Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
August 2000

Economic Evaluation of Use of Diphtheria, Tetanus, and Acellular Pertussis Vaccine or Diphtheria, Tetanus, and Whole-Cell Pertussis Vaccine in the United States, 1997

Author Affiliations

From the National Immunization Program (Drs Ekwueme, Strebel, Hadler, and Livengood) and the National Center for Infectious Diseases (Dr Meltzer), Centers for Disease Control and Prevention, Atlanta, Ga; and the Occupational Health/Preventive Medicine Department, National Naval Medical Center, Washington, DC (Dr Allen).


Copyright 2000 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2000

Arch Pediatr Adolesc Med. 2000;154(8):797-803. doi:10.1001/archpedi.154.8.797

Objective  To compare the economic costs and benefits associated with using either diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) or diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP) in the United States in 1997.

Design  Standard cost-benefit analysis, from both the societal and health care system perspectives, was performed for each combination vaccine as well as for the pertussis components singly.

Setting  A simulated cohort of 4.1 million children from birth to age 15 years.

Main outcome measures  Net costs (savings) and benefit-cost ratios (BCRs)

Results  Without a vaccination program, diphtheria, tetanus, and pertussis disease caused more than 3 million cases and more than 28,000 deaths, at a cost of $23.6 billion. From the societal perspective, net savings because of the use of DTaP and DTwP were $22.510 million and $22.623 million, respectively. The net savings from the acellular pertussis component and the whole-cell pertussis component only were $4.362 million and $4.474 million, respectively. Benefit-cost ratios for DTaP from a societal and health care system perspective were 27:1 and 9:1, respectively. Sensitivity analyses of key variables did not result in appreciable changes in results.

Conclusions  Compared with no program, vaccination with DTaP or DTwP resulted in substantial savings, regardless of the perspective taken and for all sensitivity analyses conducted. Compared with DTwP, use of DTaP generated a small cost increase that might be offset by the value of other factors, such as increased confidence in pertussis vaccination resulting from reduced adverse events.

THE INTRODUCTION and widespread use of a combined diphtheria and tetanus toxoids and whole-cell pertussis vaccines (DTwP) in the late 1940s in the United States led to a reduction of more than 95% in morbidity and mortality from each of these diseases.1 Although the use of diphtheria and tetanus toxoids has been strongly supported, use of whole-cell pertussis vaccine has been controversial because of the frequency of local and systemic adverse events and an alleged association with permanent brain damage. Although this latter association has not been proven, it led to reduced acceptance of DTwP in the United Kingdom, Sweden, Japan, and Germany in the 1980s.2 Acellular pertussis vaccines, made from purified components of Bordetella pertussis, were developed to reduce vaccine-related adverse events.3,4

Recent studies have found combined diphtheria and tetanus toxoids and acellular pertussis vaccines (DTaP) to be safe and to have an efficacy against pertussis disease similar to that previously published for DTwP.58 In 1997, DTaP was recommended for routine use among infants and young children in the United States.9,10 Although DTaP vaccines are associated with significantly fewer adverse events,11,12 they are more expensive than DTwP. Few investigators in the United States have conducted an economic analysis of the benefits and costs of using either DTaP or DTwP.13,14 An analysis by Batelle using 1994 cost estimates found a benefit-cost ratio (BCR) for DTwP of 30:1 from the societal perspective and 6:1 from the health sector perspective.14 This analysis did not consider use of DTaP for the full vaccination series.

To quantify possible economic differences between DTaP and DTwP vaccines, we analyzed 2 scenarios: exclusive use of each vaccine according to the recommended schedule for childhood immunization in the United States compared with no vaccination program.


