vaccine efficacy

Vaccine efficacy differs from vaccine effectiveness in the same way that an {{Clarify|text=explanatory clinical trial differs from an intention-to-treat trial|date=June 2020|reason=The link given doesn't explain further how vaccine efficacy differs from vaccine effectiveness, or how "explanatory clinical trial" differs from "intention-to-treat trial". Maybe dropping this simile would be simpler?}}: vaccine efficacy shows how effective a vaccine could be given ideal circumstances and 100% vaccine uptake (such as the conditions within a controlled clinical trial); vaccine effectiveness measures how well a vaccine performs when it is used in routine circumstances in the community.{{Cite web |date=2016-01-29 |title=How flu vaccine effectiveness and efficacy are measured |url=https://www.cdc.gov/flu/vaccines-work/effectivenessqa.htm?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fflu%2Fprofessionals%2Fvaccination%2Feffectivenessqa.htm |access-date=2020-05-06 |publisher=Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, US Department of Health and Human Services}} What makes vaccine efficacy relevant is that it shows the disease attack rates as well as a tracking of vaccination status.{{Technical inline|date=June 2020}} Vaccine effectiveness is relatively inexpensive to measure than vaccine efficacy. The measurement of vaccine effectiveness relies on observational studies which are usually easier to perform, whereas a vaccine efficacy measurement requires randomized controlled trials which are time and capital intensive.{{cite journal |last1=Ferreira |first1=Juliana Carvalho |last2=Patino |first2=Cecilia Maria |year=2016 |title=Choosing wisely between randomized controlled trials and observational designs in studies about interventions |journal=Jornal Brasileiro de Pneumologia |volume=42 |issue=2016 |page=165-165 |doi=10.1590/S1806-37562016000000152 |pmc=5569603 |pmid=27383927}} Because a clinical trial is based on people who are taking the vaccine and those who are not, there is a risk for disease, and optimal treatment is needed for those who become infected.

The advantages of measuring vaccine efficacy is having the ability to control for selection bias, 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.{{Failed verification|date=June 2020|reason=The reasons mentioned here aren't mentioned directly in the referenced web page, but maybe in the references that the web page itself uses. Also, not knowing what the "right" contents should be, it's currently impossible to fix this obviously run-on sentence.}} 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. Vaccine effectiveness estimates obtained from observational studies are usually subject to selection bias.{{cite journal |last1=Jackson |first1=Michael |last2=Phillips |first2=Hallie |last3=Benoit |first3=Joyce |last4=Kiniry |first4=Erika |last5=Madziwa |first5=Lawrence |last6=Nelson |first6=Jennifer |last7=Jackson |first7=Lisa |date=2018 |title=The impact of selection bias on vaccine effectiveness estimates from test-negative studies |journal=Vaccine |volume=36 |issue=5 |pages=751–757 |doi=10.1016/j.vaccine.2017.12.022 |pmid=29254838}} Since 2014, epidemiologists have used quasi-experimental designs to obtain unbiased estimates of vaccine effectiveness.{{cite journal |last1=Basta |first1=Nicole |last2=Halloran |first2=Elizabeth |date=2019 |title=Evaluating the effectiveness of vaccines using a regression discontinuity design |journal=American Journal of Epidemiology |volume=188 |issue=6 |pages=987–990 |doi=10.1093/aje/kwz043 |pmc=6580688 |pmid=30976806}}{{cite journal |last1=Bor |first1=Jacob |last2=Moscoe |first2=Ellen |last3=Mutevedzi |first3=Portia |last4=Newell |first4=Marie-Louise |last5=Barnighausen |first5=Till |date=2014 |title=Regression discontinuity designs in epidemiology: causal inference without randomized trials |journal=Epidemiology |volume=25 |issue=5 |pages=729–737 |doi=10.1097/EDE.0000000000000138 |pmc=4162343 |pmid=25061922}}{{cite journal |last1=Mukherjee |first1=Abhiroop |last2=Panayotov |first2=George |last3=Sen |first3=Rik |last4=Dutta |first4=Harsha |last5=Ghosh |first5=Pulak |date=2022 |title=Measuring vaccine effectiveness from limited public health datasets: Framework and estimates from India's second COVID wave |journal=Science Advances |volume=8 |issue=18 |pages=eabn4274 |bibcode=2022SciA....8N4274M |doi=10.1126/sciadv.abn4274 |pmc=9075799 |pmid=35522748}}

