Talk:Epidemiological modelling

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Argument moved from Talk:Economic evaluation:

----K3: . In the latest published FinIP data for pneumonia the data seem to show a higher than expected effeciveness for PCV10. We want to suggest that this data should be cosidered in light of a recent study in Sweden where PCV10 and PCV13 are both used in a real life setting in the same healthcare system. From this study, based on the Swedish National Inpatient Registry held by the National Board of Health and Welfare, it was found that PCV13 has significanlty lower pneumonia rates in infants and that PCV13 may save more in-patient cost due to pneumonia in infants compared to PCV10.[1] --Pfizer Oy, 2014-08-27 13:47:39 - R upload in Economic evaluation (type: truth; paradigms: science: comment)

----Kauq1: . We are aware of the potential impact of including other than invasive endpoints in the vaccine evaluation. The currently available data are not sufficient to (e.g.) pneumonia as one of the endpoints. Nevertheless, taking into account all evidence, the pneumococcal conjugate vaccination programme is likely to be cost saving in Finland. The implications of this on vaccine comparison will be discussed elsewhere. Kauq, Sep 7, 2014] (type: truth; paradigms: science: comment)

Comments about Question

  • "The focus is on the incidence of invasive pneumococcal disease (IPD) cases in different age groups covering the whole population."
⇤--GSK1: . Because the epidemiological model neglects the benefits of prevention of respiratory infection episodes, which effectively represent majority of the vaccine preventable disease burden[2], the outcomes are considered insufficient to inform the cost effectiveness analyses, unless supplemented with estimates for reductions in the respiratory illness, including pneumonia and acute otitis media endpoint. -- GSK 12:33, 3 September 2014 (UTC) (type: truth; paradigms: science: attack)
----#: . This comment is included in the discussion on Talk:Comparison criteria and it has had an impact on the resolution. --Jouni (talk) 10:58, 8 September 2014 (UTC) (type: truth; paradigms: science: comment)
←--Kauq2: . The above comment is true. Pneumococcal conjugate vaccination is clearly more cost effective than inferred on the basis of invasive disease alone. In fact, it is likely to be cost saving. However, in the absence of reliable data on the vaccine-preventable incidence of respiratory disease, we have deferred including respiratory infections in the analysis for the time being. See also our responses to the corresponding discussion on page Comparison criteria. Kauq, Sep 6, 2014 (type: truth; paradigms: science: defence)
  • "The coverage of vaccination and vaccine efficacy against carriage are assumed to be high enough to justify the assumption of complete elimination of vaccine-type carriage among both the vaccinated and also, due to substantial herd effects, among the unvaccinated members of the population."
⇤--GSK2: . The assumption that vaccine type (VT) disease will be reduced to zero, at a steady state, in children, should be extended to VT-related types, where effectiveness has been demonstrated.
For adults and elderly, a recent review[3], which has reviewed almost a decade of experience with PCVs in UMV has shown that while there was a dramatic reduction (nearly elimination) of VT/VT-related disease in children, in adults and elderly, the VT continue to cause disease years after implementation of the programme. Therefore, the assumption about complete elimination of VT disease in these age groups, even at a steady state, is not supported by available data.
Assuming the adult disease is reduced to zero would be a gross overestimation of what can be realistically expected from a PCV programme based on the experience with PCVs so far. The assumption should be therefore adjusted based on the findings reported[3], except where there is clear evidence suggesting no impact of the vaccine on nasopharyngeal carriage for a particular serotype. --GSK 12:33, 3 September 2014 (UTC) (type: truth; paradigms: science: attack)
⇤--Kauq3: . Even assuming the time frame of 5-10 after vaccination onset, it may be true that full elimination is not obtained for some serotypes, even if there would be indirect effects through reduced transmission. Then again, the available data on both PCV10 and PCV13 vaccines have not accumulated for long enough to make any definitive statements. Moreover, for comparing the effectiveness of two vaccines, it is likely that exact assumptions about the eventual extent of vaccine-serotype elimination are not too important.
Of note, the current analysis includes efficacy and/or effectiveness for some cross-reactive serotypes in the two currently available conjugate vaccines, in particular serotypes 6A and 6C (see the discussion on Comparison criteria and the analysis in Economic evaluation). A sensitivity analysis was performed to investigate the importance of assumptions of cross-immunity on vaccine comparisons. Kauq, Sep 6, 2014 (type: truth; paradigms: science: attack)
  • "Vaccine-type carriage will be completely replaced by carriage of the non-vaccine types whose disease causing potential is not altered by vaccination."
⇤--GSK3: . There is some uncertainty with respect to the assumption of the extent of replacement for respective vaccine formulations[4][5]. Because this could extensively impact on the outcomes of the model, this uncertainty should be acknowledged and preferentially also be reflected in the weight which is attributed to the outcomes of the modelling in the award criteria. --GSK 12:33, 3 September 2014 (UTC) (type: truth; paradigms: science: attack)
⇤--Kauq4: . There is considerable evidence about the impact of serotype replacement on the effectiveness of PCV vaccination. The same assumptions have been made regarding the 10 common serotypes in the two currently available pneumococcal conjugate vaccines. Regarding the three additional serotypes in PCV13 (3, 6A, and 19A), special attention has been given to evaluate the impact of assumptions regarding their efficacy (direct protection) or expected effectiveness (indirect protection). This includes e.g. possible cross-immunity against 6A for PCV10 as well as possible cross-immunity against 6C for PCV13. Kauq, Sep 6, 2014 (type: truth; paradigms: science: attack)
  • "The replacement model was built to reflect the accumulated 15 year long experience on use of pneumococcal conjugate vaccines worldwide and the related scientific research activity."
⇤--GSK4: . Given the limitations and uncertainties around the assumptions of the model, especially on the replacement and consecutively net impact of PCVs in adults and elderly, as highlighted in the previous comments, it should be considered to take a conservative approach and assume similar replacement in disease and consequently similar net effect in adults and elderly with both formulations, that was observed with the first generation PCV, as a base case of the model. --GSK 12:33, 3 September 2014 (UTC) (type: truth; paradigms: science: attack)
⇤--Kauq5: . We have not adopted this approach. Some important differences between the two vaccines regard the effect of serotype replacement in the adult population. The current sensitivity analysis indicates that, depending on the assumptions, either of the two currently available vaccines may be more effective in the general population. Kauq, Sep 6, 2014 (type: truth; paradigms: science: attack)


  1. Berglund A., Ekelund M., Nyman L., poster from ISPPD-9
  2. Palmu et al, ESPID, 2014
  3. 3.0 3.1 Feikin et al, Plos Medicine, 2013
  4. Vesikari, ECCMID, 2013
  5. Dagan, CID, 2013.