Felicia Ratnaraj - 2013

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Quantifying the Extent of Human Papillomavirus quadrivalent recombinant vaccine (HPV4) Wastage in a Safety Net Population Felicia Ratnaraj 1 ; Diane M. Harper 1,2 Inge Verdenius 3 , Anne Arey 1,2 , Beth Rosemergey 1,2 , Gerard J Malnar 1,2 , Jeffrey Wall 1 1 University of Missouri-Kansas City School of Medicine, 2 Truman Medical Center, 3 Radboud University, Nijmegen, the Netherlands Introduction: Results for Insufficient Numbers of Doses : Discussion: Human Papillomavirus quadrivalent recombinant vaccine (HPV4), a vaccine requiring three timed doses, provides efficacy against oncogenic Human Papillomaviruses (HPV types 16 and 18). 1 Currently, at $98.60 per dose via the CDC and at $135.45 per dose via private sector, HPV4 is the most expensive prophylactic vaccine marketed on an individual and national basis. 2 The completion rates of the on-time three-dose HPV4 series range from 12-37% within the US. 3 Other three dose vaccines have a 40-45% on-time completion rate for adolescents and young adults, with only 1-2% receiving mistimed doses. 4 However, the cost of those vaccines are 1/10 the cost of HPV4. 1 The primary purpose of this study is to quantify the wastage of HPV4 in a safety net health care system and to determine the predictors of wastage by HPV4 dose, to guide future cost-effective prevention programs. Methods: A retrospective study of HPV4 usage was conducted between July 1, 2006 and October 1, 2009, the time frame when HPV4 was the exclusive HPV vaccine approved by the FDA. The date, dose number, visit type and subject characteristics were abstracted from the electronic medical records for all females 10-26 years old who received HPV4 in the TMC system. Unique dose wastage was classified as a dose given too early or too late from the prior dose, defined for dose 1-2 as < 4 weeks, for dose 2-3 as < 12 weeks and for dose 1-3 as < 24 weeks; or for dose 1-2 > 26 weeks or 1-3 > 52 weeks. Dose wastage was also defined as less than three doses in a series (singleton or doublets) or the fourth dose when a fourth dose was given. This research was approved by the TMC Privacy Board and the UMKC Adult Health Sciences Institutional Review Board. Three quarters of the wasted doses were either singletons (651/1961) (missed second and third dose) or doublets (818/1961) (missed third dose) (Figure 1). Over half of the singleton and doublet doses were administered at a visit without a physician at which only HPV4 was provided, termed a HPV4-only visit (Figure 2). Singleton doses were administered significantly more frequently at postpartum visits and in the year 2009 compared to a dose in a doublet. A doublet dose occurred significantly more often than a singleton dose if it was given at a HPV4-only visit, a preventive visit, a follow up from an acute illness visit or in 2010 (Figure 2 and 3). Studies of HPV4 and other vaccines to date have shown that compliance with dosing intervals is critical for the induction of immune response and long term memory. Insufficient numbers of and mistimed HPV4 doses have had little rigorous attention but substantially and negatively impact the cost effectiveness of the vaccination program. Our study showed that HPV4 doses as administered in our safety net system cannot provide the expected efficacy to reduce abnormal Pap screening, colposcopies, and treatment procedures. 5 The vast majority of the wasted doses in our study were due to insufficient numbers of doses. Thus HPV2, which is effective in less than three doses, might be more cost effective. 6 Among uniquely mistimed doses, significantly fewer doses were early (92/225) than late (133/225) (41% vs. 59%). Among early doses, third doses were early from the first dose significantly more often than second doses from the first (26% vs. 2%); likewise, among the late doses, third doses were late from the first dose significantly more often than second doses from the first (38% vs. 21%) (Figure 4). Mistimed second doses occurred significantly less often than mistimed third doses when provided at a HPV4-only visit (37% vs. 53%) and more often when provided at a postpartum visit (22% vs. 8%) (Figure 5). After adjusting for all visit types and year of administration , only the postpartum visit administration increased the likelihood of a mistimed second dose compared to a mistimed third dose (aOR=5.56 (95% CI: 2.21, 14.04). Likewise, the likelihood of a mistimed second dose was significantly higher than a mistimed third dose in years 2008, 2009 and 2010 of the HPV4 implementation program. Conclusion: Until behavioral changes can be implemented to ensure three doses are administered on time, using HPV2, as it is effective in less than three doses, or encouraging adherence to screening guidelines will offer more cost effective cervical cancer prevention. Reference: 1. Human Papillomavirus Vaccine. h5p://www.cdc.gov/vaccinesafety/Vaccines/HPV/Index.html . Accessed February 9, 2013. 2. CDC Vaccine Price List. h5p://www.cdc.gov/vaccines/programs/vfc/awardees/ vaccin emanagement/pricelist/. Accessed February 10, 2013. 3. Centers for Disease Contr ol and PrevenLon. NaLonal and State VaccinaLon Coverage Among Adolescents Aged 13 Through 17 Years — United States, 2011. MMWR. 2012;61:671677. 4. Nelson JC, Bi5ner RC, Bounds L, et al. Compliance with mulLpledose vaccine schedules among older children, adolescents, and adults: results fr om a vaccin e safety d atalink study. Am J Public Health. 2009;99(suppl 2):S38997. 5. Harper DM, Vierthaler SL, Santee JA. Review of Gardasil. Journal of Vaccines and VaccinaLon. 1:107. doi:10.4172/21577560.10001. 6. K reimer AR, Rodriguez AC, Hildesheim A, et al. Proofofprinciple evaluaLon of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine. J Natl Cancer Inst. 2011;103(19):144451. Results for Mistimed Doses: Figure 4: Mistimed doses among Triplet and Quadruplets doses 2993 doses of HPV4 were administered between July 1, 2006 and October 1, 2009 in the TMC health care system. 66% (1961/2993) of patients received insufficient number of or mistimed HPV4 doses to induce the expected immune response necessary for HPV infection prevention. Results: Results for Insufficient Numbers of Doses vs. Mistimed HPV4 Doses : Insufficient number of doses occurred significantly more commonly than mistimed doses when the dose was given to an older female and at a postpartum exam (Table 1). Mistimed doses occurred significantly more commonly than insufficient numbers of doses when the dose was provided earlier in the program administration and if given at a follow up visit (Table 1). Adjusted OR (95% CI) Year of Administration 0.997 (0.996, 0.997) Age 1.07 (1.02, 1.13) Visit Type HPV4-only referent Acute Illness 1.23 (0.66, 2.32) Follow up after an acute illness 0.36 (0.15, 0.83) Preventive Visit 0.80 (0.49, 1.32) Postpartum Visit 6.27 (3.55, 11.07) Other 1.07 (0.57, 2.01) Red indicates significance Table 1: Predictors of Insufficient HPV4 Dose numbers vs. Mistimed HPV4 Doses

