Societal Impact of Combination Vaccines: Experiences of Physicians, Nurses, and Parents

Increased Compliance and Reduced Pain 

Anxiety related to the pain and discomfort associated with multiple injections may prevent parents from completing their child's required immunization program on time.

Combination vaccines offer an effective and well-tolerated method of reducing the number of injections infants require at each visit, consequently reducing the distress experienced by a child (Dodd, 2003, Mullany, 2003). Decreasing the number of injections administered at each visit, while maintaining the appropriate number of antigens given on schedule, may encourage provider and parent compliance with the childhood immunization schedule (Koslap-Petraco and Parsons, 2003, Meyerhoff et al., 2004). Thus, a telephone survey revealed that most parents (95%) expressed a preference for combination vaccines to reduce the number of injections administered (Lugo et al., 2003). Furthermore, in a recent study of physicians in Switzerland, more than 94% of those polled (n = 1097) stated that they would use a pentavalent combination vaccine for their own children (Posfay-Barbe, Heininger, Aebi, Desgrandchamps, Vaudaux, & Siegrist, 2005).

Timeliness of Vaccination 

Combination vaccines have been shown to improve vaccine coverage rates. However, while high vaccine coverage rates are important, they often mask a substantial delay in vaccination during the first 2 years of a child's life (Heininger and Zuberbuhler, 2006, Hull and McIntyre, 2006, Kalies et al., 2006, Luman et al., 2005, Luman et al., 2005, Luman et al., 2002, Strine et al., 2003). Vaccination delays increase with dose and age (Hull & McIntyre), and it has been reported that the number of immunizations, the complexity of the schedule, and the pain and discomfort associated with multiple injections are primary reasons for vaccine dose deferrals. A study in the United States recently demonstrated that while at least one vaccine dose was deferred in 26% of all visits when three doses or less were due, this deferral rate increased to 48% when five doses were due (Meyerhoff & Jacobs, 2005). Furthermore, vaccine coverage rates at 2 years were lower for children who had one dose or more deferred (Meyerhoff & Jacobs). Subsequently, in a study by Kalies and colleagues (Kalies et al., 2006), combination vaccines were shown to be associated with improved timeliness of vaccination, with the percentage of subjects completing the full immunization series on time increasing with the use of higher valence vaccines (Figure 2).

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Figure 2. Percentage of children in Germany born between 1996 and 2003 who received their full immunization of the respective vaccine type on time. From Kalies et al. (2006). The use of combination vaccines has improved timeliness of vaccination in children. Pediatric Infectious Disease Journal, 25, 510. Reprinted with permission from Lippincott Williams and Wilkins. DTaP, Diphtheria and tetanus toxoids and acellular pertussis; Hib, Haemophilus influenzae type b; HepB, hepatitis B. †Within 14.9 months of age. Children were grouped according to the predominant vaccine type used at year of birth.

Financial Considerations 

The financial impact of switching to combination vaccines, which are sometimes more expensive than the component vaccines, may be of concern to those who manage health care practices. In addition, because administration fees are paid for each injection given, fewer injections can result in a reduced income. However, in an evaluation of the economic impact of combination vaccines on health care providers, fewer than 1% of pediatricians reported a significant decrease in revenue (Freed et al., 2006, Jacobson et al., 2005). In fact, the use of combination vaccines can improve the day-to-day efficiency of the practice because they reduce the need to stock separate vaccines, decrease workload, and simplify record keeping (Koslap-Petraco & Parsons, 2003). As fewer vaccination visits are required per patient and fewer injections are given per visit, use of the DTaP-HepB-IPV vaccine is expected to reduce office vaccination costs (Centers for Disease Control and Prevention, 1999, Meyerhoff et al., 2003) and costs to parents (Koslap-Petraco & Parsons, 2003). Recent studies have demonstrated that the use of combination vaccines results in substantial time saving for nurses (Pellissier et al., 2000, Meyerhoff et al., 2003). For example, it has been reported that the time taken by nurses to administer each additional injection increases by 2.4 minutes in the examination room setting (Pellissier et al.).

