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In addition, assumptions about the role of 6A in PCV10 is important.  
In addition, assumptions about the role of 6A in PCV10 is important.  


If serotype 3 is not included as a vaccine type in PCV13, then the differences between PCV10 and PCV13 in IPD, quality adjusted life years gained and medical costs are small (see Tables 1-7 in Section 1 below). Considering the magnitudes of these differences in view of the intrinsic uncertainties in the model, PCV10 and PCV13 can be regarded as equally effective.  
If serotype 3 is not included as a vaccine type in PCV13, then the differences between PCV10 and PCV13 in IPD, quality adjusted life years gained and medical costs are small (see Tables 1-7 in Section A below). Considering the magnitudes of these differences in view of the intrinsic uncertainties in the model, PCV10 and PCV13 can be regarded as equally effective.  


== Rationale ==
== Rationale ==
<br>
<br>
 
Cost-effectiveness sensitivity analysis results are divided into sections A,B and C.
==1.Vaccine effects on IPD, QALYs and costs by age group for alternative scenarios==
<br>
==A.Vaccine effects on IPD, QALYs and costs by age group for alternative scenarios==
<br>
<br>


  Quantities tabulated:
'''Quantities tabulated:'''
    
    
   IPD  =  number of IPD cases per year in Finland
   IPD  =  number of IPD cases per year in Finland
Line 24: Line 25:
    
    
   QALYs lost = QALYs lost due to IPD per year in Finland, in years
   QALYs lost = QALYs lost due to IPD per year in Finland, in years
               QALY=quality adjusted life year
              (QALYs related to IPD only)
               QALY = quality adjusted life year
   QALYs gained = QALYs gained due to the first mentioned vaccine
   QALYs gained = QALYs gained due to the first mentioned vaccine
    
    
   Medical costs = Medical costs due to IPD per year in Finland in 1000 euros  
   Medical costs = Medical costs due to IPD per year in Finland in 1000 euros  
   Medical savings = Difference in medical costs in 1000 euros per year in favor of the first  mentioned  vaccine
                  (costs related to IPD only)
   Medical savings = Difference in medical costs in 1000 euros per year  
                    in favor of the first  mentioned  vaccine


  Vaccine formulation considered:
'''Vaccine formulation considered:'''
    
    
   PCV10 includes the 10 serotypes in PCV10 and direct effects for serotypes 6A and 19A
   PCV10 includes the 10 serotypes in PCV10 and direct effects for serotypes 6A and 19A
   PCV10(6Af) includes the 10 serotypes in PCV10 amended by serotype 6A and direct effects (##) for 19A
   PCV10(6Af) includes the 10 serotypes in PCV10 amended  
            by serotype 6A and direct effects (##) for 19A
    
    
   PCV13 includes 12 serotypes in PCV13, serotype 3 excluded. Assumes direct effects for serotypes 3  and 6C.
   PCV13 includes 12 serotypes in PCV13, serotype 3 excluded.  
   PCV13(6Cf) includes 12 serotypes in PCV13, serotype 3 excluded and 6C added. Assumes direct effects  for serotypes 3.
        Assumes direct effects for serotypes 3  and 6C.
   PCV13(6Cf) includes 12 serotypes in PCV13, serotype 3 excluded  
            and 6C added. Assumes direct effects  for serotypes 3.


<br>
'''Results''':
<br>
   * 1.No Vaccination
   * 1.No Vaccination
   --------------                      age group
   --------------                      age group
Line 95: Line 105:
   
   


  Interpretation  
'''Interpretation''':
  -------
<br>
  Table 1 displays quantities when no vaccination is applied and Tables  2-3 display results for  
Table 1 displays quantities when no vaccination is applied and Tables  2-3 display results for  
  the default scenarios PCV10 and PCV13. The vaccines decrease QALYs and medical costs by approximately 20-25%.  
the default scenarios PCV10 and PCV13. The vaccines decrease QALYs and medical costs  
  In comparison to these effets, the differences pertaining to pairwise comparisons of various versions of the  
by approximately 20-25%.  
  vaccines (Tables 4-7) are small. Negative numbers in Tables 4-7 indicate situations favorable to PCV10.
In comparison to these effets, the differences pertaining to pairwise comparisons of various  
versions of the vaccines (Tables 4-7) are small. Negative numbers in Tables 4-7 indicate  
situations favorable to PCV10.
<br>


