Cost effectiveness sensitivity

Question

The effects of alternative vaccine compositions on the outcomes of the cost-effectiveness analysis were assessed. Five modifications for PCV10 and one for PCV13 were considered.

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 (shown below), quality adjusted life years gained (not shown) and medical costs (not shown) are relatively minor. Therefore, if the vaccine price is equal for PCV10 and PCV13, then in view of the intrinsic uncertainties in the model, PCV10 and PCV13 can be regarded as roughly equally cost-effective.

1.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
              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 
 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 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.

 * 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.

 (#)= costs and savings in 1000 euros
 
 * NOTE: 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-)

2. Acceptable price level for PCV13 for a given price of PCV10 under alternative scenarios

 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):
  [1]  pcv10       
  [2]  pcv10 + 19A(direct effects only)
  [3]  pcv10 + 6A      
  [4]  pcv10 + 19A(direct only) + 6A
 columns (vaccine composition PCV13 with or without serotype 3):
  [1]  pcv13 - 3 (excluding serotype 3)     
  [2]  pcv13

                 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 
 -------
 The inclusion of serotype 3 (with full indirect effects) in PCV13 is crucial. If serotype 3 
 is not included in PCV13 8the default scenario), then the acceptable cost for PCV13 can be 
 either above or below the cost of PCV10, depending on assumptions regarding the role of 6A in PCV10.