Standardized statements of efficacy may be parametrically expanded to include multiple categories of efficacy in a table format. While conventional efficacy/effectiveness data typically shows the 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.{{Cite journal |last1=Hodgson |first1=Susanne H. |last2=Mansatta |first2=Kushal |last3=Mallett |first3=Garry |last4=Harris |first4=Victoria |last5=Emary |first5=Katherine R. W. |last6=Pollard |first6=Andrew J. |date=February 2021 |title=What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2 |journal=The Lancet. Infectious Diseases |volume=21 |issue=2 |pages=e26–e35 |doi=10.1016/S1473-3099(20)30773-8 |issn=1474-4457 |pmc=7837315 |pmid=33125914}}

Biological exposures such as parasites affect the immune responses after vaccination.{{Cite journal |last1=Cunnington |first1=Aubrey J |last2=Riley |first2=Eleanor M |date=April 2010 |title=Suppression of vaccine responses by malaria: insignificant or overlooked? |url=http://www.tandfonline.com/doi/full/10.1586/erv.10.16 |journal=Expert Review of Vaccines |language=en |volume=9 |issue=4 |pages=409–429 |doi=10.1586/erv.10.16 |pmid=20370551 |issn=1476-0584|url-access=subscription }} This can be seen in areas with a high burden of parasitic infections where vaccine responses are low for vaccines such as BCG.{{Cite journal |last=Fine |first=P.E.M. |date=1995-11-18 |title=Variation in protection by BCG: implications of and for heterologous immunity |url=https://linkinghub.elsevier.com/retrieve/pii/S0140673695923489 |journal=The Lancet |language=en |volume=346 |issue=8986 |pages=1339–1345 |doi=10.1016/S0140-6736(95)92348-9|pmid=7475776 |url-access=subscription }} Infections like malaria suppress immune responses to polysaccharide vaccines. A potential solution is to give curative treatment before vaccination in areas where malaria is present. The effect of parasites on vaccine response has also been observed in individuals infected by helminths in areas that have a high burden of infectious diseases. Established helminth infections at the time of vaccination affect vaccine responses.{{Cite journal |last1=Natukunda |first1=Agnes |last2=Zirimenya |first2=Ludoviko |last3=Nassuuna |first3=Jacent |last4=Nkurunungi |first4=Gyaviira |last5=Cose |first5=Stephen |last6=Elliott |first6=Alison M. |last7=Webb |first7=Emily L. |date=17 June 2022 |title=The effect of helminth infection on vaccine responses in humans and animal models: A systematic review and meta-analysis |journal=Parasite Immunology |language=en |volume=44 |issue=9 |pages=e12939 |doi=10.1111/pim.12939 |issn=0141-9838 |pmc=9542036 |pmid=35712983}}

Other biological factors such as smoking, age, sex, and nutrition also affect vaccine responses. In the case of hepatitis B vaccine, for example, increasing age, being male, having a body mass index > 25, and smoking can result in lower seroprotection rates.{{Cite journal |last1=Yang |first1=Shigui |last2=Tian |first2=Guo |last3=Cui |first3=Yuanxia |last4=Ding |first4=Cheng |last5=Deng |first5=Min |last6=Yu |first6=Chengbo |last7=Xu |first7=Kaijin |last8=Ren |first8=Jingjing |last9=Yao |first9=Jun |last10=Li |first10=Yiping |last11=Cao |first11=Qing |last12=Chen |first12=Ping |last13=Xie |first13=Tiansheng |last14=Wang |first14=Chencheng |last15=Wang |first15=Bing |date=2016-06-21 |title=Factors influencing immunologic response to hepatitis B vaccine in adults |journal=Scientific Reports |language=en |volume=6 |issue=1 |page=27251 |doi=10.1038/srep27251 |issn=2045-2322 |pmc=4914839 |pmid=27324884|bibcode=2016NatSR...627251Y }}