  (#)= costs and savings in 1000 euros
'''(*)'''= In the calculations above, the original observed/predicted number of IPD cases
among under 3 year old children is multiplied 3.75. This adjustment was made to
better reflect the actual disease incidence 
(reference: Palmu et al. (2014) Vaccine effectiveness of the pneumococcal..,
The Lancet Resp. Med.Vol2,9,p.717-)
 
'''(#)'''= costs and savings are given in 1000 euros
    
    
  * NOTE: In the calculations above, the original observed/predicted number of IPD cases among under 3 year  
'''(##)'''= a vaccine with "only direct effects" for a particular serotype means that,
  old children is multiplied 3.75. This adjustment was made to better    reflect the actual disease incidence
for vaccinated persons, vaccine efficacy against IPD caused by this serotype is 90% with
  (reference: Palmu et al. (2014) Vaccine effectiveness of the pneumococcal..,The Lancet Resp. Med.Vol2,9,p.717-)
a waning rate of 10% per year. In practise this means that approximately 70% of the  
serotype-specific IPD is eliminated among the <5 year olds. The implications of
this modification to the results pertaining to the population as a whole
are quite small and correspond closely to assuming no vaccine efficacy against 
the serotype in question.
 
<br>
 
==B. Vaccine effects on IPD, QALYs and costs for alternative scenarios, summary==
<br>


   (##) = Above, a vaccine with "only direct effects" for a particular serotype means that,
'''Quantities tabulated''':
  for vaccinated persons, vaccine efficacy against IPD caused by this serotype is 90% with
  a waning rate of 10% per year. In practise this means that approximately 70% of the  
   IPD decrease = decrease in IPD due to the vaccine appearing in
  serotype-specific IPD is eliminated among the <5 year olds. The implications of
                the column label vs the vaccine appearing in the row
  this modification to the results pertaining to the population as a whole
   QALYs gained = same for QALYS gained (QALYs related to IPD only)
   are quite small and correspond closely to assuming no vaccine efficacy against
   Medical savings = same for saving in medical costs (costs related to IPD only)
   the serotype in question.


'''Vaccine formulations considered''':
PCV10(a) vaccine including all of the 10 serotypes
PCV10 includes the 10 serotypes in PCV10 and direct effects for serotypes 6A and 19A
PCV10(6Af) includes the 10 serotypes in PCV10 amended
            by serotype 6A and direct effects (##) for 19A
PCV13(a) vaccine including all of the 13 serotypes, including serotype 3
PCV13  includes 12 serotypes in PCV13, serotype 3 excluded.
        Assumes direct effects for serotypes 3  and 6C.
PCV13(6Cf) includes 12 serotypes in PCV13, serotype 3 excluded
            and 6C added. Assumes direct effects  for serotypes 3.


<br>
'''Results''':
<br>
  IPD decrease                                                                                         
  ------------                         
                PCV13(a) PCV13  PCV13(6Cf)
                ------  -----  ----------     
  PCV10(a)    227      95      50           
  PCV10        137      4      -40           
  PCV10(6Af)  187      54      10           
  QALYs gained                                                                                         
  ------------                     
                PCV13(a) PCV13  PCV13(6Cf)       
                ------  -----  ----------
  PCV10(a)    305      5      -79           
  PCV10        260      -42    -123         
  PCV10(6Af)  357      57      -24         
  Medical costs saved (in 1000 euros)                                                                               
  -------------------
                PCV13(a) PCV13  PCV13(6Cf)
                ------  -----  ----------
  PCV10(a)    1294    125    -215   
  PCV10        1035    -143    -474   
  PCV10(6Af)  1425    256    -75   


'''Interpretation''':
<br>
<br>
These are summaries of Tables 4-7 in Section A now also
including "full" 10- and 13- valent versions of the vaccines.
The crucial effect of inclusion of serotype 3 in PCV13
is clear.


==2. Acceptable price level for PCV13 for a given price of PCV10 under alternative scenarios==
<br>
<br>
  Three separate tables are displayed, each corresponding to a different quantity.
 
