Whilst at ISPOR Vienna, I attended a lively session on national health economic guidelines in Southern Europe that highlighted how current practice has to catch-up with recent developments in the field. ISPOR Milan chapter’s Lorenzo Mantovani, author of the first Italian pharmacoeconomic guidelines in 1997, noted the absence of methods such as probability sensitivity analysis (PSA) in current practice in the region. Much loved by England’s NICE; PSA is a sophisticated approach to deal with the uncertainty associated with input parameters in an economic model. There were also no measures of health benefits in the form of Quality Adjusted Life Years (QALYs) in the 1997 guidelines, although now there are Italian based values for EQ-5D.

Italy focuses on indirect costs

Under the Italian Medicine Agency (AIFA)’s June 2016 economic guidelines, manufacturers have to submit a new structured dossier to secure a pricing and reimbursement decision from the National Health Service (NHS). The dossier has to contain the following elements:

  • Final HTA report based on scientific advice
  • Budget impact model
  • Cost- effectiveness model
  • Time to off-treatment curves

In the new guidelines, “innovation” must showcase an improvement with regards to effectiveness and/or safety in relation to the standard of reference used in the Italian welfare context and not the NHS; so therefore a wider societal perspective. Thus innovation is assessed via HTA studies to obtain the incremental cost-effectiveness ratio (ICER) versus the standard of reference. Until now, the assessment of innovation was centred on the effects on quality of care, with the cost of attaining it often ignored, according to Franscesco Mennini, the head of the ISPOR Rome chapter.

For the first time, AIFA has specified that if a societal perspective is adopted, it is mandatory to include indirect costs associated with productivity loss, informal care along with other indirect costs. The guidelines also recommend, whenever possible, to cluster costs by type of event associated with the natural clinical disease development, such as a transplant or a cardiovascular event, amongst others. But Mennini highlighted there is lack of consensus in terms of which indirect costs calculation method should be used. Much of this debate centres on whether one of the methods results in overestimation of the productivity loss value, thereby increasing the risk of manufacturers trying to push the argument of delivery of significant benefits to make their technologies appear very cost-effective.

Portugal needs to update

Inclusion of productivity loss value also requires clarification in the Portuguese economic guidelines published in 1999, which clearly need to be updated to keep up with scientific and methodological progress, such as how to deal with mixed treatment comparisons or adjustment for crossovers. According to health economist Luis Silva Miguel, secretary/treasurer of the ISPOR Portugal chapter, inclusion of QALYs is not mandatory, plus there should be a discussion about using Portuguese or international standards. Other missing elements are PSAs and guidance on budget impact, i.e. on adoption of a state or a NHS perspective, and if it is preferable to have multiple comparators.

The guidelines also require to include an adequate definition of the comparator chosen as they state it should be the “most used, most efficacious or the cheapest.” Sometimes the comparator can be the one used in the clinical trial, not always appropriate to the Portuguese scenario, or it can be based on expert opinion and not necessarily hard evidence. Miguel also revealed there seems to be an unspoken arrangement between national drug regulator Infarmed and the generics industry that results in waiting for the introduction of a generic drug to be used as the comparator. Besides causing delays in the reimbursement approvals of branded drugs, there is a motivation to reduce their prices by waiting for a generic market entry.

The need for updating the guidelines comes as the new national system of HTA (SINATS) faces the huge challenge of evaluating all technologies (drugs and medical devices) and the reassessment of reimbursement decisions under its 2015 mandate. This will ultimately result in a disinvestment decision-making process which should be underpinned by clear regulation. Infarmed could clearly learn from AIFA’s experience, since the latest Italian guidelines have ushered in greater transparency in terms of methodology, whilst focusing on indirect costs and generally placing greater attention on cost instead of price.

The Italian and Portuguese experiences showcase why the European Network for Health Technology Assessment (EUnetHTA) is working towards setting a general framework for an economic evaluation methodology as there is no single European view. EUnetHTA is working precisely to eliminate unnecessary methodological differences as a way to build a common European platform, which in turn will improve comparability, transferability and overall usefulness of health economic evaluations.