Box 2.

Examples of variation in HTA committees’ interpretations of the conditions for innovation set out by NICE policy

Novelty condition

Novelty of classes of drugs

In TA426, the HTA committee stated that although “second-generation” tyrosine kinase inhibitors represented an “important development in terms of pharmacological progress”, the “critical innovation” had been the development of the “first-in-class” drug (NICE, 2016d). In contrast, in TA375 the committee concluded that “the biological DMARDs [disease-modifying anti-rheumatic drugs] should be considered an innovative class of drugs” despite several of its members being “second-generation” DMARDs (Kristensen et al., 2011; NICE, 2016c)

Health benefits as ipso facto evidence of novelty

In TA384, the committee acknowledged that the cancer drug nivolumab’s mechanism of action was not “unique”, but accepted its “low toxicity” and “favourable adverse effect profile” alone as evidence of innovation (NICE, 2016e). Ixekizumab, appraised in TA442, also offered health benefits, but the committee noted that it “did not differ substantially in its mechanism of action” from existing treatments and did not class it as innovative (NICE, 2017b)

Novel use within an existing indication

In TA387, the committee acknowledged that abiraterone was “not a new” prostate cancer drug, but concluded that it could be considered innovative because “it was the first active treatment available for this position in the treatment pathway” (NICE, 2016f). In contrast, in TA326 the committee stated that although using imatinib at a novel stage in the treatment of gastrointestinal stromal tumours could offer benefits, it had “been available as a treatment […] for many years” and consequently could not be considered innovative (NICE, 2014a)

Novelty of developing an existing drug for a new indication

In TA300, the committee recalled that three anti-viral therapies for hepatitis C “were likely to have been innovative” when first used in adults, but judged that they could “no longer be considered innovative” when later used in children (NICE, 2013d). In contrast, committees have judged nivolumab to be innovative for several cancer types (e.g. renal cell carcinoma (NICE, 2016g), Hodgkin lymphoma (NICE, 2017c) and lung cancer (NICE, 2017d)), despite one acknowledging that “it was not the first checkpoint inhibitor to gain a marketing authorisation for treating cancer” (NICE, 2016g)

Novelty after many years of established use

In TA369, the committee concluded that ciclosporin—first licensed in 1983—“was not a novel technology”, despite its novel formulation (NICE, 2015g). In contrast, in TA373 the committee concluded that although the drugs in question had “been in use for a long time” (since the late 1990s), they “remain a step‑change in the management of JIA [juvenile idiopathic arthritis] […] and, as such, are innovative” (NICE, 2015b)

Substantial benefits condition

Magnitude of substantial benefits

In TA388, the committee concluded that sacubitril valsartan offered a “small step-change” in patient outcomes for chronic heart failure, despite “non-significant results” in the most relevant trial population (NICE, 2016b). In contrast, in TA282 the committee concluded that pirfenidone’s “modest [treatment] effect” meant that it could not be considered “a step change [sic] in the management of idiopathic pulmonary fibrosis” (NICE, 2013c)

Psychological benefits

In TA358, the committee recognised the “positive psychological benefit” that patients suffering from a genetic kidney disorder would derive from having an additional option for treatment of a condition with high unmet need (NICE, 2015c). In contrast, in TA403 the committee concluded that “having an extra treatment option” available in another area of high unmet need—advanced non-small-cell lung cancer—did not constitute a relevant benefit (NICE, 2016h)

Indirect health benefits

In TA269, the committee acknowledged that the development of the mutation-specific TKI vemurafenib had “advanced the understanding” of malignant melanoma and took this into account in recommending the drug (NICE, 2012a). In contrast, in TA259 the committee judged that “health benefits likely to accrue” from publicly funded research financed by sales of abiraterone fell “outside of NICE’s policy regarding innovation” (NICE, 2012b)

Non-health benefits

In TA363, the committee recognised the “improved earning capacity” of hepatitis C patients receiving treatment with ledipasvir–sofosbuvir and recognised the reduction in ICER this would bring about (NICE, 2015d). In contrast, in TA415 the committee rejected the manufacturer’s claim that certolizumab pegol’s effect “on workplace and household productivity” should be taken into account in adjusting the technology’s likely ICER (NICE, 2016i)

Demonstrable and uncounted benefits condition

Demonstrability of benefits

In TA388, the committee judged sacubitril valsartan to constitute a “step-change” in the treatment of heart failure despite “considerable uncertainties” about the magnitude of its benefits (NICE, 2016b). In contrast, in TA282, the committee considered that pirfenidone could not be considered a “step change [sic]” treatment for pulmonary fibrosis, in part because its apparent benefits had only been observed over “short duration” (NICE, 2013c)