  The three quantities of interest are:
  * PCV13adv.inIPD =  PCV13 advantage in IPD
    = (IPD under PCv10) - (IPD under PCV13)
      if positive, PCV13 saves IPD cases compared to PCV10
  * price of PCV13
    =  if PCV10 price set at 20e, what is the matching price for PCV13?
  * ICER
    = incremental cost-effectiveness ratio for PCV10 at price 20e
      (in this table, this value is also average cost per QALY)


  rows (vaccine composition PCV10 and its 5 modifications):
==C. Acceptable price level under alternative scenarios for PCV13 when price of PCV10 set at 20 and 30==
   [1] pcv10     
 
   [2] pcv10 + 19A(direct effects only)
<br>
   [3]  pcv10 + 6A      
 
   [4]  pcv10 + 19A(direct only) + 6A
'''Quantities tabulated and vaccine formulations considered''':
  columns (vaccine composition PCV13 with or without serotype 3):
 
   [1]  pcv13 - 3 (excluding serotype 3)    
<br>
   [2] pcv13
Column and row labels as in tables as in Section B. The entries
are prices acceptable for PCV13 when PCV10 price is 10 or 20.
Any price below the given value is acceptable for PCV13.
<br>
 
In addition, the incremental cost effectiveness ratio (ICER)is given.
This is the ICER either when the more effective vaccine is
compared to the other or when the less effective is compared to 
the "no vaccination" scenario. It corresponds to the average
price of a QALY gain when either of the vaccines is chosen 
assuming the indicated price level.
 
<br>
 
'''Results''':
<br>
 
   Max price for PCV13 when price of PCV10 = 20  
   --------------------------------------------
                                                       
                PCV13(a) PCV13 PCV13(6Cf)  ICER(#)
                ------  -----  ----------  ----
   PCV10(a)    38      21     16          6.27   
   PCV10        33      18      14          4.85   
  PCV10(6Af)   44      24      18          7.92   
 
 
 
  Max price for PCV13 when price of PCV10 = 30
  --------------------------------------------
                                                           
              PCV13(a) PCV13  PCV13(6Cf)    ICER(#)
              ------  -----  ----------   ----
  PCV10(a)   57      31      24          11.6   
  PCV10      50      27      21          9.63   
   PCV10(6Af) 66      36      27          14.3   


                  PCV13adv.inIPD  price of PCV13    ICER
                  ==============  ==============    ===============
                  PCV13-3  PCV13  PCV13-3  PCV13    PCV13-3  PCV13
                    ---    ---    -------  -----    -----    ----
  pcv10            12    150      18    38        8077    8077
  pcv10+19Ad        -2    134      17    37        7714    7714
  pcv10+6A          50    188      25    55      13590    13590
  pcv10+19Ad+6A    32    169      24    52      12724    12724
                                  ----------------
                                  (PCV10 price=20)


  Interpretation
'''Note''':
  -------
<br>
  The inclusion of serotype 3 (with full indirect effects) in PCV13 is crucial. If serotype 3
(#)= in 1000 euros
  is not included in PCV13 8the default scenario), then the acceptable cost for PCV13 can be
<br>
  either above or below the cost of PCV10, depending on assumptions regarding the role of 6A in PCV10.


These tables are calculated taking into account benefits
related to IPD only. If other disease entities are taken into
accoount, the vaccines may well be cost saving (in terms of
total health care costs) and these tables are to be
interpreted with caution. Nevertheless, they indicate
that if serotype 3 is not included in PCV13, then the
differences between the vaccines are much smaller and,
depending on assumptions, may be in favor of either
one of the vaccines.


<br>
<br>

Latest revision as of 10:35, 14 September 2014


Question

The effects of alternative vaccine compositions on the outcomes of the cost-effectiveness analysis were assessed. Results are reported for PCV10 with modified effects for serotypes 19A and 6A and for PCV13 with modified effects for serotypes 3 and 6C.

Answer

Conclusion: The assumption about serotype 3 in PCV13 is crucial. In addition, assumptions about the role of 6A in PCV10 is important.

If serotype 3 is not included as a vaccine type in PCV13, then the differences between PCV10 and PCV13 in IPD, quality adjusted life years gained and medical costs are small (see Tables 1-7 in Section A below). Considering the magnitudes of these differences in view of the intrinsic uncertainties in the model, PCV10 and PCV13 can be regarded as equally effective.

Rationale


Cost-effectiveness sensitivity analysis results are divided into sections A,B and C.