We adapted the standard cost-benefit model used by Batelle Inc, Arlington, Va, to evaluate the benefits and costs of a US vaccination program to prevent diphtheria, tetanus, and pertussis in which either DTaP or DTwP was used compared with no vaccination program.14,15 We examined the impact of vaccination on a hypothetical US birth cohort of 4.1 million children, evaluated from birth through age 15 years.16 The 1997 childhood immunization schedule, which recommends 5 doses of vaccine (1 dose at age 2 months, 4 months, 6 months, 15 to 18 months, and 4-6 years), was assumed. We conducted the analyses from 2 perspectives (societal and health care system).

The equations for the standard cost-benefit model used in this study are presented below:

Image not available

where the net present value (NPV) (or net benefit of vaccination with DTaP or DTwP) is the sum of the discounted benefits from vaccination program minus the sum of the discounted costs; j, vaccine candidate (j = 1, diphtheria, j = 2, tetanus, and j = 3, pertussis); Bt, benefits from the vaccination program in year t; Ct, costs of the vaccination program in year t; T, the planning horizon (15 years); and r, discount rate.

The equation used for calculating the benefits of a vaccination program is Bt = total disease burden without vaccination program−total disease burden with vaccination program. In this formula, disease burden is defined as the costs of all hospitalized cases plus costs of nonhospitalized cases. The equation used for calculating the costs of a vaccination program is Ct = total costs of vaccination+total costs of vaccine-associated adverse events.

These 3 equations were used to estimate the BCR of vaccination with either DTaP or DTwP, compared with no vaccination. This is expressed as follows:

Image not available

Benefit-cost ratios for the acellular pertussis and whole-cell pertussis components were calculated using vaccine price plus the cost of treating vaccine-related adverse events as the program costs. Costs associated with vaccine administration, transportation of parent and child, and lost parental productivity were assumed to be borne by the diphtheria and tetanus component.


When no published data were available, the conclusions of an expert panel conducted by Batelle Inc on February 22, 1993, were used (Table 1).14 The panel members were Kathryn Edwards, MD, Scott Halperin, MD, Erik Hewlett, MD, and Edward A. Mortimer, Jr, MD. Based on review of diphtheria incidence rates in the prevaccine era17 and after the introduction of diphtheria toxoid, the expert panel estimated that in the absence of vaccination, the age-specific incidence of diphtheria would be similar to that observed during the prevaccine period. The expected number of tetanus cases in the absence of vaccination was estimated from the rate of tetanus observed among unvaccinated children in the US during 1981-1991.14 The age-specific risk of contracting pertussis was calculated based on incidence data from Sweden during the early 1980s18 and US data from the 1920s,19 both of which suggested a cumulative pertussis incidence of 70% by age 15 years. The age-specific likelihood of hospitalization was based on a study of bacteriologically confirmed case patients hospitalized in Sweden.20

Table 1a. 
Image not available
Input Variables and References*
Table 1b. 
Image not available
Input Variables and References*

To determine the number of cases of diphtheria, tetanus, and pertussis occurring in the presence of a vaccination program, we used the average of the annual number of reported cases for each disease between 1986 and 1996 in the United States stratified by age (<1 year, 1-4 years, 5-9 years, and 10-14 years).2131 Based on studies showing comparable efficacy of DTaP and DTwP, the same reduction in disease burden was used for DTaP and DTwP in the base case. Rates for each disease were adjusted for underreporting and applied to the birth cohort of 4.1 million. We assumed that 50% of diphtheria (Centers for Disease Control and Prevention, unpublished data) and 80% of tetanus cases32 were unreported. For pertussis, the age-specific disease burden was estimated from national surveillance data on hospitalized cases33 (adjusted for 70% underreporting34), and divided by the probability of hospitalization.3537


Minor vaccine-associated adverse events were defined as local reactions at the injection site (eg, pain, redness, swelling) or mild systemic reactions, such as low-grade fever, vomiting, and anorexia. The frequency of minor adverse events associated with both DTaP and DTwP was estimated by averaging the results of clinical trials for vaccines licensed for use in the United States in 1997 (Table 1).5,6,12