Transcript of Felicia Ratnaraj - 2013

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Quantifying the Extent of Human Papillomavirus quadrivalent !recombinant vaccine (HPV4) Wastage in a Safety Net Population!

Felicia Ratnaraj1; Diane M. Harper1,2!

Inge Verdenius3, Anne Arey1,2, Beth Rosemergey1,2, Gerard J Malnar1,2, Jeffrey Wall1 !1 University of Missouri-Kansas City School of Medicine, 2 Truman Medical Center, 3 Radboud University, Nijmegen, the Netherlands!

Introduction: !!

Results for Insufficient Numbers of Doses :!

Discussion:!!

• Human Papillomavirus quadrivalent recombinant vaccine (HPV4), a vaccine requiring three timed doses, provides efficacy against oncogenic Human Papillomaviruses (HPV types 16 and 18).1!• Currently, at $98.60 per dose via the CDC and at $135.45 per dose via private sector, HPV4 is the most expensive prophylactic vaccine marketed on an individual and national basis.2 !• The completion rates of the on-time three-dose HPV4 series range from 12-37% within the US.3 !• Other three dose vaccines have a 40-45% on-time completion rate for adolescents and young adults, with only 1-2% receiving mistimed doses.4 However, the cost of those vaccines are 1/10 the cost of HPV4.1!• The primary purpose of this study is to quantify the wastage of HPV4 in a safety net health care system and to determine the predictors of wastage by HPV4 dose, to guide future cost-effective prevention programs.!

Methods: !!• A retrospective study of HPV4 usage was conducted

between July 1, 2006 and October 1, 2009, the time frame when HPV4 was the exclusive HPV vaccine approved by the FDA.!• The date, dose number, visit type and subject characteristics were abstracted from the electronic medical records for all females 10-26 years old who received HPV4 in the TMC system.!• Unique dose wastage was classified as a dose given too early or too late from the prior dose, defined for dose 1-2 as < 4 weeks, for dose 2-3 as < 12 weeks and for dose 1-3 as < 24 weeks; or for dose 1-2 > 26 weeks or 1-3 > 52 weeks. !• Dose wastage was also defined as less than three doses in a series (singleton or doublets) or the fourth dose when a fourth dose was given. !• This research was approved by the TMC Privacy Board and the UMKC Adult Health Sciences Institutional Review Board. !

• Three quarters of the wasted doses were either singletons (651/1961) (missed second and third dose) or doublets (818/1961) (missed third dose) (Figure 1).!• Over half of the singleton and doublet doses were administered at a visit without a physician at which only HPV4 was provided, termed a HPV4-only visit (Figure 2). !• Singleton doses were administered significantly more frequently at postpartum visits and in the year 2009 compared to a dose in a doublet. A doublet dose occurred significantly more often than a singleton dose if it was given at a HPV4-only visit, a preventive visit, a follow up from an acute illness visit or in 2010 (Figure 2 and 3).!

