The danger of development of Guillian-Barre Syndrome associated with the use of influenza vaccines other than the swine flu vaccine is unknown. However, because the possibility exists, the Advisory Committee on Immunization Practices has included a statement regarding this possible risk in its current recommendations for all influenza vaccine. EFFICACY DEFINED Mr. FLOOD. Define "efficacy" as the word is associated with influenza vaccine usage? How was the efficacy of swine flu vaccine determined? How is it planned to determine the efficacy of the Russian flu vaccine? Dr. FOEGE. The efficacy of any vaccine is the measure of the degree to which illness is reduced in vaccinees compared to nonvaccinees when they are either naturally or experimentally challenged by infection. The efficacy of a vaccine is expressed as a percent and is calculated by the following formula: vaccine efficacy=unvaccinated attack rate-vaccinated attack rate Although several large populations were under surveillance during the swine flu program to determine the efficacy of the vaccine, the failure of that strain to appear made it impossible to test the efficacy of the swine flu component. However, a study of a nursing home outbreak in Florida revealed a greater than 80 percent efficacy of the A/Victoria component of bivalent vaccine against A/Victoria illness. The efficacy of Russian flu vaccine will be measured by prospective surveillance of populations and by individual outbreak investigations. Although the efficacy of a vaccine can only be determined when vaccinees are exposed to the virus, antigenicity (the ability to stimulate an antibody response in the vaccinee) is evaluated in clinical trials prior to the vaccine's release. Extensive clinical trials utilizing 7,000 volunteers with the A/New Jersey vaccine were undertaken to determine the dosage at which maximum antibody response may be obtained with minimal local and systemic reactions. In general, an antibody titer of 1:40 or more will protect against influenza illness. The A/New Jersey vaccine was able to produce this antibody response in 80 percent of adult recipients with less than a 2 percent incidence of local or systemic reactions. Similar clinical testing of the Russian flu vaccine is now underway. When an adequate vaccine dosage is determined for this vaccine to stimulate an antibody titer of 1:40 or more, we may expect on the basis of past experience that this will correlate well with vaccine efficacy. 66 EXCESS MORTALITY Mr. FLOOD. Dr. William H. Foege in his statement to the Subcommittee said the 1968 epidemic resulted in approximately 70,000 excess deaths . . .". How many of these deaths were shown to be caused by influenza by virus isolation or antibody studies? For those deaths for which virus isolation or serologic study were not done, how has the cause of death been determined? Dr. FOEGE. Due to a printing error the number of excess deaths were printed at 70,000 in 1968, which is the number of excess deaths from the 1957 pandemic, the correct figure for the 1968 pandemic is 30,000 excess deaths. The association of excess mortality from all causes and the occurrence of influenza epidemics was made on epidemiologic grounds as early as 1848, and the relationship has been noted consistently since that time. Only a small number of these deaths are verified by laboratory means as being due to influenza. Serologic confirmation of an influenza death is usually not practical since patients frequently die before they develop diagnostic rises. The limited number of laboratories capable of isolating influenza viruses creates additional logistical difficulties for physicians who consider the diagnosis. However, laboratory confirmation of the epidemiologic relationship has been obtained in numerous studies which documented the presence of epidemic influenza infection during periods of excess mortality as well as the presence of influenza virus in autopsy material. With the advent of increased influenza laboratory surveillance in the 1970's, further evidence supports influenza as the precipitating factor for excess mortality. When epidemic influenza occurs, large numbers of positive specimens are obtained; and the periods of peak recovery of influenza virus from clinical specimens coincide with periods of peak excess mortality. A further sensitive indicator of epidemic influenza activity is the number of deaths due specifically to pneumonia and influenza (P&I). The frequency of these deaths is recorded weekly from death certificates in 121 U.S. cities. By constructing baseline values from numbers of deaths due to P&I during nonepidemic years, the occurrence of excess deaths due to these conditions can be detected during influenza epidemics. For example, during 1976-1977, very little influenza A activity was detected by the largest influenza morbidity and virus surveillance system ever employed in the United States. Further, no increase in P&I deaths and no excess mortality occurred during that year. For the past influenza season, 1977-1978, all influenza morbidity indicators were elevated and P&I as well as total excess deaths exceeded the epidemic threshold for nine weeks. POLYVALENT FLU VACCINE Mr. FLOOD. If Russian flu is the expected flu danger in the winter of 1978-79 as elaborated on page 2 of Dr. Foege's statement why is it proposed to use in 1978-79 a polyvalent flue vaccine in which Russian flu is one of several flu strains rather than make use of a monovalent Russian flu vaccine? Please incorporate in your answer the degree of certainty or uncertainty in the science or art of ininfluenza epidemic predictions. Dr. FOEGE. During the 1977-78 influenza season, co-circulation of A/Texas and A/USSR influenza strains were documented in the USSR and in this country. There is no reason to assume that they will not be prevalent in 1978-79. It should be noted that in any given year, an epidemic strain rarely attacks more than 30 