Major reactions to DTaP or DTwP were those identified in the 1991 and 1994 Institute of Medicine reports as having scientific evidence of a causal relationship with DTwP.38,39 These reactions were hypotonic hyporesponsive episodes, uncomplicated seizures, protracted crying or screaming, anaphylaxis, and acute encephalopathy with no permanent sequelae. Probabilities for these conditions were based on published estimates1113,38,39 and clinical trials (Table 1).5,6,9,10 The base-case analysis for DTwP included the possibility of vaccine-associated encephalopathy occurring at a frequency of 0.57 cases per 100,000 doses. In the base-case analysis, it was assumed that DTaP was not associated with acute encephalopathy.


Data on costs of disease and adverse events were obtained from a variety of published studies,13,40 the 1987 National Medical Expenditures Survey,41 and from the Codman Research Group's 1990 hospital discharge database.42 All diphtheria and tetanus cases were assumed to be hospitalized and disease burden costs were calculated from the average length of hospital stay and average costs per case.14 Information on the probabilities of pertussis-related complications and their associated costs was used to calculate pertussis disease burden costs. Physician costs for inpatients were based on average hospital stay, assuming 1 physician visit per day of hospitalization.43,44 All costs were standardized to 1997 dollars, using the medical care component of the consumer price index.45 All costs and benefits that were assumed to occur in the future were discounted at a 3% annual rate.


The direct cost of vaccination was the sum of vaccine price per dose, vaccine administration costs, and costs associated with vaccine adverse events. It was assumed that 50% of vaccinations are given in the public sector and 50% in the private sector. For DTaP, a weighted average vaccine price of $13.87 (Table 1) was used based on the 1997 private sector and federal contract vaccine prices for licensed DTaP vaccines (Centers for Disease Control and Prevention, unpublished data). For DTwP, a weighted average vaccine price of $5.71 was used based on the 1996 private sector and federal contract vaccine prices (Centers for Disease Control and Prevention, unpublished data). Prices included $2.25 per dose tax that supports the National Vaccine Injury Compensation Program.46

Direct nonmedical costs included travel to the clinic or physician's office at $3 for a round trip drive of 10 miles or $1.50 each way for public transportation. The weighted average cost of administering either DTaP or DTwP was estimated to be $12.65 per dose. To calculate indirect costs, we assumed that a caretaker's time off from work to take his or her child for vaccination was an average of 2 hours of lost productivity at a cost of $17.50.47

Vaccination coverage rates by age and number of doses administered were obtained for children aged 0 to 6 years (Centers for Disease Control and Prevention, unpublished data). The data reflect recent gains in vaccination coverage rates, with 93% of 19- to 35-month-old children having received 3 or more doses of DTP/diphtheria and tetanus vaccinations.48 We estimated that by age 6 years, 98% of children have received 4 or more doses of DTwP/DTaP. To calculate the maximum number of doses of vaccine required for the program, we assumed 21.5% vaccine wastage.49


Univariate sensitivity analyses were performed to test the effect of the following key parameters on the cost-benefit of DTaP: (1) a lower (80%) and upper bound (98.5%) for acellular pertussis vaccine effectiveness; (2) higher program costs of $12.2 million (Table 1); (3) a discount rate of 5%; and (4) variation of the probabilities of some major vaccine-related adverse events (hypotonic hyporesponsive episodes, uncomplicated seizures, and protracted crying) (Table 1).

Threshold values for the price of DTaP and the effectiveness of the acellular pertussis vaccine were calculated. The threshold value for DTaP price was the price at which the net present value (NPV) of the DTaP vaccination program equaled the NPV of the DTwP program. The threshold value for the effectiveness of acellular pertussis vaccine was the vaccine effectiveness at which the NPV of an acellular pertussis vaccine program equaled the NPV of the whole-cell pertussis program.