Combination vaccines have the potential to reduce costs and improve office efficiency, while still allowing for completion of the immunization series on time (Koslap-Petraco and Parsons, 2003, Meyerhoff et al., 2003). Time saving also can allow more time for patient education over a broad range of health care issues, increasing the quality of care that health care providers can offer (Pellissier et al., 2000).

Safety 

Using a combination vaccine also may improve safety for both vaccinators and children. Because fewer injections need to be given, use of a combination vaccine reduces the incidence of needlestick injuries to vaccine administrators. Similarly, fewer injections result in fewer sites for local reactions. The DTaP-HepB-IPV vaccine is available in a prefilled syringe, minimizing the risk of contamination and the incidence of administration errors, thus further improving safety for the vaccine recipient (Roessling, 2005).

Vaccine Interchangeability 

Incorporating combination vaccines into the immunization schedule requires an understanding of the interchangeability of the separate vaccine components and of different combination vaccines.

The interchangeability of the DTaP-HepB-IPV vaccine with its component DTaP, HepB, and IPV vaccines can be made with confidence because the immunogenicity and safety profiles of the combined vaccine are comparable with their constituent vaccines (CDC, 2003). Regarding the interchangeability of vaccines from different manufacturers, only vaccines with serologic correlates of immunity can be evaluated (Greenberg & Feldman, 2003). For example, HepA, HepB, and Hib vaccines have established immunologic response indicators that predict protection against each respective disease. To be licensed, new vaccines must confer immunity comparable with that provided by other commercially available vaccines (CDC, 1999). Thus, for HepA, HepB, and Hib vaccines, a vaccine from any manufacturer for a specific disease may be used at any point in the vaccination series (CDC, 1999).

The absence of a clear serologic correlate of protection for pertussis makes direct comparison of combination vaccines that contain a pertussis component difficult (Centers for Disease Control and Prevention, 1999, Greenberg and Feldman, 2003, Greenberg et al., 2002). Furthermore, there are limited data regarding the safety and immunogenicity of successive doses of different combination vaccines that contain an acellular pertussis vaccine. However, one study has indicated that the administration of one or two doses of Tripedia (DTaP; Sanofi Pasteur Inc., Swiftwater, Pa.) followed by Infanrix (DTaP; GlaxoSmithKline, Research Triangle Park, NC) for the subsequent one or two doses is comparable to three doses of Tripedia with regard to immunogenicity (Greenberg et al.). Therefore, while the same brand of a DTaP vaccine should be used for all doses of the series whenever feasible, if the type of DTaP vaccine previously administered cannot be determined or is unavailable, any licensed DTaP vaccine can be used to continue or complete the series (CDC, 1999). Vaccinations should not be deferred because the brand used for previous doses cannot be determined.

Implementation Concerns 

One area of concern with combination vaccines has been the potential for a child to receive more than the recommended number of doses of a certain antigen. For example, it is now recommended that all infants should receive a birth dose of a monovalent HepB vaccine (CDC, 2007). Subsequent doses of the HepB vaccine are then required at 1 to 2 and 6 to 18 months of age. Infants who receive a birth dose of HepB, followed by a primary series of the DTaP-HepB-IPV vaccine as indicated at 2, 4, and 6 months of age, will receive an additional dose of HepB at 4 months of age. However, administration of four doses of a HepB vaccine due to the use of a combination vaccine has not been found to be harmful (Centers for Disease Control and Prevention, 2003, Centers for Disease Control and Prevention, 2007, Pichichero et al., 2002). Another common concern is that administering too many vaccines to infants at one time could overload the immune system (Gellin et al., 2000, Hilton et al., 2006). This concern is unfounded, because infants' immune systems are sufficiently mature and able to handle many more antigens than are presented by the vaccines given in a typical office visit (Offit et al., 2002). When administering combination vaccines, it is therefore important that this concern be addressed with parents by a health care professional.

