This Article Extract Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Puliyel, J. M. Search for Related Content PubMed PubMed Citation Articles by Puliyel, J. M. Related Collections Related AAP Red Book topics: Measles Smallpox (Variola) Poliovirus Infections Social Bookmarking                         What's this?

PEDIATRICS Vol. 110 No. 1 July 2002, pp. 193

The Dummies’ Guide to Risk-Benefit Analysis of Vaccines

Jacob M. Puliyel, MD, MRCP, MPhil
Department of Pediatrics
St Stephens Hospital
Tis Hazari
Delhi-110054, India

To the Editor.—

In her article ‘The Rotavirus Vaccine Story: A Clinical Investigator’s View’ (Pediatrics 2000;106:123–125), Dr Margaret B. Rennels asks, "How many children are required to satisfy us that a vaccine is safe to licence and recommend?" In the case of rotavirus vaccine the excess risk of intussusception was 1 per 5000 vaccinated children. She says the risk-benefit decisions such as "how many serious adverse events are acceptable to save a life" are difficult to make. The author feels strongly about a vaccine she has helped develop and thinks "although the ACIP and AAP have withdrawn recommendations for use of the vaccine, the vaccine may still be indicated in other areas of the world." The issues raised are not as difficult as it is made out to be. The risk-benefit calculations used by health economists are actually quite easy to comprehend.

1. Let a represent the lifetime risk of an individual getting the disease in the community (usually given as a fraction, say 1 in a 1000).
   
2. Let b represent the fraction of those with disease likely to develop a serious complication (usually given as fractions say 1 in 100 or 1 in 1000 etc).
   
3. Let x represent the fraction of those vaccinated who develop a serious complication attributable to the vaccine.
   
4. Then a multiplied by b represents benefit and x represents the risk.
   

If x is greater than a multiplied by b, the vaccine should not be used as the risk of vaccine-related-complication is more than the risk of acquiring the disease in the community and getting a serious complication from it.

Assume that 1 in 10 of the population develops measles and assume 1 in a 1000 of those with measles develop subacute sclerosing panencephalitis (SSPE). Then the chance of SSPE is 1/10 (a) multiplied 1/1000 (b) = 1/10 000. Suppose 1 in a 100 000 of those who receive measles vaccine develops SSPE then the risk x is 1/100 000. The benefit is higher than the risk.

The factor x remains constant for any given vaccine. The factor b remains constant for a given illness. However, the factor a is different in different populations and changes with time.

x, a and b could also be reckoned in terms of economic costs of the disease and side effects.

The chance of contracting hepatitis A is much lower in Europe than in Asia. Thus, with its good sanitation, the vaccine risk may be too high for Europe but acceptable for its benefits in Asia. Smallpox risk is an example of how time alters the risk-benefit ratio. As long as smallpox was epidemic, the, risks of disease were more, compared with the risks of vaccination. However, after smallpox was eradicated, the risks of continuing with the vaccination program became unacceptably high compared with risk from the disease. The same is the problem with vaccine-induced polio in developed countries, where the risk of acquiring wild polio is now nearly eliminated.

Refinements may be incorporated to this simple formula. For a vaccine that has a very limited duration of protection (for example viral-influenza vaccination that must be given each year) instead of lifetime risk, the risk of the acquiring the disease each year may be considered.

A vaccine does not protect all those vaccinated. Suppose the vaccine protects 1 in 2 of those vaccinated, the benefit is reduced, and must be multiplied by a fraction c = in this case. a multiplied b, multiplied c must be greater than x.

The risk-benefit ratio is thus a dynamic mathematical solution to the question of, "Is the cure (prevention) worse than the disease?¹"

REFERENCE

1. Puliyel JM, Agarwal KS. Issues and controversies in contemporary immunization. In: Recent Advances in Pediatrics. 10th ed. Gupte S. Jaypee Brothers Medical Publishers; Delhi, India: 2000

---

PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Extract Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Puliyel, J. M. Search for Related Content PubMed PubMed Citation Articles by Puliyel, J. M. Related Collections Related AAP Red Book topics: Measles Smallpox (Variola) Poliovirus Infections Social Bookmarking                         What's this?