A.Vaccine effects on IPD, QALYs and costs by age group for alternative scenarios


Quantities tabulated: 

 IPD  =  number of IPD cases per year in Finland
 IPD decrease = decrease in IPD due to the first mentioned vaccine
 
 QALYs lost = QALYs lost due to IPD per year in Finland, in years
              (QALYs related to IPD only)
              QALY = quality adjusted life year
 QALYs gained = QALYs gained due to the first mentioned vaccine
 
 Medical costs = Medical costs due to IPD per year in Finland in 1000 euros 
                 (costs related to IPD only)
 Medical savings = Difference in medical costs in 1000 euros per year 
                   in favor of the first   mentioned   vaccine

Vaccine formulation considered: 

 PCV10 includes the 10 serotypes in PCV10 and direct effects for serotypes 6A and 19A
 PCV10(6Af) includes the 10 serotypes in PCV10 amended 
            by serotype 6A and direct effects (##) for 19A
 
 PCV13  includes 12 serotypes in PCV13, serotype 3 excluded. 
        Assumes direct effects for serotypes 3   and 6C.
 PCV13(6Cf) includes 12 serotypes in PCV13, serotype 3 excluded 
            and 6C added. Assumes direct effects   for serotypes 3.


Results: 

 * 1.No Vaccination
 --------------                       age group
                   0- 4    5- 19    20- 44    44- 64    65- 100  Total
                   ----    -----     -----     -----     ------  -----
 IPD                330       26       124       236        302   1017
 QALYs lost         156       12       284       605        558   1615
 Medical costs (#)  918       70      1279      2431       2146   6843

 * 2.PCV10 vs "No Vaccination"
 --------------                       age group
                   0- 4    5- 19    20- 44    44- 64    65- 100  Total
                   ----    -----     -----     -----     ------  -----
 IPD decrease       225       15        49        30         45    362
 QALYs gained       105        7       102        76         86    376
 Medical savings(#) 608       37       504       306        320   1774

 * 3.PCV13 vs "No Vaccination"
 --------------                       age group
                   0- 4    5- 19    20- 44    44- 64    65- 100  Total
                   ----    -----     -----     -----     ------  -----
 IPD decrease       246       15        43        16         47    366
 QALYs gained       114        7        86        39         89    334
 Medical savings    656       38       443       160        335   1631

 * 4.PCV13 vs PCV10
 --------------                       age group
                   0- 4    5- 19    20- 44      44- 64  65- 100  Total 
                   ----    -----     -----     -----     ------  -----
 IPD decrease        21        0        -6         -14        2      4
 QALYs gained         9        0       -16         -37        3    -42
 Medical savings     48        1       -61        -146       15   -143

   * 5.PCV13(6Cf) vs PCV10
 --------------                       age group
                     0- 4    5- 19    20- 44    45- 64   65-100  Total
                     ----    -----    ------   -------   ------  -----
 IPD decrease          11     -1       -11       -29      -10      -40
 QALYs gained           4     -1       -29       -76      -21     -123
 Medical savings       17     -2      -116      -299      -74     -474

 * 6.PCV13 vs PCV10(6Af)
 --------------                       age group
                     0- 4    5- 19    20- 44    45- 64   65- 100 Total
                     ----    -----    ------   -------   ------  -----
 IPD decrease          31      2         1         6       14       54
 QALYs gained          15      1         1        13       28       57
 Medical savings       83      5        10        55      103      256

 * 7.PCV13(6Cf) vs PCV10(6Af)
 --------------                       age group
                    0- 4    5- 19    20- 44    45- 64   65- 100  Total
                     ----    -----    ------   -------   ------  -----
 IPD decrease         21      1        -4        -9        2        10
 QALYs gained         10      0       -12       -26        4       -24
 Medical savings      52      2       -45       -98       14       -75

Interpretation:
Table 1 displays quantities when no vaccination is applied and Tables 2-3 display results for the default scenarios PCV10 and PCV13. The vaccines decrease QALYs and medical costs by approximately 20-25%. In comparison to these effets, the differences pertaining to pairwise comparisons of various versions of the vaccines (Tables 4-7) are small. Negative numbers in Tables 4-7 indicate situations favorable to PCV10.

(*)= In the calculations above, the original observed/predicted number of IPD cases among under 3 year old children is multiplied 3.75. This adjustment was made to better reflect the actual disease incidence (reference: Palmu et al. (2014) Vaccine effectiveness of the pneumococcal.., The Lancet Resp. Med.Vol2,9,p.717-)

(#)= costs and savings are given in 1000 euros

(##)= a vaccine with "only direct effects" for a particular serotype means that, for vaccinated persons, vaccine efficacy against IPD caused by this serotype is 90% with a waning rate of 10% per year. In practise this means that approximately 70% of the serotype-specific IPD is eliminated among the <5 year olds. The implications of this modification to the results pertaining to the population as a whole are quite small and correspond closely to assuming no vaccine efficacy against the serotype in question.


