Abstract

PIP: This paper describes the epidemiological techniques available for measuring vaccine efficacy and recommends a practical approach to their use. The efficacy of vaccines in clinical use can be determined by a variety of means, including screening, outbreak investigations, secondary attack rates in families or clusters, vaccine coverage assessment, and case-control studies. They all offer a means of monitoring vaccine programs under conditions of day-to-day vaccine use. A table summarizes the different techniques for measuring efficacy. The screening technique is the most useful and rapid means of determining whether there is a problem with a vaccine. All that is required is a reliable estimate of the proportion of cases occurring in vaccinated individuals and an estimate of the vaccine coverage in the population at risk. If the estimated efficacy is within expected limits, more detailed studies are not warranted. If the results suggest low efficacy, more rigorous methods are necessary to assess the efficacy more accurately. Of the more accurate methods available, outbreak investigation offers the simplest means of measuring vaccine efficacy and is the preferred technique if the situation permits. The biases inherent in the method can be minimized, particularly if the disease incidence rate is high during the outbreak and accurate records exist. In large populations, the underlying immunization status prior to the outbreak can be estimated using the same cluster sampling method used in coverage assessments. Calculation of secondary attack rates in families is also an excellent and accurate means of measuring vaccine efficacy and is an acceptable alternative to the outbreak investigation. Vaccine coverage methods in endemic areas are best suited to urban areas where the measles incidence rate is high after age 11 months and low before 12 months, and maternal histories of disease are thought to be accurate. Case-control studies are best suited to areas where reliable personal immunization records may be difficult to find but other information, such as clinic records, may be available. No epidemiological method is perfect because it cannot exactly duplicate the experimental conditions of a prospective randomized clinical trial. The most accurate results will be obtained when biases are anticipated and corrective measures are taken whenever possible. Clinical vaccine efficacy determinations are carried out in order to assess whether the observed pattern of illness is consistent with the proper use of a highly effective vaccine. The components of a vaccine efficacy evaluation -- case definition, case ascertainment, and vaccination status determination -- apply to studies on all vaccines.