percent of the population. Therefore, a large number of susceptibles are left in the population and the strain often reappears in the subsequent year. Even in these "interpandemic periods", excess mortality has been observed, generally among persons above the age of 64, or persons below this age with preexisting medical problems. The program for this year is planned as a part of a long range strategy to reduce morbidity and mortality in this high-risk target population. It anticipates the use of vaccine against all strains of influenza which, based on current information, may circulate next year. Use of appropriate polyvalent influenza vaccine is the more cautious use of resources for the long range reduction of disease and mortality in high-risk populations, since prediction of which strains will circulate is difficult. It is impossible to predict with certainty in any year either the extent of influenza activity or which virus may become prevalent. Therefore, any decision to vaccinate carries with it an inherent element of uncertainty regarding the effectiveness of the vaccine in protecting against the next year's prevalent influenza virus. However, in practice, a totally incorrect vaccine formulation is rare. REPORTING SYSTEM Mr. FLOOD. Please provide specific information to answer the following: How many serious side effects occur in immunization programs supported in whole or in part by the Federal government, what costs are thereby generated, how many individuals recover losses through claims or suits and how many individuals absorb the costs themselves? Dr. FOEGE. A comprehensive system for the reporting of illness and/or reactions following vaccination was established during the National Influenza Immunization Program. This resulted in reports of 4,621 reports during the fall of 1976 through May 25, 1977, including 222 deaths, 2,569 non-fatal illnesses in civilians and 1,830 non-fatal illnesses in military personnel. Most of the deaths were ascribed to cardiovascular diseases and appeared to be coincidental to vaccination. Guillain-Barre Syndrome was found to differ from all other illnesses reported occurring in a higher incidence than expected and in a nonrandom distribution following immunization. No other serious illnesses were clearly related to influenza immunization through this surveillance system. As of April 7, 1978, a total of 1,363 claims have been filed under the Swine Flu immunization program for a total of $699,192,555.96. Of these, 402 are for Guillain-Barre for a total of $342,290,620.38. No dollar amount was specified for 17 claims. A total of 216 claims have been denied for a total of $27,079,155.85. Three claims for $363.40 have been allowed. The level and types of reactions to the commonly used vaccines are carefully examined in conjunction with vaccine related studies. Recording of vaccine reactions as they occur through immunization programs relies on a passive report ing system originating with health care providers. This system is sensitive enough to detect unusual occurrence of reactions to any vaccine, but has not been as active as the system established for the "Swine Flu" program described above, and does not result in the reporting of all reactions. Similarly, there is not a central clearinghouse for all claims filed for vaccine related reactions. Data are particularly incomplete on claims settled out of court. The Department is currently attempting to update information about the claims experience of the manufacturers and the insurance industry, and to analyze all data which are available on the costs of vaccine reactions. In addition, the Center for Disease Control and the Bureau of Biologics are actively encouraging physicians and other health care providers to report all vaccine reactions. 'Based on studies and on the experience of past years, we estimate that the following major risks are associated with commonly used vaccines, and have included these statements on the information forms provided to potential vaccinees: Polio Vaccine.-"Once in about every 4 million vaccinations, persons who have been vaccinated or who come in close contact with those who have recently been vaccinated are permanently crippled and may die." Measles Vaccine.-"About 1 out of every 5 children will get a rash or slight fever 1 or 2 weeks after the shot. Although experts are not sure, it seems that about 1 out of a million children who get the shot may have a more serious reaction such as inflammation of the brain (encephalitis)." Rubella Vaccine.- "About 1 out of every 7 children will get a rash or some swelling in the glands of the neck 1 or 2 weeks after the shot. About 1 out of every 20 children who get the shot will have some aching or swelling of the joints." Mumps Vaccine.- "Although experts are not sure, it seems that about 1 out of a million children who get the shot may have a serious reaction, such as inflammation of the brain (encephalitis)." DTP/DT/Td Vaccines.-"About 1 out of every 7,000 children who get the shots will have a serious side effect such as: high fever, convulsions, abnormal crying for several hours, or going into shock and getting pale. Rarely, about once in every 100,000 shots, inflammation of the brain (encephalitis) or brain damage may occur. Death may occur, even more rarely." As indicated, these risks are described in the Information Statements which each potential vaccinee (or parent or guardian) must read and sign prior to vaccination in public clinics. Over the past two years, the following number of doses of childhood vaccines has been administered by the public sector: TOTAL DOSES OF VACCINE (IN MILLIONS) BY TYPE AND YEAR Mr. FLOOD. Dr. John Seal testified before the subcommittee that fewer than 4,000 volunteers will be employed in the clinical trials of Russian flu vaccine and that the trials will be completed within 10 weeks after they begin. Is this number of volunteers sufficient to detect serious