• Studies of HPV4 and other vaccines to date have shown that compliance with dosing intervals is critical for the induction of immune response and long term memory. !• Insufficient numbers of and mistimed HPV4 doses have had little rigorous attention but substantially and negatively impact the cost effectiveness of the vaccination program. !• Our study showed that HPV4 doses as administered in our safety net system cannot provide the expected efficacy to reduce abnormal Pap screening, colposcopies, and treatment procedures.5!• The vast majority of the wasted doses in our study were due to insufficient numbers of doses.!• Thus HPV2, which is effective in less than three doses, might be more cost effective.6!

• Among uniquely mistimed doses, significantly fewer doses were early (92/225) than late (133/225) (41% vs. 59%). !• Among early doses, third doses were early from the first dose significantly more often than second doses from the first (26% vs. 2%); likewise, among the late doses, third doses were late from the first dose significantly more often than second doses from the first (38% vs. 21%) (Figure 4). !• Mistimed second doses occurred significantly less often than mistimed third doses when provided at a HPV4-only visit (37% vs. 53%) and more often when provided at a postpartum visit (22% vs. 8%) (Figure 5).!• After adjusting for all visit types and year of administration , only the postpartum visit administration increased the likelihood of a mistimed second dose compared to a mistimed third dose (aOR=5.56 (95% CI: 2.21, 14.04). !• Likewise, the likelihood of a mistimed second dose was significantly higher than a mistimed third dose in years 2008, 2009 and 2010 of the HPV4 implementation program. !

!

Conclusion:!!• Until behavioral changes can be implemented to ensure

three doses are administered on time, using HPV2, as it is effective in less than three doses, or encouraging adherence to screening guidelines will offer more cost effective cervical cancer prevention. !

Reference:!!1. Human  Papillomavirus  Vaccine.  h5p://www.cdc.gov/vaccinesafety/Vaccines/HPV/Index.html.  Accessed  February  9,  2013.    

2. CDC  Vaccine  Price  List.  h5p://www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-­‐management/price-­‐list/.  Accessed  February  10,  2013.    

3. Centers  for  Disease  Control  and  PrevenLon.  NaLonal  and  State  VaccinaLon  Coverage  Among  Adolescents  Aged  13  Through  17  Years  —  United  States,  2011.  MMWR.  2012;61:671-­‐677.  

4. Nelson  JC,  Bi5ner  RC,  Bounds  L,  et  al.  Compliance  with  mulLple-­‐dose  vaccine  schedules  among  older  children,  adolescents,  and  adults:  results  from  a  vaccine  safety  datalink  study.  Am  J  Public  Health.  2009;99(suppl  2):S389-­‐97.    

5. Harper  DM,  Vierthaler  SL,  Santee  JA.    Review  of  Gardasil.    Journal  of  Vaccines  and  VaccinaLon.  1:107.  doi:10.4172/2157-­‐7560.10001.      

6. Kreimer  AR,  Rodriguez  AC,  Hildesheim  A,  et  al.  Proof-­‐of-­‐principle  evaluaLon  of  the  efficacy  of  fewer  than  three  doses  of  a  bivalent  HPV16/18  vaccine.  J  Natl  Cancer  Inst.  2011;103(19):1444-­‐51.  

     

 

Results for Mistimed Doses:!

Figure 4: Mistimed doses among !Triplet and Quadruplets doses!

• 2993 doses of HPV4 were administered between July 1, 2006 and October 1, 2009 in the TMC health care system. !• 66% (1961/2993) of patients received insufficient number of or mistimed HPV4 doses to induce the expected immune response necessary for HPV infection prevention.  !

!

Results:!!

Results for Insufficient Numbers of Doses vs. Mistimed HPV4 Doses : !• Insufficient number of doses occurred significantly more

commonly than mistimed doses when the dose was given to an older female and at a postpartum exam (Table 1).!• Mistimed doses occurred significantly more commonly than insufficient numbers of doses when the dose was provided earlier in the program administration and if given at a follow up visit (Table 1).!  ! Adjusted OR (95% CI)!

Year of Administration! 0.997 (0.996, 0.997)! Age! 1.07 (1.02, 1.13)! Visit Type!  ! HPV4-only! referent! Acute Illness! 1.23 (0.66, 2.32)! Follow up after an acute illness! 0.36 (0.15, 0.83)! Preventive Visit! 0.80 (0.49, 1.32)! Postpartum Visit! 6.27 (3.55, 11.07)! Other! 1.07 (0.57, 2.01)!Red  -­‐  indicates  significance    

Table 1: Predictors of Insufficient HPV4 Dose numbers vs. Mistimed

HPV4 Doses !