Without a vaccination program, for a cohort of 4.1 million children, the model estimated that 2.87 million pertussis cases would occur, resulting in 1131 deaths; 276,750 diphtheria cases, resulting in 27,675 deaths; and 165 tetanus cases, resulting in 25 deaths. From the societal perspective, these cases would cost $23,536.5 million with approximately $18,772.4 million (80%) for diphtheria and $4770.1 million (20%) for pertussis (Table 2).

Table 2. 
Image not available
Results of the Base-Case Analyses of Health and Economic Outcomes and Benefit-Cost Ratios of DTaP/DTwP and Acellular/Whole-Cell Pertussis Vaccination Program*†

In the presence of either a DTaP or DTwP vaccination program, the number of diphtheria, tetanus, and pertussis cases would be reduced by more than 99%, 93%, and 96%, respectively (Table 2). The societal cost of vaccinating with DTaP was estimated at $866.5 million, which is $113 million greater than the $753.7 million that would be spent on a DTwP vaccination program (Table 2). From a societal perspective, the BCR for the DTaP vaccination program was 27:1, and the BCR for the DTwP vaccination program was 31:1 (Table 2). The BCR for DTaP, from the health care system perspective, was estimated to be 9:1.

The incremental costs of vaccinating with acellular pertussis vs whole-cell pertussis was $113 million ($148.7 million in additional vaccine costs minus $35.8 million for reduced costs of vaccine adverse events) (Table 2). Cost savings for vaccination with acellular pertussis were $4360.8 million and for vaccinating with whole-cell pertussis were $4473.7 million (Table 2). From the societal perspective, BCRs were estimated to be 20:1 for acellular pertussis and 41:1 for whole-cell pertussis.


The BCRs for DTaP when acellular pertussis effectiveness was set at 80% and 98.5% were 26:1 and 27:1, respectively (Table 3). With higher program costs, the BCR decreased from 27:1 to 25:1 at the 3% discount rate. Using higher program costs, a discount rate of 5%, and lower and higher estimates of vaccine adverse events only slightly reduced the BCRs of DTaP vaccination (Table 3). The threshold price for a dose of DTaP ranged from $13.87 at 98.5% vaccine effectiveness to $7.65 at 96% vaccine effectiveness (Figure 1). At current vaccination costs, the NPV of acellular pertussis equaled that of whole-cell pertussis if vaccine effectiveness was 98.5% (Figure 2).

Table 3. 
Image not available
Univariate Sensitivity Analysis of the Impact of Altering Health and Economic Outcomes for Vaccination With DTaP or Acellular Pertussis Alone*†
Figure 1.
Image not available

Sensitivity analysis of the impact of varying the cost of vaccination and vaccine effectiveness (VE) on the net present value (NPV) of combined diphtheria, tetanus, and acellular pertussis (DTaP) vaccination compared with the NPV of combined diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccination. Total costs indicate both direct and indirect costs.

Figure 2.
Image not available

Sensitivity analysis of the changes in the net present value (NPV) of acellular pertussis vaccine with changes in vaccine effectiveness compared with the NPV of whole-cell pertussis vaccine.


Diphtheria, tetanus, and pertussis are major public health concerns in the United States because of their potential to cause a substantial health and economic burden. Our study shows that a vaccination program that achieves high coverage levels with either DTaP or DTwP is highly cost beneficial and results in substantial cost savings. Regardless of the vaccine used or the perspective taken, the BCR (which measures the return for every dollar invested) of the vaccination program was always more than 1.0. These findings provide a compelling case for public and private sectors in the United States to maintain the high vaccination coverage levels achieved among infants and young children.

Sensitivity analyses of the effect of higher program costs, lower pertussis vaccine effectiveness, a discount rate of 5%, or a higher frequency of major adverse events associated with DTaP did not greatly alter the positive BCR. Benefit-cost ratios remained more than 25:1 from the societal perspective and more than 7:1 from the health care system perspective for each of these analyses, indicating the robustness of the base-case estimates.