Implementation of the DTaP-HepB-IPV Vaccine in Your Practice 

As with the addition of any vaccine to the immunization schedule, staff education is essential for successful implementation. Introduction of the DTaP-HepB-IPV vaccine into a health care practice should include a discussion among staff as to how the vaccine will affect the childhood immunization schedule, record-keeping procedures, and inventory management. The DTaP-HepB-IPV vaccine fits well into the current schedule at 2, 4, and 6 months of age, replacing the separate administration of the DTaP, HepB, and IPV vaccines and reducing the number of injections administered in infancy (Jacobson et al., 2005, Marshall, 2004). Table 1 details how the DTaP-HepB-IPV vaccine can be used to complete the primary vaccination series for DTaP, HepB, and Hib. The DTaP-HepB-IPV vaccine can be administered for the primary series, provided that at least one antigen is indicated and no antigen is contraindicated, and the infant or child is at least 6 weeks of age (Centers for Disease Control and Prevention, 2007, GlaxoSmithKline, 2003). The vaccine also can be used for children up to 7 years of age who need one or more of the antigens (GlaxoSmithKline, 2003). Record-keeping and inventory management also can be simplified with combination vaccines. Because the DTaP-HepB-IPV combination vaccine can replace the separate DTaP, HepB, and IPV vaccines, fewer vaccines need to be ordered, stocked, and monitored. Charting time can be reduced because only one combination vaccine needs to be recorded rather than three separate vaccines. Record-keeping for office purposes also is reduced because there are fewer lot numbers to be recorded.

Table 1. Incorporation of the DTaP-HepB-IPV vaccine into the practice schedule for the primary vaccination series∗

		Age at vaccination (mo)
	Patient history	Birth	2	4	6	15	18	20	22
	Infants (2 mo of age) who have received a HepB birth dose but no other vaccines†	HepB	DTaP-HepB-IPV	DTaP-HepB-IPV	DTaP-HepB-IPV
	Infants (4 mo of age) who have received a HepB birth dose and the separate component vaccines at 2 mo of age†	HepB	HepB DTaP‡ IPV	DTaP-HepB-IPV	DTaP-HepB-IPV
	Infants (4 mo of age) who have received a HepB birth dose and DTaP‡ and IPV at 2 mo of age	HepB	DTaP‡ IPV	DTaP-HepB-IPV	DTaP-HepB-IPV
	Infants (4 mo of age) who have received a HepB birth dose and combination HepB and Hib, DTaP‡ and IPV at 2 mo of age	HepB	HepB/Hib DTaP‡ IPV	Hib§ DTaP-HepB-IPV	DTaP-HepB-IPV
	Infants (15 mo of age) who have received a HepB birth dose and separate vaccines for the first and second dose but the third dose has been missed	HepB	DTaP‡ IPV	HepB DTaP‡ IPV		DTaP-HepB-IPV
	Children who are unvaccinated at 18 mo of age¶						DTaP-HepB-IPV	DTaP-HepB-IPV	DTaP-HepB-IPV

DTaP, Diphtheria and tetanus toxoids and acellular pertussis; HepB, hepatitis B; IPV, inactivated polio virus; Hib, Haemophilus influenzae type b.

∗ Standard text refers to separate component vaccines; text in bold refers to the DTaP-HepB-IPV pentavalent vaccine. † It is permissible to administer four doses of HepB (e.g., when combination vaccines are given after the first birth dose) (CDC, 2007). ‡ Diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed, given as Infanrix (GlaxoSmithKline Biologicals, Rixensart, Belgium). § PedvaxHIB (Haemophilus b Conjugate Vaccine [Meningococcal Protein Conjugate]) (Merck & Co, Inc., Whitehouse Station, NJ). ¶ DTaP-HepB-IPV can be used for the primary series for DTaP, HepB, and IPV in infants born of HBsAg-negative mothers from 6 weeks of age and up to 7 years of age (GlaxoSmithKline, 2003).