The composition of the gut microbiota might impact responses to vaccination, although there is insufficient evidence for the gut microbiota directly affecting vaccine efficacy.{{Cite journal |last1=Lynn |first1=David J. |last2=Benson |first2=Saoirse C. |last3=Lynn |first3=Miriam A. |last4=Pulendran |first4=Bali |date=17 May 2021 |title=Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms |journal=Nature Reviews Immunology |language=en |volume=22 |issue=1 |pages=33–46 |doi=10.1038/s41577-021-00554-7 |issn=1474-1733 |pmc=8127454 |pmid=34002068}}

{{See also|Relative risk reduction}}

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.{{Cite journal|last1=Weinberg|first1=Geoffrey A.|last2=Szilagyi|first2=Peter G.|date=2010-06-01|title=Vaccine Epidemiology: Efficacy, Effectiveness, and the Translational Research Roadmap|journal=The Journal of Infectious Diseases|volume=201|issue=11|pages=1607–1610|doi=10.1086/652404|pmid=20402594|s2cid=29528780 |issn=0022-1899|doi-access=}}{{Cite journal|last1=Clemens|first1=J.|last2=Brenner|first2=R.|last3=Rao|first3=M.|last4=Tafari|first4=N.|last5=Lowe|first5=C.|date=1996-02-07|title=Evaluating new vaccines for developing countries. Efficacy or effectiveness?|url=https://pubmed.ncbi.nlm.nih.gov/8569019/|journal=JAMA|volume=275|issue=5|pages=390–397|doi=10.1001/jama.1996.03530290060038|issn=0098-7484|pmid=8569019}}{{Cite journal|last1=Orenstein|first1=W. A.|last2=Bernier|first2=R. H.|last3=Hinman|first3=A. R.|date=1988|title=Assessing vaccine efficacy in the field. Further observations|url=https://pubmed.ncbi.nlm.nih.gov/3066628/|journal=Epidemiologic Reviews|volume=10|pages=212–241|doi=10.1093/oxfordjournals.epirev.a036023|issn=0193-936X|pmid=3066628}}

The basic formula{{cite journal |vauthors=Orenstein WA, Bernier RH, Dondero TJ, Hinman AR, Marks JS, Bart KJ, Sirotkin B |title=Field evaluation of vaccine efficacy |journal=Bull. World Health Organ. |volume=63 |issue=6 |pages=1055–1068 |date=1985 |pmid=3879673 |pmc=2536484 }} is written as:$$VE\; =\; \backslash frac\{ARU\; -\; ARV\}\{ARU\}\; \backslash times\; 100\backslash \%,$$with

• $VE$ = Vaccine efficacy,
• $ARU$ = Attack rate of unvaccinated people,
• $ARV$ = Attack rate of vaccinated people.

An alternative, equivalent formulation of vaccine efficacy is: $$VE\; =\; (1\; -\; RR)\; \backslash times\; 100\backslash \%,$$where $RR$ is the relative risk of developing the disease for vaccinated people compared to unvaccinated people.

The design of clinical trials ensures that regulatory approval is issued only for effective vaccines. However, during research, it is possible that an intervention actually increases the risk of participants, for example, in the STEP and Phambili studies, which were both intended to test an experimental HIV vaccine .{{Cite journal |vauthors=Fauci AS, Marovich MA, Dieffenbach CW, Hunter E, Buchbinder SP |date=2014-04-04 |title=Immune Activation with HIV Vaccines: Implications of the Adenovirus Vector Experience |journal=Science |volume=344 |issue=6179 |pages=49–51 |doi=10.1126/science.1250672 |issn=0036-8075 |pmc=4414116 |pmid=24700849}} In these cases, the formula would yield a negative efficacy value because $ARV\; >\; ARU$. A negative efficacy value is sometimes present in the lower limit of a confidence interval of an estimate of vaccine efficacy for specific clinical endpoints. While this means that the intervention may actually have a negative effect, it could also be simply due to small sample size or sample variability.

