Cost effectiveness sensitivity

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 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 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 should be interpreted with great 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.