Provider Perspective 

Providers were first asked “what they considered to be the main value of combination vaccines, such as the DTaP-HepB-IPV vaccine.” The overwhelming response (71%) was “fewer shots” (Table 2). Several respondents (32%) noted increased staff efficiency and ease in tasks such as preparation of vaccines, record-keeping, and utilization of resources. Thirty-one percent of providers stated that parents seemed more satisfied with the vaccination process and experienced less stress because their children were receiving fewer injections. Many providers noted overall benefits for the immunization schedule, such as simplification (15%) and better compliance (26%).

Table 2. Provider survey responses (n = 62)

	Question	Response	%
	What do you see as the main value of combination vaccines, such as DTaP-HepB-IPV vaccine? (n = 62)	Fewer injections	71
		Increased office efficiency	32
		Decreased stress on patients and parents	31
		Increased compliance	26
		Simpler schedule	15
		Increased office morale	11
		Decreased medication errors	5
	What scheduling challenges have you experienced when implementing DTaP-HepB-IPV vaccine in your practice? (n = 54)	None	35
		Changing office procedures	28
		Cost	19
		Staff education	17
		Parent acceptance	4
	Does a birth dose of HepB impact upon your decision to use DTaP-HepB-IPV vaccine? (n = 60)	No	98
		Yes	2
	Do you think DTaP-HepB-IPV vaccine increases immunization compliance? (n = 61)	No	16
		Yes	84

DTaP, Diphtheria and tetanus toxoids and acellular pertussis; HepB, hepatitis B; IPV, inactivated polio virus.

The second question was “whether providers experienced scheduling challenges in implementing the DTaP-HepB-IPV vaccine in their practice”; this question was explained to the participants as relating to any difficulties they had encountered in incorporating the combination vaccine into the schedule, replacing what had previously been three separate vaccines. More than a third (35%) of providers did not experience any scheduling challenges (Table 2), although some providers mistakenly believed that they would still need to stock the component vaccines to complete a child's immunization series if it was started prior to the availability of the combination vaccine. A number of providers (17%) also suggested that nurse and physician confusion or resistance to change posed difficulties. In addition, reimbursement and other cost constraints were cited by a few providers (19%). Others (28%) mentioned that ensuring that the final dose of HepB was given at no earlier than 6 months of age could be a problem, and a few providers mentioned that transferring infants from a lower valence vaccine schedule to the DTaP-HepB-IPV vaccine can be challenging.

The next question was “whether a birth dose of HepB vaccine had an impact upon the providers' decision to use the DTaP-HepB-IPV vaccine.” Nearly all (98%) of the providers responded “No” (Table 2). A few providers indicated that initial resistance could be overcome by education, and a few mentioned concerns regarding increased costs for the extra dose of the HepB vaccine.

The final question on the survey was “whether providers thought the DTaP-HepB-IPV vaccine increased immunization compliance.” A large majority (84%) responded “Yes” (Table 2). When asked why they believed compliance was increased, a number of respondents replied that fewer shots would result in greater patient acceptance of all of the recommended vaccines. A few providers attributed improved compliance to decreased staff resistance to administering multiple injections, thus reducing the chance of delaying a dose to a subsequent visit. Only one provider, whose practice achieved greater than 95% compliance with the existing immunization schedule, suggested that combination vaccines were not likely to result in additional increases in vaccine coverage rates.

Nurse and Business Manager Perspective 

Nurse and business managers were first asked “what they considered to be the main value of combination vaccines, such as the DTaP-HepB-IPV vaccine.” More than half of those asked cited “fewer injections” (52%) (Table 3), with increased compliance for staff (13%) and parent satisfaction (12%) cited as other reasons for favoring use of the combination vaccine.