Using DTaP instead of DTwP led to a net increase in vaccination program costs; however, DTaP was still shown to be highly cost beneficial. For the net savings of the DTaP vaccination program to equal those of the DTwP program, the average price for a dose of DTaP would need to decrease from $13.87 per dose to $7.65 per dose. A decrease in vaccine price might occur in the future with increased competition and higher volumes of vaccine purchased.

Adding either acellular or whole-cell pertussis to an existing 5-dose schedule of diphtheria and tetanus toxoids resulted in prevention of an estimated 2.75 million pertussis cases and 1090 pertussis deaths. These disease burden costs outweighed the costs of either vaccine and any associated adverse events. Regardless of the perspective taken or the vaccine used, net cost savings of vaccination against pertussis were positive. This finding is similar to that in an earlier study by Koplan et al,40 which found a savings of $1.1 billion in direct medical costs from a health sector perspective and a BCR of 3:1. In 1984, Hinman and Koplan13 updated the earlier estimates using more current disease incidence data and rates of adverse events and still found net cost savings and a BCR of 11:1.

It is possible that our model over estimates some of the economic benefits obtained when vaccinating against diphtheria, tetanus, and pertussis. When calculating benefits, we used the consensus from an expert panel that the disease burden without vaccination would be equal to that of the prevaccination era before the introduction of mass immunizations. In developed countries, however, the incidence of many infectious diseases, including diphtheria, tetanus, and pertussis, were declining before the introduction of universal immunization.50,51

In 1997, after licensure of DTaP vaccines in the United States, the Advisory Committee on Immunization Practices, American Academy of Pediatrics, and American Academy of Family Physicians recommended routine use of acellular pertussis vaccines among infants and young children in the United States.9,10 Although policymakers were mindful of the slight economic advantage of DTwP over DTaP as shown in this study, the following factors played a role in the decision to use acellular pertussis vaccines: (1) parents and providers would have increased confidence in vaccination from the use of a vaccine associated with fewer adverse events; (2) the production of acellular pertussis vaccines could be better standardized with more rigorous quality control than could production of whole-cell pertussis vaccines; and (3) acellular pertussis vaccines may be used as a booster dose in adolescents and adults with potential further decrease in pertussis disease. These considerations, and the fact that the use of DTaP generates net savings, support the decision to switch from using DTwP to DTaP.

Back to top
Article Information

Accepted for publication February 24, 2000.

We thank Alan Hinman, MD, Melinda Wharton, MD, and Trudy Murphy, MD, and Mary McCauley, MTSC, for reviewing early drafts of the article.

Presented in part at the Annual Meeting of the Pediatric Academic Societies, San Francisco, Calif, May 4, 1999.

Corresponding author: Donatus U. Ekwueme, PhD, National Immunization Program, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop E-35, Atlanta, GA 30333 (e-mail:

