could include prevention of outcomes categorized to include symptom class, viral damage minor/serious, hospital admission, ICU admission, death, various viral shedding levels, etc. Capturing effectiveness at preventing each of these "outcome categories" is typically part of any study and could be provided in a table with clear definitions instead of being inconsistently presented in study discussion as is typically done in past practice. Some 2021 era COVID-19 studies appear to be implementing similar methods and presentation. Improved methods and presentation remain desirable.[8][9]


Risks to be consideredEdit

Vaccine efficacy is calculated on a population basis. It is therefore relatively easy to misunderstand its application.[further explanation needed]

Cases studiedEdit

The NEJM did a study on the A flu efficacy Influenza virus. A total of 1952 subjects were enrolled and received study vaccines in the fall of 2007. Influenza activity occurred from January through April 2008, with the circulation of influenza types:

  • A (H3N2) (about 90%)
  • B (about 9%).

Absolute efficacy against both types of influenza, as measured by isolating the virus in culture, identifying it on real-time polymerase-chain-reaction assay, or both, was 68 percent (95 percent confidence interval [CI], 46 to 81) for the inactivated vaccine and 36 percent (95 percent CI, 0 to 59) for the live attenuated vaccine. In terms of relative efficacy, there was a 50 percent (95 percent CI, 20 to 69) reduction in laboratory-confirmed influenza among subjects who received inactivated vaccine as compared with those given live attenuated vaccine. Subjects were healthy adults. The efficacy against the influenza A virus was 72 percent and for the inactivated was 29 percent with a relative efficacy of 60 percent.[10] The influenza vaccine is not 100% efficacious in preventing disease, but it is as close to 100% safe, and much safer than the disease.[11][medical citation needed]

Since 2004, clinical trials testing the efficacy of the influenza vaccine have been drifting in: 2058 people were vaccinated in October and November 2005. Influenza activity was prolonged but of low intensity; type A (H3N2) was the virus that was generally going around the population, which was very like the vaccine itself. The efficacy of the inactivated vaccine was 16% (95% confidence interval [CI], -171% to 70%) for the virus identification end point (virus isolation in cell culture or identification through polymerase chain reaction) and 54% (95% CI, 4%-77%) for the primary end point (virus isolation or increase in serum antibody titer). The absolute efficacies of the live attenuated vaccine for these end points were 8% (95% CI, -194% to 67%) and 43% (95% CI, -15% to 71%).[12]

With serologic end points included, efficacy was demonstrated for the inactivated vaccine in a year with low influenza attack rates. 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.

ReferencesEdit

  1. ^ a b Zimmer, Carl (20 November 2020). "2 Companies Say Their Vaccines Are 95% Effective. What Does That Mean? You might assume that 95 out of every 100 people vaccinated will be protected from Covid-19. But that's not how the math works". The New York Times. Retrieved 21 November 2020.
  2. ^ (Weinburg, G., & Szilagyi, P. (2010). Vaccine Epidemiology: Efficacy, Effectiveness, and the Translational Research Roadmap. Journal of Infectious Diseases, 201(11), 1607-1610.)
  3. ^ Weinberg, Geoffrey A.; Szilagyi, Peter G. (2010-06-01). "Vaccine Epidemiology: Efficacy, Effectiveness, and the Translational Research Roadmap". The Journal of Infectious Diseases. 201 (11): 1607–1610. doi:10.1086/652404. ISSN 0022-1899.
  4. ^ Clemens, J.; Brenner, R.; Rao, M.; Tafari, N.; Lowe, C. (1996-02-07). "Evaluating new vaccines for developing countries. Efficacy or effectiveness?". JAMA. 275 (5): 390–397. ISSN 0098-7484. PMID 8569019.
  5. ^ Orenstein, W. A.; Bernier, R. H.; Hinman, A. R. (1988). "Assessing vaccine efficacy in the field. Further observations". Epidemiologic Reviews. 10: 212–241. doi:10.1093/oxfordjournals.epirev.a036023. ISSN 0193-936X. PMID 3066628.
  6. ^ Orenstein WA, Bernier RH, Dondero TJ, Hinman AR, Marks JS, Bart KJ, Sirotkin B (1985). "Field evaluation of vaccine efficacy". Bull. World Health Organ. 63 (6): 1055–68. PMC 2536484. PMID 3879673.
  7. ^ a b c d "How flu vaccine effectiveness and efficacy are measured". Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, US Department of Health and Human Services. 2016-01-29. Retrieved 2020-05-06.
  8. ^ "Clearly Defining Re-exposure Protection And Vaccine Efficacy Statistical Results". OSF Preprints.
  9. ^ "Rapid Response: Re: Covid-19: Past infection provides 83% protection for five months but may not stop transmission, study finds". British Medical Journal.
  10. ^ Crislip (2009) cited Monto, Arnold S.; Ohmit, Suzanne E.; Petrie, Joshua G.; Johnson, Emileigh; Truscon, Rachel; Teich, Esther; Rotthoff, Judy; Boulton, Matthew; Victor, John C. (2009). "Comparative Efficacy of Inactivated and Live Attenuated Influenza Vaccines". New England Journal of Medicine. 361 (13): 1260–1267. doi:10.1056/NEJMoa0808652. ISSN 0028-4793. PMID 19776407.
  11. ^ Crislip, M (2009-10-09). "Flu Vaccine Efficacy". Science-Based Medicine. Archived from the original on 2020-06-01.
  12. ^ Crislip (2009) cited Ohmit, Suzanne E.; Victor, John C.; Teich, Esther R.; Truscon, Rachel K.; Rotthoff, Judy R.; Newton, Duane W.; Campbell, Sarah A.; Boulton, Matthew L.; Monto, Arnold S. (2008). "Prevention of Symptomatic Seasonal Influenza in 2005–2006 by Inactivated and Live Attenuated Vaccines". The Journal of Infectious Diseases. 198 (3): 312–317. doi:10.1086/589885. ISSN 0022-1899. PMC 2613648. PMID 18522501.