Table 3. Nurse and business manager survey responses (n = 100)

	Question	Response	%
	What do you see as the main value of combination vaccines, such as DTaP-HepB-IPV vaccine? (n = 100)	Fewer injections	52
		Increased compliance for staff	13
		Increased compliance for parents	1
		Simpler schedule	4
		Easier record keeping	9
		Parent satisfaction	12
		Decreased medication errors	9
	What scheduling challenges have you experienced when implementing DTaP-HepB-IPV vaccine in your practice? (n = 86)	None	58
		Changing office procedures	17
		Cost	2
		Staff education	7
		Parent acceptance	2
	Does a birth dose of HepB impact upon your decision to use DTaP-HepB-IPV vaccine? (n = 100)	No	99
		Yes	1
	Do you think DTaP-HepB-IPV vaccine increases immunization compliance? (n = 100)	No	4
		Yes	96

DTaP, Diphtheria and tetanus toxoids and acellular pertussis; HepB, hepatitis B; IPV, inactivated polio virus.

The second question was “whether providers experienced scheduling challenges in implementing the DTaP-HepB-IPV vaccine in their practice.” Although most (58%) stated that they had experienced no difficulties (Table 3), some (17%) stated that use of the combination vaccine had resulted in a change in office procedure and some (7%) had required staff education. Furthermore, some practices were still unclear about how the DTaP-HepB-IPV vaccine would fit into different administration and scheduling scenarios. However, the nurse and business managers reported that nursing morale was drastically improved with the use of the DTaP-HepB-IPV vaccine because of the decreased stress associated with fewer syringes to prepare, fewer injections to administer, and less record-keeping. They also believed that the combination vaccine was useful for catch-up vaccination in children who were behind schedule with their immunizations. Similarly, this group of managers thought that older children (up to 7 years of age) who had not finished the primary series could benefit from use of the DTaP-HepB-IPV vaccine.

The next question was “whether a birth dose of HepB vaccine had an impact upon the providers' decision to use the DTaP-HepB-IPV vaccine.” Nearly all of the nurse and business managers responded “No” (Table 3).

The final question on the survey was “whether they thought the DTaP-HepB-IPV vaccine increased immunization compliance.” Most (96%) of those surveyed answered “Yes” to this question (Table 3). However, this group also stressed the importance of addressing parental concerns and fears regarding the use of combination vaccines. They believed it was important to emphasize to parents that the DTaP-HepB-IPV vaccine was not a “new” vaccine but a combination of several vaccines that have a long history of use.

Parent Perspective 

Nearly all of the parents checked “Agree” with all four statements listed on the survey (Table 4), indicating that they were in favor of using combination vaccines to protect their children from vaccine-preventable diseases and had positive experiences with the DTaP-HepB-IPV vaccine. Three percent of the parents surveyed reported mild injection-site reactions, low-grade fever, and irritability after their children received the DTaP-HepB-IPV vaccine. Written comments included: “I feel better when my baby does not get as many shots at one time,” and “I hope more combination shots will be available soon.” These responses suggest that parents want their children to receive fewer shots, and they expect the vaccines to be safe and effective for their children.

Table 4. Parent survey responses (n = 92)

	Question	Agree (%)	Disagree (%)
	I like that we can use vaccines to prevent many childhood diseases (n = 92)	100	0
	I am in favor of using combination vaccines to reduce the number of injections my baby receives (n = 91)	100	0
	I did not encounter any problems after my baby received DTaP-HepB-IPV vaccine (n = 88)	97	3
	I hope that new vaccines to prevent childhood diseases will be available in combination form so infants don't have to get too many shots (n = 78)	100	0

DTaP, Diphtheria and tetanus toxoids and acellular pertussis; HepB, hepatitis B; IPV, inactivated polio virus.

Despite the limitations of these surveys, including small sample size and lack of survey validation, it can be seen that the DTaP-HepB-IPV vaccine was well received among most providers, nurse and business managers, and parents. The nurse and business manager survey, however, highlighted some of the concerns addressed previously (“Implementation of combination vaccines”) and the importance of staff and parent education.