adverse effects that might occur in 1 of 100,000, vaccinees? Is the completion time of 10 weeks adequate to detect those adverse effects that have onsets time after 10 weeks? Please give the name of the statistician or names of statisticians who attested to the adequacy of the sampling number and duration interval employed in the clinical trials described by Dr. John Seal in this testimony of April 24, 1978. Dr. FOEGE. Dr. Seal has provided an answer to this question which in effect says that the clinical trials are not designed to uncover adverse effects that may occur as rarely as 1 in 100,000 vaccinees. Undertaking a trial with such an objective would require at least 2 million vaccinees and 2 million unvaccinated control subjects. This is beyond the possibility of accomplishment in the time framework and financing envisioned. The purpose of the trials is to obtain data on the dosages of each of the four manufacturers' vaccine products which will give satisfactory immunization without excessive local or febrile reactions to the vaccines. The completion time is the time from the first dose of vaccine to obtaining the blood specimen after the second dose of vaccine, plus the time needed to perform antibody testing and to enter the data into the computer, analyze them and report them to the Advisory Committees. All subjects are to be followed for three years so any late adverse effects will be later reported. No such late effects were observed in the 7,000 subjects involved in clinical testing of the "Swine Flu" vaccines. The names of the scientists are Drs. Walter Dowdle and Gary Noble of the Center for Disease Control, Drs. William Jordan, George Curlin and William Blackwolder of the National Institute of Allergy and Infectious Diseases, and Drs. Harry Meyer and Paul Parkman of the Bureau of Biologics. All have planned and carried out vaccine testing and are familiar with the design and sampling methods used in many studies. The Center for Disease Control agrees with Dr. Seal's answers and endorses the design of the studies. PARTICIPATING STATES Mr. FLOOD. Please give specific reasons provided by the 20 States (as of April 20, 1978) who have refused to participate (3 States) or are undecided as to whether or not they will participate (17 States) in the proposed Russian flu immunization program. Dr. FOEGE. All 50 States, 5 territories and 8 cities (all the current immunization grantees) were surveyed February 24 to determine their intent to apply for an influenza immunization grant and comment about problems in implementation. Only 42 responses were received. Of these 42 respondents, 3 responded that they did not intend applying for a grant. Of the 3 negative responses, only 1 enlarged on the response and expressed concern about the level of Federal funding both now and in future years as well as the limitations of the objective. There were 9 States that were undecided. Of these 2 are awaiting Federal guidelines, 3 are awaiting guidelines and clarification of Federal financial support, 1 is concerned about the increased burden on the existing public health system, 1 is only concerned about the level of Federal support, 1 is concerned about guidelines and legal liability, and 1 is concerned about financial requirements and legal liability. The remaining 21 locations have not responded. Since the survey was undertaken, one additional State (New Jersey) has indicated that it will not participate in the program unless there is a national solution to the problem of liability protection for employees and agencies engaged in providing vaccinations. Although they supported the concept of public influenza immunization programs directed toward high-risk groups, they also expressed concern about possible interference with childhood programs, the level of Federal grant support, and the limited goals of the program. Mr. MICHEL. Now, if the Federal Government provides a model consent formwhich is then used by the States, but it is subsequently found to be deficient— is the Federal Government then liable for inadequate informed consent? Answer. The potential liability of the Federal Government for an inadequate consent form would depend upon the nature of the alleged deficiencies in the form. The Government is liable under the Federal Tort Claims Act (FTCA) for the negligence or wrongful acts or omissions of its employees acting within the scope of their employment. 28 U.S.C. 2672. The Act, however, exempts claims based upon the "exercise or performance or the failure to exercise or perform a discretionary function or duty on the part of a Federal agency or an employee of the Government, whether or not the discretion involved be abused". 28 U.S.C. 2680 (a). The "discretionary function" exception has been interpreted by the courts to be available where decisions of Government officials involve considerations of policy judgments. If a plaintiff could establish that the statement of benefits and risks in the consent form was so deficient as to constitute negligence, e.g., failure of the form to include a warning of the danger of inoculation to persons allergic to eggs, the Government might be held liable under the FTCA. In general, however, the content of the consent form, i.e., the determination of what the risks of vaccinations are, which depends largely upon interpretation of data from the clinical testing of the vaccine and from other flu vaccine programs, would likely be deemed by the courts to be a matter within the discretion of the Government officials involved. The development of an adequate statement of benefits and risks in inocu lation would require the kind of exercise of judgment that the courts have held exempt the government from liability under FTCA. The following additional data was submitted by AFW prior to nmittee action.] Thank you for your letter of May 22, requesting clarification Sincerely yours, James J. Sielism 150 Julius B. Richmond, M.D. Enclosure |