Güris  DStrebel  PMBardenheier  B  et al.  Changing epidemiology of pertussis in the United States: increasing reported incidence among adolescents and adults 1990-1996. Clin Infect Dis. 1999;281230- 1237Article
Hinman  AR The pertussis vaccine controversy. Public Health Rep. 1984;99255- 258
Centers for Disease Control, Diphtheria-tetanus-pertussis vaccine shortage–United States. MMWR Morb Mortal Wkly Rep. 1984;33695- 696
Gonzalez  ER TV report on DTP galvanizes US pediatricians. JAMA. 1982;24812- 420- 22Article
Greco  DSalmaso  SMastrantonio  P  et al. for the Progetto Pertosse Working Group, A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. N Engl J Med. 1996;334341- 348Article
Gustafsson  LHallander  HOOlin  PReizenstein  EStorsaeter  J A controlled trial of two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine. N Engl J Med. 1996;334349- 355Article
Güris  DStrebel  PMTachdjian  RBardenheier  BWharton  MHadler  SC Effectiveness of the pertussis vaccination program as determined by use of the screening method: United States, 1992-1994. J Infect Dis. 1997;176456- 463Article
Onorato  IMWassilak  SGMeade  B Efficacy of whole-cell pertussis vaccine in preschool children in the United States. JAMA. 1992;2672745- 2749Article
Centers for Disease Control and Prevention, Pertussis vaccination: use of acellular pertussis vaccines among infants and children: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 1997;46 ((RR-7)) 1- 25
American Academy of Pediatrics, Pertussis. Peter  Ged.1997 Red Book Report of the Committee on Infectious Diseases 24th ed. Elk Grove Village, Ill American Academy of Pediatrics1997;394- 407
Cody  CLBaraff  LICherry  JDMary  SMManclark  CR Nature and rates of adverse reactions associated with DTP and DT immunizations in infants and children. Pediatrics. 1981;68650- 660
Decker  MDEdwards  KMSteinhoff  MC  et al.  Comparison of 13 acellular pertussis vaccines: adverse reactions. Pediatrics. 1995;96 ((3, pt 2)) 557- 566
Hinman  ARKoplan  JP Pertussis and pertussis vaccine: reanalysis of benefits, risks, and costs. JAMA. 1984;2513109- 3113Article
Hatziandreu  EPalmer  CSBrown  REHalpern  MT A Cost-benefit Analysis of the Diphtheria-Tetanus-Pertussis (DTP) Vaccine: Report Prepared for the Centers for Disease Control and Prevention.  Arlington, Va Battelle Inc1994;
Clemmer  BHaddix  AC Cost-benefit analysis. Haddix  ACTeutsch  SMShaffer  PADunet  DOeds.Prevention Effectiveness A Guide to Decision Analysis and Economic Evaluation New York, NY Oxford University Press1996;85- 102
US Bureau of the Census, Statistical Abstract of the United States: 1998. 118th ed. Washington, DC US Bureau of the Census1998;
Frost  WH Papers of Wade Hampton Frost, MD: A Contribution of Epidemiological Method. Macy  KFed. New York, NY Commonwealth Fund1941;
Isacson  JKrantz  ITaranger  JTroilfors  B Cumulative incidence of pertussis in nonvaccinated 10-year-old children in Sweden, a nonvaccinating country since 1979. Manclark  CRed.The Sixth International Symposium on Pertussis, Abstracts Bethesda, Md Dept of Health and Human Services1990;193- 194DHHS publication (FDA)90-1162
Collins  SA Age incidence of the common communicable diseases in children. Public Health Rep. 1992;44763- 826Article
Romanus  VJonsell  RBergquist  SO Pertussis in Sweden after the cessation of general immunization in 1979. Pediatr Infect Dis J. 1987;6364- 371Article
Centers for Disease Control, Summary of notifiable diseases, United States, 1986. MMWR Morb Mortal Wkly Rep. 1987;351- 57
Centers for Disease Control, Summary of notifiable diseases, United States, 1987. MMWR Morb Mortal Wkly Rep. September16 1988;361- 59
Centers for Disease Control, Summary of notifiable diseases, United States, 1988. MMWR Morb Mortal Wkly Rep. October6 1989;371- 57
Centers for Disease Control, Summary of notifiable diseases, United States, 1989. MMWR Morb Mortal Wkly Rep. 1990;381- 59
Centers for Disease Control, Summary of notifiable diseases, United States: 1990. MMWR Morb Mortal Wkly Rep. 1991;391- 61