First, the baseline risk can be calculated for each group and then vaccine efficacy (RRR) as follows:

• \{24\backslash over\; 12221\}=0.196\; \backslash \% for the vaccinated group (24 infections)
• $\{106\backslash over\; 12198\}=0.86\; \backslash \%$ for the placebo group (106 infections)
• The relative risk, $RR=\{0.196\; \backslash over\; 0.86\}\; \backslash approx\; 0.23$

Then, $VE=(1-RR)\; \backslash times\; 100\; \backslash implies\; (1-0.23)\; \backslash times\; 100\; \backslash approx\; 77\backslash \%$

Also, the absolute risk reduction (ARR) for any vaccine can simply be obtained from calculating the difference of risks between the groups i.e. 0.86%–0.196% which renders a value of about 0.66% for the above example.

The New England Journal of Medicine did a study on the efficacy of a vaccine for the influenza A virus. A total of 1,952 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% (95% confidence interval [CI], 46 to 81) for the inactivated vaccine and 36% (95% CI, 0 to 59) for the live attenuated vaccine. In terms of relative efficacy, there was a 50% (95% 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% and for the inactivated was 29% with a relative efficacy of 60%.{{harvp | Crislip |2009 }} cited {{cite journal|last1=Monto|first1=Arnold S.|last2=Ohmit|first2=Suzanne E.|last3=Petrie|first3=Joshua G.|last4=Johnson|first4=Emileigh|last5=Truscon|first5=Rachel|last6=Teich|first6=Esther|last7=Rotthoff|first7=Judy|last8=Boulton|first8=Matthew|last9=Victor|first9=John C.|title=Comparative Efficacy of Inactivated and Live Attenuated Influenza Vaccines|journal=New England Journal of Medicine|volume=361|issue=13|year=2009|pages=1260–1267|issn=0028-4793|doi=10.1056/NEJMoa0808652|pmid=19776407|s2cid=205090564 |doi-access=free}} The influenza vaccine is not 100% efficacious in preventing disease, but it is close to 100% safe, and much safer than the disease.{{Cite journal |last1=Gidengil |first1=Courtney |last2=Goetz |first2=Matthew Bidwell |last3=Newberry |first3=Sydne |last4=Maglione |first4=Margaret |last5=Hall |first5=Owen |last6=Larkin |first6=Jody |last7=Motala |first7=Aneesa |last8=Hempel |first8=Susanne |date=2021-06-23 |title=Safety of vaccines used for routine immunization in the United States: An updated systematic review and meta-analysis |url=https://pubmed.ncbi.nlm.nih.gov/34049735 |journal=Vaccine |volume=39 |issue=28 |pages=3696–3716 |doi=10.1016/j.vaccine.2021.03.079 |issn=1873-2518 |pmid=34049735|s2cid=235241761 }}{{cite web | last1 = Crislip | first1 = M | date = 2009-10-09 | title = Flu Vaccine Efficacy | url = http://www.sciencebasedmedicine.org/flu-vaccine-efficacy | publisher = Science-Based Medicine | archive-url = https://web.archive.org/web/20200601042917/https://sciencebasedmedicine.org/flu-vaccine-efficacy/ | archive-date = 2020-06-01 | url-status = live }}

Since 2004, clinical trials testing the efficacy of the influenza vaccine have been slowly coming in: 2,058 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 spreading 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%).{{harvp | Crislip |2009 }} cited {{cite journal|last1=Ohmit|first1=Suzanne E.|last2=Victor|first2=John C.|last3=Teich|first3=Esther R.|last4=Truscon|first4=Rachel K.|last5=Rotthoff|first5=Judy R.|last6=Newton|first6=Duane W.|last7=Campbell|first7=Sarah A.|last8=Boulton|first8=Matthew L.|last9=Monto|first9=Arnold S.|title=Prevention of Symptomatic Seasonal Influenza in 2005–2006 by Inactivated and Live Attenuated Vaccines|journal=The Journal of Infectious Diseases|volume=198|issue=3|year=2008|pages=312–317|issn=0022-1899|doi=10.1086/589885|pmid=18522501|pmc=2613648}}

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.

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Category:Vaccination