Nermina Ferizovic | Health Economics Expert

Almost all HEOR professionals have come across the ISPOR value flower which provides detail on broader elements of value which the authors argue may “warrant consideration in value assessment of medical technologies”. The value elements the authors defined are as follows: quality-adjusted life years (QALYs), net costs, productivity, adherence-improving factors, value of knowing, insurance value, fear of contagion and disease (when relevant), severity of disease, value of hope, real option-value, equity and scientific spillovers. QALYs and net costs are ‘core elements of value’ with productivity and adherence-improving factors ‘common but inconsistently used elements of value’; the remaining elements of value are considered more novel, and it is these that this blog post will focus on. 

Although not mentioned explicitly, the assumption is that these value elements also apply to advanced therapy medicinal products (ATMPs). Of note, there are discussions on the merits of the value flower which the reader is directed to, if interested. This blog post briefly explores, whether the value flower, primarily the novel elements, are applicable to ATMPs. This blog post will not consider how these elements, if applicable, could be implemented in HTA including in economic modelling. 

We begin with the definitions of the (novel) value elements as given by the authors (Table 1).

Table 1. Description of novel elements of value

Novel Value Element	Description
Value of knowing	Treatment effectiveness which may assist poor responders in moving to alternative options or identification of cases which could benefit; relevant when the treatment is accompanied by a companion diagnostic
Fear of contagion and disease	When an intervention provides benefits beyond the treated patient specifically when being treated for an infectious disease; relevant when dealing with treatments for infectious disease
Insurance value	The combination of physical risk protection and financial risk protection; relevant when baseline health status is particularly poor
Severity of disease	Disease severity might make the treatment more valuable; relevant when considering treatments for end-of-life care or high-severity conditions
Value of hope	The risk that a particular treatment may or may not work; relevant when therapies have uncertain effects that cannot be predicted beforehand by a diagnostic test
Real option value	When a health technology extends life and creates opportunities for the patient to benefit from other future advances in therapy; relevant when technology extends the life of patient
Scientific spillovers	The knowledge the mechanism works might lead to other more valuable drugs in the future; relevant when technology identifies a new mechanism of action or model of delivery

We can immediately rule out the ‘fear of contagion and disease’ as this is specific to infectious diseases which ATMPs do not treat. The ‘value of knowing’, relevant when a companion diagnostic is required before patients can be safely treated, is of (potentially some) relevance to ATMPs. Although companion diagnostics have come to be known as diagnostic tests used in companion with a therapy, many patients undergoing treatment with ATMPs have specific genetic mutations, for instance. And there may well be ATMPs in the future which are associated with a ‘companion’ diagnostic.  

Insurance value is of specific relevance in private health markets and is thus context dependent. As ATMPs are high-cost treatments, financial risk protection is of importance. This may not necessarily apply ONLY to healthcare costs as there may be other financial impacts felt by the patient and their families such as out-of-pocket costs. It is unclear whether the authors intended the standard definition of financial risk protection to apply under ‘insurance value’ but insurance value is certainly applicable to ATMPs. 

Next, we have severity of disease. The authors point out that this is relevant when considering treatments for end-of-life care or high-severity conditions. As ATMPs have a high treatment burden, they are not administered as end-of-life care therapies. However, the conditions currently being treated with ATMPs are considered severe (e.g., ADA SCID, haemophilia) meaning that this value attribute does apply to ATMPs. 

In terms of value of hope, the authors highlight that this is relevant when the treatment effect cannot be predicted beforehand by a diagnostic. Arguably, this is too strong a definition for ATMPs given their mechanism of action. As noted in a previous blog post, value of hope is commonly cited by patients and their caregivers regarding ATMPs in the context of ‘desired’ treatment effects of ATMPs. Perhaps a different definition is required for value of hope where ATMPs are concerned, and this is something which should be explored further in this context? 

Real option value is of strong relevance to ATMPs, although not in all contexts. Patients who are treated unsuccessfully may not be eligible for future treatment with an as-yet unavailable ATMP treatment option meaning that choosing to undergo therapy and remaining ‘uncured’ would limit their options for future treatment. 

Finally, scientific spillovers. ATMPs are novel treatment options of high uncertainty including of treatment effect, adverse events, durability of effect, to name a few, so there is much to gain from the benefits of scientific spillovers. A key area to benefit would be the manufacture of ATMPs. However, this value attribute will not be perpetually relevant and may not be relevant in all ATMP contexts, for instance in tissue-engineered products. 

Avid readers will note that equity has not been included in this blog post. The author agrees with the authors of the value flower in that careful consideration should be given to equity as its concept is difficult to define.

Overall, the novel elements of value described by the value flower are largely applicable to ATMPs, but thought should be given to their definitions and the context.