B. Vaccine effects on IPD, QALYs and costs for alternative scenarios, summary


Quantities tabulated: 

 IPD decrease = decrease in IPD due to the vaccine appearing in 
                the column label vs the vaccine appearing in the row
 QALYs gained = same for QALYS gained (QALYs related to IPD only)
 Medical savings = same for saving in medical costs (costs related to IPD only)

Vaccine formulations considered: 

PCV10(a) vaccine including all of the 10 serotypes
PCV10 includes the 10 serotypes in PCV10 and direct effects for serotypes 6A and 19A
PCV10(6Af) includes the 10 serotypes in PCV10 amended 
           by serotype 6A and direct effects (##) for 19A

PCV13(a) vaccine including all of the 13 serotypes, including serotype 3
PCV13  includes 12 serotypes in PCV13, serotype 3 excluded. 
       Assumes direct effects for serotypes 3   and 6C.
PCV13(6Cf) includes 12 serotypes in PCV13, serotype 3 excluded 
           and 6C added. Assumes direct effects   for serotypes 3.


Results: 

  IPD decrease                                                                                          
  ------------                          
               PCV13(a) PCV13  PCV13(6Cf) 
               ------   -----  ----------       
  PCV10(a)     227      95      50             
  PCV10        137      4       -40            
  PCV10(6Af)   187      54      10             

  QALYs gained                                                                                          
  ------------                      
               PCV13(a) PCV13  PCV13(6Cf)        
               ------   -----  ----------
  PCV10(a)     305      5       -79            
  PCV10        260      -42     -123           
  PCV10(6Af)   357      57      -24           

  Medical costs saved (in 1000 euros)                                                                                
  -------------------
               PCV13(a) PCV13  PCV13(6Cf) 
               ------   -----  ----------
  PCV10(a)     1294     125     -215    
  PCV10        1035     -143    -474    
  PCV10(6Af)   1425     256     -75


Interpretation:
These are summaries of Tables 4-7 in Section A now also including "full" 10- and 13- valent versions of the vaccines. The crucial effect of inclusion of serotype 3 in PCV13 is clear.


C. Acceptable price level under alternative scenarios for PCV13 when price of PCV10 set at 20 and 30


Quantities tabulated and vaccine formulations considered:


Column and row labels as in tables as in Section B. The entries are prices acceptable for PCV13 when PCV10 price is 10 or 20. Any price below the given value is acceptable for PCV13.

In addition, the incremental cost effectiveness ratio (ICER)is given. This is the ICER either when the more effective vaccine is compared to the other or when the less effective is compared to the "no vaccination" scenario. It corresponds to the average price of a QALY gain when either of the vaccines is chosen assuming the indicated price level.


Results: 

  Max price for PCV13 when price of PCV10 = 20  
  --------------------------------------------
                                                        
               PCV13(a) PCV13  PCV13(6Cf)   ICER(#)
               ------   -----  ----------   ----
  PCV10(a)     38       21      16          6.27     
  PCV10        33       18      14          4.85     
  PCV10(6Af)   44       24      18          7.92     



  Max price for PCV13 when price of PCV10 = 30
  --------------------------------------------
                                                            
              PCV13(a) PCV13  PCV13(6Cf)    ICER(#)  
              ------   -----  ----------    ----
  PCV10(a)    57       31      24           11.6    
  PCV10       50       27      21           9.63    
  PCV10(6Af)  66       36      27           14.3


Note:
(#)= in 1000 euros

These tables are calculated taking into account benefits related to IPD only. If other disease entities are taken into accoount, the vaccines may well be cost saving (in terms of total health care costs) and these tables are to be interpreted with caution. Nevertheless, they indicate that if serotype 3 is not included in PCV13, then the differences between the vaccines are much smaller and, depending on assumptions, may be in favor of either one of the vaccines.


See also

Tendering process for pneumococcal conjugate vaccine
Parts of the assessment

Comparison criteria for vaccine   · Epidemiological modelling   · Economic evaluation

Background information

Sensitivity analysis · Replacement   · Pneumococcal vaccine products   · Finnish vaccination schedule   · Selected recent publications

Help for discussion and wiki editing

Pages in Finnish

Pneumokokkirokotteen hankinta  · Rokotteen vertailuperusteet · Epidemiologinen malli · Taloudellinen arviointi · Pneumokokkirokotteen turvallisuus

Work scheduling · Monitoring the effectiveness of the pneumococcal conjugate vaccine · Glossary of vaccine terminology


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