Centers for Disease Control and Prevention, Summary of notifiable diseases, United States: 1991. MMWR Morb Mortal Wkly Rep. 1992;401- 63
Centers for Disease Control and Prevention, Summary of notifiable diseases, United States, 1992. MMWR Morb Mortal Wkly Rep. 1993;401- 73
Centers for Disease Control and Prevention, Summary of notifiable diseases, United States, 1993. MMWR Morb Mortal Wkly Rep. 1994;421- 73
Centers for Disease Control and Prevention, Summary of notifiable diseases, United States, 1994. MMWR Morb Mortal Wkly Rep. 1995;431- 80
Centers for Disease Control and Prevention, Summary of notifiable diseases, United States 1995. MMWR Morb Mortal Wkly Rep. October25 1996;441- 87
Centers for Disease Control and Prevention, Summary of notifiable diseases, United States, 1996. MMWR Morb Mortal Wkly Rep. 1997;451- 87
Sutter  RWCochi  SLBrink  EWSirotkin  BI Assessment of vital statistics and surveillance data for monitoring tetanus mortality, United States, 1979-1984. Am J Epidemiol. 1990;131132- 142
Farizo  KMCochi  SLZell  ERBrink  EWWassilak  SGPatriarca  PA Epidemiological features of pertussis in the United States, 1980-1989. Clin Infect Dis. 1992;14708- 719Article
Sutter  RWCochi  SL Pertussis hospitalizations and mortality in the United States, 1985-1988: evaluation of the completeness of national reporting. JAMA. 1992;267386- 391Article
Pollack  TMMiller  ELobb  J Severity of whooping cough in England before and after the decline in pertussis immunization. Arch Dis Child. 1984;59162- 165Article
Miller  CLFletcher  WB Severity of notified whooping cough. Br Med J. 1976;1117- 119Article
Halperin  SABortolussi  RMacLean  DChisholm  N Persistence of pertussis in an immunized population: results of the Nova Scotia Enhanced Pertussis Surveillance Program. J Pediatr. 1989;115 ((5, pt1)) 686- 693Article
Howson  CPedHowe  CJedFineberg  HVed Adverse Effects of Pertussis and Rubella Vaccines.  Washington, DC National Academy Press1991;
Stratton  KRedHowe  CJedJohnson  RBed DTP Vaccine and Chronic Nervous System Dysfunction: A New Analysis: Institute of Medicine.  Washington, DC National Academy Press1994;
Koplan  JPSchoenbaum  SCSmith  DGWeinstein  MCFraser  DW Pertussis vaccine: an analysis of benefits, risks, and costs. N Engl J Med. 1979;301906- 911Article
Agency for Healthcare Policy and Research, National Medical Expenditures Survey: Ambulatory Medical Visit Data [Public Use Tape 14.5].  Rockville, Md US Dept of Health and Human Services1987;
Not Available, 1990 Hospital Discharge Data [database online].  Lebanon, NH Codman Research Group Inc1991;
American Hospital Association, 1991 National Hospital Panel Survey: expenses per inpatient day. Overview of Entitlement Programs Background Material and Data on Programs Within the Jurisdiction of the Committee on Ways and Means Washington, DC US Congress House of Representatives1992;
Crane  M What your colleagues are charging. Med Econ. October19 1992;69190- 196199- 202207- 208
Gibson  G Measuring price change for medical care in the CPI. Updated: July 7, 1998. Available at:
Centers for Disease Control, National Childhood Vaccine Injury Act: requirements for permanent vaccination records and reporting of selected events after vaccination. MMWR Morb Mortal Wkly Rep. 1988;27197- 200
US Department of Labor, Current Population Survey (CPS).  Washington, DC Bureau of Labor Statistics1997;
Centers for Disease Control and Prevention, State and national vaccination coverage levels among children aged 19-35 months: United States, April-December, 1994. MMWR Morb Mortal Wkly Rep. 1995;44613619621- 623
Centers for Disease Control, US Biologics Surveillance, 1987-1990, Report No 93.  Washington, DC US Dept of Health and Human Services1991;
McKinlay  JBMcKinlay  SM The questionable contribution of medical measures to the decline of mortality in the United States in the twentieth century. Milbank Mem Fund Q Health Soc. Summer1977;55405- 428Article
Peery  TM The new and old diseases: a study of mortality trends in the United States, 1900-1969. Am J Clin Pathol. 1975;63453- 474